Směrnice Komise 2000/32/XX
xx xxx 19. května 2000,
xxxxxx xx po xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx pokroku xxxxxxxx Xxxx 67/548/EHS x xxxxxxxxxx xxxxxxxx x xxxxxxxxx předpisů xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx x označování xxxxxxxxxxxx xxxxx [1]
(Xxxx x xxxxxxxx pro XXX)
XXXXXX XXXXXXXXXX SPOLEČENSTVÍ,
s ohledem xx Xxxxxxx o xxxxxxxx Xxxxxxxxxx společenství,
s xxxxxxx xx xxxxxxxx Xxxx 67/548/XXX xx xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx se xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], naposledy xxxxxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Rady 1999/33/ES [3], x xxxxxxx xx xxxxxx 28 xxxxxxx xxxxxxxx,
xxxxxxxx k xxxxx důvodům:
(1) Xxxxxxx X směrnice 67/548/EHS xxxxxxxx seznam xxxxxxxxxxxx xxxxx společně s xxxxxxxxxx xxxxx x xxxxxxxxxxx a xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxx, xx xx xxx být xxxxxx nebezpečných xxxxx x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxxxxx a xxxxxxx X x xxxxxxx X.
(2) Xxxxxxx XXX xxxxxxxx 67/548/EHS xxxxxxxx xxxxxx xxx udávajících xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx a xxxxxxxxx. Xxxxxxx XX směrnice 67/548/XXX xxxxxxxx seznam xxx s bezpečnostními xxxxxx xxxxxxxxxx se xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/EHS xxxxxxxx xxxxx xx klasifikaci x k označování xxxxxxxxxxxx xxxxx a xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx určitých xxxxxx xxxxxx XXX, XX x VI.
(3) V xxxxxxx V směrnice 67/548/XXX xx xxxxxxx xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, xxxxxxxx x ekotoxicity xxxxx x xxxxxxxxx. Je xxxxxxxx přizpůsobit xxxx xxxxxxx technickému xxxxxxx.
(4) Xxxxxxx IX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx xx uzávěrů xxxxxxxx xxxxx xxxxxxxx xxxxx. Tyto předpisy xx xxxx xxx xxxxxxxxxxxx x xxxxxxxxxxxxx. Xx xxxxxxxx xxxxxxxx xxxxxx, kde xx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx používají.
(5) Xxxxxxxx xxxx xxxxxxxx xxxx x souladu xx stanoviskem Xxxxxx xxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx xxx xxxxxxxxxx xxxxxxxxxxx překážek xxxxxxx xx xxxxx xxxxxxxxxxxx látek x xxxxxxxxx,
XXXXXXX XXXX SMĚRNICI:
Xxxxxx 1
Xxxxxxxx 67/548/XXX xx xxxx takto:
1. Xxxxxxx X xx xxxx xxxxx:
x) odpovídající xxxxxxxx v xxxxxxxxx xx xxxxxxxxx xxxxxxxxx X x příloze 1X této xxxxxxxx;
x) xxxxxxxxxxxx řádky x xxxxxxx X xx xxxxxxxxx xxxxx x xxxxxxx 1X xxxx xxxxxxxx;
x) xxxxxxxxxxxx položky xx nahrazují xxxxxxxxx x xxxxxxx 1X xxxx směrnice;
d) xxxxxxxx xx xxxxxxx v xxxxxxx 1X této xxxxxxxx.
2. Xxxxxxxxxxxx věta x xxxxxxx III xx xxxxxxxxx xxxxxxxxxx xxxxx označující xxxxxxxxxxx xxxxxxxxxx v příloze 2 xxxx xxxxxxxx.
3. Xxxxxxx XX xx xxxx xxxxx:
x) xxxxxxxxxxxx xxxxxx v xxxxxxx XX xx nahrazují xxxxxxxxxxxx xxxxxx xxx xxxxxxxx xxxxxxxxx v xxxxxxx 3X xxxx xxxxxxxx;
x) xxxxxxxxxxxx xxxxxx x xxxxxxx XX xx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxx pro xxxxxxxx xxxxxxxxx x xxxxxxx 3X xxxx xxxxxxxx.
4. Část X xxxxxxx V se xxxx xxxxx:
x) xxxxxxxx X.10 xx xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx směrnice;
b) xxxxxxxx B.11 xx xxxxxxxxx textem v xxxxxxx 4X této xxxxxxxx;
x) xxxxxxxx X.12 xx xxxxxxxxx xxxxxx x xxxxxxx 4C xxxx xxxxxxxx;
x) xxxxxxxx X.13 x B.14 xx xxxxxxxxx textem x xxxxxxx 4X xxxx xxxxxxxx;
x) xxxxxxxx X.17 xx nahrazuje xxxxxx x xxxxxxx 4X xxxx xxxxxxxx;
x) xxxxxxxx X.23 xx xxxxxxxxx textem v xxxxxxx 4X xxxx xxxxxxxx. Název kapitoly X.23 xx xxxxxxxxxxx xx mění xxxxxxxxxxxxx xxxxxxxx;
x) xxxxxx xx xxxx v xxxxxxx 4X této xxxxxxxx.
5. Xxxxxxx se xxxxxx xxxxxxx xxxxxxxx xxxxx x xxxxx X xxxxxxx X.
6. Odpovídající xxxxx v příloze XX xx nahrazují xxxxx x xxxxxxx 5 této xxxxxxxx.
7. Xxxxxxx XX xx xxxx způsobem uvedeným x xxxxxxx 6 xxxx xxxxxxxx.
Článek 2
1. Členské xxxxx uvedou x xxxxxxxx xxxxxx x xxxxxxx xxxxxxxx nezbytné xxx xxxxxxxx souladu x touto směrnicí xxxxxxxxxx do 1. xxxxxx 2001. Xxxxxxxxxx x nich uvědomí Xxxxxx.
Xxxx předpisy xxxxxxx xxxxxxxxx xxxxx musí xxxxxxxxx odkaz xx xxxx xxxxxxxx xxxx xxxx takový xxxxx xxx učiněn xxx xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx xxxxxx xx xxxxxxx členské xxxxx.
2. Xxxxxxx xxxxx xxxxx Xxxxxx znění hlavních xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx xxxxxxx x xxxxxxx xxxxxxxxxx xxxx xxxxxxxx, x xxxxxxxxxx xxxxxxx mezi xxxxxxxx x přijatými xxxxxxxxxxxxxx ustanoveními.
Xxxxxx 3
Xxxx xxxxxxxx xxxxxxxx x xxxxxxxx xxxxxx xxxx xx xxxxxxxxx x Xxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx.
Xxxxxx 4
Xxxx xxxxxxxx xx určena xxxxxxxx xxxxxx.
X Xxxxxxx xxx 19. xxxxxx 2000.
Xx Xxxxxx
Xxxxxx Xxxxxxxöx
xxxxxx Xxxxxx
[1] Přijato xx xxxxxxxxxxxx xx dvacáté xxxxx.
[2] Xx. xxxx. 196, 16.8.1967, s. 1.
[3] Úř. xxxx. X 199, 30.7.1999, x. 57.
XXXXXXX 1A
PŘEDMLUVA X XXXXXXX X
Xxxxxxxxxx poznámek xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x označování xxxxx
(Xxxxxx xx xxxxxxx xxxxx)
PŘÍLOHA 1X
"XXXXXXX X
|
X |
Xxxxxx |
XX |
XX |
XX |
XX |
XX |
XX |
XX |
XX |
XX |
XX |
XX |
|
18 |
Xx |
Xxxxx |
Xxxxx |
Xxxxx |
Αργό |
Xxxxx |
Xxxxx |
Xxxxx |
Xxxxx |
Xxxxx |
Xxxxx |
Xxxxx |
|
64 |
Xx |
Xxxxxxxxx |
Xxxxxxxxxx |
Xxxxxxxxxx |
Γαδολίνιο |
Xxxxxxxxxx |
Xxxxxxxxxx |
Xxxxxxxxxx |
Xxxxxxxxx |
Xxxxxxxxxx |
Xxxxxxxxx |
Xxxxxxxxxx" |
XXXXXXX 1C
|
Indexové xxxxx |
Xxxxxxxx xxxxx |
Xxxxxxxx x xxxxxx |
Xxxxx XX |
Xxxxx XXX |
Xxxxxxxxxxx |
Xxxxxxxx |
Xxxxxxxxxxxx limity |
Poznámky x xxxxxxxxxx |
|
006–011–00–7 |
xxxxxxxx (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx |
200–555–0 |
63–25–2 |
Xxxx. kat. 3; X40 Xn; X22 X; X50 |
Xx; X X: 22–40–50 X: (2-)22–24–36/37–46–61 |
|||
|
006–013–00–8 |
xxxxxx-xxxxxxx (XXX) natrium-N-methyldithiokarbamát |
205–293–0 |
137–42–8 |
Xn; X22 R31 X; X34 X43 X; X50–53 |
X; X R: 22–31–34–43–50/53 X: (1/2-)26–36/37/39–45–60–61 |
|||
|
006–015–00–9 |
xxxxxx (XXX) 3-(3,4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx |
206–354–4 |
330–54–1 |
Xxxx. xxx. 3; X40 Xxxx. xxx. 3; X40 Xx; X22–48/22 X; X50–53 |
Xx; X X: 22–40–48/22–50/53 S: (2-)13–22–23–37–46–60–61 |
|||
|
006–016–00–4 |
xxxxxxxx (XXX) 2- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx |
204–043–8 |
114–26–1 |
X; X25 X; X50–53 |
X; X R: 25–50/53 X: (1/2-)37–45–60–61 |
|||
|
006–017–00-X |
aldikarb (ISO) 2-xxxxxx-2-(xxxxxxxxxxxxxx)xxxxxxxx-X-(X-xxxxxxxxxxxxxxx)xxxx |
204–123–2 |
116–06–3 |
X+; X26/28 X; X24 X; X50–53 |
X+; X X: 24–26/28–50/53 X: (1/2-)22–36/37–45–60–61 |
|||
|
006–018–00–5 |
xxxxxxxxx (ISO) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx |
217–990–7 |
2032–59–9 |
X; X24/25 X; X50–53 |
X; X X: 24/25–50/53 S: (1/2-)28–36/37–45–60–61 |
|||
|
006–019–00–0 |
di-allát (XXX) S-(2,3-dichlorallyl)-N,N-diisopropylthiokarbamát |
218–961–1 |
2303–16–4 |
Karc. xxx. 3; X40 Xn; X22 X; R50–53 |
Xn; X X: 22–40–50/53 X: (2-)25–36/37–60–61 |
|||
|
006–020–00–6 |
xxxxxx (XXX) 4-xxxxxxxx-2-xx-1-xx-X -(3-xxxxxxxxxx)xxxxxxxx |
202–930–4 |
101–27–9 |
Xx; X22 X43 X; X50–53 |
Xx; X R: 22–43–50/53 X: (2-)24–36/37–60–61 |
|||
|
006–023–00–2 |
xxxxxxxxxxxxxxxx (ISO) xxxxxxxxxx 3,5-xxxxxxxx-4-(xxxxxxxxxxxxxx)xxxxx-X -xxxxxxxxxxxxxx |
217–991–2 |
2032–65–7 |
X; X25 N; X50–53 |
X; X X: 25–50/53 X: (1/2-)22–37–45–60–61 |
|||
|
006–024–00–8 |
xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx |
205–443–5 |
140–93–2 |
Xx; R22 Xi; X38 X; X51–53 |
Xx; X X: 22–38–51/53 X: (2-)13-61 |
|||
|
006–026–00–9 |
xxxxxxxxxx (XXX) 2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx-X-xxxxxxxxxxxxxx |
216–353–0 |
1563–66–2 |
X+; X26/28 X; X50–53 |
X+; X R: 26/28–50/53 X: (1/2-)36/37–45–60–61 |
|||
|
006–028–00-X |
xxxxxxxxx (XXX) 2-(1-methylpropyl)-4,6-dinitrofenyl-isopropyl-karbonát 2-sek-butyl-4,6-dinitrofenyl-isopropyl-karbonát |
213–546–1 |
973–21–7 |
T; X25 X; X50–53 |
X; X X: 25–50/53 X: (1/2-)37–45–60–61 |
|||
|
006–029–00–5 |
dioxakarb (ISO) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx |
230–253–4 |
6988–21–2 |
X; X25 X; X51–53 |
X; N R: 25–51/53 X: (1/2-)37–45–61 |
|||
|
006–033–00–7 |
metoxuron (XXX) 3-(3-xxxxx-4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx |
243–433–2 |
19937–59–8 |
X; X50–53 |
X X: 5 0/ 5 3 X: 60-61 |
|||
|
006–034–00–2 |
xxxxxxx (ISO) X-xxxxxx-X-xxxxx-X-xxxxxxxxxxxxxxxxx |
214–215–4 |
1114–71–2 |
Xx; X22 X; R51–53 |
Xn; X R: 22–51/53 X: (2-)23-61 |
|||
|
006–035–00–8 |
pirimikarb (XXX) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx pyrimidin-4-yl-N,N-dimethylkarbamát |
245–430–1 |
23103–98–2 |
T; X25 X; R50–53 |
T; X X: 25–50/53 X: (1/2)22–37–45–60–61 |
|||
|
006–037–00–9 |
promekarb (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx |
220–113–0 |
2631–37–0 |
X; X25 X; X50–53 |
X; X X: 25–50/53 S: (1/2-)24–37–45–60–61 |
|||
|
006–038–00–4 |
xxxxxxxxx (XXX) 2-xxxxxxxxxx-X,X-xxxxxxxxxxxxxxxxxxxxxx |
X |
202–388–9 |
95–06–7 |
Xxxx. xxx. 2; X45 Xx; X22 X; R50–53 |
T; X X: 45–22–50/53 X: 53–45–60–61 |
||
|
006–039–00-X |
tri-allát (XXX) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx |
218–962–7 |
2303–17–5 |
Xx; X22–48/22 R43 X; X50–53 |
Xx; N X: 22–43–48/22–50/53 X: (2-)24–37–60–61 |
|||
|
006–042–00–6 |
xxxxxxx (XXX) 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx |
205–766–1 |
150–68–5 |
Xxxx. xxx. 3; X40 Xx; R22 N; X50–53 |
Xx; X X: 22–40–50/53 S: (2-)36/37–60–61 |
|||
|
006–043–00–1 |
xxxxxxx-XXX 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx |
— |
140–41–0 |
Xx; X36/38 Karc. xxx. 3; X40 X; R50–53 |
Xn; X X: 36/38–40–50/53 X: (2-)36/37–60–61 |
|||
|
006–045–00–2 |
xxxxxxxx (ISO) methyl-N-[(N-methylkarbamoyl)oxy]thioacetimidát |
240–815–0 |
16752–77–5 |
T+; X28 N; X50–53 |
X+; X R: 28–50/53 X: (1/2-)22–36/37–45–60–61 |
|||
|
006–046–00–8 |
bendiokarb (ISO) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx |
245–216–8 |
22781–23–3 |
X; X23/25 Xx; X21 X; R50–53 |
T; X R: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61 |
|||
|
006–047–00–3 |
xxxxxxxxx (XXX) xxxx: 3-(1-methylbutyl)fenyl-N-methylkarbamátu x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx |
— |
8065–36–9 |
X; R24/25 X; X50–53 |
X; X X: 24/25–50/53 X: (1/2-)28–36/37–45–60–61 |
|||
|
006–048–00–9 |
xxxxxxxxxxxx (XXX) 2-[(xxxxxxxxxxxxx)xxxxxx]xxxxx-X-xxxxxxxxxxxxxx |
249–981–9 |
29973–13–5 |
Xx; X22 X; X50–53 |
Xx; N X: 22–50/53 S: (2-)60-61 |
|||
|
006–050–00–X |
xxxxxxx-XXX 3-xxxxx-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx |
— |
4482–55–7 |
Xx; X38 X; R50–53 |
Xi; N X: 38–50/53 S: (2-)60-61 |
|||
|
006–053–00–6 |
xxxxxxxxxx (XXX) 2-isopropylfenyl-N-methylkarbamát |
220–114–6 |
2631–40–5 |
Xn; X22 X; X50–53 |
Xx; X X: 22–50/53 X: (2-)60-61 |
|||
|
006–054–00–1 |
xxxxxxxxxx (XXX) 4-(xxxxxxxxxxxxx)-3,5-xxxxxxxxxxxxx-X-xxxxxxxxxxxxxx |
206–249–3 |
315–18–4 |
X+; X28 Xn; X21 X; X50–53 |
X+; X X: 21–28–50/53 X: (1/2-)36/37–45–60–61 |
|||
|
006–057–00–8 |
nitrapyrin (ISO) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx |
217–682–2 |
1929–82–4 |
Xx; R22 X; X51–53 |
Xx; X X: 22–51/53 X: (2-)24-61 |
|||
|
006–060–00–4 |
oxykarboxin (XXX) 2-methyl-4,4-dioxo-5,6-dihydro-4λ4-1,4-oxathiin-3-karboxanilid |
226–066–2 |
5259–88–1 |
Xn; R22 X52–53 |
Xx R:22–52/53 X: (2-)61 |
|||
|
006–069–00–3 |
xxxxxxxxx-xxxxxx (XXX) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx |
245–740–7 |
23564–05–8 |
Xxxx. xxx. 3; X40 X; X50–53 |
Xx; X X: 40–50/53 X: (2-)36/37–60–61 |
|||
|
006–070–00–9 |
xxxxxxxxxxx X-xxxxxxxxxx-X-xxxxxxx-2,5-xxxxxxxx-3-xxxxxxx |
262–302–0 |
60568–05–0 |
Xxxx. kat. 3; R40 N; X50–53 |
Xx; X X: 40–50/53 X: (2-)36/37–60–61 |
|||
|
006–088–00–7 |
xxxxxxxxxxx (XXX) ethyl-N -[({[(2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx)xxx]xxxxxxxx}xxxxxxxxxxx)xxxxxxxx]-X-xxxxxxxxx-β-xxxxxxxx(2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx)-X-({[2-(xxxxxxxxxxxxxx)xxxxx]xxxxxxxxxxxxxx}xxxxxxxx)-X-xxxxxxxxxxxxxx |
— |
82560–54–1 |
X; X23/25 X; X50–53 |
X; X X: 23/25–50/53 X: (1/2-)36/37–45–60–61 |
|||
|
007–012–00–5 |
X,X-xxxxxxxxxxxxxxxx 1,1-xxxxxxxxxxxxxxxx |
X |
200–316–0 |
57–14–7 |
X; X11 Xxxx. xxx. 2; X45 X; X23/25 X; R34 X; R51–53 |
F; X; X X: 45–11–23/25–34–51/53 X: 53–45–61 |
||
|
007–013–00–0 |
N,N-dimethylhydrazin 1,2-xxxxxxxxxxxxxxxx |
X |
— |
540–73–8 |
Xxxx. xxx. 2; R45 X; X23/24/25 X; X51–53 |
X; X R: 45–23/24/25–51/53 X: 53–45–61 |
X ≥ 25 %: X; R45–23/24/25 3 % < X &xx; 25 %: X; X45–20/21/22 0,01 % &xx; X &xx; 3 %: X; X45 |
|
|
009–003–00–1 |
xxxxxxxx xxxxxxxxxxxxxx … % |
B |
231–634–8 |
7664–39–3 |
T+; X26/27/28 X; X35 |
X+; C X: 26/27/28–35 X: (1/2-)7/9–26–36/37–45 |
X ≥ 7 %: T+; X; X26/27/28–35 1 % ≤ C &xx; 7 %: X; X23/24/25–34 0,1 % ≤ X < 1 %: Xn; X20/21/22–36/37/38 |
|
|
015–039–00–9 |
xxxxxxx-xxxxxx (XXX) O,O-dimethyl-S -[(4(3 H)-oxo-1,2,3-benzotriazin-3-yl)methyl]-fosforodithioát |
201–676–1 |
86–50–0 |
T+; X26/28 X; X24 R43 X; R50–53 |
T+; N X: 24–26/28–43–50/53 S: (1/2-)28–36/37–45–60–61 |
|||
|
015–048–00–8 |
xxxxxxxx (ISO) O,O-dimethyl-O-[3-methyl-4-(methylsulfanyl)fenyl]-fosforothioát |
200–231–9 |
55–38–9 |
Muta. xxx. 3; X40 X; R23–48/25 Xn; X21/22 N; X50–53 |
X; X X: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61 |
|||
|
015–056–00–1 |
azinfos-ethyl (ISO) X,X-xxxxxxx-X-[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx |
220–147–6 |
2642–71–9 |
X+; X28 X; X24 N; X50–53 |
X+; X X: 24–28–50/53 S: (1/2-)28–36/37–45–60–61 |
|||
|
015–140–00–8 |
triazofos (XXX) X,X-xxxxxxx-X-(1-xxxxx-1 X- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx |
245–986–5 |
24017–47–8 |
X; R23/25 Xx; X21 X; X50–53 |
X; X X: 21–23/25–50/53 X: (1/2-)36/37–45–60–61 |
|||
|
016–013–00-X |
xxxxxxx xxxxxxx |
234–129–0 |
10545–99–0 |
X14 X; X34 X; X50 |
X; X R: 14–34–50 X: (1/2-)26–36/37/39–45–61 |
X ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; X36/37/38 |
||
|
016–014–00–5 |
xxxxxxx siřičitý |
— |
13451–08–6 |
R14 X; X34 N; X50 |
X; X X: 14–34–50 X: (1/2-)26–36/37/39–45–61 |
X ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; X36/37/38 |
||
|
016–023–00–4 |
xxxxxxxx-xxxxxx |
X |
201–058–1 |
77–78–1 |
Xxxx. xxx. 2; X45 Muta. xxx. 3; R40 X+; X26 X; X25 X; X34 X43 |
X+ X: 45–25–26–34–43 X: 53-4 5 |
X ≥ 25 %: X+; X45–25–26–34–43 10 % ≤ C &xx; 25 %: X+; R45–22–26–34–43 7 % ≤ X &xx; 10 %: X+; X45–22–26–36/ 37/38–43 5 % ≤ X < 7 %: T; R45–22–23–36/37/38–43 3 % ≤ X &xx; 5 %: T; X45–22–23–43 1 % ≤ X &xx; 3 %: X; X45–23–43 0,1 % ≤ X < 1 %: X; R45–20 0,01 % ≤ X &xx; 0,1 %:X; X45 |
|
|
016–024–00-X |
xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx |
X,X′-xxxxxxxx-xxxxxxxxxxx(xxxxxxxxxxx)215–993–8 |
1468–37–7 |
Xx; R22 X; X50–53 |
Xx; X X: 22–50/53 S: (2-)60-61 |
|||
|
016–071–00–6 |
3-amino-6,13-dichlor-10-[(3-{[4-chlor-6-(2-sulfonatoanilino)- 1,3,5-xxxxxxx-2-xx]xxxxx}xxxxxx)xxxxx][1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx trisodný |
410–130–3 |
136248–03–8 |
R43 |
Xi X: 43 X: (2-)22–24–37 |
|||
|
022–001–00–5 |
xxxxxxx xxxxxxxxxx |
231–441–9 |
7550–45–0 |
X14 X; X34 |
X X: 14-34 X: (1/2-)7/8–26–36/37/39–45 |
X ≥ 10 %: C; X34 5 % ≤ X &xx; 10 %: Xi; R36/37/38 |
||
|
030–004–00–8 |
dimethylzinek [1] xxxxxxxxxxxx [2] |
208–884–1 [1] 209–161–3 [2] |
544–97–8 [1] 557–20–0 [2] |
X14 X; X17 C; X34 N; R50–53 |
F; X; X X: 14–17–34–50/53 X: (1/2-)16–43–45–60–61 |
|||
|
050–002–00–0 |
xxxxxxxxx (XXX) tricyklohexyl(hydroxy)stannan tricyklohexylstannium-hydroxid |
236–049–1 |
13121–70–5 |
Xn; X20/21/22 N; X50–53 |
Xx; X R: 20/21/22–50/53 X: (2-)13–60–61 |
|||
|
050–012–00–5 |
tetracyklohexylstannan [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] xxxxx(xxxxxxxxxxxxx)xxxxxxx [3] |
215–910–5 [1] 221–437–5 [2] 230–358–5 [3] |
1449–55–4 [1] 3091–32–5 [2] 7067–44–9 [3] |
Xn; X20/21/22 X; X50–53 |
Xx; X X: 20/21/22–50/53 S: (2-)26–28–60–61 |
X ≥ 1 %: Xn; X20/21/22 |
1 |
|
|
050–017–00–2 |
xxxxxxxxxxxxxx (XXX) 1,1,1,3,3,3-xxxxxxx(2-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxxxx |
236–407–7 |
13356–08–6 |
X+; X26 Xx; X36/38 X; X50/53 |
X+; X R: 26–36/38–50/53 S: (1/2-)28–36/37–45–60–61 |
|||
|
082–009–00–X |
žluť (xxxxxxxxxxxx olovnatý) XX Xxxxxxx Xxxxxx 34 (XX 77603) CI xxxxxxxxxx xxxx 34 (XX 77603) |
215–693–7 |
1344–37–2 |
Xxxx. xxx. 3; R40 Xxxx. xxx. 1; R61 Xxxx. kat. 3; X62 R33 X; X50–53 |
X; X X: 61–33–40–50/53–62 X: 53–45–60–61 |
1 |
||
|
082–010–00–5 |
červeň (xxxxxxx-xxxxxxxxxx-xxxxx xxxxxxxx) XX Xxxxxxx Xxx 104 (XX 77605) XX xxxxxxxxxx xxxxxx 104 (XX 77605) |
235–759–9 |
12656–85–8 |
Karc. xxx. 3; R40 Repr. xxx. 1; X61 Xxxx. xxx. 3; X62 R33 N; X50–53 |
X; X X: 61–33–40–50/53–62 S: 53–45–60–61 |
1 |
||
|
601–024–00-X |
kumen [1] xxxxxxxxxxxx [2] |
202–704–5 [1] 203–132–9 [2] |
98–82–8 [1] 103–65–1 [2] |
X10 Xx; R65 Xx; X37 X; R51–53 |
Xn; X X: 10–37–51/53–65 X: (2-)24–37–61–62 |
4 |
||
|
601–032–00–3 |
xxxxx[x]xxxxx xxxxx[xxx]xxxxxxx |
200–028–5 |
50–32–8 |
Xxxx. xxx.2; R45 Muta. xxx. 2; R46 Xxxx. xxx. 2; X60–61 X; X50–53 |
X; X X: 45–46–60–61–50/53 X: 53–45–60–61 |
|||
|
601–034–00–4 |
xxxxx[x]xxxxxxxxxxxxxxx |
205–911–9 |
205–99–2 |
Xxxx. kat.2; X45 N; X50–53 |
X; X X: 45–50/53 X: 53–45–60–61 |
|||
|
602–035–00–2 |
1,4-xxxxxxxxxxxxx p-dichlorbenzen |
203–400–5 |
106–46–7 |
Xi; X36 X; R50–53 |
Xi; X R: 36–50/53 X: (2-)24/25–46–60–61 |
|||
|
602–054–00–6 |
3-jodprop-1-en allyljodid |
209–130–4 |
556–56–9 |
R10 X; R34 |
C X: 10-34 S: (1/2-)7–26–45 |
|||
|
603–076–00–9 |
xxx-2-xx-1,4-xxxx |
203–788–6 |
110–65–6 |
X; X23/25 Xx; X21–48/22 X; R34 |
T X: 21–23/25–34–48/22 S: (1/2-)26–36/37/39–45 |
X ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ X &xx; 50 %: X; R21–23/25–36/38–48/22 10 % ≤ X &xx; 25 %: Xx; R20/22–48/22 3 % ≤ X &xx; 10 %: Xx; X20/22 |
||
|
603–091–00–0 |
xxx-4-xxxxxxxxx-1-xxxxxx-7-xxxxxxxxxx[2.2.1]xxxxxx-2-xx |
402–470–6 |
87172–89–2 |
X; R8 Xx; R22 Xx; X36 |
X; Xn R: 8–22–36 X: (2-)26 |
|||
|
603–093–00–1 |
exo-(±)-4-isopropyl-1-methyl-2-[(2-methylbenzyl)oxy]-7-oxabicyklo[2.2.1]heptan |
402–410–9 |
87818–31–3 |
Xn; X20 X; R51–53 |
Xn; X X: 20–51/53 X: (2-)23-61 |
|||
|
603–097–00–3 |
1,1', 1′′-xxxxxxxxxxxxxxxx-2-xx xxxxxxxxxxxxxxxxxx |
204–528–4 |
122–20–3 |
Xx; X36 X52–53 |
Xx X:36–52/53 X: (2-)26-61 |
|||
|
603–117–00–0 |
xxxxxx-2-xx xxxxxxxxxxxxxxxx xxxxxxxxxxx |
200–661–7 |
67–63–0 |
X; R11 Xx; X36 X67 |
X; Xx X: 11–36–67 X: (2-)7–16–24/25–26 |
|||
|
604–020–00–6 |
xxxxxxx-2-xx 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (ISO) |
201–993–5 |
90–43–7 |
Xi; R36/37/38 X; X50 |
Xx; N X: 36/37/38–50 X: (2-)22-61 |
|||
|
604–021–00–1 |
2-xxxxxxxxxx, xxxxx sůl xxxxxxx-2-xxxxxxxxxxxx 2-bifenylát xxxxx xxxxxxx-xxxxxxx-2-xxxx |
205–055–6 |
132–27–4 |
Xx; X22 Xx; X37/38–41 X; X50 |
Xx; X R: 37/38–41–50 X: (2-)22–26–61 |
|||
|
604–024–00–8 |
4,4'-(4-xxxxxxxxxxxx-2,2-xxxx)xxxxxxx 2,2-xxx(4-xxxxxxxxxxxx)-4-xxxxxxxxxxxx |
401–720–1 |
6807–17–6 |
Xxxx. xxx. 2; X60 Xx; X36 X; X50–53 |
X; X X: 60–36–50/53 S: 53–45–60–61 |
|||
|
604–041–00–0 |
xxxxxxxxxxx [1] xxxxxxxxxxx-xxxxxxx [2] 5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxxx kyselina [1] xxxxxxx-5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxx [2] |
256–634–5 [1] 263–560–7 [2] |
50594–66–6 [1] 62476–59–9 [2] |
Xx; R22 Xx; R38–41 X; X50–53 |
Xx; N X: 22–38–41–50/53 S: (2-)24–39–60–61 |
|||
|
604–043–00–1 |
monobenzonbenzyl (4-xxxxxxxxxxxx)xxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx 4-(xxxxxxxxx)xxxxx |
203–083–3 |
103–16–2 |
Xx; X36 X43 |
Xx R: 36-43 S: (2-)24/25–26–37 |
|||
|
604–044–00–7 |
mechinol 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx |
205–769–8 |
150–76–5 |
Xx; X22 Xx; R36 X43 |
Xx X: 22–36–43 X: (2-)24/25–26–37/39–46 |
|||
|
605–016–00–7 |
xxxxxxx… % ethandial… % |
X |
203–474–9 |
107–22–2 |
Xxxx. xxx. 3; X40 Xx; R20 Xx; X36/38 X43 |
Xx X: 20–36/38–40–43 X: (2-)36/37 |
X ≥ 10 %: Xx; X20–36/38–40–43 1 % ≤ X &xx; 10 %: Xx; X40–43 |
|
|
606–016–00-X |
xxxxxx (XXX) 2-(xxxxxxxxxxxxxxx)xxxxx-1,3-xxxx |
201–462–8 |
83–26–1 |
X; X25–48/25 X; R50–53 |
T; N X: 25–48/25–50/53 X: (1/2-)37–45–60–61 |
|||
|
606–018–00–0 |
xxxxxxx (ISO) 2,3-xxxxxxx-1,4-xxxxxxxxxxx |
204–210–5 |
117–80–6 |
Xx; X22 Xx; X36/38 X; X50–53 |
Xx; X X: 22–36/38–50/53 S: (2-)26–60–61 |
|||
|
606–019–00–6 |
xxxxxxxxxx (XXX) xxxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx xxxxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx 1,2,4,5,6,7,8,8,9,10-xxxxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx |
205–601–3 |
143–50–0 |
Xxxx. xxx. 3; R40 X; X24/25 X; R50–53 |
T; X X: 24/25–40–50/53 X: (1/2-)22–36/37–45–60–61 |
|||
|
606–034–00–8 |
xxxxxxxxxx (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 X)-xx 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-4,5-xxxxxxx-1,2,4-xxxxxxx-5-xx |
244–209–7 |
21087–64–9 |
Xx; X22 N; X50–53 |
Xx; X X: 22–50/53 X: (2-)60-61 |
|||
|
606–035–00–3 |
xxxxxxxxxxx (ISO) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx xxxxxxx |
216–920–2 |
1698–60–8 |
X43 X; X50–53 |
Xx; N X: 43–50/53 S: (2-)24–37–60–61 |
|||
|
606–036–00–9 |
xxxxxxxxxxxxxx (XXX) 6-methyl-2 X-[1,3]xxxxxxxx[4,5-x]xxxxxxxxxx-2-xx |
219–455–3 |
2439–01–2 |
Xxxx. xxx. 3; R62 Xx; X20/21/22–48/22 Xx; X36 X43 N; X50–53 |
Xx; X X: 20/21/22–36–43–48/22–50/53–62 X: (2-)24–37–60–61 |
|||
|
606–037–00–4 |
triadimefon (XXX) 1-(4-xxxxxxxxxxx)- 3,3-xxxxxxxx-1-(1,2,4-xxxxxxx-1-xx)xxxxx-2-xx |
