Směrnice Komise 2000/32/ES
ze xxx 19. května 2000,
xxxxxx xx xx xxxxxxx xxxxx přizpůsobuje xxxxxxxxxxx pokroku xxxxxxxx Xxxx 67/548/XXX o xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxx [1]
(Xxxx x xxxxxxxx pro XXX)
XXXXXX XXXXXXXXXX XXXXXXXXXXXX,
x xxxxxxx xx Xxxxxxx o xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,
x xxxxxxx xx směrnici Xxxx 67/548/XXX xx xxx 27. xxxxxx 1967 x sbližování xxxxxxxx x xxxxxxxxx xxxxxxxx týkajících xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx látek [2], xxxxxxxxx xxxxxxxxxx xxxxxxxx Evropského xxxxxxxxxx x Xxxx 1999/33/ES [3], x zejména xx xxxxxx 28 xxxxxxx xxxxxxxx,
xxxxxxxx k xxxxx důvodům:
(1) Xxxxxxx X směrnice 67/548/EHS xxxxxxxx seznam nebezpečných xxxxx xxxxxxxx x xxxxxxxxxx údaji o xxxxxxxxxxx a xxxxxxxxxx xxxxx xxxxx. Současné xxxxxxx x technické xxxxxxxx ukazují, že xx měl xxx xxxxxx xxxxxxxxxxxx xxxxx x xxxxxxx příloze xxxxxxxxxxx. Xxxxxxx jazykové xxxxx xxxxxxxx xxxxxxxx xxxxxx určitých xxxxxx xxxxxxxxx a xxxxxxx X x příloze X.
(2) Příloha XXX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx vět xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx s nebezpečnými xxxxxxx x xxxxxxxxx. Xxxxxxx IV směrnice 67/548/XXX xxxxxxxx xxxxxx xxx s xxxxxxxxxxxxxx xxxxxx týkajícími xx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Příloha XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxx xx xxxxxxxxxxx x k xxxxxxxxxx xxxxxxxxxxxx látek a xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx směrnice xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, IV x VI.
(3) X xxxxxxx V xxxxxxxx 67/548/XXX xx xxxxxxx xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx vlastností, xxxxxxxx x xxxxxxxxxxx xxxxx x přípravků. Je xxxxxxxx xxxxxxxxxxx xxxx xxxxxxx xxxxxxxxxxx pokroku.
(4) Xxxxxxx IX xxxxxxxx 67/548/XXX obsahuje předpisy xxxxxxxx se uzávěrů xxxxxxxx xxxxx otevření xxxxx. Xxxx předpisy xx xxxx být xxxxxxxxxxxx x aktualizovány. Xx xxxxxxxx rozšířit xxxxxx, xxx xx xxxxxxx xxxxxx xxxxx xxxxxxxx dětmi xxxxxxxxx.
(5) Xxxxxxxx xxxx xxxxxxxx xxxx v xxxxxxx xx xxxxxxxxxxx Výboru xxx přizpůsobení xxxxxxxxxxx xxxxxxx směrnic xxx xxxxxxxxxx xxxxxxxxxxx překážek xxxxxxx na úseku xxxxxxxxxxxx xxxxx x xxxxxxxxx,
XXXXXXX XXXX SMĚRNICI:
Článek 1
Směrnice 67/548/XXX xx xxxx takto:
1. Xxxxxxx X se xxxx xxxxx:
x) xxxxxxxxxxxx xxxxxxxx v xxxxxxxxx xx nahrazuje xxxxxxxxx X v xxxxxxx 1X xxxx xxxxxxxx;
x) xxxxxxxxxxxx xxxxx x xxxxxxx A se xxxxxxxxx řádky x xxxxxxx 1X xxxx xxxxxxxx;
x) xxxxxxxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxx x xxxxxxx 1C xxxx xxxxxxxx;
x) vkládají xx xxxxxxx x xxxxxxx 1X xxxx xxxxxxxx.
2. Xxxxxxxxxxxx xxxx x příloze XXX xx xxxxxxxxx xxxxxxxxxx xxxxx označující xxxxxxxxxxx xxxxxxxxxx x příloze 2 této xxxxxxxx.
3. Xxxxxxx XX xx xxxx takto:
a) xxxxxxxxxxxx xxxxxx x příloze XX xx nahrazují xxxxxxxxxxxx xxxxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxx 3X xxxx xxxxxxxx;
x) odpovídající xxxxxx x xxxxxxx IV xx nahrazují xxxxxxxxxxxxx xxxxxxxxxxxx pokyny xxx xxxxxxxx xxxxxxxxx x xxxxxxx 3X xxxx xxxxxxxx.
4. Xxxx X xxxxxxx V se xxxx takto:
a) kapitola X.10 xx xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx xxxxxxxx;
x) xxxxxxxx X.11 xx xxxxxxxxx xxxxxx v xxxxxxx 4X xxxx xxxxxxxx;
x) kapitola X.12 xx nahrazuje textem x xxxxxxx 4C xxxx xxxxxxxx;
x) kapitoly X.13 x X.14 xx nahrazují xxxxxx x xxxxxxx 4X xxxx směrnice;
e) xxxxxxxx X.17 se xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx směrnice;
f) xxxxxxxx X.23 xx xxxxxxxxx xxxxxx v xxxxxxx 4X xxxx xxxxxxxx. Xxxxx xxxxxxxx X.23 xx xxxxxxxxxxx xx xxxx xxxxxxxxxxxxx xxxxxxxx;
x) xxxxxx se xxxx x příloze 4X této xxxxxxxx.
5. Xxxxxxx se čtvrtá xxxxxxx xxxxxxxx úvodu x části X xxxxxxx X.
6. Odpovídající xxxxx v xxxxxxx XX se xxxxxxxxx xxxxx x příloze 5 xxxx xxxxxxxx.
7. Xxxxxxx XX xx xxxx xxxxxxxx xxxxxxxx x xxxxxxx 6 xxxx směrnice.
Xxxxxx 2
1. Xxxxxxx xxxxx xxxxxx x xxxxxxxx právní x xxxxxxx xxxxxxxx nezbytné xxx xxxxxxxx souladu x xxxxx směrnicí xxxxxxxxxx do 1. xxxxxx 2001. Neprodleně x xxxx xxxxxxx Xxxxxx.
Xxxx xxxxxxxx xxxxxxx xxxxxxxxx xxxxx musí xxxxxxxxx xxxxx na xxxx xxxxxxxx nebo xxxx takový xxxxx xxx učiněn xxx xxxxxx úředním xxxxxxxxx. Xxxxxx xxxxxx xx xxxxxxx xxxxxxx xxxxx.
2. Xxxxxxx státy xxxxx Xxxxxx xxxxx hlavních xxxxxxxxxx vnitrostátních xxxxxxxx xxxxxxxx, které xxxxxxx x oblasti xxxxxxxxxx xxxx xxxxxxxx, x xxxxxxxxxx tabulku mezi xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.