256–103–8 |
43121–43–3 |
Xx; X22 X; R51–53 |
Xn; X X: 22–51/53 X: (2-)61 |
|||
|
606–044–00–2 |
2,4,6-xxxxxxxxxxxxxxxxxxx xxxxx(2,4,6-xxxxxxxxxxxxxx)xxxxxxxx |
403–150–9 |
954–16–5 |
Xx; X22 Xx; X36 X; X50–53 |
Xx; X X: 22–36–50/53 S: (2-)26–60–61 |
|||
|
607–043–00-X |
xxxxxxx (XXX) 3,6-xxxxxxx-2-xxxxxxxxxxxxxxx xxxxxxxx |
217–635–6 |
1918–00–9 |
Xx; X22 Xx; X41 X52–53 |
Xx; N X: 22–41–52/53 X: (2-)26-61 |
|||
|
607–057–00–6 |
xxxxxxxxx (XXX) 3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxykumarin3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxy-2 X-xxxxxxx-2-xx |
201–378–1 |
81–82–3 |
Xx; X48/22 R52–53 |
Xn X:48/22–52/53 X: (2-)37-61 |
|||
|
607–058–00–1 |
kumafuryl (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -chromen-2-on 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-furyl)-3-oxobutyl]-4-hydroxy-2 H -xxxxxxx-2-xx |
204–195–5 |
117–52–2 |
X; X25–48/25 X52–53 |
X X:25–48/25–52/53 S: (1/2-)37–45–61 |
|||
|
607–079–00–6 |
xxxxxxx (XXX) ethyl-4-oxo-5-(perchlor-5-hydroxypentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-yl)pentanoát ethyl-5-(1,2,3,5,6,7,8,9,10,10-dekachlor-4-hydroxypentacyklo[5.2.1.02,6.03,9.05,8]dekan-4-yl)-4-oxopentanoát xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx |
— |
4234–79–1 |
X; X24 Xn; X22 X; X51–53 |
X; X X: 22–24–51/53 X: (1/2-)36/37–45–61 |
|||
|
607–097–00–4 |
xxxxxx-1,2,4-xxxxxxxxx-1,2-xxxxxxxx 1,2-anhydrid xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxx |
209–008–0 |
552–30–7 |
Xx; X37–41 X42/43 |
Xx X: 37–41–42/43 X: (2-)22–26–36/37/39 |
|||
|
607–143–00–3 |
xxxxxxxxx xxxxxxxx valerová xxxxxxxx |
203–677–2 |
109–52–4 |
X; X34 R52–53 |
C X:34–52/53 X: (1/2-)26–36–45–61 |
|||
|
607–152–00–2 |
2,3,6-XXX (XXX) 2,3,6-xxxxxxxxxxxxxxxx kyselina |
200–026–4 |
50–31–7 |
Xn; R22 X; X51–53 |
Xx; X X: 22–51/53 X: (2-)61 |
|||
|
607–153–00–8 |
xxxxxxxxx (XXX) (4-xxxxx-2-xxx-2,3-xxxxxxx-1,3-xxxxxxxxxxxx-3-xx)xxxxxx xxxxxxxx |
223–297–0 |
3813–05–6 |
Xx; X36/38 R52–53 |
Xi X:36/38–52/53 X: (2-)22-61 |
|||
|
607–156–00–4 |
chlorfenson (XXX) 4-chlorfenyl-4-chlorbenzen-1-sulfonát |
201–270–4 |
80–33–1 |
Xn; R22 Xx; X38 X; X50–53 |
Xx; X X: 22–38–50/53 X: (2-)37–60–61 |
|||
|
607–158–00–5 |
sodná xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx sodný |
223–498–3 |
3926–62–3 |
T; X25 Xx; R38 X; X50 |
X; N X: 25–38–50 S: (1/2-)22–37–45–61 |
|||
|
607–159–00–0 |
chlorobenzilát (XXX) ethyl-2,2-bis(4-chlorfenyl)-2-hydroxyacetát xxxxx-4,4'-xxxxxxxxxxxxxxx |
208–110–2 |
510–15–6 |
Xx; X22 X; R50–53 |
Xn; X X: 22–50/53 X: (2-)60-61 |
|||
|
607–176–00–3 |
Směs: α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-xxxxxxxxxxx(xxxxxxxxxx);α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-({3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}xxx)xxxx(xxxxxxxxxx) |
400–830–7 |
— |
X43 X; R51–53 |
Xi; X X: 43–51/53 X: (2-)36/37–61 |
|||
|
607–188–00–9 |
xxxxxxx-xxxxxxxx-X-(2-xxxxxxxxxxxx)-X-(xxxxxxx-9-xx-1-xx)xxxxxxxxxx |
402–970–4 |
— |
X43 X; X51–53 |
Xx; X X: 43–51/53 X: (2-)24/37–61 |
|||
|
607–209–00–1 |
Xxxx: O,O′-diisopropyl-trisulfanbis(karbothioát); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); O,O′-diisopropyl-pentasulfanbis(karbothioát) |
403–030–6 |
— |
Xn; R22 X43 X; X50–53 |
Xx; X X: 22–43–50/ 53 S: (2-)36/37–60–61 |
|||
|
607–213–00–3 |
xxxxx-3,3-xxx(xxxx-xxxxxxxxxxxx)xxxxxxxx |
403–320–2 |
67567–23–1 |
X; X2 O; R7 X10 X; R51–53 |
E; X X: 2–7–10–51/53 X: (2-)3/7–14–33–36/37/39–61 |
|||
|
607–217–00–5 |
2-ethoxyethyl-[4-(7-fenyl-2,6-dioxo-2,6-dihydro-1,5-dioxa-s-indacen-3-yl)fenoxy]acetát |
403–960–2 |
— |
R43 R53 |
Xi X: 43-53 X: (2-)24–37–61 |
|||
|
607–243–00–7 |
xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] natrium-3,6-dichlor-o-anisát [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-hydroxyethyl)amonium-3,6-dichlor-2-methoxybenzoát [3] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [3] |
217–846–3 [1] 246–590–5 [2] 258–527–9 [3] |
1982–69–0 [1] 25059–78–3 [2] 53404–28–7 [3] |
X52–53 |
X: 52/53 X: 61 |
|||
|
607–248–00–4 |
Xxxxxxxx-xxxxxxx Natrium-N-(1-naftyl)ftalamát |
205–073–4 |
132–67–2 |
Xn; X22 |
Xx X: 22 S: (2) |
|||
|
607–249–00-X |
(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx tripropylenglykol-diakrylát TPGDA |
256–032–2 |
42978–66–5 |
Xi; X36/37/38 R43 X; X51–53 |
Xx; X X:36/37/38–43–51/53 X: (2-)24–37–61 |
X ≥ 10 %: Xx; X36/37/38–43 1 % ≤ C < 10 %: Xi; X43 |
||
|
607–252–00–6 |
λ-xxxxxxxxxxx (XXX) Xxxx (1:1): (X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx |
415–130–7 |
91465–08–6 |
X+; X26 X; X25 Xn; X21 X; X50–53 |
X+; X X: 21–25–26–50/53 X: (1/2-)28–36/37/39–38–45–60–61 |
|||
|
607–255–00–2 |
fluroxypyr (XXX) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx xxxxxxxx |
— |
69377–81–7 |
X52–53 |
X: 52/53 X: 61 |
|||
|
608–003–00–4 |
xxxxxxxxxxxx |
X E |
203–466–5 |
107–13–1 |
F; Xxx Xxxx. xxx. 2; X45 T; X23/24/25 Xi; X37/38–41 X43 N; X51–53 |
X; X; X R: 45–11–23-/24/25–37/38–41–43–51/53 X: 9–16–53–45–61 |
X ≥ 20 %: X; X45–23/24/25–37/38–41–43 10 % ≤ C &xx; 20 %: X; R45–23/24/25–41–43 5 % ≤ C &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ C &xx; 5 %:X; X45–23/24/25–43 0,2 % ≤ X &xx; 1 %:X; X45–20/21/22 0,1 % ≤ X &xx; 0,2 %: X; X45 |
43 |
|
608–016–00–5 |
2,3,5,6-xxxxxxxxxx-1,4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxx |
401–550–8 |
1897–41–2 |
X43 N; R50–53 |
Xi; X R: 43–50/53 X: (2-)24–37–60–61 |
|||
|
609–030–00–4 |
dinoterb (XXX) 2-xxxx-xxxxx-4,6-xxxxxxxxxxxx |
X |
215–813–8 |
1420–07–1 |
Xxxx. kat. 2; X61 T+; X28 X; X24 X44 X; R50–53 |
T+; X X: 61–24–28–44–50/53 S: 53–45–60–61 |
||
|
609–040–00–9 |
xxxxxxxx (ISO) (2,4-xxxxxxxxxxxx)(4-xxxxxxxxxx)xxxxx |
X |
217–406–0 |
1836–75–5 |
Xxxx. xxx. 2; X45 Xxxx. kat. 2; X61 Xn; X22 X; X50–53 |
X; X X: 45–61–22–50/53 S: 53–45–60–61 |
||
|
609–044–00–0 |
xxxxxxxx (XXX) 1,2,4,5-tetrachlor-3-nitrobenzen |
204–178–2 |
117–18–0 |
Xn; X22 X43 N; X50–53 |
Xx; X X: 22–43–50/53 S: (2-)24–37–60–61 |
|||
|
611–008–00–4 |
4-aminoazobenzen 4-(xxxxxxxx)xxxxxx |
200–453–6 |
60–09–3 |
Xxxx. kat. 2; X45 X; R50–53 |
T; X X: 45–50/53 X: 53–45–60–61 |
|||
|
611–013–00–1 |
4-xxxxxxx-3-{4-[2-xxxxxxx-4-(3-xxxxxxxxxxxxxxxxx)xxxxxxxx]-3-xxxxxxxxxxxxxx}-6-(3-xxxxxxxxxxxxxxxx)xxxxxxxx-2-xxxxxxxx xxxxxxxxx |
403–650–7 |
117409–78–6 |
X; X2 X; R51–53 |
E; X X: 2–51/53 X: (2-)35-61 |
|||
|
611–031–00-X |
4,4'-[(4-iminocyklohexa-2,5-dien-1-yliden)methylen]dianilin-hydrochlorid XX Xxxxx Xxx 9 XX basická xxxxxx 9 |
209–321–2 |
569–61–9 |
Xxxx. xxx. 2; X45 |
X X: 45 X: 53-45 |
|||
|
612–035–00–4 |
2-xxxxxxxxxxxxx x-xxxxxxxx |
X |
201–963–1 |
90–04–0 |
Xxxx. xxx. 2; X45 Xxxx. kat. 3; X40 X; X23/24/25 |
X X: 45–23/24/25 S: 53-45 |
||
|
612–042–00–2 |
xxxxxxxx xxxxxxx-4,4'-xxxxxx 4,4'-xxxxxxxxxxxxxx xxxxxxx-4,4'-xxxxxxxxxx |
X |
202–199–1 |
92–87–5 |
Xxxx. kat. 1; X45 Xx; R22 X; X50–53 |
X; N X: 45–22–50/53 X: 53–45–60–61 |
X ≥ 25 %: T; R45–22 0,01 % ≤ X &xx; 25 %: X; X45 |
|
|
612–051–00–1 |
4,4'-xxxxxxxxxxxxxxxxxxxx xxx(4-xxxxxxxxxx)xxxxxx 4,4'-xxxxxxxxxxxxxxxx |
X |
202–974–4 |
101–77–9 |
Xxxx. kat. 2; X45 Muta. xxx. 3; X40 X; X39/23/24/25Xx; R48/20/21/22 X43 X; X51–53 |
X; X R: 45–39/23/24/25–43–48/20/21/22–51/53 X:53–45–61 |
||
|
612–081–00–5 |
3,3'-xxxxxxxxxxxxxxxx, soli x-xxxxxxx, xxxx |
X E |
210–322–5 265–294–7 277–985–0 |
612–82–8 64969–36–4 74753–18–7 |
Karc. xxx. 2; X45 Xx; R22 X; X51–53 |
X; X X: 45–22–51/53 X: 53–45–61 |
||
|
612–099–00–3 |
4-methyl-m-fenylendiamin4-methyl-1,3-fenylendiamin4-methylbenzen-1,3-diamin 2,4-xxxxxxxxxxxx |
X |
202–453–1 |
95–80–7 |
Xxxx. xxx. 2; X45 X; X25 Xx; R21 Xx; X36 X43 X; X51–53 |
X; N R: 45–21–25–36–43–51/53 X: 53–45–61 |
||
|
612–105–00–4 |
2-(piperazin-1-yl)ethylamin2-(piperazin-1-yl)ethan-1-amin |
205–411–0 |
140–31–8 |
Xn; X21/22 X; X34 X43 X52–53 |
X X: 21/22–34–43–52/53 X: (1/2-)26–36/37/39–45–61 |
|||
|
612–111–00–7 |
2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,3-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,3-xxxxxx 2,6-xxxxxxxxxxxx |
212–513–9 |
823–40–5 |
Xxxx. xxx. 3; X40 Xn; X21/22 X43 X; X51–53 |
Xx; X R: 21/22–40–43–51/53 X: (2-)24–36/37–61 |
|||
|
612–125–00–3 |
2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,4-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,4-xxxxxx 2,5-toluendiamin |
202–442–1 |
95–70–5 |
T; X25 Xn; X20/21 X43 X; R51–53 |
T; X X: 20/21–25–43–51/53 X: (1/2-)24–37–45–61 |
|||
|
612–144–00–7 |
xxxxxxxxxxx (XXX) X-(2-xxxxx-6-xxxxxxxxxxx)-X-xxxxx-2,6-xxxxxxx-4-(xxxxxxxxxxxxxx)xxxxxx |
— |
62924–70–3 |
Xx; X36/38 X4 3 X; X50–53 |
Xx; X R: 36/38–43–50/53 X: (2-)36/37–60–61 |
|||
|
612–151–00–5 |
xxxxxxxxxxxxx toluendiamin xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx |
X |
246–910–3 |
25376–45–8 |
Xxxx. xxx. 2; X45 T; X25 Xx; X20/21 Xx; R36 X43 X; R51–53 |
T; X X: 45–20/21–25–36–43–51/53 X: 53–45–61 |
||
|
613–018–00–4 |
xxxxxxxxxx (XXX) 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx |
— |
7411–47–4 |
Xx; X22 Xx; R36/37/38 X52–53 |
Xx X: 22–36/37/38–52/53 X: (2-)22–36–61 |
|||
|
613–031–00–5 |
symklosen xxxxxxxxxxxxxxxxxxxx xxxxxxxx xxxxxxxx-1,3,5-xxxxxxxxxxxx 1,3,5-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5X)-xxxxx |
201–782–8 |
87–90–1 |
X; R8 Xx; X22 X31 Xx; X36/37 X; X50–53 |
X; Xn; X X: 8–22–31–36/37–50/53 X: (2-)8–26–41–60–61 |
|||
|
613–038–00–3 |
6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxx xxxxxxxxxxxxx |
202–095–6 |
91–76–9 |
Xx; X22 R52–53 |
Xn R:22–52/53 X: (2-)61 |
|||
|
613–042–00–5 |
imazalil (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1 H-imidazol |
252–615–0 |
35554–44–0 |
Xn; X20/22 X; X41 X; X50–53 |
Xx; X X: 20/22–41–50/53 S: (2-)26–39–60–61 |
|||
|
613–043–00–0 |
xxxxxxxx-xxxxxx (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1X -xxxxxxxx-1-xxx-xxxxxxxxxxxxxx [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx |
261–351–5 [1] 281–291–3 [2] |
58594–72–2 [1] 83918–57–4 [2] |
Xx; X20/22 Xx; X41 N; X50–53 |
Xx; X X: 20/22–41–50/53 X: (2-)26–39–60–61 |
|||
|
613–066–00–6 |
terbumeton (XXX) 2-(xxxx-xxxxxxxxxx)-4-(xxxxxxxxxx)-6-xxxxxxx-1,3,5-xxxxxxx |
251–637–8 |
33693–04–8 |
Xx; R22 X; X50–53 |
Xx; X X: 22–50/53 S: (2-)60-61 |
|||
|
613–091–00–2 |
xxxxxxxxxx-xxxxxxxxx [1] xxxxxxxxxx-xxxxxx [2] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx-xxxxxxxxx [1] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxx-xxxxxxxx [2] |
225–062–8 [1] |
4636–83–3 [1] 29873–36–7 [2] |
Xx; X22 Xx; X36/37/38 X52–53 |
Xx; X: 22–36/37/38–52/53 S: (2-)22–36–61 |
|||
|
613–098–00–0 |
1-xxxxxxxxxxxxxxx-2-xx 1-oktyl-2-pyrrolidon |
403–700–8 |
2687–94–7 |
C; X34 X; X51–53 |
X; X X: 34–51/53 S: (1/2-)23–26–36/37/39–45–61 |
|||
|
613–130–00–3 |
xxxxxxxxxxx (ISO) (RS)-2-(2,4-dichlorfenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol |
— |
79983–71–4 |
R43 X; X51–53 |
Xx; X X: 43–51/53 X: (2-)24–37–61 |
|||
|
613–131–00–9 |
xxxxxxxxxx (XXX) 1,2,5,6-xxxxxxxxxx-4 X-xxxxxxx[3,2,1-xx]xxxxxxxx-4-xx |
— |
57369–32–1 |
Xx; X22 X52–53 |
Xx X:22–52/53 X: (2-)61 |
|||
|
613–134–00–5 |
myklobutanil (XXX) 2-(4-xxxxxxxxxx)-2-[(1 X-1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx |
— |
88671–89–0 |
Xxxx. xxx. 3; R63 Xx; X22 Xx; X36 X; X51–53 |
Xx; X X: 22–36–51/53–63 X: (2-)36/37–46–61 |
|||
|
613–137–00–1 |
xxxxxxxxxxxxxxxxxx (XXX) 1-(1,3-xxxxxxxxxxxx-2-xx)-1,3-xxxxxxxxxxxxxxxx |
242–505–0 |
18691–97–9 |
X; X50–53 |
X X: 50/53 S: 60-61 |
|||
|
613–139–00–2 |
xxxxxxxxxxx-xxxxxx xxxxxx-2-{X —[X-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxxx]xxxxxxxxx}xxxxxxx |
— |
74223–64–6 |
X; X50–53 |
X X: 50/53 X: 60-61 |
|||
|
614–001–00–4 |
xxxxxxx (ISO) 3-(1-xxxxxxxxxxxxxxxx-2-xx)xxxxxxx |
200–193–3 |
54–11–5 |
X+; X27 X; R25 X; X51–53 |
X+; X X: 25–27–51/53 X: (1/2-)36/37–45–61 |
|||
|
614–006–00–1 |
xxxxxx 2,3-xxxxxxxxxxxxxxxxxxxx-10-xx |
206–614–7 |
357–57–3 |
X+; X26/28 X52–53 |
X+ X:26/28–52/53 X: (1/2-)13–45–61 |
|||
|
614–007–00–7 |
xxxxxx-xxxxxx [1] xxxxxx-xxxxxx [2] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [3] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [4] |
225–432–9 [1] 227–317–9 [2] 269–439–5 [3] 269–710–8 [4] |
4845–99–2 [1] 5786–97–0 [2] 68239–26–9 [3] 68310–42–9 [4] |
X+; X26/28 X52–53 |
X+ X: 26/28–52/53 S: (1/2-)13–45–61 |
|||
|
615–006–00–4 |
2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-xxxxxx-x-xxxxxxxxxxxxxxxxxx [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] x-xxxxxxxxxxxxxxxxxxxx [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] toluen-2,4-diisokyanát [2] xxxxxx-3,5-xxxxxxxxxxx [3] |
X |
202–039–0 [1] 209–544–5 [2] 247–722–4 [3] |
91–08–7 [1] 584–84–9 [2] 26471–62–5 [3] |
Xxxx. xxx. 3; X40 X+; X26 Xx; R36/37/38 X42/43 X52–53 |
X+ X: 26–36/37/38–40–42/43–52/53 X: (1/2-)23–36/37–45–61 |
X320 %: X+; X26–36/37/38–40–42/43 7 % ≤ C &xx; 20 %: X+; R26–40–42/43 1 % ≤ C &xx; 7 %: X; X23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42 |
2 |
|
616–010–00–9 |
xxxxxxx-xxxxxxxxxxxxxx X-xxxxx-4-xxxxxxxxxxxx-1-xxxxxxxxxx, xxxxx xxx |
204–854–7 |
127–65–1 |
Xx; X22 X31 X; X34 R42 |
C X: 22–31–34–42 X: (1/2-)7–22–26–36/37/39–45 |
|||
|
616–034–00-X |
xxxxxxxxxxxx (XXX) 6-xxxxxx-3,4-xxxxxxx-2X-xxxxx-5-xxxxxxxxxxxx |
246–419–4 |
24691–76–7 |
X52–53 |
X: 52/53 S: 61 |
|||
|
616–035–00–5 |
xxxxxxxxx X -[(ethylamino)karbonyl]-2-kyan-2-(methoxyimino)acetamid 1-ethyl-3-[2-kyan-2-(methoxyimino)acetyl]močovina |
261–043–0 |
57966–95–7 |
Xn; X22 R43 X; X50–53 |
Xx; X R: 22–43–50/53 S: (2-)36/37–60–61 |
|||
|
617–004–00–9 |
(1,2,3,4-tetrahydro-1-naftyl)hydroperoxid xxxxxxxxxxxxxxxxxxxx |
212–230–0 |
771–29–9 |
X; X7 Xx; X22 X; X34 X; R50–53 |
O; X; X X: 7–22–34–50/53 X:(1/2-)3/7–14–26–36/37/39–45–60–61 |
X325 %: X; X22–34 10 % ≤ X < 25 %: C; X34 5 % ≤ C &xx; 10 %: Xx; X36/37/38 |
||
|
617–006–00-X |
xxx(α, α-xxxxxxxxxxxxxx)xxxxxxx bis(2-fenylpropan-2-yl)peroxid xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx xxxxxxxxxxxxxx |
201–279–3 |
80–43–3 |
X; X7 Xx; X36/38 N; X51–53 |
X; Xx; X X: 7–36/38–51/53 X: (2-)3/7–14–36/37/39–61 |
|||
|
617–008–00–0 |
xxxxxxxxxxxxxxxx |
202–327–6 |
94–36–0 |
X; X2 Xi; X36 X43 |
X; Xi; X: 2–36–43 S: (2-)3/7–14–36/37/39 |
|||
|
650–007–00–3 |
xxxxxxxxxxxxx (XXX) X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx |
228–200–5 |
6164–98–3 |
Xxxx. xxx. 3; X40 Xx; X21/22 X; R50–53 |
Xn; X X: 21/22–40–50/53 S: (2-)22–36/37–60–61 |
|||
|
650–008–00–9 |
xxxxxxxxxx (XXX) 4-[(2-chlorfenyl)hydrazono]-3-methylisoxazol-5(4 X)-xx |
227–197–8 |
5707–69–7 |
X; R25 N; X50–53 |
X; X X: 25–50/53 X: (1/2-)22–24–36/37–45–60–61 |
|||
|
650–009–00–4 |
chlordimeform-hydrochlorid X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx N2-(4-chlor-o-tolyl)-N1,N1-dimethylformamidin-hydrochlorid |
243–269–1 |
19750–95–9 |
Karc. xxx. 3; X40 Xx; X22 X; X50–53 |
Xx; X R: 22–40–50/53 X: (2-)22–36/37–60–61 |
|||
|
650–033–00–5 |
xxxxxxxxxxxx (XXX) [(S)-(3-fenoxyfenyl)kyanmethyl]-(S)-2-(4-chlorfenyl)-3-methylbutanoát (X)-3-xxxxxx-α-xxxxxxxxxx-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx |
— |
66230–04–4 |
X; X23/25 X43 N; X50–53 |
X; X R: 23/25–43–50/53 X: (1/2-)24–36/37/39–45–60–61 |
|||
|
650–041–00–9 |
xxxxxxxxxxxx (XXX) 1-[2-(2-chlorethoxy)benzen-1-sulfonyl]-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)močovina |
— |
82097–50–5 |
N; X50–53 |
X X: 50/53 X: 60-61 |
XXXXXXX 1X
|
Xxxxxxxx číslo |
Chemický xxxxx |
Xxxxxxxx k látkám |
Číslo XX |
Xxxxx XXX |
Xxxxxxxxxxx |
Xxxxxxxx |
Xxxxxxxxxxxx limity |
Poznámky x přípravkům |
|
006–090–00–8 |
2-[(3-jodprop-2-yn-1-yl)oxy]ethyl-N-fenylkarbamát |
408–010–0 |
88558–41–2 |
Xn; X20 Xx; X41 R52–53 |
Xn X: 20–41–52/53 S: (2-)22–26–39–61 |
|||
|
014–016–00–0 |
Xxxx: 1,3-di(hex-5-en-1-yl)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx x 1,3-di(hex-x-en-1-yl)- 1,1,3,3-tetramethyldisiloxan |
406–490–6 |
— |
N; X51–53 |
X R: 51/53 X: 61 |
|||
|
015–164–00–9 |
xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx xxxxxxxx |
400–480–5 |
36669–85–9 |
X52–53 |
X:52/53 X: 61 |
|||
|
015–165–00–4 |
Xxxx: X, X, X', S''-tetrafenyl-4,4'-sulfandiylbis(fenylsulfonium)-bis(hexafluorofosfát) x difenyl[4-(fenylsulfanyl)fenyl]sulfonium-hexafluorofosfát |
404–986–7 |
— |
Xi; X41 X; R50–53 |
Xi; N X: 41–50/53 X: (2-)15–26–39–60–61 |
|||
|
015–166–00-X |
3,9-xxx(2,6-xx-xxxx-xxxxx-4-xxxxxxxxxxxx)-2,4,8,10-xxxxxxxx-3,9-xxxxxxxxxxxx[5.5]xxxxxxx |
410–290–4 |
80693–00–1 |
X53 |
X:53 X: 61 |
|||
|
015–167–00–5 |
3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx |
411–200–6 |
14657–64–8 |
Xx; X41 |
Xx X: 41 X: (2-)26-39 |
|||
|
601–050–00–1 |
X10-X13-xxxxxxxxxxxxx xxxxxxx |
267–051–0 |
67774–74–7 |
X; X50 |
X R: 50 X: 61 |
|||
|
601–051–00–7 |
4-fenylbut-1-en |
405–980–7 |
768–56–9 |
Xi; X38 N; X51–53 |
Xx; X R: 38–51/53 X: (2-)37-61 |
|||
|
602–083–00–4 |
pentabromderivát xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx |
251–084–2 |
32534–81–9 |
Xx; X48/21/22 R64 X; X50–53 |
Xx; N X: 48/21/22–50/53–64 X: (1/2-)36/37–45–60–61 |
|||
|
602–084–00-X |
1,1-xxxxxxx-1-xxxxxxxxxx |
404–080–1 |
1717–00–6 |
X; X52–53–59 |
X X: 52/53–59 X: 59-61 |
|||
|
603–128–00–0 |
2-(fenylmethoxy)naftalen |
405–490–3 |
613–62–7 |
R53 |
R:53 X: 61 |
|||
|
603–129–00–6 |
1-xxxx-xxxxxxxxxxxx-2-xx |
406–180–0 |
57018–52–7 |
X10 Xi; X41 |
Xx X: 10-41 X: (2-)26-39 |
|||
|
603–130–00–1 |
Xxxx xxxxxxx: α-(xxxxxxxxxxxxxxxxx)-ω-xxxxxxxxxxx(xxxxxxxxxx) |
406–325–8 |
— |
Xx; R22 X52–53 |
Xx X:22–52/53 X: (2-)39-61 |
|||
|
603–131–00–7 |
Směs (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-deoxy-1-[methyl(1-oxotetradecyl)amino]-D-glucitol |
407–290–1 |
— |
Xi; X41 |
Xx X: 41 S: (2-)26-39 |
|||
|
603–132–00–2 |
2-(xxxxxxxxxxxxx)-6-xxxxxxxxx-9-xxxxxx-1,4-xxxxxxxxxx[4.5]xxxxx |
408–200–3 |
63187–91–7 |
Xx; R38–41 X52–53 |
Xx X:38–41–52/53 S: (2-)26–37/39–61 |
|||
|
603–133–00–8 |
Xxxx:3-(4-xxxxx-2-xxxxx-5-xxxxxxxxxxxx)xxxxxx-1,2-xxxx x 3,3'-[(2-xxxxx-5-xxxxx-1,4-xxxxxxx)xxxxxxx]xx(xxxxxx-1,2-xxxx) |
408–240–1 |
— |
Xx; X22 X52–53 |
Xx X:22–52/53 S: (2-)22–36–61 |
|||
|
603–134–00–3 |
Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx x xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (dodecyl x xxxxxxxxxx xxxxxxxxxxxx) |
410–450–3 |
— |
X53 |
X: 53 X: 61 |
|||
|
603–135–00–9 |
bis[2-(2-methoxyethoxy)ethanolato]bis(2,2', 2-xxxxxxxxxxxxxxx-1-xxxxx-X,X)xxxxxxxxxx xxxxxxx |
410–500–4 |
— |
Xx; X41 X; X51–53 |
Xx; X X: 41–51/53 X: (2-)26–39–61 |
|||
|
603–136–00–4 |
3-{4-[xxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxxx}xxxxxx-1-xx |
410–910–3 |
104226–19–9 |
X43 X52–53 |
Xx R:43–52/53 X: (2-)24–37–61 |
|||
|
603–137–00-X |
Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx |
411–130–6 |
— |
Xx; X41 |
Xx X: 41 X: (2-)26-39 |
|||
|
603–138–00–5 |
3-(2,2-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-dimethyl-3-(3-methylfenyl)propan-1-ol |
403–140–4 |
103694–68–4 |
R52–53 |
R:52/53 X: 61 |
|||
|
604–050–00-X |
4-xxxxx-x-xxxxxx 4-chlor-2-methylfenol |
216–381–3 |
1570–64–5 |
T; X23 C; X 35 N; X50 |
X; X; X X: 23–35–50 S: (1/2-)26–36/37/39–45–61 |
X ≥ 25 %: X; C; X23–35 10 % ≤ X < 25 %: X;X20–35 5 % ≤ C &xx; 10 %: X;X20–34 3 % ≤ C &xx; 5 %: Xn;R20–36/37/38 1 % ≤ X < 3 %:Xx;X36/37/38 |
||
|
604–051–00–5 |
3,5-xxx(3,5-xx-xxxx-xxxxx-4-xxxxxxxxxxxxx)-2,4,6-xxxxxxxxxxxxxx |
401–110–5 |
87113–78–8 |
X52–53 |
X:52/53 X: 61 |
|||
|
604–052–00–0 |
2,2'-methylenbis[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -xxxxxxxxxxxx-2-xx)- 4,4'-bis(1,1,3,3-tetramethylbutyl)- 2,2'-xxxxxxxxxxxxxxx |
403–800–1 |
103597–45–1 |
X53 |
X:53 X: 61 |
|||
|
604–053–00–6 |
4-terc - xxxxx-2-xxxxxx-6-(1-xxxxxxxxxxxxxxxx)xxxxx |
410–760–9 |
157661–93–3 |
Xx; X38 X43 X; R50–53 |
Xi; X R: 38–43–50/53 X: (2-)24–37–60–61 |
|||
|
604–054–00–1 |
Směs:2-methoxy-4-(4-methylidentetrahydropyran-2-yl)fenol x 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -xxxxx-2-xx)xxxxx |
412–020–0 |
— |
X43 X52–53 |
Xx X:43–52/53 S: (2-)24–37–61 |
|||
|
604–055–00–7 |
4,4'-xxx[(2,3-xxxxxxxxxxx)xxx]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx |
413–900–7 |
85954–11–6 |
Xxxx. Xxx.3; R40 |
Xn X: 40 S: (2-)22–36–37 |
|||
|
605–027–00–7 |
Xxxx:3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X-xxxxx-6-xxxxxxxxxxx x 3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X - xxxxx-5-xxxxxxxxxxx |
410–480–7 |
— |
X43 X; X51–53 |
Xx; X X: 43–51/53 X: (2-)24–37–61 |
|||
|
606–051–00–0 |
4-xxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxx-1-xx |
4–406–670–4 |
61203–83–6 |
X; X51–53 |
X X: 51/53 X: 61 |
|||
|
606–052–00–6 |
4-(N, X-xxxxxxxxxxxx)-2-xxxxxxx-2'-xxxxxxxxxxxxxxxxx 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx kyselina |
410–410–5 |
54574–82–2 |
R52–53 |
R:52/53 X: 61 |
|||
|
607–272–00–5 |
xxxxxxxxxxx-xxxxxx (XXX) [1] xxxxxxxxxx-xxxxxxxxx (XXX) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-xxxxxx-1-xxxxxxxxxxx)-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [2] |
279–752–9 [1] — |
81406–37–3 [1] 154486–27–8 [2] |
X; X50–53 |
X X: 50/53 X: 60-61 |
|||
|
607–273–00–0 |
amonium-7-{2,6-dimethyl-8-[(2,2-dimethylbutanoyl)oxy]- 1,2,6,7,8,8x-xxxxxxxxx-1-xxxxxx}-3,5-xxxxxxxxxxxxxxxxxx |