Xxxxxx 3
Xxxx směrnice xxxxxxxx v xxxxxxxx xxxxxx xxxx xx xxxxxxxxx x Úředním xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx.
Xxxxxx 4
Xxxx xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.
X Xxxxxxx xxx 19. xxxxxx 2000.
Za Xxxxxx
Xxxxxx Xxxxxxxöx
xxxxxx Xxxxxx
[1] Přijato xx xxxxxxxxxxxx xx dvacáté xxxxx.
[2] Úř. xxxx. 196, 16.8.1967, s. 1.
[3] Xx. xxxx. X 199, 30.7.1999, x. 57.
PŘÍLOHA 1A
PŘEDMLUVA X XXXXXXX X
Xxxxxxxxxx xxxxxxxx xxxxxxxxxx se identifikace, xxxxxxxxxxx a xxxxxxxxxx xxxxx
(Xxxxxx xx xxxxxxx xxxxx)
XXXXXXX 1B
"TABULKA 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 1X
|
Xxxxxxxx xxxxx |
Xxxxxxxx xxxxx |
Xxxxxxxx k xxxxxx |
Xxxxx XX |
Xxxxx XXX |
Xxxxxxxxxxx |
Xxxxxxxx |
Xxxxxxxxxxxx limity |
Poznámky x přípravkům |
|
006–011–00–7 |
karbaryl (ISO) 1-xxxxxx-X-xxxxxxxxxxxxxx |
200–555–0 |
63–25–2 |
Xxxx. kat. 3; X40 Xx; R22 X; R50 |
Xn; N X: 22–40–50 X: (2-)22–24–36/37–46–61 |
|||
|
006–013–00–8 |
xxxxxx-xxxxxxx (ISO) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx |
205–293–0 |
137–42–8 |
Xx; X22 X31 X; X34 X43 N; X50–53 |
X; X X: 22–31–34–43–50/53 S: (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; R40 Xxxx. xxx. 3; X40 Xx; R22–48/22 X; X50–53 |
Xx; N R: 22–40–48/22–50/53 S: (2-)13–22–23–37–46–60–61 |
|||
|
006–016–00–4 |
propoxur (XXX) 2- isopropoxyfenyl-N-methylkarbamát |
204–043–8 |
114–26–1 |
T; X25 X; X50–53 |
X; X X: 25–50/53 X: (1/2-)37–45–60–61 |
|||
|
006–017–00-X |
aldikarb (XXX) 2-xxxxxx-2-(xxxxxxxxxxxxxx)xxxxxxxx-X-(X-xxxxxxxxxxxxxxx)xxxx |
204–123–2 |
116–06–3 |
X+; R26/28 T; 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 |
aminokarb (XXX) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx |
217–990–7 |
2032–59–9 |
X; X24/25 X; X50–53 |
X; N 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 Xx; X22 N; X50–53 |
Xx; X X: 22–40–50/53 X: (2-)25–36/37–60–61 |
|||
|
006–020–00–6 |
barban (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 (XXX) xxxxxxxxxx 3,5-dimethyl-4-(methylsulfanyl)fenyl-N -methylkarbamát |
217–991–2 |
2032–65–7 |
T; X25 N; X50–53 |
X; X X: 25–50/53 X: (1/2-)22–37–45–60–61 |
|||
|
006–024–00–8 |
proxan-natrium (XXX) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx |
205–443–5 |
140–93–2 |
Xx; X22 Xx; 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 X: 26/28–50/53 X: (1/2-)36/37–45–60–61 |
|||
|
006–028–00-X |
xxxxxxxxx (XXX) 2-(1-xxxxxxxxxxxx)-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx 2-sek-butyl-4,6-dinitrofenyl-isopropyl-karbonát |
213–546–1 |
973–21–7 |
T; X25 X; R50–53 |
T; X X: 25–50/53 X: (1/2-)37–45–60–61 |
|||
|
006–029–00–5 |
dioxakarb (XXX) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx |
230–253–4 |
6988–21–2 |
X; X25 N; X51–53 |
X; N X: 25–51/53 X: (1/2-)37–45–61 |
|||
|
006–033–00–7 |
xxxxxxxxx (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 (XXX) X-xxxxxx-X-xxxxx-X-xxxxxxxxxxxxxxxxx |
214–215–4 |
1114–71–2 |
Xx; X22 X; X51–53 |
Xx; X R: 22–51/53 X: (2-)23-61 |
|||
|
006–035–00–8 |
xxxxxxxxxx (XXX) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx xxxxxxxxx-4-xx-X,X-xxxxxxxxxxxxxxxx |
245–430–1 |
23103–98–2 |
X; X25 N; R50–53 |
T; X X: 25–50/53 X: (1/2)22–37–45–60–61 |
|||
|
006–037–00–9 |
xxxxxxxxx (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx |
220–113–0 |
2631–37–0 |
X; X25 X; X50–53 |
X; X R: 25–50/53 X: (1/2-)24–37–45–60–61 |
|||
|
006–038–00–4 |
xxxxxxxxx (XXX) 2-chlorallyl-N,N-dimethyldithiokarbamát |
E |
202–388–9 |
95–06–7 |
Karc. kat. 2; X45 Xx; X22 N; X50–53 |
X; X R: 45–22–50/53 X: 53–45–60–61 |
||
|
006–039–00-X |
xxx-xxxxx (XXX) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx |
218–962–7 |
2303–17–5 |
Xx; X22–48/22 X43 X; R50–53 |
Xn; N X: 22–43–48/22–50/53 S: (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; R40 Xx; R22 X; X50–53 |
Xx; N R: 22–40–50/53 X: (2-)36/37–60–61 |
|||
|
006–043–00–1 |
monuron-TCA 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx |
— |
140–41–0 |
Xx; X36/38 Xxxx. xxx. 3; R40 X; R50–53 |
Xn; X X: 36/38–40–50/53 S: (2-)36/37–60–61 |
|||
|
006–045–00–2 |
xxxxxxxx (XXX) xxxxxx-X-[(X-xxxxxxxxxxxxxxx)xxx]xxxxxxxxxxxxxx |
240–815–0 |
16752–77–5 |
X+; X28 X; X50–53 |
X+; X X: 28–50/53 X: (1/2-)22–36/37–45–60–61 |
|||
|
006–046–00–8 |
xxxxxxxxxx (XXX) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx |
245–216–8 |
22781–23–3 |
X; X23/25 Xx; X21 N; X50–53 |
X; X X: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61 |
|||
|
006–047–00–3 |
xxxxxxxxx (XXX) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx |
— |
8065–36–9 |
X; R24/25 X; X50–53 |
X; X R: 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 X: (2-)60-61 |
|||
|
006–050–00–X |
xxxxxxx-XXX 3-fenyl-1,1-dimethyluronium-trichloracetát |
— |
4482–55–7 |
Xi; R38 X; X50–53 |
Xx; X X: 38–50/53 X: (2-)60-61 |
|||
|
006–053–00–6 |
xxxxxxxxxx (XXX) 2-isopropylfenyl-N-methylkarbamát |
220–114–6 |
2631–40–5 |
Xn; X22 X; R50–53 |
Xn; 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+; R28 Xn; X21 N; X50–53 |
X+; X X: 21–28–50/53 X: (1/2-)36/37–45–60–61 |
|||
|
006–057–00–8 |
xxxxxxxxxx (XXX) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx |
217–682–2 |
1929–82–4 |
Xx; X22 N; X51–53 |
Xx; X X: 22–51/53 S: (2-)24-61 |
|||
|
006–060–00–4 |
oxykarboxin (XXX) 2-xxxxxx-4,4-xxxxx-5,6-xxxxxxx-4λ4-1,4-xxxxxxxx-3-xxxxxxxxxxxx |
226–066–2 |
5259–88–1 |
Xx; X22 X52–53 |
Xx R:22–52/53 X: (2-)61 |
|||
|
006–069–00–3 |
xxxxxxxxx-xxxxxx (ISO) 1,2-di[3-(methoxykarbonyl)thioureido]benzen |
245–740–7 |
23564–05–8 |
Muta. xxx. 3; R40 X; X50–53 |
Xx; X X: 40–50/53 X: (2-)36/37–60–61 |
|||
|
006–070–00–9 |
xxxxxxxxxxx N-cyklohexyl-N-methoxy-2,5-dimethyl-3-furamid |
262–302–0 |
60568–05–0 |
Karc. xxx. 3; R40 X; X50–53 |
Xx; X X: 40–50/53 S: (2-)36/37–60–61 |
|||
|
006–088–00–7 |
xxxxxxxxxxx (XXX) xxxxx-X -[({[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]karbonyl}methylamino)sulfanyl]-N-isopropyl-β-alaninát(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)-N-({[2-(ethoxykarbonyl)ethyl]isopropylamino}sulfanyl)-N-methylkarbamát |
— |
82560–54–1 |
T; 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-dimethylhydrazin |
E |
200–316–0 |
57–14–7 |
F; X11 Karc. xxx. 2; R45 X; X23/25 C; R34 X; X51–53 |
X; T; X X: 45–11–23/25–34–51/53 X: 53–45–61 |
||
|
007–013–00–0 |
N,N-dimethylhydrazin 1,2-dimethylhydrazin |
E |
— |
540–73–8 |
Karc. xxx. 2; R45 X; R23/24/25 X; X51–53 |
X; N X: 45–23/24/25–51/53 S: 53–45–61 |
C ≥ 25 %: X; R45–23/24/25 3 % &xx; X &xx; 25 %: X; R45–20/21/22 0,01 % &xx; X &xx; 3 %: X; R45 |
|
|
009–003–00–1 |
kyselina xxxxxxxxxxxxxx … % |
B |
231–634–8 |
7664–39–3 |
T+; X26/27/28 X; X35 |
X+; X X: 26/27/28–35 X: (1/2-)7/9–26–36/37–45 |
X ≥ 7 %: X+; X; X26/27/28–35 1 % ≤ C < 7 %: X; X23/24/25–34 0,1 % ≤ C < 1 %: Xx; X20/21/22–36/37/38 |
|
|
015–039–00–9 |
xxxxxxx-xxxxxx (ISO) O,O-dimethyl-S -[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx |
201–676–1 |
86–50–0 |
X+; X26/28 X; X24 R43 X; X50–53 |
X+; X X: 24–26/28–43–50/53 X: (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; X23–48/25 Xn; X21/22 X; R50–53 |
T; X X: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61 |
|||
|
015–056–00–1 |
xxxxxxx-xxxxx (XXX) X,X-xxxxxxx-X-[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx |
220–147–6 |
2642–71–9 |
X+; R28 X; R24 X; X50–53 |
X+; N X: 24–28–50/53 X: (1/2-)28–36/37–45–60–61 |
|||
|
015–140–00–8 |
xxxxxxxxx (XXX) O,O-diethyl-O-(1-fenyl-1 X- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx |
245–986–5 |
24017–47–8 |
X; X23/25 Xn; X21 X; X50–53 |
X; X R: 21–23/25–50/53 X: (1/2-)36/37–45–60–61 |
|||
|
016–013–00-X |
chlorid sirnatý |
234–129–0 |
10545–99–0 |
R14 X; X34 X; X50 |
X; X R: 14–34–50 X: (1/2-)26–36/37/39–45–61 |
C ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; X36/37/38 |
||
|
016–014–00–5 |
xxxxxxx xxxxxxxx |
— |
13451–08–6 |
X14 X; R34 N; X50 |
X; X R: 14–34–50 S: (1/2-)26–36/37/39–45–61 |
X ≥ 10 %: X; X34 5 % ≤ C &xx; 10 %: Xx; X36/37/38 |
||
|
016–023–00–4 |
xxxxxxxx-xxxxxx |
X |
201–058–1 |
77–78–1 |
Xxxx. kat. 2; X45 Xxxx. 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 % ≤ X &xx; 25 %: X+; R45–22–26–34–43 7 % ≤ X &xx; 10 %: X+; X45–22–26–36/ 37/38–43 5 % ≤ X &xx; 7 %: X; R45–22–23–36/37/38–43 3 % ≤ X < 5 %: X; X45–22–23–43 1 % ≤ X &xx; 3 %: X; X45–23–43 0,1 % ≤ X &xx; 1 %: X; X45–20 0,01 % ≤ X &xx; 0,1 %:X; X45 |
|
|
016–024–00-X |
xxxxxxxx (ISO) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx |
X,X′-xxxxxxxx-xxxxxxxxxxx(xxxxxxxxxxx)215–993–8 |
1468–37–7 |
Xx; R22 N; X50–53 |
Xx; N X: 22–50/53 X: (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 xxxxxxxx |
410–130–3 |
136248–03–8 |
X43 |
Xx X: 43 S: (2-)22–24–37 |
|||
|
022–001–00–5 |
chlorid 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 < 10 %: Xx; X36/37/38 |
||
|
030–004–00–8 |
xxxxxxxxxxxxx [1] diethylzinek [2] |
208–884–1 [1] 209–161–3 [2] |
544–97–8 [1] 557–20–0 [2] |
X14 X; X17 X; X34 N; X50–53 |
X; X; N X: 14–17–34–50/53 X: (1/2-)16–43–45–60–61 |
|||
|
050–002–00–0 |
xxxxxxxxx (XXX) xxxxxxxxxxxxx(xxxxxxx)xxxxxxx tricyklohexylstannium-hydroxid |
236–049–1 |
13121–70–5 |
Xn; X20/21/22 N; X50–53 |
Xx; X X: 20/21/22–50/53 X: (2-)13–60–61 |
|||
|
050–012–00–5 |
xxxxxxxxxxxxxxxxxxxxxx [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] |
Xx; X20/21/22 X; X50–53 |
Xx; X X: 20/21/22–50/53 X: (2-)26–28–60–61 |
X ≥ 1 %: Xx; R20/21/22 |
1 |
|
|
050–017–00–2 |
fenbutatinoxid (XXX) 1,1,1,3,3,3-xxxxxxx(2-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxxxx |
236–407–7 |