404–520–2 |
— |
X52–53 |
X:52/53 X: 61 |
|||
|
607–274–00–6 |
{2-[benzyl(methyl)amino]ethyl}-3-aminobut-2-enoát |
405–350–1 |
54527–73–0 |
R43 X; X51–53 |
Xx; X X: 43–51/53 X: (2-)24–37–61 |
|||
|
607–275–00–1 |
xxxxxxx-4-(xxxxxxxxxx)xxxxxx-1-xxxxxxxx |
405–450–5 |
66531–87–1 |
X43 |
Xx X: 43 X: (2-)24-37 |
|||
|
607–276–00–7 |
[xxx(2-xxxxxxxxxxxxxx) bis(1-methylimidazol)]zinečnatý xxxxxxx |
405–635–0 |
— |
Xx; X38–41 X; X50–53 |
Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61 |
|||
|
607–277–00–2 |
Xxxx:2-(xxxxxxxxxxxxx)xxxxxxxxx-xxxxxxxxxxxx x xxxxxxx-xxxxxxxxx |
405–720–2 |
— |
Xx; X22 Xi; X41 X43 N; X51–53 |
Xx; X X: 22–41–43–51/53 S: (2-)24–26–37/39–61 |
|||
|
607–278–00–8 |
Směs:alkyl(C7-C9 xxxxxxxxxx x xxxxxxxxxxxx)-3-[3-(2 X - xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx |
405–760–0 |
— |
Xx; X41 X43 X52–53 |
Xx X: 41–43–52/53 X: (2-)24–26–37/39–61 |
|||
|
607–279–00–3 |
Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) x (oktadecylimino)diethylen-(hydrogen-ftalát)-(hydrogen-maleinát) |
405–960–8 |
— |
R43 X; X51–53 |
Xx; X X: 43–51/53 S: (2-)24–37–61 |
|||
|
607–280–00–9 |
4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx sodný xxxxxxx-4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx |
406–190–5 |
54322–20–2 |
Xx; X22 Xx; X36 X43 |
Xx R: 22–36–43 X: (2-)22–26–36/37 |
|||
|
607–281–00–4 |
Směs:alkyl(C7-C9 rozvětvené x lineární)-3-[3-(2H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty |
407–000–3 |
127519–17–9 |
N; X51–53 |
X X: 51/53 X: 61 |
|||
|
607–282–00-X |
2-(xxxxxxxxxxxxx)-4-(xxxxxxxxx)xxxxx-xxxxxx |
407–140–5 |
131266–10–9 |
X52–53 |
X: 52/53 S: 61 |
|||
|
607–283–00–5 |
xxxxx-(X)-4-xxxxx-4-xxxxxx-2-xxxxxxxxxx-(X)-4-xxxxx-4-xxxxxxxxxxx |
408–040–4 |
15121–89–8 |
Xx; R21/22 Xi; X38–41 R43 X; X50–53 |
Xx; X R: 21/22–38–41–43–50/53 S: (2-)26–36/37/39–60–61 |
|||
|
607–284–00–0 |
Xxxx (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) a xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) |
410–040–4 |
136213–76–8 |
X; X51–53 |
X R: 51/53 X: 61 |
|||
|
607–285–00–6 |
Xxxx:7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxxx kyselina, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx a natrium-7-(3-aminobenzensulfonamido)naftalen-1,3-disulfonát |
410–065–0 |
— |
R43 |
Xi X: 43 X: (2-)22–24–37 |
|||
|
607–286–00–1 |
Xxxx:xxxxxx- a xxxxxxx-7-[4-({4-[(2-xxxxxxx-1-xxxxxx)xxx]xxxxx}xxx)xxxxxxxxxxxxxxxxx]xxxxxxxx-1,3-xxxxxxxxxx |
410–070–8 |
141880–36–6 |
X43 X52–53 |
Xx R:43–52/53 X: (2-)22–24–37–61 |
|||
|
607–287–00–7 |
xxxxxx-[1-xxxxxx-2-(xxxxxxxxxxxxxxx)xxxxx]-1,2,3,6-xxxxxxxxxxxxxxxx |
410–140–8 |
— |
X52–53 |
X:52/53 S: 61 |
|||
|
607–288–00–2 |
[x-(X -{3-[(1-{3-[(2,6(4,6)-xxxxxxx-5-xxxxxxxxxxxxx-4(2)-xx)xxxxxxxxxxx]xxxxxx}-2-xxxxxxx-4-xxxxxx-6-xxx-1,6-xxxxxxx-3-xxxxxxx)xxx]-4-xxxxxxxxxxxxxx}xxxxxxxxx)-x,x,x -xxxxxxxxxxxxxxxxxxxxxxx]xxxxxxxxx xxxxxxx, xxxxxxxxxx xxx; x = 15, 16, 17 nebo 18, x = 1, 2, 3 xxxx 4, x = 8, 9, 10 xxxx 11, x = 22, 23, 24 xxxx 25 |
410–160–7 |
148732–74–5 |
Xi; X36 R43 R52–53 |
Xi X: 36–43–52/53 S: (2-)22–26–36/37–61 |
|||
|
607–288–00–8 |
3-[(3-{X —[4-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxx]xxxxxxxxx}-4-xxxxxxx-1-xxxxxx)xxxxxxxx]xxxxxxxxx xxxxxxxx |
410–370–9 |
105488–33–3 |
X53 |
X:53 X: 61 |
|||
|
607–290–00–3 |
Xxxx (x xxxxxxxx xxxxxx):xxxxxxx-1-xxxxx(X14-X18)-4-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx a xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx |
410–540–2 |
— |
Xx; X38 X43 X; R50–53 |
Xi; X X: 38–43–50/53 S: (2-)24–37–60–61 |
|||
|
607–291–00–9 |
xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx |
410–630–1 |
104051–92–5 |
X53 |
X: 53 X: 61 |
|||
|
607–292–00–4 |
Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(alkyl(C14)oxy)-1-(methoxymethyl)]octová xxxxxxxx |
410–640–6 |
— |
Xx; X38–41 X; X50–53 |
Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61 |
|||
|
607–293–00-XXxxx: |
1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx x 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx |
410–650–0 |
— |
Xx; R41 X43 X; X51–53 |
Xx; X X: 41–43–51/53 X: (2-)26–36/37/39–61 |
|||
|
607–294–00–5 |
xxxxxxx-2-(xxxxxxxxxx)-1-xxxxxxxxxxxx-1-xxxxxxxx |
410–680–4 |
— |
X43 |
Xx X: 43 X: (2-)24-37 |
|||
|
607–295–00–0 |
Xxxx:xxxxxxxxxxxx-xxxxxxxxxxxxxxxxx x xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx |
410–800–5 |
— |
X43 N; X51–53 |
Xx; X X: 43–51/53 X: (2-)24–37–61 |
|||
|
607–296–00–6 |
Xxxx:xxxxxxxxxxx pentaerythritolu, xxxxxxxxx kyselina x 2-xxxxxxxxxxxxx xxxxxxxx |
410–830–9 |
— |
X53 |
X: 53 X: 61 |
|||
|
607–297–00–1 |
3,3'-(1,4-fenylendimethyliden)bis(2-oxobornan-10-sulfonová xxxxxxxx)2,2'-xxxxx-3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(1,7,7-xxxxxxxxxxxxxxxx[2.2.1]xxxxxx-1-xxxxxxxxxxxxxxx xxxxxxxx) |
410–960–6 |
92761–26–7 |
Xx; X41 |
Xx X: 41 X: (2-)26-39 |
|||
|
607–298–00–7 |
[2-(xxxxxxxxxxxxxxx)xxxxx]-4-xxxxxxxxxxxxxxxx |
411–010–3 |
— |
X43 |
Xx X: 43 X: (2-)22–36/37 |
|||
|
607–299–00–2 |
xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx |
411–040–7 |
97101–46–7 |
Xx; R22 R43 X; X50–53 |
Xx; N X: 22–43–50/53 S: (2-)24–37–60–61 |
|||
|
607–300–00–6 |
[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, d-sulfonatoftalocyanin]měďnatý xxxxxxx, xxxxxxxx xxx; a = 1,2,3 xxxx 4, b = 8, 9, 10 xxxx 11, x = 15, 16, 17 xxxx 18, x = 22, 23, 24 xxxx 25 |
411–430–7 |
— |
X43 |
Xx X: 43 X: (2-)22–24–37 |
|||
|
607–301–00–1 |
Xxxx:xxxxxxxxxx xxxxxxxx x xxxxxxxxxxx oligo(1-7)laktátů |
411–860–5 |
— |
Xi; X38–41 X43 X; X51–53 |
Xx; X X: 38–41–43–51/53 X: (2-)24–26–37/39–61 |
|||
|
607–302–00–7 |
Xxxx:xxxxxxxxxxxxx xxxxxxxx x tetradekanoáty xxxxx(1-7)xxxxxxx |
411–910–6 |
— |
Xx; R38–41 X43 X; X51–53 |
Xx; X X: 38–41–43–51/53 X: (2-)24–26–37/39–61 |
|||
|
607–303–00–2 |
1-xxxxxxxxxxx-6,7-xxxxxxx-4-xxx-1,4-xxxxxxxxxxxxxxx-3-xxxxxxxxxxx xxxxxxxx |
413–760–7 |
93107–30–3 |
Xxxx. xxx.3; X62 X52–53 |
Xx X: 62–52/53 X: (2-)22–36/37–61 |
|||
|
608–023–00–3 |
4-(4-xxxxxxxxxx)-2-xxxxx-2-[(1X- 1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx |
406–140–2 |
114369–43–6 |
X; R50–53 |
N X: 50/53 X: 60-61 |
|||
|
608–024–00–9 |
2-{4-[xxxxx(xxxxxxxx)xxxxx]xxxxx}xxxxx-1,1,2-xxxxxxxxxxxxxx |
407–650–8 |
97460–76–9 |
X53 |
X:53 X: 61 |
|||
|
608–025–00–4 |
[2-xxxxx-4,5-xxx(xxxxxxxxx)xxxxx]xxxxxxxxxxx |
410–970–0 |
117568–27–1 |
X53 |
X:53 X: 61 |
|||
|
609–053–00-X |
xxxxxxxxxxx-xxxxxxxxxxxxxxxx |
414–850–9 |
— |
X; X3 O; X8 Xxxx. kat. 2; X45 X; X23/25 X43 |
X; T X: 45–3–8–23/25–43 X: 53-45 |
|||
|
610–010–00–2 |
1-xxxx-2-(2-xxxxx)-1-xxxxxxxxxx |
406–110–9 |
35950–52–8 |
Xx; X22–48/22 X; X34 X43 N; X50–53 |
X; X R: 22–34–43–48/22–50/53 X: (1/2-)22–26–36/37/39–45–60–61 |
|||
|
611–043–00–5 |
Xxxx (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx, [xxx{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-amino-6-hydroxyfenyl)azo]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx xxxxxxxx x[{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx |
402–850–1 |
Xx X: 41–52/53 X: (2-)26–39–61 |
|||||
|
611–044–00–0 |
Směs:[bis(5-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx a[(4(5)-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato) (3-xxxxx-5-xxxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx |
403–720–7 |
117527–94–3 |
X; R51–53 |
Xi; R41 X52–53 |
|||
|
611–045–00–6 |
2-({4-[(4-xxxxxxxxxxxx)xxxxxxxxxx]-2-xxxxxxxxxxx}xxx)-3-xxxxxx-5-xxxxxxxxxxxx |
404–830–8 |
— |
X53 |
X:53 X: 61 |
N X: 51/53 X: 61 |
||
|
611–046–00–1 |
4,4'-xxxxxxx-2-xxxxxxxxxxxxxxx2-xxxxxxxxxxxxxxx-4,4'-xxxxxx |
407–590–2 |
43151–99–1 |
X; R25 Xx; X48/22 X43 X; X50–53 |
X; N R: 25–43–48/22–50/53 X: (1/2-)22–28–36/37–45–60–61 |
|||
|
611–047–00–7 |
Xxxx (1:1):2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx |
407–890–3 |
111381–11–4 |
X53 |
X: 53 X: 61 |
|||
|
611–048–00–2 |
Směs (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx |
407–900–6 |
111381–12–5 |
X53 |
X: 53 X: 61 |
|||
|
611–049–00–8 |
Xxxx (2:1:1)7-[(4-{[3-(xxxxxxxxxxxx)xxxxxx]xxxxx}-6-{[3-(xxxxxxxxxxxxx)xxxxxx]xxxxx}-1,3,5-xxxxxxx-2-xx)xxxxx]-3-{[4-(xxxxxxxx)xxxxx]xxx}-4-xxxxxxxxxxxxxxx-2-xxxxxxxx, xxxxxxxx octová x mléčná kyselina (2:1:1) |
408–000–6 |
118658–98–3 |
Xx; X48/22 X43 X52–53 |
Xx R: 43–48/22–52/53 X: (2-(22–36/37–61 |
|||
|
611–051–00–9 |
2-({4-[xxxxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxx}xxx)-6-xxxxxxx-3-xxxxxxxxxxxxxxxxxxxxx-xxxxxxx |
411–110–7 |
136213–74–6 |
X; R50–53 |
N X: 50/53 X: 60-61 |
|||
|
611–052–00–4 |
[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) xxx]-6-[(6-xxxxxxxxx-1-xxxxxx)xxx]xxxxxx-1,3-xxxxxxx}]xxxxxxxxx xxxxxxx, xxxxx xxx |
400–720–9 |
— |
X52–53 |
X: 52/53 X: 61 |
|||
|
612–156–00–2 |
Směs:trihexadecyl(methyl)amonium-chlorid x xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx |
405–620–9 |
— |
Xx; X41 N; X50–53 |
Xx; X X: 41–50/53 X: (2-)26–39–60–61 |
|||
|
612–157–00–8 |
(X)-1-(1-xxxxxxxxxxxx-2-xx)xxxxx-1-xx-xxxx-xxxxxxxxxxxx |
410–780–8 |
— |
Xx; X22–48/22 Xi; X41 X43 N; X51–53 |
Xx; X X: 22–41–43–48/22–51/53 X: (2-)22–26–36/37/39–61 |
|||
|
612–158–00–3 |
Xxxx:[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxxxxxxxxxxxxxxxx |
410–820–4 |
— |
X53 |
X: 53 X: 61 |
|||
|
612–159–00–9 |
xxxxxxx produkty xxxxx 2,2,4-xxxxxxxxx- a 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x xxxxxxx XXXXXX), xxxxxxxx [(alkyl(C10-C16)oxy)methyl]oxiranu (Xxxxxx 8) a 4-xxxxxxxxxxxx-1-xxxxxxxxx xxxxxxxx |
410–880–1 |
— |
Xx; X22 X; X34 N; X50–53 |
X; X X: 22–34–50/53 X: (1/2-)23–26–36/37/39–45–60–61 |
|||
|
613–149–00–7 |
2-terc-butyl-5-[(4-terc-butylbenzyl)sulfanyl]-4-chlorpyridazin-3(2H)-on |
405–700–3 |
96489–71–3 |
T; X23/25 X; X50–53 |
X; X X: 23/25–50/53 X: (1/2-)36/37–45–60–61 |
|||
|
613–150–00–2 |
2,2'-[xxxxxxxxx-1,4-xxxxxx(xxxxxx-1,3-xxxx)]xxx(xxxxxxxxxxx[2,1-x]xxxxx[xxx][3,8]xxxxxxxxxxxx-1,3,6-xxxxx) |
406–295–6 |
— |
X53 |
X:53 S: 61 |
|||
|
613–151–00–8 |
1-(2-xxxxx-3-X-xxxxx-5-X-xxxxxx-β-X-xxxxx-xxxxxxxxxxxxxx)-5-xxxxxxxxxxxxxxx-2(1X), 4(3 H)-dion |
406–360–9 |
104218–44–2 |
R53 |
R:53 X: 61 |
|||
|
613–152–00–3 |
xxxxx-X-(4,6-xxxxxxxxxxxxxxxxxx-2-xx)xxxxxxxx |
406–600–2 |
89392–03–0 |
X43 X; X51–53 |
Xx; X R: 43–51/53 X: (2-)24–37–61 |
|||
|
613–153–00–9 |
2,3,5-xxxxxxxxxxxxxxx |
407–270–2 |
16063–70–0 |
X52–53 |
X:52/53 S: 61 |
|||
|
613–154–00–4 |
2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx |
410–050–9 |
5734–64–5 |
Xx; X22 |
Xx X: 22 X: (2-)22 |
|||
|
613–155–00-X |
5-xxxxx-2,3-xxxxxxxxxxxxxx |
410–090–7 |
89402–43–7 |
X10 Xx; R22 X52–53 |
Xx X: 10–22–52/53 X: (2-)23–36–61 |
|||
|
613–156–00–5 |
2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-xxxxx-5-xxxxxxxxxxxxx-4-xxxxxxxxxxx |
410–260–0 |
83857–96–9 |
X43 N; X51–53 |
Xx; X R: 43–51/53 X: (2-)24–37–61 |
|||
|
613–157–00–0 |
2,4-xxxxxxx-5-(xxxxxxxxxxxxx)xxxxxxxxx 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx |
410–330–0 |
54236–98–5 |
Xx; X22–48/22 Xx; X36 |
Xx R: 22–36–48/22 X: (2-)22–26–36 |
|||
|
613–158–00–6 |
2,3-xxxxxxx-5-(xxxxxxxxxxxxxx)xxxxxxx |
410–340–5 |
69045–84–7 |
Xx; R20/22 Xx; X41 X43 X; X51–53 |
Xx; X X: 20/22–41–43–51/53 X: (2-)24–26–37/39–61 |
|||
|
613–159–00–1 |
4-[2-(4-xxxx-xxxxxxxxxx)xxxxxx]xxxxxxxxxx |
410–580–0 |
120928–09–8 |
X; R25 Xn; X20 X; X50–53 |
X; X X: 20–25–50/53 X: (1/2-)37–45–60–61 |
|||
|
613–160–00–7 |
2-xxxxxx-2,5-xxxxxxxxxxxx[2.2.1]xxxxxx-xxxxxxxxxxxxx |
411–000–9 |
125224–62–6 |
X43 |
Xx X: 43 X: (2-)24-37 |
|||
|
615–022–00–1 |
xxxxxx-3-(xxxxxxxxxxxxxxxxxx)xxxxxxx-2-xxxxxxxxxx |
410–550–7 |
79277–18–2 |
X; X2 X14 Xx; X48/22 X42/43 |
X; Xx X: 2–14–42/43–48/22 S: (2-)22–30–35–36/37 |
|||
|
615–023–00–7 |
xxxxxxxxxxx 2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxxx kyselinymethyl-2-[(isokyanatosulfonyl)methyl]benzoát |
410–900–9 |
83056–32–0 |
R10 X14 Xxxx. xxx. 3; X40 Xn; X20–48/22 Xi; X41 X42 |
Xx X: 10–14–20–40–41–42–48/22 X: (2-)23–26–36/37/39 |
|||
|
616–044–00–4 |
X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)-2-(3-xxxxxxxxxxxxxxxx)xxxxxxxxx |
402–510–2 |
— |
X; X51–53 |
X X: 51/53 X: 61 |
|||
|
616–045–00-X |
2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxxxxx |
405–190–2 |
122371–93–1 |
X43 R53 |
Xi X: 43-53 S: (2-)22–24–37–61 |
|||
|
616–046–00–5 |
X -[2-(6-xxxxx-7-xxxxxxxxxxxxxx[1,5-x][1,2,4]xxxxxxx-4-xx)xxxxxx]-2-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxxxxxx |
406–390–2 |
— |
X; R50–53 |
N X: 50/53 S: 60-61 |
|||
|
616–047–00–0 |
Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx x X, X′,X″,X′′′ - xxxxxxxxxx(X18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx |
406–640–0 |
— |
X43 |
Xx X: 43 S: (2-)24-37 |
|||
|
616–048–00–6 |
3'-(trifluormethyl)isobutyranilid |
406–740–4 |
1939–27–1 |
Xn; X48/22 N; R51–53 |
Xn; X X: 48/22–51/53 X: (2-)22–36–61 |
|||
|
616–049–00–1 |
2-(2,4-di-terc-butylfenoxy)-N-(3,5-dichlor-4-ethyl-2-hydroxyfenyl)hexanamid |
408–150–2 |
99141–89–6 |
R53 |
R:53 X: 61 |
|||
|
616–050–00–7 |
1-[2,5-xxxxxxx-4-(1,1,2,3,3,3-xxxxxxxxxxxxxxxx)xxxxx]-3-(2,6-xxxxxxxxxxxx)xxxxxxxx |
410–690–9 |
103055–07–8 |
X43 N; X50–53 |
Xx; X R: 43–50/53 X: (2-)24–37–60–61 |
|||
|
616–051–00–2 |
Xxxx:3,3'-xxx(4-xxxxxxxxxxx)- 1,1'-(4-methyl-1,3-fenylen)dimočovina x 3,3'-xxx(4-xxxxxxxxxxx)-1,1'-(2-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx Směs:2,4-bis[3-(4-methylfenyl)ureido]toluen x 2,6-bis[(3-(4-methylfenyl)ureido]toluen |
411–070–0 |
— |
R53 |
R: 53 X: 61 |
|||
|
617–015–00–9 |
bis(4-methylbenzoyl)peroxid |
407–950–9 |
895–85–2 |
E; X2 X; R7 X; X50–53 |
X; X X: 2–7–50/53 S: (2-)7–14–36/37/39–47–60–61 |
|||
|
650–032–00-X |
xxxxxxxxxxxx (XXX) (2X, 3X)-, (2 X, 3 X)-, (2 X, 3 S)-, (2 X, 3 R)-2-(4-chlorfenyl)-3-cyklopropyl-1-(1H- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx |
— |
94361–06–5 |
Xxxx. kat. 3; X63 Xx; X22 X; X50–53 |
Xx; N X: 22–50/53–63 X: (2-)36/37–60–61 |
XXXXXXX 2
XXXXXX XXXXXXXXXXXX XXXXX XXXXXXXXX S XXXXXXXXXXXX XXXXXXX X XXXXXXXXX
Xxx směrnice Xxxxxx 2001/59/XX,
Xx. xxxx. L 332, 28.12.2000, x. 81.
XXXXXXX 3X
XXXXXXXXXX POKYNY XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX
Xxx xxxxxxxx Xxxxxx 2001/59/ES,
Úř. věst. X 332, 28.12.2000, x. 81.
PŘÍLOHA 3X
XXXXXXXXXX XXXXXX XXX XXXXXXXX ZACHÁZENÍ X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY
Viz xxxxxxxx Xxxxxx 2001/59/ES,
Úř. věst. X 332, 28.12.2000, x. 81.
PŘÍLOHA 4A
"B.10 XXXXXXXXXX — XXXXXXX XX XXXXXXXXXXXX XXXXXXX X XXXXX IN VITRO
1. XXXXXX
Xxxx xxxxxx je xxxxxxxx xxxxxx OECD XX 473 — Xxxxxxx na xxxxxxxxxxxx xxxxxxx x xxxxx xx vitro (1997).
1.1 XXXX
Xxxxxxx na chromozomové xxxxxxx x xxxxx xx xxxxx xx xxxxxxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx aberací: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx chemických xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx xx schopnost xxxxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx mutace a xxxxxxx jevy xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, že chromozomové xxxxxx x x xxxx xxxxxxxxxxx jevy xxxxxxxxxxx změny x xxxxxxxxxx x x xxxxxx somatických buněk xxxxxxxxx nádory, xxxx xxxxx na indukci xxxxxxxx x člověka x x xxxxxxxxx xxxxxx.
Xx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxx mohou xxx xxxxxxx xxxxxxxxxxxxx buněčné xxxxx, buněčné xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx. Xxxxxxx buňky xxxx xxxxxxx na xxxxxxx schopnosti xxxxx x xxxxxxx, stálosti xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx a xxxxxxxxx četnosti chromozomových xxxxxxx.
Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Tento xxxxxxxxxxx aktivační xxxxxx xxxxxx zcela napodobit xxxxxxxx xx xxxx x savců. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx k xxx xxxxx změnou xX, osmolality xxxx xxxxxxxx úrovní xxxxxxxxxxxx (4, 5).
Tato zkouška xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx je xxxx xxxxxxx xxxxxxxxx, xxxx pro xxxxx xxxxxxxxxxx; xxxx xxxxx xxxxxxxx a karcinogenitou xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx závisí xx xxxxxxxx xxxxx x xxxxxxxxx důkazy x xxx, že xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx zjištěny xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx mechanismy xxx přímým poškozením XXX.
Xxx xxxx Xxxxxx xxxx, část X.
1.2 XXXXXXXX
Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx zlomu xxxxxxxxxxxx chromatid xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.
Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx x spojení xxxx xxxxxxxxx x xxxxxx xxxxx.
Xxxxxxxxxxxxxxx : xxxxxx, xxx xxxxxx v xxxxx xx X-xxxx xxxxxxxxx DNA xxxxxxx x xxxxxx, xxxxx xxxxxxxxx další X-xxxx. Xxxxxxxxx jsou chromozomy xx 4, 8, 16… xxxxxxxxxxxx.
Xxx : xxxxxxxxxxxx xxxx xxxxx xxx xxxxx xxxxx xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.
Xxxxxxxxx xxxxx : xxxxx xxxxx, které xx xxxxxxxxx v xxxxxxxx, x xxxxxxxxx počtu xxxxx x xxxxxxxx; xxxxx stupeň proliferace xxxx xxxxxxxx.
Xxxxxxxxx aberace : xxxxxxxx xxxxx xxxxxxxxxx xx xxxxxxxxxx xxxxx xxxxxxxxx u xxxxxxxxx typu xxxxx.
Xxxxxxxxxxx : xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxxx sad (x), xxxx xxx xxxxxxxxx (tj. 3 x, 4 x xxx.).
Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx dělení ve xxxxxx xxxxxxxx; jeví xx xxxx delece x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.
1.3 XXXXXXXX XXXXXXXX XXXXXX
Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, a xx x xxxxxxxxxxxx xxxxxxxx x bez xx. X xxxxxx xxxxxxxxxxx intervalech po xxxxxxxx látce xx xx xxxxxxxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx), kultury xx xxxxxx, xxxxxx x přítomnost xxxxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxxx xxxxx.
1.4 XXXXX ZKUŠEBNÍ XXXXXX
1.4.1 Xxxxxxxxx
1.4.1.1 Xxxxx
Xxxxx být xxxxxxx různé xxxxxxx xxxxx, xxxxx nebo xxxxxxxx xxxxxxx xxxxxxx, xxxxxx xxxxxxxx buněčných xxxxx (xxxx. fibroblasty xxxxxx čínského, lymfocyty xxxxxxxxx krve člověka xxxx xxxxxx savců).
1.4.1.2 Xxxxx a xxxxxxxxxx xxxxxxxx
Xxx udržování xxxxxx xx xxxx být xxxxxxx vhodná xxxxxxxxxx xxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, teplota x xxxxxxx). U xxxxxxxxxxxxxxx xxxxxxxxx linií x xxxxx xx xxxx xxx rutinně xxxxxxxxxxxx xxxxxxxxx modální xxxxxxx xxxxx chromozomů x xxxx by xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx mykoplasmaty; x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Pro použité xxxxx a xxxxxxxxx xxxxxxxx xx měla xxx známa xxxxxxxx xxxxx xxxxxxxxx cyklu.
1.4.1.3 Xxxxxxxx kultur
Stabilizované xxxxxxx xxxxx a xxxxx: xxxxx se pomnoží x xxxxxxxxx kultur, xxxxxx se xx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxxx, xxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx, x xxxxxxxx xx xxx 37 °X.
Xxxxxxxxx: xxxx xxxxxxxx xxxxxxxxxxxxxxx (např. xxxxxxxxx) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx do xxxxxxxxxxxx xxxxx obsahujícího xxxxxxx (xxxx. xxxxxxxxxxxxxxxx) x xxxxxxxx xx při 37 °X.
1.4.1.4 Xxxxxxxxxxx xxxxxxxx
Xxxxx xx xxxx xxx vystaveny xxxxxxxx xxxxx, a xx x xxxxxxx xxxxxxxxxxxx xxxxxxxx x xxx xx. Nejčastěji xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx enzymy, xxxx xx Xxxxxxx 1254 (6, 7, 8 x 9), xxxx xxxx xxxxxxxxxxxxx x β-naftoflavonu (10, 11 x 12).
Postmitochondriální xxxxxx xx x xxxxxxxx testovacím xxxxx xxxxxxx používána x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx může záviset xx xxxxx xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. X některých xxxxxxxxx může xxx xxxxxx použít xxxx xxx jednu koncentraci xxxxxxxxxxxxxxxxxxx xxxxxx.
Xxxx xxxxxxxx xxxxxx, xxxxxx přípravy xxxxxxxxx modifikovaných xxxxxxxxx xxxxx xxxxxxxxxxxxx specifické xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx linií by xxxx být vědecky xxxxxxxxxx (xxxx. důležitostí xxxxxxxxx cytochromu P450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).
1.4.1.5 Zkoušená látka/příprava
Pevné xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx buňky xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx mohou xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx mohou být xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o stálosti xxxxxxxxxxx xxxxxxx skladování.
1.4.2 Xxxxxxxx xxxxxxxx
1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx
Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, x mělo xx xxx xxxxxxxxxx x přežitím xxxxx x x aktivitou X9. Xxxx-xx xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo by xxx jejich zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx nestálých xx xxxx by xxxx xxx použita xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.
1.4.2.2 Expoziční xxxxxxxxxxx
Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx při xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx cytotoxicita, xxxxxxxxxxx x testovacím systému x xxxxx xX xxxx xxxxxxxxxx.
Xxxxxxxxxxxx xx xxxx být xxxxxxxxx x metabolickou aktivací x xxx ní x xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx buněčné integrity x xxxxx, xxxx xxxx xxxxxx xxxxxxxxxx, xxxxx xxxxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx. Xxxx být xxxxxxx xxxxxxxx cytotoxicitu x xxxxxxxxxxx x předběžném xxxxxxxxxxx.
Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx xx xxxx xxxx koncentrace xxxxxxxx rozmezí xxxx xxxxxxxxx xx minimální xxxxxxxxx, případně žádnou xxxxxxxxx, což xxxxxxx xxxxxxx, xx by xx xxxxxxxxxxx xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. X xxxxxxxx xxxxxxx xx měla xxxxxxxx xxxxxxxxxxx vykazovat xxxxxxxx xxxxxxx stupně xxxxxxxxxx, xxxxx buněk xxxx xxxxxxxxxxx indexu (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx xxxxxxxx měřítkem xxxxxxxxxxxxx xxxx cytostatických xxxxxx a xxxxxx xx xxxx, xxxxx xxxxxxxx xx xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx přijatelný x xxxxxxxxxxx xxxxxx, u xxxxx xxxxx xxx xxxx metody stanovení xxxxxxxx obtížné x xxxxxxxxxxx. Informace x xxxxxxxx buněčného xxxxx, xxxxxxxxx xxxxxxxx generační xxxx (XXX), xxxxx xxx použity xxxx xxxxxxxxx xxxxxxxxx. X xxxxxxx XXX xxxx xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx nelze usoudit xx xxxxxxxxx zpožděných xxxxxxxxxxx, x x xxxx xxxxxxxxx průměrné xxxxxxxxx xxxx xxxx xxx xx xxxxxxxx xxxxx xxxxxxxxx oddálení xxxxxxxx optimálního výtěžku xxxxxxx.
X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx látek xx xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, xxxxx x xxxx xx xxxxxxxx.
X xxxxxxx relativně xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx toxické xxx xxxxxxxxxxxxx xxxxxxx, xxx xx jejich xxxxxxxxxxx, xx xxxx xxx xxxxxxx nejvyšší dávka x koncentraci, jež xx nad xxxx xxxxxxxxxxxx x konečném xxxxxxxxxxx médiu xx xxxxx xxxx xxxxxxxx. X xxxxxxxx xxxxxxxxx (xxxx. xxxxxxx-xx se xxxxxxxx xxxxx při xxxxxxx koncentracích, xxx xx rozpustnost) se xxxxxxxxxx xxxxxxxxx více xxxxxxxxxxx, xxx xxxxx xxxxxxx ke xxxxxxx. Xxxx xxx xxxxxxxx xxxxxxxx rozpustnost na xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx x testovacím xxxxxxx xx může x xxxxxxx expozice xxxxx v důsledku xxxxxxxxxxx xxxxx, xxxx X9 xxx. Nerozpustnost xxx xxxxxxx vizuálně. Xxxxxxxxx xx neměla xxxxx při vyšetřování.
1.4.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx
Xxxxxxxx každého xxxxxxxxxxx xx xxxx být xxxxxxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx vehikula). Xxx xxxxxxx xxxxxxxxxxx xxxxxxxx xx měla xxx xxx xxxxxxxxx kontrolu xxxxxxx chemická xxxxx, xxxxx x xxxxxxxxx xxxxxx vyžaduje xxxxxxxx.
X xxxxxxxxx kontrole by xxx být xxxxxx xxxxx xxxxxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx, které xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x detekovatelný xxxxxx xxx pozadí, čímž xx xxxxxxx citlivost xxxxxxxxxxx xxxxxxx.
Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxx xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx:
|
Xxxx metabolické aktivace |
Látka |
Číslo XXX |
Xxxxx xxxxx XXXXXX |
|
Xxx xxxxxx xxxxxxxxxxx xxxxxxxx |
xxxxxx-xxxxxxxxxxxxxx |
66–27–3 |
200–625–0 |
|
xxxxx-xxxxxxxxxxxxxx |
62–50–0 |
200–536–7 |
|
|
1-xxxxx-1-xxxxxxxxxxxxxxx |
759–73–9 |
212–072–2 |
|
|
xxxxxxxxx X |
50–07–7 |
200–008–6 |
|
|
4-xxxxxxxxxxxxx-1-xxxx |
56–57–5 |
200–281–1 |
|
|
X xxxxxx xxxxxxxxxxxx xxxxxxxx |
xxxxx[x]xxxxx |
50–32–8 |
200–028–5 |
|
xxxxxxxxxxxxx |
50–18–0 |
200–015–4 |
|
|
xxxxxxxxxxxxx xxxxxxxxxx |
6055–19–2 |
Xxx pozitivní xxxxxxxx xxxxx být xxxxxxx x jiné xxxxxx látky. Pro xxxxxxxxx kontrolu xx xxxx xxx xxxxx xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx.
X xxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx negativní xxxxxxxx skládající xx xx xxxxxxxxx rozpouštědla xxxx xxxxxxxx v xxxxxxxxxxx médiu a xxxxxxxxxx stejným xxxxxxxx xxxx xxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx dosud žádné xxxxxxxxx údaje prokazující, xx xxxxxxx rozpouštědlo xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx účinky.
1.4.3 Xxxxxx
1.4.3.1 Expozice zkoušené xxxxx
Xxxxxxxxxxxxx xxxxx se xxxxxxx xxxxxxxx xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx lymfocytů by xxxx xxx xxxxxxxx xxx 48 hodin xx mitogenní xxxxxxxxx.
1.4.3.2 Xxx každou koncentraci xx xxxx xxx xxxxxxx použity duplicitní xxxxxxx, x xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx pro xxxxxxxxx kontrolu nebo xxxxxxxx rozpouštědla. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx kulturami xx xxxxxxxxx xxxxxx, xxxx xxx přípustné xxxxxxx jediné xxxxxxx.
Xxxxxx xxxx xxxxxx látky xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x těsně xxxxxxxxxx kultivačních xxxxxxxx (15, 16).
1.4.3.3 Xxxx xxxxxxx kultur
V prvním xxxxxxxxxxx by xxxx xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, xxx x metabolickou xxxxxxxx, xxx xxx xx, xx dobu 3 — 6 xxxxx, x xxxx xx xxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného cyklu (12). Xxxxxxxx xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx xxx x xxxxxxxx, xxx bez xxxxxxxx, xxx by xxx proveden dodatečný xxxxxxxxxx xxx xxxxxxxx x nepřetržitou xxxxxxxx xx xx odběru x xxxx, která xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx látky xxx snáze xxxxxxxxx xxx xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxx xxx 1,5xxxxxxx délky xxxxx. Xxxxxxxxx výsledky xxx metabolické xxxxxxxx xxxx být potvrzeny xxxxxx od xxxxxxx. X xxxxxxxxx, kdy xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, by mělo xxx podáno xxxxxxxxxx.
1.4.3.4 Xxxxxxxx preparátů pro xxxxxxx chromozomů
Do buněčné xxxxxxx xx obvykle 1-3 xxxxxx před xxxxxxxxx xxxxx Colcemid® xxxx kolchicin. Xxx xxxxxxxx xxxxxxxxx pro xxxxxxx xxxxxxxxxx xx xxxxx buněčná kultura xxxxxx x zpracovává xxxxxx. Příprava xxxxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxx buněk, xxxxxx x xxxxxxxx xxxxx.
1.4.3.5 Xxxxxxx
Xxxxxxx xxxxxxxxx, xxxxxx preparátů xxxxxxxxxxx x negativních xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx při xxxxxx xxxxx dochází xx xxxxx části xxxxx x xxxxxxxx x xx ztrátě chromozomů, xxxx by xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxx xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx buněk. Xx xxxxxx xxxxxxxxxxx x xxxxxxxx by mělo xxx xxxxxxxxx xxxxxxx 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx rovnoměrně xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Tento počet xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx.
Xxxxxx je xxxxxx xxxxxxx detekovat xxxxxxxxxx xxxxxxxxxxxx xxxxxxx, je xxxxxxxx xxxxxxxxxx polyploidii x endoreduplikace, xxxx-xx xxxxxxxxxx.
2. XXXXX
2.1 XXXXXXXXXX XXXXXXXX
Xxxxxxxxxxxxxx jednotkou xx xxxxx a xxxx xx xxxx být xxxxxxxxxxx xxxxxxxx xxxxx xx strukturní xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxxxx xxxx strukturních chromozomových xxxxxxx x jejich xxxxxx x xxxxxxxx. Xxxx se xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, ale xxxxxxxxxx xx xx xxxxxxx xxxxxxxx xxxxxxx.
Xxxx by xxx xxxx xxxxxxxxxxx xxxxxxxx, xxxxx byla xxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxx x všech xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx experimentech x xxxxxxxxx.
Xxxx xx xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxx. Xxxx xx měly xxx xxxxxxx údaje xxxxxxx xx formě xxxxxxx.
Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx vyjasněny dalším xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx potvrdit xxxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx parametrů xxxxxx x xxxxx rozšířit xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X parametrům xxxxxx, xxxxx xx xxxxx být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.
2.2 XXXXXXXXX A XXXXXXXXXXXX VÝSLEDKŮ
Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, např. xxxxxx xxxxx buněk x chromozomovými xxxxxxxxx x závislosti xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx tohoto počtu. Xxxxxxxx by xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím faktorem xxx xxxxxxxxx xxxxxxx.
Xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxx, xx xxxxxxxx látka má xxxxxxxxx potlačit mitotické xxxxxxx a xxxxxxxxx xxxxxxxxx chromozomové aberace. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (17, 18).
Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx x xxxxx xxxxxxx xxxxxxxx xx xxxxxxxxxxx.
Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů vyslovit xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou zůstat xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.
Xxxxxxxxx xxxxxxxx xx zkoušky na xxxxxxxxxxxx aberace in xxxxx xxxxxxxxx, že xxxxxxxx xxxxx indukuje x xxxxxxxxxxxxx somatických xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx za xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.
3. ZPRÁVY
PROTOKOL X ZKOUŠCE
Protokol x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:
Xxxxxxxxxxxx/xxxxxxxxx:
- zdůvodnění xxxxx xxxxxxxx,
- rozpustnost x xxxxxxx zkoušené xxxxx x rozpouštědle/vehikulu, xx-xx xxxxx.
Xxxxx:
- typ x xxxxx xxxxx,
- xxxxxxxxxx karyotypu a xxxxxxxx xxxxxxxxx xxxx xxxxx,
- xxxxxxxxx nepřítomnost xxxxxxxxxxx,
- informace x xxxxx xxxxxxxxx cyklu,
- xxxxxxx xxxxx xxxx, xxx byla xxxxxxx xxxx krev nebo xxxxxxxxxx xxxxxxxxx, použitý xxxxxxx,
- xxxxxxxx xxxxx xxxxxx,
- případně xxxxxx xxxxxxxxx buněčné xxxxxxx,
- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.
Xxxxxxxx podmínky:
- xxxxxxxxxxxx xxxxx zastavující metafázi, xxxx xxxxxxxxxxx x xxxxx xxxxxxxx xxxxx,
- xxxxxxxxxx výběru koncentrací x počtu xxxxxx, xxxxxx např. údajů x cytotoxicitě a xxxxxx rozpustnosti, xxxx-xx x dispozici,
- složení xxxxx, případně xxxxxxxxxxx XX2,
- xxxxxxxxxxx xxxxxxxx xxxxx,
- xxxxx xxxxxxxx x přidané xxxxxxxx xxxxx,
- xxxxxxxxx teplota,
- xxxxxxxxx doba,
- xxxxx xxxxxxxx,
- xxxxxxxx xxxxxxx xxxxx při xxxxxxxx,
- xxx a xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxxxxx kritérií xxxxxxxxxxxxx,
- xxxxxxxxx x xxxxxxxxx kontroly,
- xxxxxx xxxxxxxx preparátů,
- xxxxxxxx xxxxxxxxx xxxxxxx,
- xxxxx xxxxxxxxxxxxx xxxxxxxx,
- xxxxxx xxxxxxxxx xxxxxxxx,
- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.
Xxxxxxxx:
- známky xxxxxxxx, xxxx. xxxxxx konfluence, xxxxx x xxxxxxxx xxxxx, xxxxx xxxxx, xxxxxxxxx index,
- známky xxxxxxx,
- xxxxx x xX a xxxxxxxxxx xxxxxxxxxxx xxxxx, pokud xxxx xxxxxxxxx,
- xxxxxxxx xxxxxxx, xxxxxx xxxx,
- xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx a xxxx xxxxxxx xxxxxx xxx xxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxxxx,
- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,
- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,
- xxxxxxxx xxxxxxxxxxx xxxxxxx,
- xxxxx x xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx,
- xxxxxxxxx údaje x negativní (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx.
Xxxxxx xxxxxxxx.
Xxxxxx.
4. XXXXXXXXXX
1) Xxxxx, X. X. (1976), Xxxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, xx: Chemical Xxxxxxxx, Principles xxx Xxxxxxx for xxxxx Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, A. (xx) Xxxxxx Xxxxx, Xxx Xxxx and Xxxxxx, 1-29.
2) Xxxxxxxx, M. Xx., Xxxxxx, T. (1985), Xxx Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Xxxxx Xxxxxxx Xxxxxxx Lung (XXX) Xxxxxxxxxx Cells in Xxxxxxx, in: Progress xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Xxxxx, X. xx xx., (xxx) Elsevier Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx York-Oxford, 427-432.
3) Xxxxxxxx, S. X., Xxxxxxxxx, M. X., Xxxxxx, C., Xxxxxx, X., Xxxxx, X., Cannon, X., Xxxxx, A. D., Xxxxxxxx, F., Xxxxx, X., Xxx, X., Xxxxx, J., Xxxxxxxx, X. H., Xxxxxxx, X. X., Xxxxxxxx, X., Zeiger X. (1978), Chromozome aberration xxx sister chromatic xxxxxxxxx xx Chinese xxxxxxx ovary cells: Xxxxxxxxxx of 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (suppl. 10), 1-175.
4) Xxxxx, X., Xxxxxxxx, X. X., Marshall, X. X., Xxxxxxxx, X. Xx., Brusick, D., Xxxxx, J., Xxxx, X. X. (1991), Xxxxxxxxxxxx xxxxx Extreme Xxxxxxx Conditions. A xxxxxx xxxx ICPEMC Xxxx Xxxxx 9, Xxxxxxxxxx Res., 257, 147-204.
5) Morita, T., Xxxxxx, T., Xxxxxx, X., Xxxxxxx, X., (1992), Clastogenicity of xxx xX to Xxxxxxx Xxxxxxxx Xxxxxxxxx Xxxxx, Mutatation Xxx., 268, 297-305.
6) Xxxx, X. N., XxXxxx, X., Yamasaki, X. (1975), Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx with xxx Xxxxxxxxxx/Xxxxxxxxx Microsome Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 31, 347-364.
7) Maron, X. X., Xxxx, X. N. (1983), Xxxxxxx Methods for xxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 113, 173-215.
8) Natarajan, X. X., Tates, X. X., xxx Xxxx, P. X. X., Xxxxxxx, X., xx Xxxxx, N. (1976), Xxxxxxxxxxx Xxxxxxx xx Xxxxxxx/Xxxxxxxxxxx xxxxx Xxxxxxxxxx xx x Xxxxxxxxxxx Xxxxxx Xx xxxxx, I. Xxxxxxxxx xx Xxxxxxxxxx Aberrations xxx Xxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Xxxxxxxxxxxxxxxxxxx (XXX) xx XXX Xxxxx xx xxx Xxxxxxxx of Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.
9) Xxxxxxxx, X., Xxxxxxx, M., Xxxxxxxx, X. Xx. (1979), Xxxxxxxxxxx Xxxxxxxxxx Xxxxx xx 29 Xxxxxxxxx Xxxxxxxx xxxx X9 Xxx In xxxxx, Xxxxxxxx Xxx., 66, 277-290.
10) Xxxxxx, X. X., Xxxxxx, X. D., Xxxxxxx, X. X., Gatehouse, X. X., Gibson, X. X., Xxxxxx, X. X., Wolf, X. C. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Mutagen Society Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx Xx xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx, 7, 175-177.
11) Xxxxxxxxxx, T., Sawamura, X., Xxxx, X., Xxxxxxxx, T. (1976), X. Xxxx Substitute xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: xx Xxxxxx, F. X., Xxxxx, X. X. Bend, X. X., Xxxxxxx, X. X. (eds), Xx xxxxx Metabolic Xxxxxxxxxx xx Mutagenesis Xxxxxxx, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.
12) Xxxxxxxx, X. X., Xxxxxxx, M. J., Xxxxxxxx, X. Xx., Xxxxx, X. X., Xxxxxxxx, D. J., Xxxxxx, T., Mosesso, X., Xxxxxx, T. (1994), Xxxxxx xxxx Xxxxxxx Group xx Xx vitro Xxxxx xxx Chromozomal Aberrations, Xxxxxxxxxx Xxx., 312, 241-261.
13) Xxxxxxxxxx, C., Xxxxxxxx, X. X., Xxxxx, X. A., Xxxxxxxx, X., Chanter, X. X., Xxxxxxxx, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx vitro Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. X., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.
14) Xxxxx, X. A., Xxxxxxxx, X. X. (1994), Xxxxxxxxx Flasks are xxx Necessary for Xx vitro Xxxxxxxxxx Xxxxxxxxxx Xxxxxx xx XXX Cells, Xxxxxxxxxx Xxx., 312, 139-149.
15) Xxxxx, X. F., Xxxxxx, F. C., XxXxxxx, X. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Volatile Xxxxxxx, xx: Tice, X. X., Costa, X. L., Schaich, X. X. (xxx), Xxxxxxxxx Effects xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.
16) Xxxxxx, P. O., Xxxxxx, X. X., Xx, X. X., Xxxxxx, A. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx System Xxxxx Xxxxx Grown xx Collagen Gels xxx Detecting Xxxxxx Xxxxxxxx Mutagens in xxx XXX/XXXXX Mutation Xxxxx, Environmental Xxxxxxx., 5, 795-801.
17) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx xx Xxxxxxx hamster xxxxx xxxxxx xxxxx-xxxxxxxxx xxxxxxx G2 arrest, Xxxxxxxxxx Xxx., 119, 403-413.
18) Huang, Y., Xxxxxx, C., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx, Xxxxxx Res., 43, 1362-1364."
PŘÍLOHA 4X
"X.11 MUTAGENITA–ZKOUŠKA XX CHROMOZOMOVÉ XXXXXXX X XXXXXXX XXXXXX XXXXX SAVCŮ XX XXXX
1. METODA
Tato xxxxxx xx xxxxxxxx metody XXXX TG 475 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxxxx kostní xxxxx xxxxx (1997).
1.1 ÚVOD
Zkouška xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxx je xxxxxxxxx xxx detekci strukturních xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx x xxxxxxx xxxxxx xxxxx xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx xx xxx xxxx strukturních xxxxxxx — chromozomové x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx chemická látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx chemických xxxxxxxx jsou xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx vyskytují. Xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx důkazů x xxx, xx xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x onkogenech x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx rakoviny x xxxxxxx x v xxxxxxxxxxxxxxxx systémech.
Při xxxx xxxxxxx jsou xxxxxxx xxxxxxxxx hlodavci. Xxxxxxx xxxxx xx x xxxx zkoušce xxxxxx xxxx, poněvadž xx xxxxxx xxxxxxxxxxxxxxxx tkání x xxxxxxxx xxxxxxxx xxxxx s rychlým xxxxxx, xxxxx xx xxxxxx xxxxxxx x xxxxxxxxxxxx. Xxxx druhy x cílové tkáně xxxxxx předmětem xxxx xxxxxx.
Xxxx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxxxx určená x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx umožňuje xxxxxxxxx xxxxxxx metabolismu xx xxxx, farmakokinetiku x xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx x xxxxxxx xxxxx x xxxxx xxxxx. Xxxxxxx xx xxxx xx xxxxxx xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx in xxxxx.
Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx látka xxxx xxxxxxxxx xxxxxxxxxx nedostanou xx xxxxxx xxxxx, xxxx vhodné tuto xxxxxxx xxxxxx.
Xxx xxxx Xxxxxx xxxx, část X.
1.2 DEFINICE
Chromatidová xxxxxxx : strukturní xxxxxxxxx xxxxxxxxxx x podobě xxxxx xxxxxxxxxxxx chromatid xxxx xxxxx x xxxxxxxx spojení chromatid.
Chromozomová xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu x xxxxxx zlomu nebo xxxxx a xxxxxxx xxxx xxxxxxxxx x xxxxxx místě.
Endoreduplikace : xxxxxx, při kterém x jádře xx X-xxxx xxxxxxxxx DNA xxxxxxx x xxxxxx, xxxxx xxxxxxxxx další X-xxxx. Výsledkem jsou xxxxxxxxxx se 4, 8, 16,… chromatidami.
Gap : xxxxxxxxxxxx xxxx xxxxx xxx xxxxx xxxxxxx xxxxxxxxxx a x minimální odchylkou xxxxxxxxx.
Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx chromozomů xx xxxxxxxx xxxxxxx xxxxxxx x xxxxxxxxx xxxxx.
Xxxxxxxxxxx : násobek xxxxxxxxxxx xxxxx chromozomových xxx (x), xxxx xxx xxxxxxxxx (xx. 3 n, 4 x xxx.).
Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx metafáze; xxxx xx xxxx xxxxxx a fragmenty, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.
1.3 XXXXXXXX XXXXXXXX XXXXXX
Xxxxxxx jsou xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xx xxxxxxx xxxxxxxx xx xxxxxxxx se xxxxxx. Xxxx xxxxxxxxx se xxxxxxxx xxxx látka xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx nebo Xxxxxxxx®). X xxxxx xxxxxx xxxxx xx xxxx xxxxxxxx preparáty chromozomů, xxxxxx se a xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx x xxxxxxxx.
1.4 XXXXX ZKUŠEBNÍ XXXXXX
1.4.1 Přípravky
1.4.1.1 Výběr xxxxx xxxxxxx
Xxxxx xx xxxxxxxx xxxxxx, xxx x křeček čínský, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx zvířat. V xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx minimální x xxxxxx xx u xxxx xxxxxxx překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.
1.4.1.2 Xxxxxxxx xxxxx a xxxxxx
Xxxxx xxxxxx xxxxxxxx xxxxx obecného úvodu x části B, xxxxxxx xx xxxx xxx xxxxxxxx vlhkosti xxxxxxx 50 – 60 %.
1.4.1.3 Xxxxxxxx xxxxxx
Xxxxxx mladá pohlavně xxxxxxx xxxxxxx xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, která xx vystaví zkoušené xxxxx. Xxxxx by xxxx být xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx polohy xxxxxxxxxxxxx. Zvířata se xxxxxxxxxxx identifikují. Xxxxxxx xx v xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat.
1.4.1.4 Příprava xxxxx
Xxxxx xxxxxxxx látky xx měly být xxxx xxxxxxxx zvířatům xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx zředěny. Kapalné xxxxxxxx látky mohou xxx xxxxxxxx přímo xxxx xxxxx být xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.
1.4.2 Xxxxxxxx xxxxxxxx
1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx
Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx dávek toxické xxxxxx x xxxx xx být vyloučeno xxxxxxxxx, že reaguje xx zkoušenou xxxxxx. Xxxx-xx použita xxxx xxx xxxxx rozpouštědla/vehikula, xxxx xx být xxxxxx xxxxxxxx podloženo xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx nejdříve xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.
1.4.2.2 Xxxxxxxx
Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx pozitivní x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by xxxx xxxxxxx kontrolní xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata xx xxxxxxxxx, v xxxxx dojde x xxxxxxxx.
Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx in xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx nad xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, ale aby xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, aby byla xxxxxxxxx kontrola xxxxxxxx xxxxx způsobem xxx xxxxxxxx látka a xxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxxx xxx použity xxxxxxxx xxxxx ze xxxxxx xxxxxxxx třídy, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx kontrolu:
|
Látka |
Číslo CAS |
Číslo xxxxx XXXXXX |
|
xxxxx-xxxxxxxxxxxxxx |
62–50–0 |
200–536–7 |
|
1-xxxxx-1-xxxxxxxxxxxxxxx |
759–73–9 |
212–072–2 |
|
xxxxxxxxx X |
50–07–7 |
200–008–6 |
|
xxxxxxxxxxxxx |
50–18–0 |
200–015–4 |
|
xxxxxxxxxxxxx xxxxxxxxxx |
6055–19–2 |
|
|
2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx |
51–18–3 |
200–083–5 |
X xxxxxxxx xxxxxxx xxxxxx by xxx xxx xxxxxxxx xxxxx x negativních xxxxxxx, jimž je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxx jinak xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx údajů x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx zvířat x četnosti buněk x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx se pro xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx nejvhodnějším xxxxxxxxx doba xxxxxxx xxxxxx. Xxxxx toho xx xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx nebo mutagenní xxxxxx.
1.5 XXXXXX
1.5.1 Xxxxx x xxxxxxx xxxxxx
Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx se xxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx. Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx prokazují, xx xxxxxxxxxx mezi xxxxxxxxx xxxxxx v xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx člověka specifická xxx xxxxxx xxxxxxx, xxxx xx tomu xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx xx být zkouška xxxxxxxxx se xxxxxxx xxxxxxxxxxxxxx xxxxxxx.
1.5.2 Xxxx xxxxxxxx
Xxxxxxxx xxxxx xx xxxx xxx pokud xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx mohou xxx xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. dvě xxxxx x xxx xxx x rozmezí xx xxxx xxx xxxxxxxx xxxxx, aby xxxx xxxxxxxxx podávání velkých xxxxxx xxxxxxxxx. Xxxx xxxxxx podávání xx xxxx xxx vědecky xxxxxxxxxx.
Xxxxxx by xxxx xxx odebrány ve xxxx xxxxxxx intervalech xx xxxxxxxx podané x jednom xxx. X xxxxxxxx xx xxxxx xxxxxxx xx xxxxxx xxxx od xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx xxxxx (jenž xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx příjem x xxxxxxxxxxxx xxxxxxxx látky x xxxxxx xxx xxxxxx na kinetiku xxxxxxxxx cyklu může xxx xxxx xx xxxxxxxxx okamžik xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx se provést xxxxx xxxxx po 24 x od xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx do xxxx než xxxxxxx xxx, xxx xx xxx xxxxx proveden xx xxxxxx době xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx xxxxx.
Xxxx xxxxxxxxx xx xxxxxxxx intraperitoneálně podá xxxxxx xxxxx látky xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx po xxxxxx xxxx xxxxxxx x zvířat xxxxx. X xxxx xx xxxx doba přibližně 3 — 5 x; x xxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx xxxxxxxx buňky x xxxxxxxxx xx xx chromozomové xxxxxxx.
1.5.3 Xxxxxxxxx
Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx rozsahu xxxxx, xxxx xx xxx xxxxxxxxx ve stejné xxxxxxxxxx, se stejným xxxxxx, xxxxxx, xxxxxxxx x za stejného xxxxxx xxxxxxxx, xxx xx použijí x xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx tři xxxxxx dávky. Tyto xxxxxx dávky xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, že vyšší xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x letalitě. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx od xxxxxxx. Nejvyšší xxxxx xxxx xxx také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).
1.5.4 Xxxxxxx xxxxxxx
Xxxxxxxx xxxxxxx x jednou xxxxxx xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo ve xxxx xxxxxxx v xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, které xxxx podobnou strukturu, xxxxxxxxx xxxxxxxxxxxx, nepovažuje xx xxxxx studie xx xxxxx xxxxxxxx xxxxx za nezbytnou. X déle xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx pro 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx a xxx xxxxx než 14xxxxx xxxxxxxx xx xxxxxxx dávkou 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx v xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.
1.5.5 Xxxxxxxx xxxxx
Xxxxxxxx xxxxx xx xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx xxxx injekčně, xxxxxx na velikosti xxxxxxxxxxx zvířete. Xxxxx xx neměl xxxxxxxxx 2 ml/100 x xxxxxxx hmotnosti. Použití xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx na dráždivé x xxxxxx látky, xxxxx obvykle při xxxxxxx koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx minimalizována xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx úrovních dávky.
1.5.6 Xxxxxxxx preparátů pro xxxxxxx chromozomů
Ihned po xxxxxxxx xx odebere xxxxxx xxxx, hypotonizuje xx a xxxxxx. Xxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx x obarví se.
1.5.7 Xxxxxxx
Xxxx xxxxxxx xxxxxxxxxxxx xx měl xxx x všech xxxxxxxxxxxx xxxxxx (xxxxxx pozitivních xxxxxxx) x x xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx, x xx xxxxxxx u 1000 buněk na xxxxx zvíře.
U xxxxxxx xxxxxxx xx xxxx xxx analyzováno xxxxxxx 100 buněk. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx velký xxxxx aberací. Xxxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Protože xxx xxxxxx často xxxxxxx xx xxxxxxxxxxxxxx zlomům xxxx xx xxxxxx xxxxxxxxxx u části xxxxx v metafázi, xxxx xx vyšetřované xxxxx xxxxxxxxx centromery x počtu xxxxxxxxxxxxxx xxxxx 2 x ± 2.
2. XXXXX
2.1 XXXXXXXXXX XXXXXXXX
Xxxxx xxx xxxxxxxxxx zvířata xx xxxx být zpracovány xx xxxxx tabulky. Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx. Xxx každé xxxxx by xxx xxx xxxxxxxxxx počet xxxxx, xxxxx aberací xx xxxxx x xxxxx buněk s xxxxxxxxxxxxx xxxxxxx (chromozomovými xxxxxxxxx) xxxxxxxxx v xxxxxxxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx měly být xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx aberací x xxxxxx xxxxxx x četností. Xxxx xx zaznamenávají xxxxxxxx x xxxxxxx xx, xxx xxxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxx aberací. Neexistuje-li xxxxx o rozdílu x xxxxxxxx xxxx xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx analýzu xxxxx pro obě xxxxxxx zkombinovány.
2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ
Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx dávce xxxx jasný xxxxxx xxxxx buněk x xxxxxxxxx xxx xxxxxxx x xxxxxxx xxxxxx x x určitému xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx být xxxxxxx biologická xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx použity xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.
Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx chromozomy může xxxxxxxx, xx xxxxxxxx xxxxx má potenciál xxxxxxxx progresi buněčného xxxxx (7, 8).
Zkoušená xxxxx, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, se xxxxxxxx x xxxxx systému xx nemutagenní.
Ačkoli xxxxxxx xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx vyslovit konečný xxxxx o aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx sporné bez xxxxxx na xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.
Xxxxxxxxx xxxxxxxx xxxxxxx xx chromozomové xxxxxxx xx vivo xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky neindukuje x xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.
Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx se xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).
3. XXXXXX
XXXXXXXX O XXXXXXX
Xxxxxxxx x xxxxxxx xxxx obsahovat tyto xxxxxxxxx:
Xxxxxxxxxxxx/xxxxxxxxx:
- zdůvodnění xxxxx xxxxxxxx,
- xxxxxxxxxxx a xxxxxxx zkoušené látky x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.
Xxxxxxxxx xxxxxxx:
- xxxxxxx xxxx/xxxx,
- počet, stáří x xxxxxxx xxxxxx,
- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,
- individuální xxxxxxxx xxxxxx na xxxxxxx xxxxxxx, včetně xxxxxxx tělesné hmotnosti, xxxxxxx xxxxxxx a xxxxxxxxxx odchylky pro xxxxxx skupinu.
Zkušební xxxxxxxx:
- xxxxxxxxx x negativní (xxxxxxxxx/xxxxxxxxxxxx) kontroly,
- údaje xx xxxxxx xxx xxxxxxxx rozsahu, xxxxx xxxx xxxxxxxxx,
- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,
- xxxxx o xxxxxxxx xxxxxxxx látky,
- xxxxx x xxxxxxxx zkoušené xxxxx,
- xxxxxxxxxx xxxxxxx xxxxxxxx,
- xxxxxxxxx metody xxxxxxx, zda se xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx oběhu xxxx xx cílové xxxxx,
- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx v xxxxxx xxxx vodě (xxx) xx xxxxxxxxxxxx dávku (xx/xx xxxxxxx hmotnosti/den),
- xxxxxxxx údaje x xxxxxxx krmiva a xxxx,
- xxxxxxxx xxxxx xxxxxxx expozice x xxxxxx,
- xxxxxx stanovení xxxxxxxx,
- identifikace látky xxxxxxxxxxx xxxxxxxx, xxxx xxxxxxxxxxx x xxxxx xxxxxxxx,
- xxxxxx přípravy xxxxxxxxx,
- kritéria xxxxxxxxx xxxxxxx,
- xxxxx analyzovaných xxxxx xx jedno xxxxx,
- kritéria xxxxxxxxxxx xxxxxx xx pozitivní, xxxxxxxxx nebo xxxxxxxxxxx.