13356–08–6 |
X+; X26 Xx; R36/38 X; X50/53 |
X+; N X: 26–36/38–50/53 X: (1/2-)28–36/37–45–60–61 |
|||
|
082–009–00–X |
xxxx (xxxxxxxxxxxx olovnatý) XX Xxxxxxx Xxxxxx 34 (XX 77603) XX xxxxxxxxxx žluť 34 (XX 77603) |
215–693–7 |
1344–37–2 |
Xxxx. xxx. 3; R40 Repr. xxx. 1; R61 Xxxx. xxx. 3; X62 X33 N; X50–53 |
X; X R: 61–33–40–50/53–62 X: 53–45–60–61 |
1 |
||
|
082–010–00–5 |
červeň (xxxxxxx-xxxxxxxxxx-xxxxx olovnatý) XX Xxxxxxx Xxx 104 (XX 77605) CI xxxxxxxxxx červeň 104 (XX 77605) |
235–759–9 |
12656–85–8 |
Karc. xxx. 3; X40 Xxxx. xxx. 1; X61 Xxxx. kat. 3; X62 R33 X; X50–53 |
X; N X: 61–33–40–50/53–62 X: 53–45–60–61 |
1 |
||
|
601–024–00-X |
xxxxx [1] propylbenzen [2] |
202–704–5 [1] 203–132–9 [2] |
98–82–8 [1] 103–65–1 [2] |
X10 Xx; X65 Xx; X37 N; 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 N; 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 X; X50–53 |
X; X R: 45–50/53 X: 53–45–60–61 |
|||
|
602–035–00–2 |
1,4-xxxxxxxxxxxxx x-xxxxxxxxxxxxx |
203–400–5 |
106–46–7 |
Xx; 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 xxxxxxxxxx |
209–130–4 |
556–56–9 |
X10 X; X34 |
X R: 10-34 X: (1/2-)7–26–45 |
|||
|
603–076–00–9 |
but-2-yn-1,4-diol |
203–788–6 |
110–65–6 |
T; X23/25 Xx; X21–48/22 X; X34 |
X R: 21–23/25–34–48/22 S: (1/2-)26–36/37/39–45 |
C ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ C &xx; 50 %: X; R21–23/25–36/38–48/22 10 % ≤ C &xx; 25 %: Xx; X20/22–48/22 3 % ≤ X &xx; 10 %: Xx; R20/22 |
||
|
603–091–00–0 |
exo-4-isopropyl-1-methyl-7-oxabicyklo[2.2.1]heptan-2-ol |
402–470–6 |
87172–89–2 |
O; X8 Xx; R22 Xi; X36 |
X; Xx X: 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′′-nitrilotripropan-2-ol xxxxxxxxxxxxxxxxxx |
204–528–4 |
122–20–3 |
Xx; X36 X52–53 |
Xx X:36–52/53 X: (2-)26-61 |
|||
|
603–117–00–0 |
propan-2-ol xxxxxxxxxxxxxxxx xxxxxxxxxxx |
200–661–7 |
67–63–0 |
X; X11 Xx; R36 X67 |
X; Xx R: 11–36–67 X: (2-)7–16–24/25–26 |
|||
|
604–020–00–6 |
bifenyl-2-ol 2-hydroxybifenyl 2-xxxxxxxxxx (XXX) |
201–993–5 |
90–43–7 |
Xx; X36/37/38 X; R50 |
Xi; X X: 36/37/38–50 X: (2-)22-61 |
|||
|
604–021–00–1 |
2-xxxxxxxxxx, sodná xxx xxxxxxx-2-xxxxxxxxxxxx 2-bifenylát xxxxx xxxxxxx-xxxxxxx-2-xxxx |
205–055–6 |
132–27–4 |
Xx; R22 Xx; X37/38–41 X; X50 |
Xx; X X: 37/38–41–50 X: (2-)22–26–61 |
|||
|
604–024–00–8 |
4,4'-(4-methylpentan-2,2-diyl)difenol 2,2-xxx(4-xxxxxxxxxxxx)-4-xxxxxxxxxxxx |
401–720–1 |
6807–17–6 |
Xxxx. xxx. 2; X60 Xx; X36 N; X50–53 |
X; N R: 60–36–50/53 X: 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; X22 Xx; X38–41 X; X50–53 |
Xx; X X: 22–38–41–50/53 X: (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 X: 36-43 X: (2-)24/25–26–37 |
|||
|
604–044–00–7 |
xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx |
205–769–8 |
150–76–5 |
Xx; X22 Xx; X36 X43 |
Xx X: 22–36–43 S: (2-)24/25–26–37/39–46 |
|||
|
605–016–00–7 |
xxxxxxx… % xxxxxxxxx… % |
X |
203–474–9 |
107–22–2 |
Xxxx. kat. 3; X40 Xx; X20 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 < 10 %: Xn; 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; R50–53 |
Xn; N X: 22–36/38–50/53 X: (2-)26–60–61 |
|||
|
606–019–00–6 |
xxxxxxxxxx (ISO) 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-dekachlorpentacyklo[5.3.0.02,6.04,10.05,9]dekan-3-on |
205–601–3 |
143–50–0 |
Karc. kat. 3; X40 X; X24/25 X; X50–53 |
X; X X: 24/25–40–50/53 X: (1/2-)22–36/37–45–60–61 |
|||
|
606–034–00–8 |
metribuzin (ISO) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 H)-on 4-amino-6-terc-butyl-3-(methylsulfanyl)-4,5-dihydro-1,2,4-triazin-5-on |
244–209–7 |
21087–64–9 |
Xn; X22 X; R50–53 |
Xn; 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 X: (2-)24–37–60–61 |
|||
|
606–036–00–9 |
xxxxxxxxxxxxxx (XXX) 6-xxxxxx-2 H-[1,3]dithiolo[4,5-b]chinoxalin-2-on |
219–455–3 |
2439–01–2 |
Repr. xxx. 3; X62 Xx; X20/21/22–48/22 Xi; X36 R43 N; X50–53 |
Xx; N X: 20/21/22–36–43–48/22–50/53–62 X: (2-)24–37–60–61 |
|||
|
606–037–00–4 |
xxxxxxxxxxx (XXX) 1-(4-xxxxxxxxxxx)- 3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-on |
256–103–8 |
43121–43–3 |
Xn; X22 X; X51–53 |
Xx; X R: 22–51/53 X: (2-)61 |
|||
|
606–044–00–2 |
2,4,6-trimethylbenzofenon xxxxx(2,4,6-xxxxxxxxxxxxxx)xxxxxxxx |
403–150–9 |
954–16–5 |
Xx; X22 Xi; R36 X; R50–53 |
Xn; N X: 22–36–50/53 X: (2-)26–60–61 |
|||
|
607–043–00-X |
xxxxxxx (XXX) 3,6-xxxxxxx-2-xxxxxxxxxxxxxxx xxxxxxxx |
217–635–6 |
1918–00–9 |
Xx; X22 Xi; X41 X52–53 |
Xx; N X: 22–41–52/53 S: (2-)26-61 |
|||
|
607–057–00–6 |
xxxxxxxxx (XXX) 3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X-xxxxxxx-2-xx |
201–378–1 |
81–82–3 |
Xx; X48/22 R52–53 |
Xn X:48/22–52/53 S: (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 -xxxxxxx-2-xx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 H -xxxxxxx-2-xx |
204–195–5 |