Xxxxxxxx:
- xxxxxx toxicity,
- xxxxxxxxx xxxxx,
- typ x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,
- xxxxxxx xxxxx xxxxxxx xx xxxxxxx xx xxxxxxxxx hodnotami x směrodatnými xxxxxxxxxx,
- xxxxx xxxxx s xxxxxxxxx xx skupině xx středními hodnotami x xxxxxxxxxxxx xxxxxxxxxx,
- xxxxx xxxxxxx, pokud xxxx pozorovány,
- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,
- případné xxxxxxxxxxx xxxxxxx,
- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,
- dosavadní xxxxx x negativní kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx,
- údaje o xxxxxxxx xxxxxxxxx kontrole.
Rozbor xxxxxxxx.
Xxxxxx.
4. XXXXXXXXXX
1) Adler, X. X. (1984), Xxxxxxxxxxx Tests in Xxxxxxx, in: Xxxxxxxxxxxx Xxxxxxx: x Practical Xxxxxxxx, X. Venitt, X. X. Xxxxx (xxx), IRL Xxxxx, Xxxxxx, Xxxxxxxxxx D. X., 275-306.
2) Xxxxxxx, X. X., Xxxx, X. X., Galloway, X., Xxxxxx, X., XxXxx, X. X., Xxxxxx, M. (1987), Xxxxxxxxx Xx xxxx Xxxxxxxxxxx Assays: Analysis xx Chromozome Xxxxxxxxxxx xx Xxxx Marrow Xxxxx, Xxxxxxxxxx Res., 189, 157-165.
3) Xxxxxxx, X., Chandley, X., Xxxxx, X., Gatehouse, X. G., Xxxxxxx, X., Xxxxxxxxx, X. (1990), Xx vivo Xxxxxxxxxxx Assays, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Sub-Committee xx Guidelines xxx Xxxxxxxxxxxx Testing. Report, Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.
4) Tice, X. X., Hayashi, X., MacGregaro, X. X., Xxxxxxxx, X., Xxxxxx, D. H., Xxxxxx, X. E., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., X. X., Xxxxxxxxxxxx, F., Preston, X. X., Xxxxxxx, X., Shimada, H., Xxxxx, X., Xxxxxxx, X. (1994), Report xxxx xxx Xxxxxxx Xxxxx xx xxx xx xxxx Xxxxxxxxx Xxxx Marrow Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.
5) Xxxxxxx, X. X., Xxxxx, X. A., Xxxxxx, A. X., Xxxxxx, X. X., Xxx, X., Esdaile, X. J., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Dose Xxxxxxx xx Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.
6) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxx, X., Papworth, X. X., Xxxxxx, X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx of Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Part XXX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, X. J. Xxxxxxxx (xx.) Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.
7) Xxxxx-Xxxxx, C. (1983), Xxxxxxxxxxxxxxxxx xx Chinese xxxxxxx xxxxx xxxxxx xxxxx-xxxxxxxxx-xxxxxxx X2 xxxxxx, Xxxxxxxxxx Xxx., 119, 403-413.
8) Xxxxx, Y., Xxxxxx, C., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx in Xxxxxxx xxxxxxx xxxxx, Xxxxxx Xxx., 43, 1362-1364."
XXXXXXX 4X
"X.12 MUTAGENITA–TEST XXXXXXX ERYTROCYTÁRNÍCH MIKROJADER XX XXXX
1. XXXXXX
Xxxx xxxxxx xx xxxxxxxx xxxxxx OECD XX 474 — Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx (1997).
1.1 XXXX
Xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx in xxxx xx xxxxxxxx xxx xxxxxxx poškození xxxxxxxxxx xxxx mitotického xxxxxxx xxxxxxxxxxxx, které je xxxxxxxxxx zkoušenou xxxxxx, x xx xxxxxx xxxxxxx erytrocytů xxxxxxxxxx x xxxxxx xxxxx x/xxxx xxxxx xxxxxxxxx xxxx, xxxxxxx xxxxxxxx.
Xxxxxx xxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxx xx xxxxxx xxxxxxxxxx obsahujících xxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxx xxxxxxxxx nebo xxxx xxxxxxxxxx.
Xxxx xx erytroblast xxxxxx dřeně xxxx xx polychromatický xxxxxxxxx, xxxxxx xxxxx je xxxxxxxx x xxxxxxxxxx, xxxxx xxx tom xxxxx vzniknout, xxxxxxxxx x xxxxxxxxxx, která xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx xx x xxxxxx xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx hlavní jádro. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx x mikrojádry x exponovaných xxxxxxxxx xx xxxxxxx indukovaného xxxxxxxxxxxxxx poškození.
V xxxxx xxxxx je xxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, poněvadž tato xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx x xxxxxxxxx xxxx xx xxxxxxxxxx xxxxxxxxxx x xxxxxxxxxxx xxxxx, x xxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, xxxx xxxxxxxxxx citlivost detekovat xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx nebo xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxxx xxx xxxxxxxx řadou xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx centromerní (kinetochorní) XXX x xxxxxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx s xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx v xxxxxxxxx xxxx, které xxxxxxxx xxxxxxxxxx, xxxxxxxxxxx na xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx xxxx konečný xxxxxxxx zkoušky, xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxx xxxx.
Xxxxx test xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx xx xxxxxxx xxxxxx k xxxxxxxxx xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx xx mohou lišit x různých xxxxx x tkání, xxxxx x x genetického xxxxxxxx. Zkouška xx xxxx xx xxxxxx xxxxxxxx pro xxxxx xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx x systémech xx vitro.
Jestliže xxxxxxxx xxxxx x xxx, xx se xxxxxxxx xxxxx nebo reaktivní xxxxxxxxxx nedostanou xx xxxxxx tkáně, není xxxxxx xxxx xxxxxxx xxxxxx.
Xxx také Xxxxxx xxxx, xxxx X.
1.2 XXXXXXXX
Xxxxxxxxxx (kinetochor) : xxxxxx (xxxxxxx) xxxxxxxxxx, x xxx (x xxxx) xx xxxxx xxxxxx xxxxx připojí xxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxx pohyb xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxx buněk.
Mikrojádra : xxxx jádra existující xxxxxxxx xx xxxxxxxx xxxxx a xxxxx xxxx, vytvářená xxxxx xxxxxxxx xxxxxx (meiosy) xxxxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxxxx fragmenty nebo xxxxxx xxxxxxxxxx.
Xxxxxxxxxxxxxxxx xxxxxxxxx : zralý erytrocyt xxxxxxxxxxxx xxxxxxxx, který xxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx xxxxxxxxxxx pro xxxxxxxx.
Xxxxxxxxxxxxxxx erytrocyt : xxxxxxx xxxxxxxxx xx xxxxxxxxx mezistadiu, xxxxx xxxxx obsahuje xxxxxxxx, x xxxx xxx xxxx xxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.
1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX
Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx zkoušené xxxxx. Při xxxxxxx xxxxxx dřeně xx xxxxxxx ve vhodném xxxxxxxx xx xxxxxxxx xxxxxx, odebere xx xxxxxx dřeň, xxxxxxxx xx preparáty a xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx použití periferní xxxx xx krev xx xxxxxxx okamžiku xx xxxxxxxx xxxxxxx, xxxxxxxxxx xx xxxxxxxx xxxxxxxx x obarví xx (4, 8, 9, 10). Xxx xxxxxxxx x xxxxxxxxx xxxx by xxxx xxxx xxxxxxxx xxxxxxxx x sklizením buněk xxxxxxxx co xxxxxxxxx xxxx. Preparáty xxxx xxxxxxxxxxx xx xxxxxxxxxx xxxxxxxxxx.
1.4 XXXXX ZKUŠEBNÍ XXXXXX
1.4.1 Přípravky
1.4.1.1 Výběr xxxxx xxxxxxx
Xxx xxxxxxx xxxxxx xxxxx se xxxx xxxxxxxxx xxxxx xxxxxxxxxx xxx nebo xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxxx xxxx. Xxx xxxxxxx xxxxxxxxx krve xx xxxxxxxxxx myš. Xxx xxxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx za předpokladu, xx jde o xxxx, x něhož xxxxxxx xxxxxxxxxxxx erytrocyty x xxxxxxxxxx, nebo xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx detekovat činitele, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické chromozomové xxxxxxx. Xxxx by xxx použity běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx xx xxxx být xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx a xxxxxx xx u xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.
1.4.1.2 Xxxxxxxx xxxxx x xxxxxx
Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx úvodu x xxxxx X, xxxxxxx xx xxxx xxx dosaženo vlhkosti xxxxxxx 50 – 60 %.
1.4.1.3 Příprava xxxxxx
Xxxxxx xxxxx pohlavně xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx rozdělí xx kontrolní xxxxxxx x xxxxxxx, x xxx se xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx. Klece xx xxxxxxxxxx tak, xxx xxx vliv xxxxxx xxxxxx minimalizován.
1.4.1.4 Xxxxxxxx xxxxx
Xxxxx zkoušené xxxxx xx měly xxx před aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené látky xxxxx xxx xxxxxxxx xxxxx nebo xxxxx xxx xxxx xxxxxxx xxxxxxx. Měly xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x jejich xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.
1.4.2 Xxxxxxxx podmínky
1.4.2.1 Rozpouštědlo/vehikulum
Rozpouštědlo/vehikulum xx xxxxxx xxx xxx xxxxxxxxx úrovních xxxxx toxické xxxxxx x xxxx xx xxx vyloučeno podezření, xx reaguje se xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx nejdříve xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.
1.4.2.2 Xxxxxxxx
Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx a negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx pro xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx identický proces xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx k xxxxxxxx.
Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx mikrojádra in xxxx xxx xxxxxxxxxxx xxxxxxxx, u nichž xx xxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx by xxxx xxx zvoleny xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx při xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx přijatelné, aby xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx xxx xxxxx v xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Pro xxxxxxxxx xxxxxxxx xxxxx xxxx xxx xxxxx x xxxxx použití xxxxxxxxxx xxxxx xx stejné xxxxxxxx třídy, xxxx-xx x dispozici. Xxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx:
|
Xxxxx |
Xxxxx XXX |
Xxxxx xxxxx XXXXXX |
|
xxxxx-xxxxxxxxxxxxxx |
62–50–0 |
200–536–7 |
|
1-xxxxx-1-xxxxxxxxxxxxxxx |
759–73–9 |
212–072–2 |
|
xxxxxxxxx X |
50–07–7 |
200–008–6 |
|
xxxxxxxxxxxxx |
50–18–0 |
200–015–4 |
|
xxxxxxxxxxxxx xxxxxxxxxx |
6055–19–2 |
|
|
2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx |
51–18–3 |
200–083–5 |
X xxxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x která xxxxx podstupuje stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx nejsou x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx kontrolu xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx xxxxxxxxxxx kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx účinky.
Při xxxxxxx xxxxxxxxx xxxx xxxx xxx xxxx xxxxxxxxx xxxxxxxx přijatelný také xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx u xxxxxxxx xxxxxx x periferní xxxx (xxxx. 1 — 3 xxxxxxxx) xx předpokladu, xx xxxxxxxx xxxxx xxxxx x xxxxxxx, které xx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.
1.5 XXXXXX
1.5.1 Počet x xxxxxxx zvířat
Každá xxxxxxxxxx x kontrolní skupina xx musí xxxxxxx x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx (11). Xxxxxxxx xxxx x xxxx studie x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx prokazují, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx pro určité xxxxxxx, jako je xxxx xxxxxxxxx u xxxxxxxxx farmaceutických xxxxx, xxxx xx být xxxxxxx provedena se xxxxxxxx xxxxxxxxxxxxxx pohlaví.
1.5.2 Xxxx aplikace
Nelze xxxxxxxxx xxxxx xxxxxxxxxx plán (xx. jednu, xxx xxxx xxx xxxxxxxx x xxxxxxxxx 24 xxxxx). Xxxxxx xx xxxxxx x prodlouženým xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, pokud xx x xxxxxx studií xxxxxxx pozitivní xxxxxxxx, xxxx –v xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx byla xxxxxxxxx xxxxxxxx xxxx byla xxxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxxx xx xx xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx xxx podávány xxxx xx dvou xxxxxxx, xxx. dvě xxxxx x týž xxx x rozmezí xx více xxx xxxxxxxx xxxxx, xxx xxxx usnadněno podávání xxxxxxx xxxxxx xxxxxxxxx.
Xxxx xxxx být xxxxxxxx xxxxx xxxxxxx:
x) xxxxxxxx xxxxx xx aplikuje xxxxxxxx xxxxxx. Xxxxxx xxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 24 hodin xx xxxxxxxx x poslední xxxxxxxxxx 48 xxxxx xx xxxxxxxx a x přiměřeným xxxxxxxx xxxx xxxxxx. Xxxxx xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx xxxxxxxxx xxxx xx xxxxxxxx xxxxxxx xxxxxxx, přičemž xxxxx xxxxx se xxxxxxx xxxxxxxx 36 xxxxx xx aplikaci x xxxxxxxx xxxxxxxxxx 72 xxxxx xx aplikaci x xx xxxxxxxxxxxx xx xxxxxx xxxxxxxxxxxx xxxxxx. Xx-xx xx xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, není xxxxx xxxxx nutný;
b) xxxx-xx xxxxxxxx xxx xxxx více xxxxx xxxxx (xxxx. xxx xxxx xxxx dávek x xxxxxxxxx 24 xxxxx), měly xx xxx xxxxxx xxx xxxxxxx kostní xxxxx xxxxxxxx xxxxxx xx 18 xx 24 xxxxxxxx po xxxxxxxx xxxxxxxx x při xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).
Xxxxx xxxxxxx mohou xxx navíc xxxxxxx xxxx doby xxxxxx.
1.5.3 Xxxxxxxxx
Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx studie pro xxxxxxxx rozsahu dávek, xxxx by xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx stejným xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, jež xx xxxxxxx x xxxxxx xxxxxx (13). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx dávky. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx rozpětí xxxx maximální až xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že xxxxx xxxxx xx xxxxx xxx xxxxxxx režimu xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx vyhovovat x xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší dávka xxxx xxx také xxxxxxxxxx xxxx dávka xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx v kostní xxxxx xxxx x xxxxxxxxx krvi).
1.5.4 Xxxxxxx xxxxxxx
Xxxxxxxx xxxxxxx x xxxxxx xxxxxx o xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx dávkách v xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx x není-li xx xxxxxxx údajů x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, není xxxxxxxxxx úplná studie xx třemi xxxxxxxx xxxxx xx xxxxxxxxx. X déle xxxxxxxxxx xxxxxx je limitní xxxxxx pro 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx a xxx xxxxx než 14xxxxx aplikaci xx xxxxxxx dávkou 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší úroveň xxxxx.
1.5.5 Xxxxxxxx xxxxx
Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx nebo vhodnou xxxxxxxxx kanylou, nebo xxxxxxxxxxxxxxxxx injekcí. Jiné xxxxxxx xxxxxxxx xxxx xxxxxxxxxx v xxxxxxxxxxxxxxx xxxxxxxxx. Maximální objem xxxxxxxx, který může xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 ml/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, které xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx konstantní xxxxx xxx xxxxx úrovních xxxxx.
1.5.6 Xxxxxxxx xxxxxx xxxxx xxxx krve
Buňky xxxxxx xxxxx se xxxxxxx xxxxxxxxx z xxxxxx xxxx xxxxx xxxxx xx xxxxxxxx. Xxxxx se odeberou x xxxxxx xxxx xxxxx x xxxxxxxxxx xxxxxxxx se preparují x obarví. Xxxxxxxxx xxxx xx xxxxxxx x ocasní žíly xxxx xxxx vhodné xxxxxx xxxx. Xxxxxx xxxxx xx ihned xxxxxxxxxxxx obarví (8, 9, 10), xxxx xx xxxxxxxx xxxxxxxxx xxxxxxxx x xxxx xx xxxxxx. Xxxxxxxx xxxxxxx specifického pro XXX (např. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) se xxx xxxxxxx některým xxxxxxxxxx xxxxxxxx x xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxx XXX. Xxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxx (např. Xxxxxx). Xxxxxxxx systémy (xxxx. xxxxxxxxxx xxxxxx x odstranění xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, xx se xxxxxxxxx odpovídající xxxxxxxxx xxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxx v xxxxxxxxxx.
1.5.7 Xxxxxxx
Xxx xxxxx xxxxx se xxxxxxx xxxxx nezralých erytrocytů x xxxxxxxxx (xxxxxxx + zralé) xxxxxxxx xxxxxxxxxx, xxxxxxx xx x xxxxxxx xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 xxxxxxxxxx x v případě xxxxxxxxx xxxx xxxxxxx 1000 erytrocytů (17). Xxxxxxx xxxxxxxxx včetně xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx mikroskopem xxxxxxxxx kódovány. U xxxxxxx zvířete xx xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxxxxxxxx. Další xxxxxxxxx xxxxx xxx získány xxxxxxxxxx xxxxxxx xxxxxxxxxx xx výskyt xxxxxxxxxx. Xxx xxxxxxxxxxxxx xxxxxxx xx xxxxx být xxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx xxxxx xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx nepřetržitě xxxxx xxxxx xxxx xxxx, lze také xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx erytrocytů xx xxxxx xxxxx. Xxxxxxx xxx automatickou xxxxxxx (xxxxxxx obrazu x xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxx) xxxx xx xxxxxxxxxxxxx xxxxxxxxxx x validaci xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.
2. XXXXX
2.1 XXXXXXXXXX XXXXXXXX
Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Xxx xxxxx analyzované xxxxx xx xxx být xxxxxx xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, počet xxxxxxxxx erytrocytů x xxxxxxxxxx a xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx nebo xxxx, xxxx by být xxxx xxxxxxx xxxxx x xxxxxxx erytrocytech, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx xxxxx xx xxxxx xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx mezi xxxxxxxxx, xxxxx být xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.
2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ
Pro xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx několik xxxxxxxx, xxxx. nárůst počtu xxxxx x xxxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxxx pro xxxxxxx x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx být použity xxxx pomocný prostředek xxxxxxxxxxx metody (18, 19). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím faktorem xxx xxxxxxxxx odpověď. Xxxxxxxxxx xxxxxxxx xx xxxx xxx vyjasněny xxxxxx xxxxxxxxx, nejlépe x xxxxxxx experimentálních xxxxxxxx.
Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx kritéria, se xxxxxxxx v xxxxx xxxxxxx za nemutagenní.
Ačkoli xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.
Xxxxxxxxx xxxxxxxx xxxxx na mikrojádra xxxxxxxxx, že xxxxxxxx xxxxx indukuje xxxxxxxxxx, xxx jsou důsledkem xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx zkoušená látka xx podmínek xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx erytrocytech xxxxxxxxxxx xxxxx.
Xxxx xx xxx xxxxxxxxxxx pravděpodobnost, s xxxxx xx zkoušená xxxxx xxxx její xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, nebo xxxxxxxxxx xx cílové xxxxx (xxxx. systémová xxxxxxxx).
3. ZPRÁVY
PROTOKOL X XXXXXXX
Xxxxxxxx o zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:
Xxxxxxxxxxxx/xxxxxxxxx:
- xxxxxxxxxx xxxxx xxxxxxxx,
- xxxxxxxxxxx x xxxxxxx zkoušené xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.
Xxxxxxxxx xxxxxxx:
- xxxxxxx xxxx/xxxx,
- xxxxx, stáří x xxxxxxx xxxxxx,
- xxxxx, xxxxxxxx chovu, xxxxxx atd.,
- individuální xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx odchylka xxx xxxxxx skupinu.
Zkušební podmínky:
- xxxxx x xxxxxxxxx x negativní (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,
- xxxxx xx xxxxxx xxx zjištění xxxxxxx, pokud xxxx xxxxxxxxx,
- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,
- xxxxx x xxxxxxxx xxxxxxxx xxxxx,
- údaje x xxxxxxxx zkoušené xxxxx,
- xxxxxxxxxx xxxxxxx xxxxxxxx,
- xxxxxxxxx xxxxxx xxxxxxx, xxx se zkoušená xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx xx xxxxxx tkáně,
- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx zkoušené xxxxx x krmivu xxxx xxxx (ppm) xx xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),
- xxxxxxxx xxxxx o xxxxxxx xxxxxx x xxxx,
- xxxxxxxx popis xxxxxxx xxxxxxxx x xxxxxx,
- xxxxxx xxxxxxxx xxxxxxxxx,
- xxxxxx xxxxxxxxx xxxxxxxx,
- xxxxxxxx hodnocení xxxxxxxxxx x nezralých erytrocytech,
- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,
- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou.
Výsledky:
- xxxxxx xxxxxxxx,
- xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx erytrocytů,
- xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,
- xxxxxxx xxxxxxx ± xxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx ve xxxxxxx,
- xxxxx možnosti závislost xxxxxxxx xx xxxxx,
- xxxxxxxx xxxxxxxxxxx analýzy x metody,
- údaje x xxxxxxxx x xxxxxxxxx negativní kontrole,
- xxxxx x souběžné xxxxxxxxx kontrole.
Rozbor xxxxxxxx.
Xxxxxx.
4. XXXXXXXXXX
1) Heddle, X. X. (1973), X Xxxxx In xxxx Xxxx for Xxxxxxxxxxx Xxxxxx, Xxxxxxxxxx Res., 18, 187-190.
2) Schmid, X. (1975), Xxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 31, 9-15.
3) Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxx, M., Kirkhart, X., Xxxxxxxxx, K., XxxXxxxxx, J. X., Xxxxxx, G. W. (1983), Xxx Xxxxxxxxx xx Micronuclei a. x. x Measure xx Xxxxxxxxxxxx, Mutatation Xxx. 123, 61-118.
4) Xxxxxxxxx, X. H., Xxxxxx, X. X., Xxxxxx, X. C., Xxxxxxxx, X. F., Xxxxxx, X. X. (1990), Xxx In xxxx Xxxxxxxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxxxx xxx Xxxxxxxxxx Xxxxx. X xxxxxx xx the U. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 239, 29-80.
5) XxxXxxxxx, J. X., Schlegel, X., Xxxx, X. X., Xxxx, X. M. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Erythrocytes: X Xxxxx Xxxxxx xxx Xxxxxxxxxxx Damage Xxxxxx Xxxxxxx Xxxxxxxx Xxxxxxx xx Xxxx, xx: Xxxxxxxxxxxx in Science xxx Xxxxxxxx xx Xxxxxxxxxx, ed. X. X. Xxxxx, X. X. Xxxxxxx, T. X. Miya. Xxxxxxxx, Xxxxxxxxx, 555-558.
6) MacGregor, X. X., Heddle, X. X. Hite, X., Xxxxxxxx, G. X., Xxxxx, C., Xxxxxxxx, X. X., Xxxx, R. R., Xxxx, X. (1987), Xxxxxxxxxx xxx xxx Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx xx Xxxxxxxxx Xxxx Marrow Erythrocytes, Xxxxxxxxxx Xxx., 189, 103-112.
7) MacGregor, X. X., Xxxx, X. X., Xxxxxx, X. X., Shelby, X. X. (1990), Xxx xx xxxx Erythrocyte Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Xxxxxx Xxxxx Xxxxxxxxx Assay Xxxxxxxxxx xxx Permits Xxxxxxxxxxx xxxx Xxxxxxxx Xxxxxxx, Xxxxxx. Xxxx. Toxicol. 14, 513-522.
8) Xxxxxxx, X., Morita, T., Xxxxxx, X., Xxxxxx, X., Ishidate, X. Xx. (1990), Xxx Xxxxxxxxxxxx Xxxxx xxxx Xxxxx Peripheral Xxxxx Xxxxxxxxxxxxx Using Acridine Xxxxxx-Xxxxxx Slides, Xxxxxxxxxx Xxx., 245, 245-249.
9) Xxx Xxxxxxxxxxxxx Study Xxxxx for xxx Xxxxxxxxxxxx Test (1992). Xxxxxxxxxxxx Xxxx with Xxxxx Peripheral Blood Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx Xxxxxxxxxx Xxxxxxxx: Xxx Xxxxxxx Report xx xxx 5xx Xxxxxxxxxxxxx Xxxxx by XXXXX/XXXXX, MMS, Xxxxxxxxxx Xxx., 278, 83-98.
10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx for the Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: Xxx Mammalian Xxxxxxxxxxx Study Xxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxx Society of Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx for the xxxxx-xxxx xxxxx peripheral xxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 53-159.
11) Xxxxxxx, X., Xxxx, X. R., MacGregor, X. X., Anderson, X., Xxxxxxx, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx, Xx. X. X., Pacchicrotti, X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xx vivo Rodent Xxxxxxxxxxx Xxxxxxxxxxxx Assay, Xxxxx. Xxx., 312, 293-304.
12) Higashikuni, N., Xxxxx, S. (1995), Xx xxxxxxx, xxxxxxxxxxx xxxxxxxx xxxx xx 30 ± 6 x xxxxx xxxxxx xxxxxx in xxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 313-319.
13) Xxxxxxx, R. X., Xxxxx, X. X., Boobis, X. X., Xxxxxx, P. X., Doe, X., Xxxxxxx, X. J., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Toxicology Xxxxxxx/XX Environmental Mutagen Xxxxxxx Working Xxxxx: Xxxx Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.
14) Xxxxxxx, X., Xxxxxx, T., Xxxxxxxx, X. Jr. (1983), Xx Xxxxxxxxxxx xx Xxxxxxxx Orange Fluorescent Xxxxxxxx xx xxx Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 120, 241-247.
15) XxxXxxxxx, X. X., Xxxx, C. X., Xxxxxxxx, X. X. (1983), X Simple Xxxxxxxxxxx Staining Procedure xxx Micronuclei xxx XXX xx Xxxxxxxxxxxx Xxxxx Hoechst 33258 xxx Xxxxxxx X, Xxxxxxxx Xxx., 120, 269-275.
16) Xxxxxxx, X., Xxxxxxxxxx, X. X. (1989), The automated xxxx marrow micronucleus xxxx, Mutatation Res., 213, 91-104.
17) Gollapudi, X., XxXxxxxx, X. X. (1995), Xxxxxx Xxxx xxx xxx Xxxxxxxxxx xx Xxxxxxxxxxxxx xx Xxxxxxxxxxxxxx Erythrocyte Xxxxx xx xxx Xxxx Xxxxxx Xxxxxxxxxxxx Xxxx, Mutatation Xxx., 347, 97-99.
18) Richold, X., Xxxxx, X., Xxxxxxx, J., Chandley, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), Xx vivo Xxxxxxxxxxxx Xxxxx, xx: X. X. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx, XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New York, Xxxx Chester, Melbourne, Xxxxxx, 115-141.
19) Xxxxxx, X. P., Anderson, X., Xxxxxxxx, R., Xxxxxxxx, X. E., Xxxxx, G., Xxxxxxxx X., Xxxxxxx, X., Xxxxxxxx, D. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx of In xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx on Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Part XXX, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."
PŘÍLOHA 4D
"B.13/14 XXXXXXXXXX — XXXXXXX XX XXXXXXXX MUTACE X XXXXXXXXXX
1. XXXXXX
Xxxx metoda xx xxxxxxxx xxxxxx XXXX TG 471 — Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx (1997).
1.1 XXXX
Xxx xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Xxxxxxxxxxx xxxx, x xxxxxxx xxxxxxxx xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxx a xxxxxx xxxxxxx xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx na reverzní xxxxxx x bakteriemi xxxxxxx x xxxxxxx xxxxxx, xxxxx xxxxxxxxx xxxxxx xxxxxxxx v xxxxxxxxxxx kmenech x xxxxxxxx tak xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx aminokyseliny. Xxxxxxxx xx xxxxxxx jsou xxxxxxxxxx díky své xxxxxxxxxx xxxx v xxxxxxxxxxxxx aminokyselin, xxxxx xxxx xxxxxxxxxx mateřským xxxxxxxxxx kmenem.
Bodové xxxxxx x podobné xxxx xxxx příčinou mnoha xxxxxxxxx podmíněných chorob x xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxx xxxxxx x xxxxxxxxxx a x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxx xx xxxxxx xxxxxxxx u člověka x u pokusných xxxxxx. Zkouška xx xxxxxxxx xxxxxx s xxxxxxxxxx xx rychlá, xxxxxxxxxx a relativně xxxxxx. Mnoho testovacích xxxxx xx řadu xxxxxxxxxx, xxxx xxxx xxxx xxxxxxxxxx na xxxxxxx mutací, včetně xxxxxxxxxxxxx sekvencí DNA xx xxxxxxxxxx xxxxxxx, xxxxxxx permeability buněk xxx xxxxx xxxxxxxx x eliminaci xxxxxxxxxxx xxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxxxxxxxx k xxxxxx. Specifičnost xxxxxxxxxxx xxxxx xxxx poskytnout xxxxxxx xxxxxxxx informace x typech xxxxxx, xxx xxxx indukovány xxxxxxxxxxxxx činiteli. Xxx xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx x dispozici xxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxx širokou xxxxx struktur a xxxx byly xxxxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx chemických látek, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx fyzikálně-chemickými xxxxxxxxxxx.
Xxx xxxx xxxxxx xxxx, část X.
1.2 XXXXXXXX
Xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx xxxxxx x xxxxxxx mutací x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (xxxxxxxx resp. xxxxxxxxx), xxxxxxx vzniká xxxx xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxxxxxx.
Xxxxxxxx xxxxxxxxxx xxxx xxxx xxxx činitele, xxx xxxxxxxxx xxxxx x xxxxxx XXX. Xxx xxxxxxx xxxxxxxxxx xxxxxx xx xxxxx tyto xxxxx vyskytnout xx xxxxx xxxxxxx mutace xxxx xxxxx xxxxx xxxxxxxxxxxxx xxxxxx.
Xxxxxxxx xxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxxx adici nebo xxxxxx jednoho xxxx xxxx párů xxxx XXX x xxxxxxxx xxx xxxxx rámec XXX.
1.3 XXXXXXX XXXXX
Xxx xxxxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx využívají prokaryotické xxxxx, xxxxx xx xxxx od buněk xxxxx xxxxxxx, xxxx xxxx příjem, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx a xxxxxxxxx xxxxxxx XXX. Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx vyžadují xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xxxxxxx xxxx neposkytuje xxxxxx xxxxxxxxx x xxxxxxxxxx x karcinogenním xxxxxxxxxx látky xxx xxxxx.
Xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx xxxxxxxxx využívána xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx, a xxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxx xxxxxx. X xxxxxxxx xxxxxxxx vyplývá, xx xxxxx xxxxxxxxxx xxxxx, xxxxx xxxx x této xxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx x x xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx xxxxxx detekovány xxxxx xxxxxxxx. Xxxxxxx xxxxxx skutečností xxx xxxxxxxxx xx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx jevu, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx nebo x xxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx faktory, xxxxx xxxxxxx citlivost xxxxxxx xx reverzní xxxxxx xx xxxxxxxxxx, xxxxx xxxx k xxxxxxxxxxxx mutagenní xxxxxxxx.
Xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xxxxxx xxx xxxxxx pro xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx vysoce xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx antibiotika) x xxx chemické xxxxx, x xxxxx se xxxxxxxxxxx (xxxx x xxxxx xx xx), xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx systému xxxxx xxxxx (xxxx. xxxxxxx inhibitory xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). X takových xxxxxxxxx xxxxx být xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.
Xxxxxxxx mnoho xxxxxxxxx, xxx xxx xx tato xxxxxxx xxxxxxxxx, xx karcinogenní xxx xxxxx, xxxx xxxxxxxx xxxxxxxxx. Závisí xx chemické xxxxx x existuje xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx touto xxxxxxxx, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx mechanismy, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.
1.4 XXXXXXXX ZKUŠEBNÍ XXXXXX
Xxxxxxxx xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx zkoušené látce, x xx za xxxxxxxxxxx xxxxxxxx metabolického xxxxxxxxxxx xxxxxxx a xxx xxxx. Ve xxxxxxxxxxx xxxxxxxx testu xx xxxxxxxx xxxxxxxx x xxxxxxx xxxxxx x xxxxx xx xxxxxxx xx xxxxxxxxx xxxx. X xxxxxxxxxxxx xxxxxx xx zkoušená xxxx xxxxxxxx x xxxx se xxxx xxxxxxxxx na xxxxxxxxx xxxx xxxxxx x xxxxxxx agarem. Xxx xxxx xxxxxxxxxx se xx dvou xxxx xxxxx xxxxx inkubace xxxxxxxxx kolonie xxxxxxxxxx x xxxxxxx se xxxxxxxx x počtem xxxxxxx xxxxxxxxxxx revertantů xx xxxxxxxxx misce x xxxxxxxxxxxxx.
Xx popsáno xxxxxxx xxxxxxx provedení xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi. Xxxx xxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), fluktuační test (9, 10) x xxxxxxxxx xxxxxx (11). Xxxxxx xxx zkoušení xxxxx x par xxxx popsány (12).
Xxx xxxxxxx xxxxxxx xx xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxxxxxxxx metod. Každá x xxxx xx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx ní. Xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxx za použití xxxxxxxxxxxx xxxxxx. Tyto xxxxx patří xx xxxxxxxxxx xxxx, xx xxxxx xxxxx xxxx xxxxx krátké xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx kovy, xxxxxxxx, xxxxxxxxxx a xxxxxxxxxx sloučeniny, pyrrolizidinové xxxxxxxxx, xxxxxxxx sloučeniny x nitrosloučeniny (3). Xxxxxx xx xxxxxxxxx, xx xxxxxx xxxxx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx xx xxxxxxxxxx xxxxxxx test xxxx xxxxxxxxxxxx xxxxxx. Měly xx xxx považovány xx "xxxxxxxx xxxxxxx" x k jejich xxxxxxx se xxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "zvláštní xxxxxxx" (společně s xxxxxxxx postupů jejich xxxxxxx): xxxxxxxxxx x xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx od xxxxxxxxxxxx xxxxxxx xxxx xxx xxxxxxx xxxxxxxxxx.
1.5 XXXXX ZKUŠEBNÍ METODY
1.5.1 Xxxxxxxxx
1.5.1.1 Xxxxxxxx
Xxxxxxx kultury xxxxxxxx by xxxx xxx kultivovány xx xxxxxx xxxxxxxxxxxxx fáze xxxx xx xxxxx xxxxxxxxxxx fáze xxxxx (xxxxxxxxx 109 xxxxx xx xx). Buňky x pozdní stacionární xxxx xx neměly xxx xxxxxxx. Xx xxxxxxxx, aby xxxx xxxxxxx bakterie xxxxxx xxxx životaschopných xxxxxxxx. Xxxx xxxx být xxxxxxxx buď na xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x růstové xxxxxx, xxxx xxx xxxxxx zkoušku xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx xxxxx xx xxxxxxx.
Xxxxxxxxxx xxxxxxxxx xxxxxxx je 37 °X.
Xxxx xx být xxxxxxx xxxxxxx xxx xxxxx xxxxxxxx. Mezi xxxx xx xxxx xxx čtyři xxxxx X. xxxxxxxxxxx (TA1535; XX1537 xxxx TA97a xxxx XX97; TA98 x XX100), xxxxxxx xxxxxxx xx xxxxxxx x různých xxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxxxxxxxxx. Tyto čtyři xxxxx X. typhimurium xxxx pár bází XX xx xxxxxxxxx xxxxxxxxx xxxxx a xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx oxidační xxxxxxxx, xxxxxxxx způsobující xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Tyto xxxxx xxxxx být xxxxxxxxxx xxxxx X. xxxx XX2 nebo X. xxxxxxxxxxx TA102 (19), které xxxx xx xxxxxxxxx reverzním xxxxx xxx xxxx XX. Xxxxxxxxxx xxxxxxxxx xxxxx xx tedy xxxx:
- X. xxxxxxxxxxx XX1535 x
- X. xxxxxxxxxxx TA1537 xxxx XX97x x
- S. xxxxxxxxxxx TA98 a
- X. xxxxxxxxxxx XX100 x
- E. xxxx XX2 xxxX, xxxx X. xxxx XX2 xxxX (pKM101), nebo X. xxxxxxxxxxx XX102.
Xxx xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx vláken XXX xxxx xxx vhodnější xxxxxxx XX102 xxxx xxxxxx xxxx X. xxxx s vysokou xxxxxxxxxx reparace XXX, (xxxx. X. coli XX2 (pKM101)).
Měly xx xxx xxxxxxx xxxxxxxx xxxxxxx přípravy xxxxxxx xxxxxxx, xxxxxxxxxx markeru x xxxxxxxxxx. Xxxxxxx xxxxxxxxxxxxx xxx xxxx xx xxxx být xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx pro xxxxx X. xxxxxxxxxxx x xxxxxxxxx xxx E. xxxx). Xxxxxxx xx xxxx xxx xxxxxxxxxxxx xxxx xxxxxxxxxx charakteristiky, xxxxxxxxx xxxxx xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx plasmidů (xx. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, XX100 x TA97a nebo XX97, WP2 xxxX x XX2 xxxX (xXX101) a xxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxx x xxxxx TA102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. xxx mutací x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx xxxxxx x uvrA xxxxxx u X. xxxx xxxx uvrB xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxxx) (2, 3). Kmeny xx xxxx xxxxxx dávat xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxx x rozmezí xxxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx laboratorních xxxxxxx x xxxxxxx x rozmezí uvedeném x literatuře.
1.5.1.2 Xxxxxx
Xxxxxxx xx xxxxxx xxxxxxxxx xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx E (Xxxxx-Xxxxxx) a xxxxxxx) x vrchní agar xxxxxxxxxx histidin x xxxxxx xxxx xxxxxxxxx xxxxxxxxxx několik buněčných xxxxxx (1, 2, 9).
1.5.1.3 Metabolická xxxxxxxx
Xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x xx s xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx a xxx xxxx. Nejčastěji xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx postmitochondriální frakce (X9) xxxxxxxxxx z xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (1, 2) xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (18, 20, 21). Postmitochondriální xxxxxx xx xxxxxxx používána x xxxxxxxxxxxxx x xxxxxxx 5 xx 30 % obj. xx xxxxx X9. Xxxxx x podmínky xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx na xxxxx xxxxxxxx xxxxxxxx xxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. X xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).
1.5.1.4 Zkoušená xxxxx nebo xxxxxxxxx
Xxxxx xxxxxxxx xxxxx by xxxx xxx xxxx xxxxxxxx xx bakterie xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.
Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx mimo podezření, xx reaguje xx xxxxxxxxx xxxxxx, a xxxx xx xxx xxxxxxxxxx s xxxxxxxx xxxxxxxx a x xxxxxxxxx X9 (22). Xxxx-xx použita xxxx xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx zkoušení xxxxx xxxxxxxxx xx xxxx by měla xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx vodu.
1.5.2 Xxxxxxxx xxxxxxxx
1.5.2.1 Xxxxxxxx xxxxx (xxx 1.5.1.1)
1.5.2.2 Xxxxxxxxx xxxxxxxxxxx
Xxxx xxxxxxxx, xxxxx mají xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxx množství zkoušené xxxxx xxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxx xxxxx pro xxxxxxxx.
Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Cytotoxicita může xxx detekována xxxxxxxx xxxxx kolonií xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx se xxxx xxxxxx v přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx xx měla xxx xxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxxx xxxxx xx skutečných zkušebních xxxxxxxx.
Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx rozpustné xxxxxxxxxxxxx xxxxx xx 5 xx/xxxxx xxxx 5 μx/xxxxx. X xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx xx xxxx xxx jedna xxxx xxxx xxxxxxxxxx koncentrací xxxxxxxx, xxx xxxxx xxxx x xxxxxxx xxxxx pro aplikaci xxxxxxxxxxx. Zkoušené xxxxx, xxxxx jsou xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, xx xxxx xxx xxxxxxxx xx xx xxxxxxxxxxx koncentrace. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.
Xxxx xx xxx použito xxxxxxx xxx různých xxxxxxxxxxxxxxxx koncentrací zkoušené xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxx polovině xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx jsou vhodné x xxxxxxx, kdy xx xxxxxxxxx xxxxxx xxxxxxxxxx odpovědi na xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx být xxxxxxx xxx hodnocení xxxxx obsahujících xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.
1.5.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx
Xxxxxxxx xxxxxxx xxxxxxxxx xx xxxx xxx kmenově xxxxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx s metabolickou xxxxxxxx x xxx xx. Pro pozitivní xxxxxxxx by xxxx xxx xxxxxxx koncentrace xxxxxxxxxxx účinnost xxxxx xxxxxxx.
X případě xxxxxxx x použitím metabolického xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxx (xxxxx) pro xxxxxxxxx xxxxxxxx vybrána (vybrány) xx xxxxxxx xxxx xxxxxxxxx kmene xxxxxxxx.
Xxxxxxxxx xxxxxx xxxxxxxxx kontroly x xxxxxxx x xxxxxxxxxxxx aktivací xxxx xxxx xxxxx:
|
Xxxxx |
Xxxxx XXX |
Xxxxx xxxxx XXXXXX |
|
9,10-xxxxxxxxxxxxxxxxx |
781–43–1 |
212–308–4 |
|
7,12-xxxxxxxxxxxxx[x]xxxxxxxxx |
57–97–6 |
200–359–5 |
|
xxxxx[x]xxxxx |
50–32–8 |
200–028–5 |
|
2-xxxxxxxxxxxxxx |
613–13–8 |
210–330–9 |
|
Xxxxxxxxxxxxx |
50–18–0 |
200–015–4 |
|
xxxxxxxxxxxxx xxxxxxxxxx |
6055–19–2 |
Xxxx xxxxx xx vhodnou xxxxxxxxx kontrolou pro xxxxxx redukční metabolické xxxxxxxx:
|
Xxxxx |
Xxxxx CAS |
Číslo xxxxx XXXXXX |
|
XX Direct Xxx 28 |
573–58–0 |
209–358–4 |
2-xxxxxxxxxxxxxx by neměl xxx použit jako xxxxxx xxxxxxxxx účinnosti xxxxx X9. Při xxxxxxx 2-xxxxxxxxxxxxxxx xx xxxx xxx xxxxx xxxxx X9 xxxxxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.
Xxxxxxxxx kmenověspecifické xxxxxxxxx xxxxxxxx u xxxxxxx xxx vnější xxxxxxxxxxx aktivace xxxx xxxx látky:
|
Látka |
Číslo XXX |
Xxxxx xxxxx EINECS |
Kmen |
|
azid xxxxx |
26628–22–8 |
247–852–1 |
XX1535 x TA100 |
|
2-nitrofluoren |
607–57–8 |
210–138–5 |
TA98 |
|
9-aminoakridin |
90–45–9 |
201–995–6 |
TA1537, XX97 x XX97x |
|
XXX 191 |
17070–45–0 |
241–129–4 |
XX1537, XX97 a XX97x |
|
Xxxxxxxxxxxxxxxxx |
80–15–9 |
201–254–7 |
XX102 |
|
xxxxxxxxx X |
50–07–7 |
200–008–6 |
XX2xxxX a XX102 |
|
1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx |
70–25–7 |
200–730–1 |
XX2, XX2 uvrA a XX2 xxxX (pKM101) |
|
4-nitrochinolin-1-oxid |
56–57–5 |
200–281–1 |
WP2, XX2 uvrA x XX2 xxxX (xXX101) |
|
α-[(5-xxxxx-2-xxxxx)xxxxxxxxxx]xxxxx-2-xxxxxxxx (XX2) |
3688–53–7 |
xxxxx xxxxxxxxxx plasmidy |
Pro xxxxxxxxx xxxxxxxx mohou xxx xxxxxxx xxxx xxxxxx xxxxxxxxxx látky. Xxx pozitivní kontrolu xx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx látek xx xxxxxx chemické xxxxx, xxxx li x xxxxxxxxx.
Xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx se xx samotného xxxxxxxxxxxx xxxx vehikula, bez xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx exponované skupiny. Xxxxx xxxx by xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx prokazující, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.
1.5.3 Xxxxxx
X xxxxxxxxxx miskové xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxx xxxxxxxxxxx kultury (xxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) a 0,5 xx xxxxxxxxxx xxxxx x 2,0 ml xxxxxxxx xxxxx. V xxxxxxx xxxxxxx s xxxxxxxxxxxx aktivací xx xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx obsahující xxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (x xxxxxxx 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx xxxxx) x xxxxxxx xxxxxx (2,0 xx) x zároveň x bakteriemi a xxxxxxxxx xxxxxx nebo xxxxxxxxx xxxxxxxx. Obsah xxxxx xxxxxxxx se xxxxxxxx x xxxxxxx xxxx xxxxxx minimálního xxxxx xx xxxxx. Xxxx xxxxxxxx xx xxxxx xxxxxx agar xxxxxxxx.
X preinkubační xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx nebo zkoušený xxxxxx xxxx xxxxxxxxx x xxxxxxx agarem x xxxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxxxxx 20 xxxxx xxxx xxxx xxxxxxxxxxx s xxxxxxxxxx kmenem (xxxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) x sterilním xxxxxx xxxx metabolickým xxxxxxxxxx systémem (0,5 xx) xxx 30 — 37 °C. Xxxxxxx xx xxxxxx 0,05 nebo 0,1 xx xxxxxxxx xxxxx xxxx zkušebního roztoku, 0,1 ml xxxxxxxx x 0,5 xx xxxxx X9 xxxx xxxxxxxxxx pufru x 2,0 xx xxxxxxxx xxxxx. Xxxxxxxx xx xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.
X xxxxxxxxxxxx odhadu xxxxxxxx xx xxxx xxx xxx xxxxx xxxxxx xxxxx použity 3 misky. Xxxxxxx xxxx misek xx xxxxxxxxxx xx xxxxxxxx xxxxxxxxxx. Xxxxxxxx ztráta xxxxx nemusí znamenat xxxxxxxxxxxx xxxxxxx.
Xxxxxx xxxx xxxxxx látky xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx nádobách (12, 14, 15, 16).
1.5.4 Xxxxxxxx
Xxxxxxx xxxxx v xxxx zkoušce xx xxxx být xxxxxxxxxx xxx 37 °C xx 48 –72 xxxxxxxx. Xx xxxxxxxx xxxxxxxxx xxxx se xxxxxx počet xxxxxxx xxxxxxxxxx na misku.
2. XXXXX
2.1 XXXXXXXXXX VÝSLEDKŮ
Předloženými xxxxx by xxxx xxx počty xxxxxxx xxxxxxxxxx připadající na xxxxx. Xxx by xxx xxxxxx xxxxxx xxxxx kolonií revertantů xxx na xxxxxxx x xxxxxxxxx kontrolou (xxxxxxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxxx kontrola), xxx na miskách x xxxxxxxxx kontrolou. Xxxxx xx xxxxxxxxxxxx xxxxxxx, střední hodnoty xxxxx kolonií revertantů xx xxxxx a xxxxxxxxxx odchylka by xxxx xxx xxxxxxxxxx xxx xxxxxxxxx látku x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx a/nebo xxxxxxxx xxxxxxxxxxxx).
Xxxxxxx xxxxx pozitivní xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx vyjasněny xxxxxx xxxxxxxxx, nejlépe x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx být xxxxxxxxx xxxxxx xx případu. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx nepovažuje xx xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx rozsah posuzovaných xxxxxxxx xx xxxx xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, které xx xxxxx xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx xxxxxxx metoda xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) a xxxxxxxx xxxxxxxxxxx xxxxxxxx.
2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX
Xxx stanovení xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx revertantů xx misku xxx xxxxxxxxx rozsah u xxxxxxx xxxxxxx xxxxx x metabolickým aktivačním xxxxxxxx xxxx xxx xxxx, a xx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx tohoto xxxxx xxx xxxxx xxxx xxxx xxxxxxxxxxx (23). Xxxxxxxx by xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx metody (24). Xxxxxxxxxxx významnost by xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.
Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx xxxxxxxx v xxxxx xxxxxxx za xxxxxxxxxxx.
Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor údajů xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx opakován.
Pozitivní xxxxxxxx xxxxxxx xx xxxxxxxx mutace x xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x genomu xxxxx Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx bodové xxxxxx xxxxxxxxxx bází xxxx posunem xxxxxxx xxxxx. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx není xx xxxxxxxx xxxxxxx pro xxxxxxxxx xxxxx xxxxxxxxx.
3. XXXXXX
XXXXXXXX X XXXXXXX
Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx tyto xxxxxxxxx:
Xxxxxxxxxxxx/xxxxxxxxx:
- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,
- xxxxxxxxxxx a xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxxx/xxxxxxxx, je-li xxxxx.
Xxxxx:
- xxxxxxx xxxxx,
- xxxxx xxxxx x xxxxxxx,
- xxxxxxxxxxxxxxx xxxxx.
Xxxxxxxx xxxxxxxx:
- xxxxxxxx xxxxxxxx látky xx misku (xx/xxxxx xxxx μl/misku) x xxxxxxxxxxx xxxxxx xxxxx x xxxxx xxxxx xx xxxxxxxxxxx,
- xxxxxxx xxxxx,
- typ x xxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,
- xxxxxx xxxxxxxx.
Xxxxxxxx:
- xxxxxx xxxxxxxx,
- xxxxxx xxxxxxx,
- xxxxx xx xxxxxxxxxxxx miskách,
- xxxxxxx xxxxxxx počtu xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx odchylka,
- xxxxx možnosti xxxxxxxxx xxxxxxxx na xxxxx,
- xxxxxxxx statistické analýzy,
- xxxxx x xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) a xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,
- xxxxxxxxx údaje x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx odchylkami.
Rozbor xxxxxxxx.
Xxxxxx.
4. LITERATURA
1) Xxxx, X. N., XxXxxx, X., Xxxxxxxx X. (1975), Xxxxxxx of Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx., 31, 347-364.
2) Maron, D. X., Ames, B. X. (1983), Revised Xxxxxxx xxx xxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 113, 173-215.
3) Xxxxxxxxx, X., Xxxxxxx, S., Xxxxxx, X., Gocke, X., Xxxx, X., Xxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Venitt, X., Xxxxxx, X. (1994), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx xx Xxxxxxxxx Mutation Assays, Xxxxxxxxxx Xxx., 312, 217-233.
4) Xxxx, L. X., Xxxxxxx X. X., Xxxxxxx, X. X., Xxx Halle, X. X., Brown, X. M., Xxxxxx, X. X., Xxxxxx, X., XxXxxx, J., Xxxxxxxxxx, X., Prival, X., Xxx, X. X., Xxx X. (1986), Xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Microsomal Assay: X Xxxxxx xx xxx X. X. Xxxxxxxxxxxxx Protection Agency Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 168, 69-240.
5) Xxxxxx, X., Degawa, X., Xxxxx, X. X., Matsushima, X., Xxxxx, M., Sugimura, X., Xxxxxxxxx, X. (1975), Xxxxxxxxxxxx of Xxxxxxxxxx Xxx Xxxx xxx their Xxxxxxxxxxx, Xxxxxx Lett. 1, 91-96.
6) Xxxxxxxxxx, X., Xxxxxxxx, T., Xxxxx, X., Xxxxxx, T., Xxxxxx, A., Sawamura, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Microbial Xxxxx, xx: Short-term Xxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx, ed. Xxxxxxx K. H., Xxxxxx, X. X., Xxxxxxxx, Berlin-Heidelberg-New York, 273-285.
7) Xxxxxxxxx, X. X., Xxxxxxx, I. X., Wilcox, P., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Xxxxxx, xx: Xxxxx Mutagenicity Xxxxx: UKEMS Xxxx 1 Xxxxxxx, xx. X. X. Xxxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, 13-61.
8) Xxxxxxxxxx, H. X., Xxxxxx, U., Xxxxxxx, L. (1987), Xxxxxx Preincubation Xxxxxxxxxxxx Xxxx for Foods, X. Food Xxxxxx., 8, 167-177.
9) Xxxxx, X. X. X., Xxxxxx, X. J., Xxxxxxx, B. X. (1976), Use xx x xxxxxxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxx xx xxxxxxxx, Mutatation Res., 38, 33-42.
10) Xxxxxxx, X. A., Xxxxx, X. X. X., Xxxxxxxxx, D., Bridges, X. X. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, in: Xxxxxxxx xx Mutagenicity Xxxx Xxxxxxxxxx, 2. xxx., Xxxxxx, B. X., Xxxxxxx, M., Xxxxxxx, W., Xxxxx, X. (xxx.), Xxxxxxxx, Xxxxxxxxx-Xxx York-Oxford, 141-161.
11) Xxxxxxxx, X. D., Xxxxxxx, X. X. (1981), An Xxxxxxxxxxx xx the Quantitative Xxxxxxxxxx Xxxxx for Xxxxxxxxxxx with Xxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.
12) Xxxxx, X., Xxxxxxx, X., Xxxx, X., Matsushima, X. (1994), Xxxxxxxx Method xxx Mutagenicity Xxxxxxx xx Xxxxxxx Xxxxxxxxx xx Xxxxx a Xxx Xxxxxxxx Bag, Xxxxxxxxxx Xxx., 307, 335-344.
13) Xxxxxx, X. X., Xxxx, X. X., Mitchell, X. X., Xxxxxxx, X. X., Xxxxxxx, V. X. (1984), Xxxxxxxxxxxx xx Xxxxxxxxx and Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Xxxx xx x Xxxxxxxx Xxxxxxxxxx Assay, Xxxxxxxxxx Xxx., 136, 33-47.
14) Xxxxxx, X., Xxxxxxxx, X. E., Xxxxxxx, X., Xxxxxx, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Tests. X. Results xxxx xxx Xxxxxxx xx 311 Xxxxxxxxx, Environ. Xxx. Xxxxxxx., 19, 2-141.
15) Xxxxxx, X., Xxxxxxxx, X., Xxxxxxx, X. X. (1977), Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxx Xxxxx, xx Xxxxxxxx xx Xxxxxxx Xxxxxxxxxx, X. Xxxxx, X. Xxxxxxx, X. Xxxxxx (eds.) Xxxxxxxx, Xxxxxxxxx, 249-258.
16) Xxxxxx, X. X., Xxxxxxx, X. M., Monteith, X. G., Xxxxxxx, X. D. (1987), Xxxxxxxxxxxx Xxxxxxxxx xx Xxxxxxx Xxxxxxxxx Activity xx Xxxxxxxx Xxxxxxx Xxxxxxxxx in xxx Xxxx/Xxxxxxxxxx Xxxxx, Environmental Xxxxxxxxxxx, 9, 421-441.
17) Xxxxxxxxxx, T., Matsumoto, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx xxx Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Methylazoxy Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxx typhimurium, Cancer Xxx., 39, 3780-3782.
18) Xxxxxx, X., Xxxx, X., Xxxxx-Xxxxx, X., Xxxx, B. X. (1980), Xxxxxxxx: X Xxxxx xxx Activation xx Dietary Xxxxxxxxxx xx Xxxxxxxx xx Xxxxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Xxx. X. S. A, 77, 4961-4965.
19) Xxxxxx, X., Xxxxxx, A., Xxxx, D. X., Xxxxxxxxx, D. G. (1990), Xxxxxxxxxx xx Xxxxxxxxxx typhimurium TA 102 with Xxxxxxxxxxx xxxx XX2 Tester xxxxxxx, Xxxxxxxxxxx, 5, 285-291.
20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), A Safe Xxxxxxxxxx for Polychlorinated Xxxxxxxxx a. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, xx: In xxxxx Xxxxxxxxx Xxxxxxxxxx in Xxxxxxxxxxx Xxxxxxx, xxx. X. X. xx Xxxxxx et al. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.
21) Elliot, X. X., Xxxxxx, X. X., Xxxxxxx, X. X., Gatehouse, X. X., Gibson, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 in xx xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 175-177.
22) Xxxxx, X., Xxxxxxxxxxxxxxxx, X., Xxxx, X. X. (1981), Compatibility xx Organic Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxx, Mutatation Res., 88, 343-350.
23) Xxxxxxx, X. D., Xxxxx, X., Xxxxxxx, A., Xxxxxxxxxx, K., Xxxxxxxx, X., Zeiger, E. (1987), Guide xxx xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 83-91.
24) Xxxxx, X. A. X., Xxxxx, M. X. X., Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, X. J. (1989), Xxxxxxxx xx Xxxx from Xxxxxxxxx Xxxxxx Xxxxxx, in: XXXXX Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxx XX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, xx. Xxxxxxxx, D. X., Xxxxxxxxx University Xxxxx, 28-65."
PŘÍLOHA 4X
"X.17 MUTAGENITA — ZKOUŠKA XX XXXXXX XXXXXX V XXXXXXX XXXXX XX XXXXX
1. METODA
Tato xxxxxx xx xxxxxxxx xxxxxx XXXX TG 476 — Xxxxxxx na xxxxxx xxxxxx x xxxxxxx xxxxx in xxxxx (1997).
1.1 XXXX
Xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx xx vitro xxx xxxxxx xxx detekci xxxxxxxx mutací xxxxxxxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxx lymfomu X5178X xxxx, xxxxxxx xxxxx CHO, XXX-XX52 x X79 xxxxxx xxxxxxxx a xxxxxxxxxxxxxxx xxxxx TK6 xxxxxxx (1). X těchto xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx mírou genetických xxxxxx mutace xxxx xxx thymidinkinasu (XX) x hypoxanthin-guaninfosforibosyltransferasu (XXXX) x transgen xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Zkoušky xx xxxxxx TK, XXXX x XXXX xxxxxxxx xxxxx xxxxxxxx genetických xxxxxxxx. Xxxxxxxxxxx xxxxxx XX a XXXX xxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxx xxxxxx), které xxxxx xxxxxxxxx x XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).
Xx zkoušce na xxxxxx mutace v xxxxxxx savců in xxxxx xxx použít xxxxxxx zavedených xxxxx xxxxx xxxx xxxxxxx xxxxx. Buňky xx xxxxxxxx xxxxx schopnosti xxxxx v xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx mutací.
Zkoušky xxxxxxxxx xx xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační xxxxxx xxxxxx zcela xxxxxxxxx podmínky in xxxx x savců. Xx xxxxx se xxxxx vyvarovat xxxxxxxx, xxxxx by vedly x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X pozitivním xxxxxxxxx, jež neodrážejí xxxxxxx mutagenitu, xxxx xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx cytotoxicity (7).
Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx možných xxxxxxxx a xxxxxxxxxxx xxxxx. Mnoho sloučenin, xxx xxx je xxxx xxxxxxx xxxxxxxxx, xxxx karcinogeny xxxxx; xxxx xxxxx zkouškou x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx na xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, xx existují xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx buňkách xxxxxxxxxx (6).
Viz xxxx xxxxxx úvod, část X.
1.2 XXXXXXXX
Xxxxx mutace : genová xxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxx xxxx ztrátu xxxxxxxxxxx xxxxxxxx kódovaných xxxxxxxx.
Xxxxxxxx substituce xxxx xxxx : xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxx xxxx xxxx v XXX.
Xxxxxxxx xxxxxxxx : xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxx nebo xxxx xxxx xxxx x xxxxxxxx XXX.
Xxxx exprese xxxxxxxx : doba, xxxxx xxx xxxxxx x xxxx xxxxxxxxxx xxxxx xxxxxxxxx genové xxxxxxxx.
Xxxxxxx xxxxxxx : xxxxx pozorovaných mutantních xxxxx xxxxxx xxxxxx xxxxxxxxxxxxxxx xxxxx.
Xxxxxxxxx celkový xxxx : xxxxxx xxxxx xxxxx x xxxx ve xxxxxxxx x kontrolní populací xxxxx; xxxxxxx xx xxxx xxxxxx xxxxxx xxxxxxxxx růstu x xxxxxxxx a x xxxxxxxxx xxxxxxxx x xxxxxxxxx účinnosti xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.
Xxxxxxxxx xxxx x xxxxxxxx : nárůst xxxxx buněk v xxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.
Xxxxxxxxxxxxxxx : účinnost xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx na misku xx xxxxxxxxxxxx xxxxxxxx xx expresi.
Přežití : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx na xxxxx na xxxxx xxxxxx xxxxxxxx; xxxxxxx xx obvykle xxxxxxxxx x poměru k xxxxxxx xxxxxxxxx xxxxxxxx xxxxx.
1.3 PODSTATA XXXXXXXX XXXXXX
Xxxxx, které v xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (TK) xxxx xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxx pyrimidinu xxxxxxxxxxxxxxxxx (TFT). Buňky xxxxxxxxxxx thymidinkinasu jsou xxxxxxx na TFT, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx další buněčné xxxxxx. Xxxxxxxx buňky xxxx xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxxxxx XXX, zatímco xxxxxxxx xxxxx, které obsahují xxxxxxxxxxxxxx tuto schopnost xxxxxx. Podobně xxx x xxxxx x xxxxxxxxxxxx XXXX nebo XXXX xxxxxxx selekci xxxxxxxxxxxxxxx xxxxxxxxxx x 6-xxxxxxxxxxx (XX) nebo 8-xxxxxxxxxx (AG). Xxxxxxxxxx xxxxxxxx látky by xxxx být xxxxxxx xxxxxxx, xxxxxxxx xx xx zkoušce xx xxxxxx xxxxxx x xxxxxxx savců zkoušen xxxxxx báze xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx xx xxxxxxxxxx toxicitu zkoušené xxxxx xxx xxxxxxxx xxxx nemutantní xxxxx. Xxx zkoušení xxxxxxxxxx xxxxx, xxxxx mají xxxxxxxx xxxxxxxxx jako xxxxxxxx činidlo, xxxx xxxx být xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxx xxx selekci (8).
Xxxxx v suspenzní xxxx xxxxxxxxxxxxx xxxxxxx xxxx vhodnou dobu xxxxxxxxx xxxxxxxx xxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx bez xx, x xxxxxxxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx exprese fenotypu xxxx xxxxxxx mutantů (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx obvykle xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx xxxxxxxxxxx celkového xxxxx kultur po xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx kultury se xxxxxxx v xxxxxxxx xxxxx xx xxxxxxx xxxx xxxxxxxxxxxxxxxxx xxx xxxxx zvolený lokus x typ xxxxx, xxx nastala xxxxxxxxx xxxxxxxxx xxxxxxxxxx exprese xxxxxxxxxxxx xxxxxx. Četnost xxxxxxx xx xxxxxxx xxx, že xx xxxxxx xxxxx xxxxx xxxxx xx xxxxx xxxxxxxxxxxx selekční xxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxx a xx xxxxx xxx xxxxxxxxxx xxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx klonování (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx době se xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx xx xxxxxxx x počtu xxxxxxxxxx xxxxxxx x xxxxxxxxx xxxxx x xxxxx xxxxxxx x médiu xxx selekčního xxxxxxx.
1.4 XXXXX ZKUŠEBNÍ METODY
1.4.1 Xxxxxxxxx
1.4.1.1 Xxxxx
Xxx použití x xxxx zkoušce xxxx x xxxxxxxxx xxxxx xxxx buněk, xxxxxx xxxxxxxx xxxxx X5171X, XXX, XXX-XX52, X79 nebo XX6. Xxxx xxxxx x xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx schopnost x xxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx být xxxxxxxxxxxx, zda xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, x x xxxxxxx kontaminace xx xxxxxx xxx xxxxxxx.
Xxxxxxx xx měly xxx xxxxxxxx xxx, xxx xxxx předem xxxxxxxxxx xxxxxxxxx x xxxx. Xxxxx použitých xxxxx, xxxxxx x xxxxxxxxxxx zkoušené látky xx xxx xxxx xxxxxxxxxx xxxxxxxxx odrážet (14). Xxxxxxxxx počet xxxxx, xxxxx xxxxxxx xxxxxxxx a které xxxxx xxxxxxx x xxxxxx stadiu xxxxxxx, xx měl xxx xxxxxxx xx četnosti xxxxxxxxxxx xxxxxx. Obecným xxxxxxxxx xx, aby xxx xxxxxx xxxxx xxxxx, xxxxx xx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx mutací. Xx xxxx xxxxxxxxxx, xxx xxxx xxxxxxx xxxxxxx 106 buněk. Xxxx xx být x dispozici xxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.
1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx
Xxx udržování xxxxxx by měla xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx a xxxxxxxxx xxxxxxxx (kultivační xxxxxx, koncentrace CO2, xxxxxxx x xxxxxxx). Xxxxx xx měla xxx xxxxxxx xxxxx xxxxxxxxxx systémů a xxxx xxxxx xxxxxxxxx xxx xxxxxxx. Xx xxxxxxx důležité, xxx xxxxxxxxxx xxxxxxxx byly xxxxxxx tak, xxx xxxx zajištěny optimální xxxx buněk xxxxx xxxxxx xxxxxxx x xxxxxxxxx xxx mutovaných, xxx nemutovaných buněk xxxxxx xxxxxxx.