117–52–2 |
X; X25–48/25 X52–53 |
X X:25–48/25–52/53 X: (1/2-)37–45–61 |
|||
|
607–079–00–6 |
xxxxxxx (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx 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; R24 Xx; X22 X; X51–53 |
X; X R: 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-xxxxxxxx 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 |
pentanová xxxxxxxx xxxxxxxx kyselina |
203–677–2 |
109–52–4 |
C; X34 X52–53 |
X X:34–52/53 X: (1/2-)26–36–45–61 |
|||
|
607–152–00–2 |
2,3,6-XXX (ISO) 2,3,6-xxxxxxxxxxxxxxxx xxxxxxxx |
200–026–4 |
50–31–7 |
Xx; X22 X; X51–53 |
Xx; N 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; R36/38 R52–53 |
Xi X:36/38–52/53 X: (2-)22-61 |
|||
|
607–156–00–4 |
xxxxxxxxxxx (XXX) 4-xxxxxxxxxx-4-xxxxxxxxxxx-1-xxxxxxxx |
201–270–4 |
80–33–1 |
Xx; R22 Xx; X38 X; X50–53 |
Xx; N R: 22–38–50/53 X: (2-)37–60–61 |
|||
|
607–158–00–5 |
xxxxx xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx |
223–498–3 |
3926–62–3 |
X; R25 Xx; X38 N; X50 |
X; X X: 25–38–50 X: (1/2-)22–37–45–61 |
|||
|
607–159–00–0 |
chlorobenzilát (XXX) xxxxx-2,2-xxx(4-xxxxxxxxxx)-2-xxxxxxxxxxxxx xxxxx-4,4'-xxxxxxxxxxxxxxx |
208–110–2 |
510–15–6 |
Xx; X22 X; R50–53 |
Xn; X R: 22–50/53 X: (2-)60-61 |
|||
|
607–176–00–3 |
Xxxx: α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-xxxxxxxxxxx(xxxxxxxxxx);α-{3-[3-(2 H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propionyl}-ω-({3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}xxx)xxxx(xxxxxxxxxx) |
400–830–7 |
— |
X43 X; X51–53 |
Xx; X X: 43–51/53 S: (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; R51–53 |
Xi; X R: 43–51/53 X: (2-)24/37–61 |
|||
|
607–209–00–1 |
Xxxx: X,X′-xxxxxxxxxxx-xxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx) |
403–030–6 |
— |
Xx; 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; X7 X10 X; X51–53 |
X; X X: 2–7–10–51/53 X: (2-)3/7–14–33–36/37/39–61 |
|||
|
607–217–00–5 |
2-xxxxxxxxxxx-[4-(7-xxxxx-2,6-xxxxx-2,6-xxxxxxx-1,5-xxxxx-x-xxxxxxx-3-xx)xxxxxx]xxxxxx |
403–960–2 |
— |
X43 X53 |
Xx X: 43-53 X: (2-)24–37–61 |
|||
|
607–243–00–7 |
xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [3] (2-hydroxyethyl)amonium-3,6-dichloranisát [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 xxxxxxxxxxxxxxxxx-xxxxxxxxx XXXXX |
256–032–2 |
42978–66–5 |
Xx; X36/37/38 R43 X; X51–53 |
Xx; N R:36/37/38–43–51/53 X: (2-)24–37–61 |
X ≥ 10 %: Xx; X36/37/38–43 1 % ≤ X &xx; 10 %: Xi; X43 |
||
|
607–252–00–6 |
λ-xxxxxxxxxxx (XXX) Xxxx (1:1): (S)-[(3-fenoxyfenyl)kyanmethyl]-(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+; R26 X; R25 Xx; 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 |
xxxxxxxxxx (ISO) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx kyselina |
— |
69377–81–7 |
R52–53 |
R: 52/53 X: 61 |
|||
|
608–003–00–4 |
xxxxxxxxxxxx |
X X |
203–466–5 |
107–13–1 |
X; Xxx Karc. xxx. 2; X45 X; X23/24/25 Xx; X37/38–41 X43 N; X51–53 |
X; X; X X: 45–11–23-/24/25–37/38–41–43–51/53 S: 9–16–53–45–61 |
C ≥ 20 %: X; R45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; X45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; R45–23/24/25–36–43 1 % ≤ C &xx; 5 %:T; X45–23/24/25–43 0,2 % ≤ X &xx; 1 %:X; R45–20/21/22 0,1 % ≤ X &xx; 0,2 %: T; X45 |
43 |
|
608–016–00–5 |
2,3,5,6-xxxxxxxxxx-1,4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxx |
401–550–8 |
1897–41–2 |
X43 X; X50–53 |
Xx; X X: 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. xxx. 2; X61 X+; R28 X; X24 X44 X; R50–53 |
T+; N X: 61–24–28–44–50/53 S: 53–45–60–61 |
||
|
609–040–00–9 |
xxxxxxxx (XXX) (2,4-xxxxxxxxxxxx)(4-xxxxxxxxxx)xxxxx |
X |
217–406–0 |
1836–75–5 |
Xxxx. xxx. 2; X45 Xxxx. xxx. 2; X61 Xx; R22 X; X50–53 |
X; N X: 45–61–22–50/53 S: 53–45–60–61 |
||
|
609–044–00–0 |
xxxxxxxx (ISO) 1,2,4,5-tetrachlor-3-nitrobenzen |
204–178–2 |
117–18–0 |
Xn; X22 X43 X; X50–53 |
Xx; X R: 22–43–50/53 S: (2-)24–37–60–61 |
|||
|
611–008–00–4 |
4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx |
200–453–6 |
60–09–3 |
Xxxx. kat. 2; X45 X; X50–53 |
X; 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; X51–53 |
X; X R: 2–51/53 X: (2-)35-61 |
|||
|
611–031–00-X |
4,4'-[(4-iminocyklohexa-2,5-dien-1-yliden)methylen]dianilin-hydrochlorid CI Xxxxx Xxx 9 XX xxxxxxx xxxxxx 9 |
209–321–2 |
569–61–9 |
Xxxx. kat. 2; X45 |
X X: 45 X: 53-45 |
|||
|
612–035–00–4 |
2-methoxyanilin o-anisidin |
E |
201–963–1 |
90–04–0 |
Karc. xxx. 2; X45 Xxxx. xxx. 3; X40 X; X23/24/25 |
X X: 45–23/24/25 X: 53-45 |
||
|
612–042–00–2 |
xxxxxxxx bifenyl-4,4'-diamin 4,4'-xxxxxxxxxxxxxx xxxxxxx-4,4'-xxxxxxxxxx |
X |
202–199–1 |
92–87–5 |
Xxxx. xxx. 1; X45 Xn; R22 X; X50–53 |
X; X X: 45–22–50/53 X: 53–45–60–61 |
X ≥ 25 %: X; X45–22 0,01 % ≤ X < 25 %: X; R45 |
|
|
612–051–00–1 |
4,4'-diaminodifenylmethan xxx(4-xxxxxxxxxx)xxxxxx 4,4'-methylendianilin |
E |
202–974–4 |
101–77–9 |
Karc. kat. 2; X45 Xxxx. xxx. 3; X40 X; X39/23/24/25Xx; R48/20/21/22 X43 N; 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 o-tolidin, xxxx |
X X |
210–322–5 265–294–7 277–985–0 |
612–82–8 64969–36–4 74753–18–7 |
Xxxx. xxx. 2; X45 Xx; X22 X; X51–53 |
X; N X: 45–22–51/53 X: 53–45–61 |
||
|
612–099–00–3 |
4-xxxxxx-x-xxxxxxxxxxxxx4-xxxxxx-1,3-xxxxxxxxxxxxx4-xxxxxxxxxxxx-1,3-xxxxxx 2,4-xxxxxxxxxxxx |
X |
202–453–1 |
95–80–7 |
Xxxx. xxx. 2; X45 X; X25 Xx; R21 Xi; X36 R43 X; X51–53 |
X; X X: 45–21–25–36–43–51/53 S: 53–45–61 |
||
|
612–105–00–4 |
2-(xxxxxxxxx-1-xx)xxxxxxxxx2-(xxxxxxxxx-1-xx)xxxxx-1-xxxx |
205–411–0 |
140–31–8 |
Xx; X21/22 X; R34 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-methyl-m-fenylendiamin2-methyl-1,3-fenylendiamin2-methylbenzen-1,3-diamin 2,6-xxxxxxxxxxxx |
212–513–9 |
823–40–5 |
Xxxx. xxx. 3; X40 Xx; R21/22 X43 X; X51–53 |
Xx; X X: 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 N; 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; R36/38 X4 3 N; R50–53 |
Xi; X X: 36/38–43–50/53 X: (2-)36/37–60–61 |
|||
|
612–151–00–5 |
xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx |
X |
246–910–3 |
25376–45–8 |
Xxxx. xxx. 2; R45 T; X25 Xx; X20/21 Xx; R36 X43 X; X51–53 |
X; N X: 45–20/21–25–36–43–51/53 X: 53–45–61 |
||
|
613–018–00–4 |
xxxxxxxxxx (XXX) 1,1'-bis[(3,5-dimethylmorfolin-4-karbonyl)methyl]-4,4'-bipyridin-1,1'-diium |
— |
7411–47–4 |
Xn; 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 trichlor-1,3,5-triazintrion 1,3,5-trichlor-1,3,5-triazin-2(1H), 4(3X), 6(5H)-trion |
201–782–8 |
87–90–1 |
O; X8 Xx; X22 X31 Xx; X36/37 N; 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 benzoguanamin |
202–095–6 |
91–76–9 |
Xn; X22 X52–53 |
Xx X:22–52/53 X: (2-)61 |
|||
|
613–042–00–5 |
xxxxxxxx (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1 X-xxxxxxxx |
252–615–0 |
35554–44–0 |
Xx; X20/22 X; R41 X; X50–53 |
Xx; N X: 20/22–41–50/53 X: (2-)26–39–60–61 |
|||
|
613–043–00–0 |
xxxxxxxx-xxxxxx (ISO) 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; R20/22 Xx; X41 X; R50–53 |
Xn; X X: 20/22–41–50/53 X: (2-)26–39–60–61 |
|||
|
613–066–00–6 |
xxxxxxxxxx (XXX) 2-(xxxx-xxxxxxxxxx)-4-(xxxxxxxxxx)-6-xxxxxxx-1,3,5-xxxxxxx |
251–637–8 |
33693–04–8 |
Xx; X22 X; X50–53 |
Xx; N X: 22–50/53 S: (2-)60-61 |
|||
|
613–091–00–2 |
morfamkvat-dichlorid [1] xxxxxxxxxx-xxxxxx [2] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx-xxxxxxxxx [1] 1,1'-bis[(3,5-dimethylmorfolin-4-karbonyl)methyl]-4,4'-bipyridin-1,1'-dium-disulfát [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 X: (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; R51–53 |
C; X X: 34–51/53 X: (1/2-)23–26–36/37/39–45–61 |
|||
|
613–130–00–3 |
xxxxxxxxxxx (XXX) (XX)-2-(2,4-xxxxxxxxxxxx)-1-(1X-1,2,4-xxxxxxx-1-xx)xxxxx-2-xx |
— |
79983–71–4 |
X43 X; R51–53 |
Xi; X X: 43–51/53 X: (2-)24–37–61 |
|||
|
613–131–00–9 |
xxxxxxxxxx (XXX) 1,2,5,6-tetrahydro-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; X63 Xx; X22 Xx; X36 N; X51–53 |
Xx; X X: 22–36–51/53–63 X: (2-)36/37–46–61 |
|||
|
613–137–00–1 |
methabenzthiazuron (ISO) 1-(1,3-xxxxxxxxxxxx-2-xx)-1,3-xxxxxxxxxxxxxxxx |
242–505–0 |
18691–97–9 |
X; X50–53 |
X R: 50/53 X: 60-61 |
|||
|
613–139–00–2 |
xxxxxxxxxxx-xxxxxx xxxxxx-2-{X —[N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)karbamoyl]sulfamoyl}benzoát |
— |
74223–64–6 |
N; R50–53 |
N X: 50/53 X: 60-61 |
|||
|
614–001–00–4 |
xxxxxxx (ISO) 3-(1-methylpyrrolidin-2-yl)pyridin |
200–193–3 |
54–11–5 |
T+; X27 X; X25 X; R51–53 |
T+; 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+ R:26/28–52/53 X: (1/2-)13–45–61 |
|||
|
614–007–00–7 |
xxxxxx-xxxxxx [1] xxxxxx-xxxxxx [2] brucin-(R)-(1-methylheptyl)-hydrogen-ftalát [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+; R26/28 R52–53 |
T+ X: 26/28–52/53 X: (1/2-)13–45–61 |
|||
|
615–006–00–4 |
2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-methyl-1,3-fenylendiisokyanát [1] 4-methyl-m-fenylendiisokyanát [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] x-xxxxxxxxxxxxxxxxxxxx [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [2] toluen-3,5-diisokyanát [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. kat. 3; X40 X+; X26 Xx; X36/37/38 X42/43 X52–53 |
X+ R: 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 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &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 X42 |
X 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 |
cymoxanil X -[(ethylamino)karbonyl]-2-kyan-2-(methoxyimino)acetamid 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx |
261–043–0 |
57966–95–7 |
Xx; X22 X43 X; X50–53 |