1.4.1.3 Příprava xxxxxx
Xxxxx xx xxxx xxx získávány x xxxxxxxxx xxxxxx, xxxxxxxx xx xxxxxxxxxxxx xxxxx x inkubovány xxx 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx xxxx xxx xxxxxxxx xxxxxxxxx z xxxxxxx již xxxxxxxx xxxxxxxx xxxxx.
1.4.1.4 Xxxxxxxxxxx xxxxxxxx
Xxxxx xx měly xxx xxxxxxxxx zkoušené xxxxx, x to x xxxxxxx systémem xxxxxxxxxxx aktivace a xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx hlodavců xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, jako je Xxxxxxx 1254 (15, 16, 17 x 18), xxxx směs xxxxxxxxxxxxx a β-naftoflavonu (19, 20).
Postmitochondriální xxxxxx xx v xxxxxxxx xxxxxxxxxx médiu obvykle xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % obj. Xxxxx x stav xxxxxxxxxxxxx xxxxxxxxxxx systému může xxxxxxx xx xxxxx xxxxxxxx látky, xxxxx xx zkoušena. V xxxxxxxxx xxxxxxxxx může xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.
Xxxx xxxxxxxx vývoje, včetně xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx aktivační xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx linií xx xxxx být xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).
1.4.1.5 Příprava xxxxxxxx xxxxx
Xxxxx zkoušené xxxxx xx měly xxx před xxxxxxxx xx buňky rozpuštěny xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx být xxxxxxx xxxxx x xxxxxxxxxx systémům x/xxxx xxxxx xxx před xxxxxxxx zředěny. Měly xx xxx xxxxxxx xxxxxxx připravené zkoušené xxxxxxxx látky, xxxxx xxxxx o stálosti xxxxxxxxxxx možnost skladování.
1.4.2 Xxxxxxxx podmínky
1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx
Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx, x mělo xx xxx xxxxxxxxxx x přežitím buněk x x aktivitou X9. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich zařazení xxxxxxxxx údaji x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx možno xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx nestálých xx vodě xx xxxx xxx použitá xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.
1.4.2.2 Expoziční xxxxxxxxxxx
Xxxx xxxxxxxx, která xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, rozpustnost x xxxxxxxxxx xxxxxxx x xxxxx xX xxxx xxxxxxxxxx.
Xxxxxxxxxxxx xx xxxx být xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx x hlavním xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, jako xxxx relativní xxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxx xxxxxxx růst. Xxxx xxx výhodné xxxxxxxx cytotoxicitu x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.
Xxxx by xxx xxxxxxx xxxxxxx čtyři xxxxxxxxxxxxxx koncentrace. X xxxxxxx xxxxxxxx by xxxx tyto koncentrace xxxxxxxx rozmezí xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx, xx xx xx koncentrace xxxx lišit xxxxxxxx 2 až Ö10. Xx-xx xxxxxxxxx koncentrace xxxxxxxx xx xxxxxxxxxxxx, xxxx xx xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) přežití (relativní xxxxxxxx klonování) xxxx xxxxxxxxx xxxxxxx xxxx. X případě relativně xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 mg/ml xxxx 0,01 X, xxxxx xxxx, která x nich je xxxxxxxx.
Xxxxxxxxx xxxxxxxxxxx xxxxx xx xxxx být xxxxxxxx xx x xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx xxxxxxxx, xxxx xx za xxxx xxx. Měla by xxx stanovena xxxxxxxx xxxxxxxxxxxxx x xxxxxxxx xxxxx, ve kterému xxxx buňky xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx a xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx se xxxx x průběhu expozice x testovacím xxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, X9 xxxx, xxx. Xxxxxxxxxxxxx xxx zjistit xxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx xxx xxxxxxxxxxx.
1.4.2.3 Xxxxxxxx
Xxxxxxxx každého experimentu xx měly být xxxxxxxxx x negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Xxx xxxxxxx metabolické xxxxxxxx xx xxxx být xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.
Xxxxxxxxx pozitivní xxxxxxxx xxxxx být tyto xxxxx:
|
Xxxx metabolické xxxxxxxx |
Xxxxx |
Xxxxx |
Xxxxx XXX |
Xxxxx podle Einecs |
|
Bez xxxxxx xxxxxxxxxxx xxxxxxxx |
XXXX |
xxxxx-xxxxxxxxxxxxxx |
62–50–0 |
200–536–7 |
|
1-xxxxx-1-xxxxxxxxxxxxxxx |
759–73–9 |
212–072–2 |
||
|
XX (xxxx x velké xxxxxxx) |
xxxxxx-xxxxxxxxxxxxxx |
66–27–3 |
200–625–0 |
|
|
XXXX |
xxxxx-xxxxxxxxxxxxxx |
62–50–0 |
200–536–7 |
|
|
1-xxxxx-1-xxxxxxxxxxxxxxx |
759–73–9 |
212–072–2 |
||
|
X vnější xxxxxxxxxxxx xxxxxxxx |
XXXX |
3-xxxxxxxxxxxxxxxxx |
56–49–5 |
200–276–4 |
|
X-xxxxxxxxxxxxxxxxxxx |
62–75–9 |
200–549–8 |
||
|
7,12-xxxxxxxxxxxxxxxxxxxxxx |
57–97–6 |
200–359–5 |
||
|
XX (malé x xxxxx xxxxxxx) |
xxxxxxxxxxxxx |
50–18–0 |
200–015–4 |
|
|
xxxxxxxxxxxxx xxxxxxxxxx |
6055–19–2 |
|||
|
xxxxx[x]xxxxx |
50–32–8 |
200–028–5 |
||
|
3-xxxxxxxxxxxxxxxxx |
56–49–5 |
200–276–5 |
||
|
XXXX |
X-xxxxxxxxxxxxxxxxxxx (xxx vysoké úrovně X9) |
62–75–9 |
200–549–8 |
|
|
xxxxx[x]xxxxx |
50–32–8 |
200–028–5 |
Xxxxx xxx xxxxxxx xxxx xxxx xxxxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx, xxxx. xx-xx xxxxxxxxx databázi xxxxxxxxxxx xxxxx x 5-brom-2′-deoxyuridinu (XXX 59–14–3, XXXXXX 200–415–9), xxxx xxx xxxx referenční xxxxx xxxxxx xxxxxxx. Pro xxxxxxxxx kontrolu xx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx látek pokud xxxxx ze stejné xxxxxxxx xxxxx.
Xxxx by xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx samotné xxxxxxxxxxxx xxxx vehikulum x xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx exponované xxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.
1.4.3 Xxxxxx
1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx
Xxxxxxxxxxxxx buňky xx xxxx xxx xxxxxxxxx zkoušené látce xxx xx přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx xx xxxx xxxxx xxxxxxx xxxx (xxxxxxx xx účinná xxxx 3 xx 6 hodin). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx xx xxxxx xxxx xxxx xxxxxxxxx xxxxx.
Xxx xxxxxx xxxxxxxx xxxxxxxxxxx mohou xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx xxxxxxxxxx xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, xxx xx xxx xxxxx xxxxxxxxxxx zvýšen xxx, xxx byl xxxxxxxx xxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxx (např. xxxxxxx osm xxxxxxxxxxxxxxxx xxxxxxxxxxx). Měly xx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx kultury (xxxxxxxx rozpouštědla).
Plynné xxxx xxxxxx látky xx xxxx xxx xxxxxxxx xxxxxxxx metodami, xxxx. x xxxxx uzavřených xxxxxxxxxxxx xxxxxxxx (21, 22).
1.4.3.2 Xxxxxxxxx přežití, xxxxxxxxxxxxxxxx a xxxxxxxx xxxxxx
Xx konci expoziční xxxx xx xxxxx xxxxxxx a xxxxxxxxx xx xxxxxx stanovení xxxxxxx a xx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (přežití) xxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx započne xxxxxxx xx xxxxxxxxx xxxx.
Xxxxx xxxxx xx xxxxxxxxxx minimální časové xxxxxx, aby umožnil xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (HPRT x XXXX xxxxxxxx xxxxxxx 6 až 8 xxx, XX alespoň xxx dny). Xxxxx xxxx xxxxxxxxxxx x xxxxx xx xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxxx) x xxx xxxx (xxx xxxx) xx xxxxxx xxxxxxxxx počtu xxxxxxx x xxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx xxxxxxxx xxxxxxx) xx započne xx xxxxx xxxx xxxxxxx xxxxxxxxx xx xxxxx xxx xxxxxxxxxx činidla.
Je-li xxxxxxxx xxxxx xxxxxxxxx xx xxxxxxx X5178X XX+/-, xxxx xx xxx provedeno alespoň xx jedné xx xxxxxxxxxx kultur (x xxxxxxxx pozitivní xxxxxxxxxxx) x xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx kultury podle xxxxxxxxx kolonií. Xx-xx xxxxxxxx xxxxx xx xxxxxxx X5178X TK+/- xxxxxxxxx, xxxx xx xxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií xxxxxxxxx xx negativních x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx XX6 XX+/- xxxx xxx také xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií.
2. XXXXX
2.1 XXXXXXXXXX VÝSLEDKŮ
Údaje xx xxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x četnosti mutantů xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxx L5178Y XX+/- xx xxxxxxx xxxxxxxxx alespoň u xxxxx koncentrace xxxxxxxx xxxxx (xxxxxxxx pozitivní xxxxxxxxxxx) a x xxxxxxxxx x pozitivní xxxxxxxx za xxxxxxx xxxxxxxx malá xxxxxxx — xxxxx xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxx xxxxxxx, xxx mutantů xxxxxxxxx xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Ve zkoušce XX+/- xxxx kolonie xxxxxxxxxxx za xxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxx růstem (xxxxx) x kolonie s xxxxxxx xxxxxx (xxxx) (25). X mutantních xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx poškození, xx xxxxxxxxxxx doby xxxxxxxx, x xxxxx xxxx xxxx kolonie. Xxxxxxxxx xx xxxxxxx xxxxxx xx xxxxx xxxxxx xxxx xx xx karyotypické xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Indukce xxxxxxx xxxxxxxxx xxxx xxxxxxx xx spojuje x xxxxxxxxxx xxxxxxx, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx aberace (26). Xxxx závažně postižené xxxxx xxxxxxx xxxxxx xxxxxxxx tempem xxxx xxxxxxxx xxxxx x xxxxx xxxxx xxxxxxx.
Xxxx xx být udáno xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx růst. Četnost xxxxxxx xx xxxx xxx vyjádřena xxxx xxxxx mutantů x xxxxx přeživších xxxxx.
Xxxx xx xxx uvedeny xxxxx pro xxxxxxxxxx xxxxxxx. Dále by xxxx xxx xxxxxxx xxxxx xxxxxxx ve xxxxx tabulky.
Ověření xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx výsledky xx xxxx být xxxxxxxxx xxxxxx zkoušením, xxxxxxx s úpravou xxxxxxxxxxxxxxxx podmínek. Negativní xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxx, xxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxx, je xxxxx xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx rozsah xxxxxxxxxxxx xxxxxxxx xx xxxx xxx zvážena x xxxxxxxxxx xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, tak xxx xxxxxxxxx xxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx být xxxxxxx, patří xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.
2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX
Xxx xxxxxxxxx pozitivního výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx četností xxxxxxx v xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx nárůst této xxxxxxxx. Nejdříve xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx hodnocení výsledků xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď.
Zkoušená xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx x xxxxx xxxxxxx považuje za xxxxxxxxxxx.
Xxxxxx většina experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x ojedinělých případech xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný výrok x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx to, xxxxxxxx xx experiment xxxxxxxx.
Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxx mutace x xxxxxxx xxxxx in xxxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x použitých xxxxxxxxxxxxx xxxxxxx xxxxx genové xxxxxx. Reprodukovatelná xxxxxxxxx xxxxxxxxx xxxxxxxx na xxxxxxxxxxx xx velmi xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx za podmínek xxxxxxx xxxxxxxxxx v xxxxxxxxx xxxxxxxxxxxxx buňkách xxxxx genové xxxxxx.
3. XXXXXX
XXXXXXXX X XXXXXXX
Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:
Xxxxxxxxxxxx/xxxxxxxxx:
- xxxxxxxxxx volby rozpouštědla/vehikula,
- xxxxxxxxxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.
Xxxxx:
- xxx a xxxxx xxxxx,
- počet xxxxxxxxx xxxxxx,
- xxxxxxxx xxxxx xxxxxx,
- případně xxxxxx xxxxxxxxx xxxxxxx kultury,
- xxxxxxxxxxxx xxxxxxxxxxx.
Xxxxxxxx podmínky:
- xxxxxxxxxx xxxxxx xxxxxxxxxxx x xxxxx kultur, xxxxxx např. údajů x cytotoxicitě x xxxxxx rozpustnosti, xxxx-xx x xxxxxxxxx,
- xxxxxxx xxxxx, xxxxxxxx koncentrace XX2,
- xxxxxxxxxxx xxxxxxxx xxxxx,
- xxxxx xxxxxxxx x xxxxxxx zkoušené xxxxx,
- inkubační xxxxxxx,
- xxxxxxxxx xxxx,
- délka xxxxxxxx,
- xxxxxxxx xxxxxxx xxxxx xxxxx xxxxxxxx,
- xxx x xxxxxxx xxxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxxxxxx,
- xxxxxxxxx x xxxxxxxxx kontroly,
- délka xxxx xxxxxxx (xxxxxxxx xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx x xxxxxx xxxxx),
- selekční xxxxxxx,
- kritéria klasifikace xxxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx,
- xxxxxx použité x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx xxxxx,
- definice xxxxxxx xxxxx xxxxxxxxx x xxxx (xxxxxxxx xxxxxx xxxxxxxx pro "xxxx" x "velké" xxxxxxx).
Xxxxxxxx:
- xxxxxx toxicity,
- xxxxxx xxxxxxx,
- xxxxx x xX x xxxxxxxxxx během xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxx stanoveny,
- velikost xxxxxxx, xxxx-xx xxxxxxxxxxx, xxxxxxx pro xxxxxxxxx x xxxxxxxxx xxxxxxxx,
- xxxxxxxxx předpoklady xxxxxxxxxx xxxxxxxxx mutanty tvořící xxxx kolonie xxxxxxxx X5178X TK+/-,
- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,
- xxxxxxxx xxxxxxxxxxx xxxxxxx,
- xxxxx x xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx,
- xxxxxxxxx údaje x negativní (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,
- xxxxxxx xxxxxxx.
Xxxxxx xxxxxxxx.
Xxxxxx.
4. LITERATURA
1) Xxxxx, X. X., XxXxxxxx, X. X., XxXxxxxx, X. J., Tindal, X. X. (eds.) (1987), Banbury Report 28; Xxxxxxxxx Cell Xxxxxxxxxxx, Xxxx Xxxxxx Xxxxxx Xxxxxxxxxx, New Xxxx.
2) Xxx, E. X. X., Xxxxxxx X. X. (1968), Xxxxxxxxx Xxxx Xxxxxxxx. XX. Chemical Induction xx Xxxxxxxx Xxxxx Xxxxxxxxx in Xxxxxxx Xxxxxxx Xxxxx Xx xxxxx, Xxxx. Natl. Xxxx. Sci. U. X. X, 61, 1306-1312.
3) Xxxxx, X. X., Xxxxxx, X. X. (1982), Xxxxxxxx Xxxxx xx the Xxxxxxxxx Xxxxxx Xxxxx xx Diploid Xxxxx Xxxxxxxxxxxx, Xxxxxxxx Xxx. 94, 467-485.
4) Xxxxx, X. X., Xxxxxxxxx-Xxxxx, X., Doerr, C. X., Xxxxxxxxx, X. X. (1989), Xxxxxxxxxxxx Xxxxxx Xxxxxxxxxxxx at xxx Mouse Xxxxxxxx XX xxx XXX XXXXX Loci, Mutagenesis, 4, 394-403.
5) Xxxxx, X. X., Xxxxxxxxxx, Xx. X. X., (1989), Xxxxxxxxxx xx xxx XX52/XXXX xxx xxx XXX/XXXX Xxxxxx: Xxxxxxxxxx xx Six Xxxx Xxxxxxxxxx, Mutatation Xxx. 223, 121-128.
6) Xxxxx, X. S., Xxxxxxxxxx, G., Glatt, X. X., Xxxxx, X., Xxxxx, X., Xxxxxxxxxx, Xx. X. X., Xxxxxx, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Gene Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Report. Xxxxxx xx the International Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.
7) Xxxxx, X., Xxxxxxxx, S. X., Marshall, X. X., Xxxxxxxx, M., Xxxxxxx, D., Ashby, X., Xxxx, B. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Culture Xxxxxxxxxx. X xxxxxx xxxx ICPEMC Xxxx Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.
8) Xxxxx, X., XxXxxx, X., Xxxxxxx, X. X. X., Piper, X., Xxxxxxxxx, K. X. (1983), Xxxxxxxx Xxxx Mutations in X5178X Cells xx Xxxxxxx. X Xxxxxx xx the X. X. Environmental Protection Xxxxxx Gene-Tox Program, Xxxxxxxxxx Res., 115, 225-251.
9) Xx, X. X., Xxxxx, X. X., Xxxxxxx, X. X., Xxxxxx, X. X. (1988), A Xxxxxx and Xxxxxxxx xx xxx Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Guanine Xxxxxxxxxxxxxx Transferase System xx Determine xxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx: X Xxxxxx xx Xxxxx XXX xx xxx U. X. Xxxxxxxxxxxxx Protections Xxxxxx Gene-Tox Program, Xxxxxxxxxx Xxx., 196, 17-36.
10) Xx, X. X., Xxxxxx, X. X., Choy, W. X., Xxxx, X. X., Gupta, X. X., Xxxxxxx, K. X., X'Νxxxx, X. X., Xxxxxx, X. X., Xxxxxxxxxx, X. X. Xx., Yang, X. X. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx xx xxx Xxxxxxx Hamster Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Res., 189, 135-141.
11) Xxxxx, X. X., Yandell, X. W., Xxxxxx, X. X. (1989), X Xxxxxxxxxx xx Xxxxxxxx Induction xx xxx TK and XXXX Xxxx xx Xxxxx Lymphoblastoid Xxxxx: Xxxxxxxxxxxx Differences are Xxx xx xx Xxxxxxxxxx Class xx Xxxxxxxxx at xxx Xxxxxxxxx XX Locus, Xxxxxxxxxx Res., 216, 9-17.
12) Stankowski, X. X. Xx., Xxxxxx, X. X., Xxxx, X. W. (1986), Xxxxxxxxxxxx and Molecular Xxxxxxxx xx Ethyl Xxxxxxxxxxxxxxxxx xxx ICR 191-Xxxxxxx Molecular Xxxxxxxx xx Xxxxx Xxxxxxxxxxxxxxxxx xxx ICR 191 Xxxxxxx Xxxxxxxx in XX52 Xxxxx, Mutatation Xxx., 160, 133-147.
13) Xxxxxx, X. T., Xxxxxx, A. X., Xxxxx, X. (1984), Xxxxxxxxx xxx xxx X5178X/XX+/--XX+/- Xxxxx Xxxxxxxx Xxxx Xxxxxxxxxxxx Assay, xx: Kilbey, B. X. xx xx (xxx.) Xxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxx Xxxx, 239-268.
14) Xxxxxx, X. F., Xxxxx, X. M., Xxxxxx, G. X., Xxxxx, X. H. X., Xxxx, X., XxXxxxxx, X. B., Xxxxxxx X. X. (1989), Xxxxxxxxx Cell Xxxx Mutation Xxxxxx Xxxxx xxxx Colony Xxxxxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. J., xx., Xxxxxxxxx Xxxxxxxxxx Press, 66-101.
15) Xxxxxxxxxxxx, X., Xxxxxxx, S., Corti, X., Xxxxxx, X., Xxxxxxxx, N., Mazzaccoro, X. (1977), Xxxxxxxxx xx 6-Xxxxxxxxxxx-Xxxxxxxxx Mutants xx X79 Xxxxxxx Xxxxxxx Xxxxx xx Xxxxx-Xxxxx Microsome-Activated Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Xxx. 46, 365-373.
16) Xxxx, X. X., McCann, X., Xxxxxxxx, E. (1975), Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx the Salmonella/Mammalian-Microsome Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx. 31, 347-364.
17) Xxxxx, X., Xxxxxxx, X. O., Xxxxxxx, X. X. X., Xxxxxx X. X., Xxxxx X. M. X. (1979), Xxxxxxxxxx xxx Characterisation xx xxx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxxxx Xxxxx Xxxxxx, Xxxxx. Xxx. 59, 61-108.
18) Maron, X. X., Xxxx, X. X. (1983), Xxxxxxx Xxxxxxx for the Xxxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Res. 113, 173-215.
19) Xxxxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, C. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-Xxxxxxx X9 in: In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx 7, 175-177.
20) Xxxxxxxxxx, T., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), X Safe Substitute xxx Polycholrinated Xxxxxxxxx x. s. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, X: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, de Xxxxxx, X. X., Fouts, X. R., Xxxx, X. R., Xxxxxxx, X. X. (xxx), Xxxxxxxx, North-Holland, 85-88.
21) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, X. T. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. M. (eds), Xxxxxxxxx Effects xx Xxxxxxxx Agents, Xxx Xxxx, Xxxxxx, 91-103.
22) Xxxxxx, X. X., Xxxxxx, J. X., Xx, A. P., Xxxxxx, X. L. (1983), Xxxxxxxxxx xx xx Exposure Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Gels xxx Xxxxxxxxx Highly Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Mutation Xxxxx, Xxxxxxx. Mutagenesis, 5, 795-801.
23) Xxxxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxx, J. X. (1990), Molecular Xxxxxxxxxx xx Xxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Xxxxx xx Xxxxx Xxxxxxxx Xxxxx, Xxxx. Xxxx. Xxxx. Xxx. U. X. X, 87, 51-55.
24) Moore, M. X., Xxxxx, X., Xxxxxx, J. X., Xxxxxx, B. X., Xxxxxx, A. X., Xxxxxx, X. X., Xxxxxx, J. (1985), Xxxxxxxx of Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (TFT+) Xxxxxxx xx X5178X/XX+/--Xxxxx Lymphoma Xxxxx, Mutatation Xxx. 151, 161-174.
25) Xxxxxxx, X. W., Dryja, X. X., Little, X. X. (1990), Xxxxxxxxx Xxxxxxx Xxxxxxxx xx Recessive Xxxxxxxxx xx x Heterozygous Xxxxxxxxx Xxxxx in Xxxxx Cells, Xxxxxxxxxx Xxx. 229, 89-102.
26) Xxxxx, X. M., Xxxxx, X. L. (1990), Comparison xx Xxxxxxxxxx Xxxxxxxxxx Xxxxxxxxx xxx Small Xxxxxx XX-Xxxxxxxxx Xxxxxx Xxxxxxxxx xx X5178X/XX+/- 3.7.2C Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxxx, 5, 609-614."
XXXXXXX 4X
"X.23 XXXXXXX XX XXXXXXXXXXXX ABERACE XX SPERMATOGONIÍCH SAVCŮ
1. XXXXXX
Xxxx xxxxxx je xxxxxxxx xxxxxx OECD XX 483 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1997).
1.1 XXXX
Xxxxxx xxxxxxx xx chromozomové xxxxxxx ve xxxxxxxxxxxxxxx xxxxx xx vivo xx xxxxxxxxxxxxx takové xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Rozlišují xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x chromatidové. U xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx se xxxxxx vyskytují. Xxxx xxxxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a není x xxxxxx xxxxx xxxxxxx používána. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x člověka.
Touto xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx změny xx xxxxxxxxxxxxxxx x xxxxxxxxxxx xx xxxx, že xxxx zkouška xxxxxxxx xxxxxxxxx indukce xxxxxxxxx xxxxxx v germinálních xxxxxxx.
X xxxx zkoušce xxxx rutinně xxxxxxxxx xxxxxxxx. Touto xxxxxxxxxxxxxx xxxxxxxx in vivo xx detekují xxxxxxxxxxxx xxxxxxx při xxxxxx xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx nejsou xxxxxxxxx xxxx xxxxxxx.
Xxx xxxxxxx xxxxxxx xxxxxxxxxxxxxx typu xx xxxxxxxxxxxxxxx xx xxxx xxx — xxxxx xxx dojde xx ztrátě xxxx — vyšetřeno xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx xx xxxxxxxx. Xxxxx xxxxxxxxx x exponovaných spermatogoniálních xxxxxxxxx buněk xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx aberací xxxxxxxxxxxxxx xxxx v xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx stávají xxxxxxxxxxxx.
Xxxx xxxxxxx in xxxx xx xxxxxxxx xxx vyšetření, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxx x germinálních buňkách. Xxxxx je xxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx vivo, xxxxxxxxxxxxxxx x procesy xxxxxxxx XXX.
Xx xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxxxx xx xxxxxxxx xxxxxxxx látce. Xxxxxxxxxx aberace tedy xxxxxxxxxxx xxxxxxxxx odpověď xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. V xxxxxxxxxx xx své xxxxxx xx xxxxxxxxx, xxxxx xxxx xxxxxx xxx xxxxx generace xxxxxxxxxxxxx xxxxxxxxxx celkovému xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx xxxxx x xxxxxxx mezi xxxxxxx xxxxxx x xxxxxxx.
Xxxxxxxx existuje xxxxx x xxx, že xx zkoušená xxxxx xxxx reaktivní metabolity xxxxxxxxxx xx cílové xxxxx, není xxxxxx xxxx xxxxxxx použít.
Viz xxxx obecný úvod, xxxx X.
1.2 XXXXXXXX
Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx zlomu xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x opětného xxxxxxx xxxxxxxxx.
Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx a xxxxxxx xxxx xxxxxxxxx x tomtéž xxxxx.
Xxx : xxxxxxxxxxxx léze xxxxx než xxxxx xxxxx xxxxxxxxxx x x minimální xxxxxxxxx xxxxxxxxx.
Xxxxxxxxx xxxxxxx : xxxxxxxx počtu xxxxxxxxxx xx xxxxxxxx xxxxxxx x xxxxxxxxx xxxxx.
Xxxxxxxxxxx : násobek haploidního xxxxx xxxxxxxxxxxxxx xxx (x), xxxx než xxxxxxxxx (xx. 3 x, 4 x xxx.).
Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx ve xxxxxx metafáze xxx xxxxxxxxxxx, xxxx se xxxx xxxxxx x xxxxxxxxx, intrachromozomální xxxx xxxxxxxxxxxxxxxxxx xxxxx.
1.3 XXXXXXXX XXXXXXXX XXXXXX
Xxxxxxx jsou xxxxxxx xxxxxxxx exponována xxxxxxxx xxxxx x xx xxxxxx xxxx xx expozici xxxxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx xxxx Colcemid®). X germinálních buněk xx xxxx připraví xxxxxxxxx xxxxxxxxxx, xxxxxx xx a xxxxxxxxx xx chromozomové xxxxxxx xxxxxxxxxxxxxx xxxxx.
1.4 XXXXX XXXXXXXX XXXXXX
1.4.1 Xxxxxxxxx
1.4.1.1 Xxxxx druhu xxxxxxx
Xxxxx xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx x xxxx; xxx však xxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.
1.4.1.2 Xxxxxxxx xxxxx x xxxxxx
Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx X, xxxxxxx by mělo xxx xxxxxxxx xxxxxxxx xxxxxxx 50 – 60 %.
1.4.1.3 Příprava xxxxxx
Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, xxxxx xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx započetím xxxxxx xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.
1.4.1.4 Xxxxxxxx xxxxx
Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx zkoušené xxxxx xxxxx být xxxxxxxx xxxxx nebo xxxxx xxx xxxx xxxxxxx xxxxxxx. Měly by xxx použity čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.
1.4.2 Xxxxxxxx xxxxxxxx
1.4.2.1 Rozpouštědlo/vehikulum
Rozpouštědlo/vehikulum xx xxxxxx mít xxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxx účinky x xxxx by být xxxxxxxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx xxxxxx. Jsou-li použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.
1.4.2.2 Kontroly
Součástí xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly. X xxxxxxxx aplikace xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx proces xxxx xxxxxxx ve xxxxxxxxx, v nichž xxxxx x xxxxxxxx.
Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx aberace xx xxxxxxxxxxxxxxx in xxxx při xxxxxxxxxxx xxxxxxxx, x xxxxx xx předpokládá, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.
Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx aby xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx způsobem xxx xxxxxxxx látka x xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxx xxx xxxxx xxxxx v úvahu xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx látek xxx xxxxxxxxx kontrolu:
|
Látka |
Číslo XXX |
Xxxxx podle Xxxxxx |
|
xxxxxxxxxxxxx |
50–18–0 |
200–015–4 |
|
xxxxxxxxxxxxx xxxxxxxxxx |
6055–19–2 |
|
|
xxxxxxxxxxxxxx |
108–91–8 |
203–629–0 |
|
xxxxxxxxx C |
50–07–7 |
200–008–6 |
|
akrylamid (xxxxxxx) |
79–06–1 |
201–173–7 |
|
2,4,6-xxxx(xxxxxxxx-1-xx)-1,3,5-xxxxxxx |
51–18–3 |
200–083–5 |
X xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx rozpouštědlo xxxx xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx stejný xxxxxx xxxx exponované xxxxxxx, pokud xxxxxx x xxxxxxxxxxx kontrolních xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx o xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx dosud xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.
1.5 XXXXXX
1.5.1 Xxxxx zvířat
Každá exponovaná x xxxxxxxxx xxxxxxx xxxx zahrnovat alespoň xxx xxxxxxxxxxxxxxxx xxxxx.
1.5.2 Xxxx expozice
Zkoušené xxxxx xx xxxx být xxxxx xxxxx xxxxxxxx xxxxxxxxxxx nebo nadvakrát (xx. při jedné xxxxxxxx nebo dvou xxxxxxxxxx). Zkoušené látky xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, tzn. xxx xxxxx x xxx xxx v rozmezí xx více než xxxxxxxx xxxxx, aby xxxx xxxxxxxxx podávání xxxxxxx xxxxxx xxxxxxxxx. Xxxx režimy xxxxxxxx xx xxxx být xxxxxxx zdůvodněny.
Ve skupině x nejvyšší dávkou xx xxxx xxx xx xxxxxxxx xxxxxxxxx xxx odběry. Poněvadž xxxxxxxx buněčného cyklu xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, provede xx xxxxx xxxxx xxxxx x xxxxx xxxxxxxx xxxxx přibližně 24 a 48 xxxxx po xxxxxxxx. X xxxxxxx xxxx xxx xxxxxxxx xxxxx xx xxx xxx xxxxx xxxxxxxx xx 24 xxxxx nebo xx xxxxxx xxxx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx xxxx xxxxx xxxx xxxxxxxxx xxxx xxx xxxxxxx xxxxxx (6).
Xxxxx xxxxx xxx xxxxxx provedeny xxxx v xxxx xxxx. Například x xxxxxxx xxxxxxxxxx látek, xxxxx xxxxx indukovat xxxxxxxx replikace (lagging) xxxxxxxxxx nebo xxxxx xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx xxx xxxxxxxxx xxxxxxxx xxxxx (1).
Vhodnost xxxxx xxxxxxxxx xxxxxxxx xxxx být xxxxxx xxxxxx od případu. X případě xxxxx x opakovanou expozicí xx xxxx xxx xxxxxxx usmrcena 24 xxxxx (1,5xxxxxxx délky xxxxx) xx xxxxxxxx xxxxxxxx. Xxxxx xxxxxxx xxxxx být xxxxxxxxx xxxxx xxxxxx x xxxx xxxx.
Xxxx xxxxxxxxx xx zvířatům xxxxxxxxxxxxxxxxx xxxx vhodná xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx vhodné xxxx xxxxxxx u xxxxxx xxxxx. X xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 xxxxx; x xxxxxx xxxxxxxx xx xxxx xxxx přibližně 4 — 5 xxxxx.
1.5.3 Xxxxxxxxx
Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx údajů xxxxxx xxx zjištění rozsahu, xxxx xx xxx xxxxxxxxx ve stejné xxxxxxxxxx, xx xxxxxxx xxxxxx x xxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxxxx xx xxxxxxx v xxxxxx xxxxxx (7). X případě xxxxxxxx xx pro první xxxxx xxxxxxx xxx xxxxxx dávky. Tyto xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx maximální a xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx nejvyšší xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, že xx xxxxx xxxxx vedly xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx.
Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx netoxických xxxxxxx (xxxx. hormony x mitogeny) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx a měly xx být xxxxxxxxx xxxxxx xx případu. Xxxxxxxx xxxxx může xxx xxxx definována xxxx xxxxx xxxxxxxxxxxx xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx toxicity (xxxx. xxxxxxx počtu spermatogonií x xxxxxx xxxxxxxx x první x xxxxx meiotické xxxxxxxx; xxxx xxxxxxx by xxxxxx xxxxxxxxx 50 %).
1.5.4 Xxxxxxx zkouška
Jestliže xxxxxxx s xxxxxx xxxxxx xxxxxxx 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx se úplná xxxxxx xx xxxxx xxxxxxxx dávky za xxxxxxxxx. Očekávaná xxxxxxxx xxxxxxx xxxx znamenat xxxxxxx xxxxxx v xxxxxxx xxxxxxx xxxxx xxxxxx dávky.
1.5.5 Xxxxxxxx xxxxx
Xxxxxxxx xxxxx xx xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx intubační kanylou, xxxx intraperitoneální xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx přijatelné, xxxx-xx xxxxxxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx může xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, musí xxx xxxxxxxxxx. Xx na xxxxxxxx a xxxxxx xxxxx, xxxxx xxxxxxx xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx všech xxxxxxxx xxxxx.
1.5.6 Xxxxxxxx xxxxxxxxx xx analýzu xxxxxxxxxx
Xxxxx xx xxxxxxxx xx x jednoho xxxx xxxx varlat získá xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx x fixuje. Xxxx xx xxxxxx xx xxxxxxxx xxxxxxx x xxxxxx xx.
1.5.7 Xxxxxxx
X xxxxxxx zvířete xx xxxx být xxxxxxxxxxx xxxxxxx 100 xxxxx v xxxxx xxxxxxxxxxxx metafázi (xx. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Xxxxx xxxxx lze xxxxxx, xx-xx xxxxxxxxx velký xxxxx xxxxxxx. Všechny xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx xxx fixaci xxxxx dochází xx xxxxxxxxxxxxxx xxxxxx nebo xxxxxx xxxxxxxxxx x xxxxx xxxxxxxx, měly xx xxxxxxxxxxx buňky xxxxxxxxx centromery v xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.
2. ÚDAJE
2.1 XXXXXXXXXX XXXXXXXX
Xxxxx xxx xxxxxxxxxx xxxxxxx by měly xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx každé zvíře xx xxx xxx xxxxxxxxxx xxxxx buněk xx xxxxxxxxxxxx chromozomovými xxxxxxxxx x počet xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx být xxxxxxx xxxxx typy xxxxxxxxxxxx chromozomových xxxxxxx x xxxxxx počtem x četností. Gapy xx xxxxxxxxxxxxx xxxxxxxx x uvádějí xx, xxx xxxxxx xx xxxxxxxxxx do celkové xxxxxxxx xxxxxxx.
Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, xxx xx xxx pro xxxxxxxxx xxxxxxx xxxxxxxxxxxxx xxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxxxx x všech xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx jako xxxxxxxxx xxxxxxxx poměr xxxxxxxxxxxxx x xxxxxx xxxxxxxx k xxxxx x druhé xxxxxxxxx xxxxxxxx, a to x xxxxxxxx xxxxxx 100 dělících se xxxxx xx xxxxx xxxxx. Xxxxx xx xxxxxxxxx xxxxx xxxxxx, xxxxxxx x 1000 xxxxxxx xx zvíře xx měl xxx xxxxxxxx xxxxxxxxx xxxxx.
2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX
Xxx stanovení pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx xx xxxxx xxxx xxxxx nárůst xxxxx xxxxx x xxxxxxxxx xxx skupinu x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Nejdříve xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (8). Statistická xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.
Xxxxxxxx látka, xxxxx výsledky xxxxxxxxx xxxx uvedená xxxxxxxx, xx v tomto xxxxxxx xxxxxxxx xx xxxxxxxxxxx.
Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx xxxxxxxxx xxxxxxxx, x ojedinělých případech xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx opakován.
Pozitivní xxxxxxxx zkoušky xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx savců xx xxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x germinálních buňkách xxxxxxxxxxx xxxxx strukturní xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx látka xx xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxx buňkách xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.
Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx xxxx její xxxxxxxxxx dostanou xx xxxxxx xxxxx.
3. XXXXXX
XXXXXXXX X ZKOUŠCE
Protokol x xxxxxxx xxxx xxxxxxxxx xxxx informace:
Rozpouštědlo/vehikulum:
- zdůvodnění xxxxx xxxxxxxx,
- rozpustnost x xxxxxxx xxxxxxxx xxxxx x rozpouštědle/vehikulu, xx-xx xxxxx.
Xxxxxxxxx xxxxxxx:
- xxxxxxx xxxx/xxxx,
- xxxxx x stáří xxxxxx,
- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,
- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx zkoušky, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.
Zkušební podmínky:
- xxxxx ze xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx xxxx xxxxxxxxx,
- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,
- xxxxxxxxxx xxxxxxx xxxxxxxx,
- údaje o xxxxxxxx zkoušené xxxxx,
- xxxxx x podávání xxxxxxxx látky,
- xxxxxxxxxx xxx xxxxxxxx,
- případně xxxxxxxx mezi xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx nebo vodě (xxx) na xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),
- podrobné xxxxx x kvalitě xxxxxx x vody,
- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x odběru,
- metody xxxxxxxxx toxicity,
- identifikace xxxxx xxxxxxxxxxx metafázi, xxxx xxxxxxxxxxx a xxxxx xxxxxxxx,
- xxxxxx xxxxxxxx xxxxxxxxx,
- kritéria xxxxxxxxx xxxxxxx,
- xxxxx xxxxxxxxxxxxx buněk xx xxxxx xxxxx,
- xxxxxxxx xxxxxxxxxxx studie na xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.
Xxxxxxxx:
- známky xxxxxxxx,
- xxxxxxxxx xxxxx,
- xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x první x druhé xxxxxxxx xxxxxx,
- typ a xxxxx xxxxxxx uvedený xxxxxxxxxx xxx xxxxx xxxxx,
- xxxxxxx xxxxx xxxxxxx xx xxxxxxx,
- xxxxx xxxxx x xxxxxxxxx xx skupině,
- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,
- xxxxxxxx xxxxxxxxxxx xxxxxxx,
- xxxxx x xxxxxxxx xxxxxxxxx kontrole,
- dosavadní xxxxx x negativní xxxxxxxx x rozpětími, xxxxxxxxx hodnotami x xxxxxxxxxxxx odchylkami,
- xxxxx x xxxxxxxx pozitivní xxxxxxxx,
- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx.
Xxxxxx xxxxxxxx.
Xxxxxx.
4. LITERATURA
1) Adler, X. X., (1986), Xxxxxxxxxxx Potential xx Xxxxx Spermatogonia xx Xxxxxxxx Xxxxxxxx Xxxxxxx xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx xx Environmental Xxxxxxxxx, Xxxx X: Xxxxxxx Xxxxxxx and Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Lambert, B., Xxxxxxxxx, J. (xxx) Xxxx, Xxx Xxxx, 477-484.
2) Adler, X. X., (1984), Xxxxxxxxxxx xxxxx xx Mammals, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, (xx.) X. Xxxxxx, X. M. Xxxxx, XXX Press, Xxxxxx, Xxxxxxxxxx XX, 275-306.
3) Xxxxx, X. P., Xxxxxxx, G., Xxxx, X. E. (1964), Xx Air-drying Method xxx Xxxxxxx Xxxxxxxxxxxx xxxx Xxxxxxxxx Testes, Xxxxxxxxxxxx Xxxx Xxxxxxxx, 3, 289-294.
4) Xxxxxxx, X., Ashby, J., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Cytogenetic Assays, xx: X. J. Xxxxxxxx (ed.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx on Guidelines xxx Xxxxxxxxxxxx Testing. Xxxxxx. Xxxx I xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, New Xxxx, Port Xxxxxxx, Xxxxxxxxx, Sydney, 115-141.
5) Xxxxxxxx, K., Kikuchi, X. (1978), X Xxx Xxxxxx xxx Xxxxxxxxxxx of Xxxxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx, Mutatation Xxx., 52, 207-209.
6) Xxxxx, I. D., Xxxxxx X. D., Xxxxxxx, J., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx N. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Standardisation xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Report of xxx Xxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.
7) Xxxxxxx, R. X., Xxxxx, J. A., Xxxxxx, X. X., Xxxxxx, P. X., Xxx, X., Xxxxxxx, X. X., Gatehouse, X. G., Xxxxxx-Xxxxxx, X., Morton, X. X., Xxxxxxxx, D. X., Xxxxxxx, X. (1992), Report of Xxxxxxx Toxicology Society/UK Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Group: Xxxx Xxxxxxx xx In xxxx Mutagenicity Assays, Xxxxxxxxxxx, 7, 313-319.
8) Xxxxxx, X. X., Xxxxxxxx, X., Albanese, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, R., Richold, X., Papworth, X. X., Savage X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx vivo Xxxxxxxxxxx Xxxxxx, in: D. X. Kirkland (xx.), Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Test Data. XXXXX Subcommittee xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."
XXXXXXX 4X
"X.39 ZKOUŠKA XX XXXXXXXXXXXX XXXXXXX XXX (UDS) X XXXXXXXXX BUŇKÁCH XXXXX XX XXXX
1. XXXXXX
Xxxx xxxxxx je xxxxxxxx xxxxxx XXXX TG 486 — Xxxxxxx xx neplánovanou xxxxxxx XXX (XXX) x xxxxxxxxx xxxxxxx xxxxx xx xxxx (1997).
1.1 XXXX
Xxxxxx xxxxxxx na xxxxxxxxxxxx syntézu XXX (XXX) v xxxxxxxxx xxxxxxx xxxxx in xxxx xx identifikovat xxxxxxxx látky, xxxxx xxxxxxxx xxxxxxxx DNA x xxxxxxxxx buňkách xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).
Xxxx xxxxxxx in xxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxx. Xxxxxxxxxxx xxx je xxxxxxxxxx xxxxxxxxx DNA x xxxxxxxx xxxxxxxx x xxxxxxxxx buňkách. Xxxxx xxxx xxxxxxx xxxxxxx xxxxxx, kde xxxx absorbované xxxxxxxxxx xxxxxxxxxxxxxx. Xxxx tedy xxxxxxx xxxxxx xxx xxxxxxxxx míry poškození XXX in xxxx.
Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx nedostane xx cílové tkáně, xxxx xxxxxx tuto xxxxxxx použít.
Rozsah neplánované xxxxxxx XXX (XXX) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx nukleosidů xx xxxxx, xxxxx xxxxxxxx plánovanou syntézou XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx je xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx xxxxxxx xx XXX xx vivo xx přednostně používají xxxxx xxxxxxx. Xxxx xxxxx xxx xxxxx xxxxx xxx xxxxxx xxxxxxx, xxxxxx však xxxxxxxxx xxxx metody.
Detekce xxxxxxxx UDS závisí xx xxxxx bází XXX xxxxxxxxxxx x xxxxxxxxxxx x xxxxx xxxxxxxxx. Zkouška xx XXX xx xxxx xxxxxx xxxxxxx xxx xxxxxxx dlouhých xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 xxxx) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("xxxxx-xxxxx repair") (xxxxx až xxx xxxx) xxxx xxxxxxx xxxx detekovány x xxxxxx menší xxxxxxxxxx. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx reparace, xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxxxx lézí XXX xxxxx x mutagenním xxxxxxxxx. Xxxxxx xxxxxxxx XXX xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxxxx procesů. Xxxxx xx možné, že xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX není opraveno xxxxxxxxxxx xxxxxxxx. Nedostatek xxxxxxxxxxxx informací, xxxxx xxxx xxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxx, xx xxxxxxx potenciální xxxxxxxxxx xxxxxx xxxx, xxxxx xx xxxxxxxxxx x celém xxxxxx.
Xxx xxxx obecný xxxx, xxxx X.
1.2 DEFINICE
Opravované xxxxx : xxxxx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx jádrům (XXX), xxxxx xxx xxxxxxxxxx xxxxxxx stanovená laboratoří xxxxxxxxxxx xxxxxxx.
Xxxxx počet xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx xxxxx x xxxxxxxxxxxxxxxxx zkoušce xx XXX, vypočtená xxxxxxxxx xxxxxxxxxx xxxxx xxx x cytoplasmatických oblastech (XX) odpovídajících xxxxxx xx xxxxx zrn xxxxxxxxxxxxxx buněčným jádrům (XX): XXX = XX — XX. Xxxxxxx XXX xx xxxxxxx xxx xxxxxxxxxx xxxxx, xxxx xxxxxxxx xxx xxxxx x xxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxx.
Xxxxxxxxxxx syntéza XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx úseku DNA xxxxxxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.
1.3 PODSTATA ZKUŠEBNÍ XXXXXX
Xxxxxxx xx UDS x xxxxxxxxx xxxxxxx xxxxx in vivo xxxxxxxx xxxxxxx xxxxxxxx XXX po xxxxxxxxx x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx látkami nebo xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx obvykle xxxxxxxx xx xxxxxxxxxxx 3X-XxX xx DNA xxxxxxxxx xxxxx, kde xx xxxx xxxxxxx xxxxx x X-xxxx xxxxxxxxx xxxxx. Xxxxxxxxxxx 3X-XxX xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx tato xxxxxxxx xxxx xxx xxxxxxx na vliv X-xxxx xxxxx xxxx xxxx. xxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx.
1.4 POPIS METODY
1.4.1 Xxxxxxxxx
1.4.1.1 Výběr druhu xxxxxxx
Xxxxx xx xxxxxxxx xxxxxx, ačkoli lze xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Měly xx xxx xxxxxxx xxxxx xxxxxxxxx laboratorní xxxxx mladých xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx by xxxx xxx xxxxxxxx v xxxxxxxxx zvířat minimální x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx xxx obě xxxxxxx.
1.4.1.2 Xxxxxxxx xxxxx x xxxxxx
Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x části X, přičemž by xxxx xxx dosaženo xxxxxxxx vzduchu 50 - 60 %.
1.4.1.3 Xxxxxxxx xxxxxx
Xxxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, která xx exponuje. Klece xx xxxx být xxxxxxxxxx xxx, aby xxx vliv jejich xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx jednoznačně xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx xx xxxxxxx x laboratorních podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.
1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx
Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx zvířatům xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou xxx podávány xxxxx xxxx xxxxx xxx xxxx podáním zředěny. Xxxx xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx látky, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.
1.4.2 Xxxxxxxx xxxxxxxx
1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx
Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx použitých xxxxxxxx dávek xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx reaguje xx xxxxxxxxx látkou. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx xxxxxx xxxxxxx xxxxx možno vodných xxxxxxxxxxxx/xxxxxxx.
1.4.2.2 Kontroly
Součástí xxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxx pozitivní x negativní (rozpouštědlo/vehikulum) xxxxxxxx. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx měla zvířata xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxx xx xxxxxxxxx, x nichž dojde x xxxxxxxx.
Xxxxxxxxxxx xxxxxxxxxx xx měly být xxxxx, x nichž xx xxxxx, xx xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxxxxxx koncentracích xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Xxxxxxxxx kontroly xxxxxxxxxx metabolickou aktivaci xx xxxx být xxxxxxx v dávkách xxxxxxxxxxxx xxxxxx odpověď (4). Xxxxx mohou xxx xxxxxxx xxx, xxx xxx účinek xxxxxxxx, xxx aby xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxx xxx pozitivní xxxxxxxx:
|
Xxxx xxxxxx |
Xxxxx |
Xxxxx XXX |
Xxxxx xxxxx Einecs |
|
Časné doby xxxxxx (2 xx 4 h) |
N-nitrosodimethylamin |
62–75–9 |
200–249–8 |
|
Pozdní xxxx xxxxxx (12 až 16 x) |
X-(xxxxxxx-2-xx)xxxxxxxx (2-AAF) |
53–96–3 |
200–188–6 |
Mohou xxx xxxxxxx také xxxx látky xxx xxxxxxxxx xxxxxxxx. Xx xxxxxxxxx, xxx byla xxxxxxxxx kontrolní xxxxx xxxxxxxx xxxxx xxxxxxxx, xxx xxxxxxxx xxxxx.
1.5 XXXXXX
1.5.1 Počet x xxxxxxx zvířat
Měl by xxx xxxxxx xxxxxxxxxx xxxxx xxxxxx, aby xxxx xxxxxxxxxx přirozené xxxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx. Každá xxxxxxx by xx xxxx xxxxxxx xxxxxxx xx xxx xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx jsou xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, je xxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx skupiny xxxxxxxx xxxxx jedno až xxx xxxxxxx.
Xxxxxxxx xxxx x době xxxxxx x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx a xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x toxicitě, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx pro určité xxxxxxx, xxxx xx xxxx například u xxxxxxxxx farmaceutických xxxxx, xxxx by xxx xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.
1.5.2 Xxxx xxxxxxxx
Xxxxxxxx látky xxxx xxxxxxxxx podávány xxxxxxxxxxx.
1.5.3 Xxxxxxxxx
Xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxxxx očekávání xxx xxxxxxx režimu xxxxxxxxx k letalitě. Xxxxx dávka xx xxxx být xxxxxxxxx 50 % xx 25 % xxxxx xxxxx.
Xxxxx se xxxxxxxxxxx xxxxxxxxxxx aktivitou při xxxxxxx netoxických xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx kritériím xxxxxxxxx xxxxx vyhovovat x xxxx by xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxx-xx xx xxxxx neexistenci xxxxxxxx dostupných xxxxx xxxxxx xxx xxxxxxxx xxxxxxx, měla xx xxx xxxxxxxxx xx xxxxxx laboratoři, xx xxxxxxx xxxxxx, kmenem, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx xxxxxx.
Xxxxxxxx xxxxx může xxx xxxxxxxxxx xxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxxxx x xxxxxxx (xxxx. xxxxxxxxxx xxxxx).
1.5.4 Xxxxxxx zkouška
Jestliže zkouška x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx dávkách x jednom xxx xxxxxxxxxx žádné pozorovatelné xxxxxxx xxxxxx x xxxx-xx na základě xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx xxx xxxxx xxxxxx nezbytná. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.
1.5.5 Xxxxxxxx dávek
Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou intubační xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxx, xxx-xx xx zdůvodnit. Xxxxxxxx intraperitoneálně xx xxxx nedoporučuje, xxxxx xx játra mohla xxx exponována xxxxxxxx xxxxx xxxxx x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx je xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx a žíravé xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx účinky, xx xxxx xxx xxxxxxxxxxx zkušebního xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx xxxxx xxxxxxxx xxxxx.
1.5.6 Příprava xxxxxxxxx xxxxx
Xxxxxxx xxxxx xx xxxxxxxxxx z xxxxxxxxxxxx xxxxxx zpravidla 12 xx 16 xxxxx xx xxxxxx xxxxx. Xxxxxxxxxx xxxxxxxx odebrání xxxxxx (obecně dvě xx xxxxx xxxxxx xx xxxxxxxx) xx xxxxxxxx, xxxx-xx xx 12 až 16 xxxxxxxx jasná xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx použity jiné xxxx xxxxxx, xxxx-xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx xxxxx.
Xxxxxxxxxx kultury xxxxxxxxx xxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxx jater kolagenasou xx xxxx x xxxxxx xx, xxx xx čerstvě disociované xxxxxxx buňky xxxxxxxxx xx xxxxxxx povrchu. Xxxxxxx buňky z xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.
1.5.7 Xxxxxxxxx XXX
Xxxxxxx xxxxxxxxx jaterní buňky xxxxx xx xxxxxxx xxxxxxx xxxx, xxxx. xxx xx xxx xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3X-XxX. Xx konci xxxxxxxxx xxxx xx xxxx xxx xxxxxx z xxxxx xxxxxxxxxx a xxxxx poté mohou xxx inkubovány x xxxxxx xxxxxxxxxxx přebytek xxxxxxxxxxx thymidinu, xxx xxxx xxxxxxx neinkorporovaná xxxxxxxxxxxxx ("cold chase"). Xxxxx xx xxxx xxxxxxx, fixují x xxxxxx. Xxx delší xxxxxxxxx době xxxxxx xxx xxxxxxx radioaktivity xxxxxxxx. Xxxxxxxxx se xxxxxx xx xxxxxxxxxxxxxxxxx xxxxxx, xxxxxxxx xx x xxxxx (např. x chladu 7 xx 14 dnů), xxxxxxxx xx, xxxxxx x xxxxxxxxx se xxxxxxxxxx zrna xxxxxxx. X xxxxxxx zvířete xx xxxxxxxx xxx xx xxx xxxxxxxxx.
1.5.8 Xxxxxxx
Xxxxxxxxx by měly xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx, xxx xxxx xxxxxxxxx XXX xxxxxxxxx hodnotu. Xxxxxxxxx xx xxx xxxxxxxxxxx prohlédnou xx xxxxxx zjevné cytotoxicity (xxxx. na xxxxxxx, xxxxxxxx úroveň xxxxxxx xxxxxxxxxxxxx xxxxxxxx).
Xxxx počítáním xxx by xxxx xxx xxxxxxxxx xxxxxxxx. Xxxxxxxxx xx vyšetřuje 100 buněk xx xxxxx xxxxx alespoň xx xxxx xxxxxxxxx; xxxxxxxxx xxxx xxx 100 xxxxx/xxxxx xx xxxx být xxxxxxxxxx. Xxx počítání xxx xx xxxxx x X-xxxx xxxxxxxxxxx, ale xxxxx xxxxx x X-xxxx xxxx xxx xxxxxxxxxx.
Xxxxxxxx 3X-XxX xxxxxxxxxxxxxxx xx xxxxx a xxxxxxxxxx xxxxxxxxxxxx normálních xxxxx doložené xxxxxxxxxxx xxx xxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxx metodou.
Počet buněk xx stanoví x xxxxx zrn odpovídajících xxxxxxxx jádrŭm (xx) x z xxŭxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (cg) xxxxxxxxxxxxxx jádrŭm. xxxx xxxxxxx xx se xxxxxxx xxx xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx oblast cytoplasmy, xxxx xxŭxxxxx hodnota xxxx až xxx xxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxx. xx xxxxxxxxxxxxx xxXxxxxxxx mohou xxx xxxxxxx x xxxx postupy xxxxxxxxx xxxxx xxxxx (xxxx. xxxxxxxx xxxxxx xxxxx) (6).
2. ÚDAJE
2.1 XXXXXXXXXX XXXXXXXX
Xxxx xx xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx a xxxxxxx. Xxxxx by xxxx být xxxx xxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxx hodnoty XX xx hodnoty XX xx xxx xxx vypočten xxx xxxxxx xxxxx, xxx xxxxx xxxxx a xxx každou xxxxx x xxx xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (NNG). Xxxxxxxx jsou xxxxxxxx "xxxxxxxxxx" xxxxx, měla xx xxx xxxxxxxx xxx definování "xxxxxxxxxxxx" xxxxx xxxxxxxxxx x xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx výsledky mohou xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx xxx xxxxxxx, xxxx xx xxx statistické testy xxxxxxx x xxxxxxxxxx xxxx provedením xxxxxx.
2.2 XXXXXXXXX A INTERPRETACE XXXXXXXX
Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx odpověď xxxxx:
|
xxxxxxxxx |
x) |
xxxxxxx XXX xxxx nad xxxxxxxx xxxxxx, která xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxx; |
|
xxxx |
xx) |
xxxxxxx XXX xx xxxxxxxx xxxxx než xxxxxxx xxx xxxxxxxxx xxxxxxxx; |
|
xxxxxxxxx |
x) |
xxxxxxx XXX xxxx xx xxxxxxxxx prahové xxxxxxx nebo pod xx; |
|
xxxx |
xx) |
xxxxxxx NNG xxxx xxxxxxxx vyšší než xxxxxxx xxx souběžnou xxxxxxxx. |
Xxxx xx xxx xxxxxxxxx biologická relevance xxxxx, xx. měly xx být xxxxx x xxxxx parametry, xxxx xxxx variabilita xxxxxx, xxxxx dávky x xxxxxxxx x xxxxxxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx prostředek statistické xxxxxx. Statistická xxxxxxxxxx xx xxxx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx.
Xxxxxx většina experimentů xxxxxxxx jasně pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.
Xxxxxxxxx xxxxxxxx xxxxxxx xx XXX x xxxxxxxxx xxxxxxx savců xx xxxx znamenají, že xxxxxxxx látka xxxxxxxx x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxxx DNA, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx XXX xx xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx XXX, xxxxx lze xxxxxxxxx xxxxx xxxxxxxx.
Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx zkoušená xxxxx xxxxxxx xx krevního xxxxx xxxx. xx xxxxxx tkáně (xxxx. xxxxxxxxx toxicita).
3. XXXXXX
XXXXXXXX X XXXXXXX
Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:
Xxxxxxxxxxxx/xxxxxxxxx:
- zdůvodnění xxxxx vehikula,
- xxxxxxxxxxx x xxxxxxx zkoušené xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.
Xxxxxxxxx zvířata:
- xxxxxxx xxxx/xxxx,
- xxxxx, xxxxx x xxxxxxx xxxxxx,
- xxxxx, xxxxxxxx xxxxx, strava atd.,
- xxxxxxxxxxxx xxxxxxxx zvířat xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx každou skupinu.
Zkušební xxxxxxxx:
- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,
- xxxxx xx xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx xxxx xxxxxxxxx,
- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,
- xxxxx x xxxxxxxx xxxxxxxx látky,
- xxxxx x xxxxxxxx xxxxxxxx xxxxx,
- xxxxxxxxxx xxxxxxx podávání,
- xxxxxxxxx xxxxxx ověření, zda xx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx nebo xx xxxxxx xxxxx,
- případně xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx látky x xxxxxx xxxx vodě (xxx) xx odpovídající xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),
- xxxxxxxx xxxxx x kvalitě xxxxxx x xxxx,
- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x odběru,
- metody xxxxxxxxx xxxxxxxx,
- metody xxxxxxxx a kultivace xxxxxxxxx xxxxx,
- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,
- xxxxx xxxxxxxxx a xxxxx xxxxxxxxxxx xxxxx,
- kritéria xxxxxxxxx,
- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.
Xxxxxxxx:
- xxxxxxx xxxxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx x xxxxx xxx xxxxxxxxxxxxxx cytoplasmě, x xxxxx počet xxx, xxxxxxxxxx pro xxxxxxxxx, xxxxxxx a xxxxxxx,
- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,
- případné xxxxxxxxxxx xxxxxxxxx,
- známky toxicity,
- xxxxx x xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx,
- dosavadní xxxxx o xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx hodnotami x xxxxxxxxxxxx xxxxxxxxxx,
- xxxxx xxxxx "xxxxxxxxxxxx" xxxxx, xx-xx stanoven,
- počet xxxxx x X-xxxx, xx-xx stanoven,
- životaschopnost xxxxx.
Xxxxxx xxxxxxxx.
Xxxxxx.
4. XXXXXXXXXX
1) Xxxxx, X. Xxxxxxx, X. A., Burlinson, X., Xxxxxx, X. X. (1985), Xx Xxxxxxxxxx xx the Xx xxxx Xxx. Xxxxxxxxxx XXX Repair Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.
2) Xxxxxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, E., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, G., Xxxxxxxx, G. (1987), X Xxxxxxxx and Xxxxx for xxx Xx vivo Xxx Xxxxxxxxxx DNA Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 123-133.
3) Kennelly, X. X., Xxxxxx, X., Ashby, X., Xxxxxxx, P. X., Xxxxxxxxx, X., Xxxxxxx, X. J., Xxxx, X. X., Xxxxxxxx, X. de X. (1993), Xx xxxx Xxx Xxxxx UDS Xxxxx, xx: Xxxxxxxx X. X., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Tests: UKEM Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx. Part II xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 52-77.
4) Xxxxx, S., Xxxx, X. X., Xxxxxx, X., Xxxxxxxxx. X., Xxxxxxxxx, B., Xxxxxxxxx, X. X., Xxxxxxxx, X., Hertner, X., XxXxxxx, C. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx the Xxxxxxxxxxx xx UDS Xxxxx Xx xxxxx xxx Xx vivo, Xxxxx. Xxx., 312, 263-285.
5) Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Hechenberger-Freudl, X. (1993), Assessment xx xxx Xxxxxxxx Xxxxxxx xxx Initial Xxxxxxxxx xxx xxx Xxxxxxxxxx xx Xxxxxxx Xxxxxxxx Xxx Xxxxxxxxxxx Used xxx the Xx xxxx/Xx vitro XXX Xxxxxx Assay (UDS), Xxxxxxxxxx Xxx., 291, 21-27.
6) Xxxxxxxx, X. X., Xxxxx, X. X., Butterworth, X. X. (1982), Xxxxxxxxx xx Genotoxic Xxxxxxxxxxx xx xxx In xxxx/Xx xxxxx Hepalocyte XXX Xxxxxx Xxxxx, Xxxxxxx.Xxxxxxx. 4, 553-562."
XXXXXXX 5
XXXXXX POŽADAVKY XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX LÁTEK X XXXXXXXXX
Xxx směrnice Xxxxxx 2001/59/XX, Xx. xxxx. X 332, 28. 12. 2000, x. 81.
PŘÍLOHA 6
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XXXXXXX XX
XXXX X
xxxxxxxx týkající xx xxxxxxx xxxxxxxx proti xxxxxxxx dětmi
Kromě xxxxxxxxxx xx. 22 xxxx. 1 xxxx. x) xxxx směrnice, musí xxx xxxxx o xxxxxxxxx objemu xxxxxxxxxx xxxxx, x xxxxx xx xxxxxxx xxxxxx xxx xxxxxxxxxx (Xx; X 65) x xxxxx xxxx xxxxxxxxxxxxx x xxxxxxxx podle xxxx 3.2.3 přílohy XX xxxx xxxxxxxx, x výjimkou látek xxxxxxxxx na xxx xx xxxxx xxxxxxxx xxxx v xxxxxxxx xxxxxxxxxx xxxxxxxxxxx rozprašovačem, xxxxxxxx xxxxxxx odolnými xxxxx otevření xxxxx.
1. Xxxxxxxxx uzavíratelné xxxxx
Xxxxxxx xxxxxx xxxxx otevření xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx splňovat požadavky xxxxx XXX 8317 (xxxxxx ze xxx 1. xxxxxxxx 1989) "Xxxxx odolné xxxxx — Xxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx x metody jejich xxxxxxxx" xxxxxxxx Mezinárodní xxxxxxxxxx xxx xxxxxxxxxxx (XXX).
2. Xxxxxxxxx neuzavíratelné xxxxx
Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxx xxxxxxx xxxx splňovat xxxxxxxxx xxxxx CEN XX 862 (xxxxxx x března 1997) "Xxxxx — Xxxxx xxxxxx xxxxx — Xxxxxxxxx x zkušební xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx xxxxx xxxxxx xxx farmaceutických výrobků" xxxxxxxx Xxxxxxxxx výborem xxx xxxxxxxxxxx (XXX).
3. Xxxxxxxx
1. Xxxxxxxxx xxxxx x xxxx xxxxxxxxx xxxxxxx mohou osvědčovat xxxxx xxxxxxxxxx, xxxxx xxxxxxx xxxxxxxx xxxxx xxxx XX 45000.
2. Xxxxxxxxxx případy
Je-li xxxxxx, xx obal je xxxxxxxxxx bezpečný pro xxxx, xxxxx xx xxxxxxx dostat x xxxxxx xxx xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx provedena.
Ve xxxxx xxxxxxxxx případech x xxxxx xxxxxxxx xxxxxxxxx xxxxxx x pochybám x xxxxxxxxxxx uzávěru xxx dítě, xxxx xxxxxxxxxxxx orgán požadovat, xxx xxxxx odpovědná xx xxxxxxx xxxxxxx xx trh předložila xxxxxxxxxx vydaný xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx
- xxx xxxxxxx xx xxxxxx, xx xxx není xxxxxxxx xxxxxxx xxxxx xxxx uvedených norem XXX x XXX,
xxxx
- xx uzávěr xxx xxxxxxx x byl xxxxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxxx norem.
ČÁST X
Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx
Xxxxxxxxx xxxxxxxxxxx xxx xxxxxxxxxx xxxxxxxx xxxx být x xxxxxxx x normou XX XXX 11683 (xxxxxx x xxxx 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx před xxxxxxxxxx — Xxxxxxxxx".
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