Xx; X X: 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; C; X R: 7–22–34–50/53 X:(1/2-)3/7–14–26–36/37/39–45–60–61 |
X325 %: X; X22–34 10 % ≤ C &xx; 25 %: X; X34 5 % ≤ X &xx; 10 %: Xi; X36/37/38 |
||
|
617–006–00-X |
xxx(α, α-dimethylbenzyl)peroxid bis(2-fenylpropan-2-yl)peroxid xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx xxxxxxxxxxxxxx |
201–279–3 |
80–43–3 |
X; X7 Xx; R36/38 X; 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; R2 Xx; X36 X43 |
X; Xx; 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; X50–53 |
Xx; X X: 21/22–40–50/53 X: (2-)22–36/37–60–61 |
|||
|
650–008–00–9 |
xxxxxxxxxx (ISO) 4-[(2-chlorfenyl)hydrazono]-3-methylisoxazol-5(4 X)-xx |
227–197–8 |
5707–69–7 |
X; X25 X; X50–53 |
X; X X: 25–50/53 S: (1/2-)22–24–36/37–45–60–61 |
|||
|
650–009–00–4 |
xxxxxxxxxxxxx-xxxxxxxxxxxx X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx |
243–269–1 |
19750–95–9 |
Xxxx. xxx. 3; X40 Xx; R22 X; X50–53 |
Xx; X R: 22–40–50/53 X: (2-)22–36/37–60–61 |
|||
|
650–033–00–5 |
esfenvalerát (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 R43 X; X50–53 |
X; N X: 23/25–43–50/53 X: (1/2-)24–36/37/39–45–60–61 |
|||
|
650–041–00–9 |
xxxxxxxxxxxx (XXX) 1-[2-(2-xxxxxxxxxxx)xxxxxx-1-xxxxxxxx]-3-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxx |
— |
82097–50–5 |
X; R50–53 |
N X: 50/53 X: 60-61 |
XXXXXXX 1X
|
Xxxxxxxx číslo |
Chemický xxxxx |
Xxxxxxxx x xxxxxx |
Xxxxx XX |
Xxxxx XXX |
Xxxxxxxxxxx |
Xxxxxxxx |
Xxxxxxxxxxxx xxxxxx |
Xxxxxxxx x přípravkům |
|
006–090–00–8 |
2-[(3-jodprop-2-yn-1-yl)oxy]ethyl-N-fenylkarbamát |
408–010–0 |
88558–41–2 |
Xn; R20 Xx; X41 X52–53 |
Xx X: 20–41–52/53 X: (2-)22–26–39–61 |
|||
|
014–016–00–0 |
Xxxx: 1,3-xx(xxx-5-xx-1-xx)- 1,1,3,3-tetramethyldisiloxan x 1,3-di(hex-x-en-1-yl)- 1,1,3,3-tetramethyldisiloxan |
406–490–6 |
— |
N; X51–53 |
X X: 51/53 X: 61 |
|||
|
015–164–00–9 |
xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx dihydrát |
400–480–5 |
36669–85–9 |
R52–53 |
R:52/53 X: 61 |
|||
|
015–165–00–4 |
Směs: X, X, X', S''-tetrafenyl-4,4'-sulfandiylbis(fenylsulfonium)-bis(hexafluorofosfát) x xxxxxxx[4-(xxxxxxxxxxxxx)xxxxx]xxxxxxxxx-xxxxxxxxxxxxxxxx |
404–986–7 |
— |
Xx; X41 X; R50–53 |
Xi; X X: 41–50/53 S: (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 S: 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 S: 61 |
|||
|
601–051–00–7 |
4-xxxxxxxx-1-xx |
405–980–7 |
768–56–9 |
Xx; X38 X; X51–53 |
Xx; X X: 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; X X: 48/21/22–50/53–64 S: (1/2-)36/37–45–60–61 |
|||
|
602–084–00-X |
1,1-xxxxxxx-1-xxxxxxxxxx |
404–080–1 |
1717–00–6 |
X; R52–53–59 |
N X: 52/53–59 S: 59-61 |
|||
|
603–128–00–0 |
2-(xxxxxxxxxxxx)xxxxxxxx |
405–490–3 |
613–62–7 |
X53 |
X:53 X: 61 |
|||
|
603–129–00–6 |
1-xxxx-xxxxxxxxxxxx-2-xx |
406–180–0 |
57018–52–7 |
X10 Xx; X41 |
Xx X: 10-41 X: (2-)26-39 |
|||
|
603–130–00–1 |
Xxxx xxxxxxx: α-(xxxxxxxxxxxxxxxxx)-ω-xxxxxxxxxxx(xxxxxxxxxx) |
406–325–8 |
— |
Xx; X22 X52–53 |
Xx X:22–52/53 X: (2-)39-61 |
|||
|
603–131–00–7 |
Xxxx (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxxx)xxxxx]-X-xxxxxxxx |
407–290–1 |
— |
Xx; X41 |
Xx X: 41 X: (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 X: (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 X: (2-)22–36–61 |
|||
|
603–134–00–3 |
Xxxx: alkyl(C1-C10)-dodecyldifenylethery a xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (dodecyl x xxxxxxxxxx nerozvětvené) |
410–450–3 |
— |
R53 |
R: 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; R41 N; 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 X:43–52/53 X: (2-)24–37–61 |
|||
|
603–137–00-X |
Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 1-deoxy-1-[methyl(1-oxooktadecyl)amino]-D-glucitol |
411–130–6 |
— |
Xi; X41 |
Xx X: 41 X: (2-)26-39 |
|||
|
603–138–00–5 |
3-(2,2-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-xxxxxxxx-3-(3-xxxxxxxxxxx)xxxxxx-1-xx |
403–140–4 |
103694–68–4 |
X52–53 |
X:52/53 X: 61 |
|||
|
604–050–00-X |
4-xxxxx-x-xxxxxx 4-chlor-2-methylfenol |
216–381–3 |
1570–64–5 |
T; X23 X; R 35 N; X50 |
X; X; X X: 23–35–50 S: (1/2-)26–36/37/39–45–61 |
C ≥ 25 %: X; X; X23–35 10 % ≤ X &xx; 25 %: X;X20–35 5 % ≤ X &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 S: 61 |
|||
|
604–052–00–0 |
2,2'-xxxxxxxxxxx[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -xxxxxxxxxxxx-2-xx)- 4,4'-xxx(1,1,3,3-xxxxxxxxxxxxxxxx)- 2,2'-xxxxxxxxxxxxxxx |
403–800–1 |
103597–45–1 |
X53 |
X:53 S: 61 |
|||
|
604–053–00–6 |
4-xxxx - xxxxx-2-xxxxxx-6-(1-xxxxxxxxxxxxxxxx)xxxxx |
410–760–9 |
157661–93–3 |
Xx; R38 X43 X; R50–53 |
Xi; X X: 38–43–50/53 X: (2-)24–37–60–61 |
|||
|
604–054–00–1 |
Xxxx:2-xxxxxxx-4-(4-xxxxxxxxxxxxxxxxxxxxxxxxx-2-xx)xxxxx a 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -xxxxx-2-xx)xxxxx |
412–020–0 |
— |
X43 X52–53 |
Xx X:43–52/53 X: (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 X: (2-)22–36–37 |
|||
|
605–027–00–7 |
Xxxx:3x, 4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-karbaldehyd a 3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X - xxxxx-5-xxxxxxxxxxx |
410–480–7 |
— |
X43 X; R51–53 |
Xi; X R: 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-(X, N-dibutylamino)-2-hydroxy-2'-karboxybenzofenon 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx xxxxxxxx |
410–410–5 |
54574–82–2 |
X52–53 |
X:52/53 S: 61 |
|||
|
607–272–00–5 |
xxxxxxxxxxx-xxxxxx (XXX) [1] xxxxxxxxxx-xxxxxxxxx (ISO) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-butoxy-1-methylethyl)-[(4-amino-3,5-dichlor-6-fluor-2-pyridyl)oxy]acetát [2] |
279–752–9 [1] — |
81406–37–3 [1] 154486–27–8 [2] |
N; X50–53 |
X R: 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-[xxxxxx(xxxxxx)xxxxx]xxxxx}-3-xxxxxxxx-2-xxxxx |
405–350–1 |
54527–73–0 |
X43 N; X51–53 |
Xx; N 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) xxx(1-xxxxxxxxxxxxxx)]xxxxxxxxx komplex |
405–635–0 |
— |
Xi; X38–41 X; X50–53 |
Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61 |
|||
|
607–277–00–2 |
Směs:2-(hexylsulfanyl)ethylamin-hydrochlorid x xxxxxxx-xxxxxxxxx |
405–720–2 |
— |
Xx; X22 Xi; X41 X43 N; X51–53 |
Xx; X X: 22–41–43–51/53 X: (2-)24–26–37/39–61 |
|||
|
607–278–00–8 |
Směs:alkyl(C7-C9 xxxxxxxxxx a xxxxxxxxxxxx)-3-[3-(2 X - benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty |
405–760–0 |
— |
Xi; X41 X43 R52–53 |
Xi X: 41–43–52/53 S: (2-)24–26–37/39–61 |
|||
|
607–279–00–3 |
Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) x (xxxxxxxxxxxxxx)xxxxxxxxx-(xxxxxxxx-xxxxxx)-(xxxxxxxx-xxxxxxxx) |
405–960–8 |
— |
X43 X; X51–53 |
Xx; N X: 43–51/53 X: (2-)24–37–61 |
|||
|
607–280–00–9 |
4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx xxxxx xxxxxxx-4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx |
406–190–5 |
54322–20–2 |
Xx; X22 Xi; X36 X43 |
Xx X: 22–36–43 X: (2-)22–26–36/37 |
|||
|
607–281–00–4 |
Xxxx:xxxxx(X7-X9 rozvětvené x xxxxxxxx)-3-[3-(2X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx |
407–000–3 |
127519–17–9 |
X; R51–53 |
N 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 X43 X; X50–53 |
Xx; X X: 21/22–38–41–43–50/53 X: (2-)26–36/37/39–60–61 |
|||
|
607–284–00–0 |
Směs (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) x lithium-3,3'-{(1,4-fenylen)bis[(karbonylimino)(propan-3,1-diyl)imino]}bis(10-amino-6,13-dichlor[1,4]benzoxazino[2,3-b]fenoxazin-4,11-disulfonát) |
410–040–4 |
136213–76–8 |
N; X51–53 |
X X: 51/53 X: 61 |
|||
|
607–285–00–6 |
Směs:7-(3-aminobenzensulfonamido)naftalen-1,3-disulfonová xxxxxxxx, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx x xxxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx |
410–065–0 |
— |
X43 |
Xx X: 43 X: (2-)22–24–37 |
|||
|
607–286–00–1 |
Xxxx:xxxxxx- x 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 X:43–52/53 S: (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 X: 61 |
|||
|
607–288–00–2 |
[c-(N -{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 sůl; x = 15, 16, 17 xxxx 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 |
Směs (x xxxxxxxx poměru):amonium-1-alkyl(C14-C18)-4-[3-(allyloxy)-2-hydroxypropyl]-2-sulfonatobutandioát x xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx |
410–540–2 |
— |
Xx; R38 X43 X; X50–53 |
Xx; 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-(xxxxx(X14)xxx)-1-(xxxxxxxxxxxxx)]xxxxxx 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-XSměs: |
1-(2-aminoethyl)piperazin-1,4-diium-[(2,4,6-trimethylnonyl)fenoxy]benzendisulfonát x 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx |
410–650–0 |
— |
Xx; R41 X43 X; R51–53 |
Xi; X X: 41–43–51/53 S: (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 |
Směs:tetranatrium-fosfonobutandioát a xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx |
410–800–5 |
— |
X43 X; R51–53 |
Xi; X X: 43–51/53 X: (2-)24–37–61 |
|||
|
607–296–00–6 |
Směs:tetraestery pentaerythritolu, xxxxxxxxx xxxxxxxx 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; R41 |
Xi 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; X22 X43 X; X50–53 |
Xx; X X: 22–43–50/53 X: (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, x-xxxxxxxxxxxxxxxxxxxx]xxxxxxx komplex, xxxxxxxx xxx; x = 1,2,3 xxxx 4, b = 8, 9, 10 xxxx 11, x = 15, 16, 17 nebo 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 kyselina x dodekanoáty xxxxx(1-7)xxxxxxx |
411–860–5 |
— |
Xx; X38–41 X43 X; X51–53 |
Xx; X R: 38–41–43–51/53 S: (2-)24–26–37/39–61 |
|||
|
607–302–00–7 |
Xxxx:xxxxxxxxxxxxx xxxxxxxx x tetradekanoáty xxxxx(1-7)xxxxxxx |
411–910–6 |
— |
Xx; X38–41 X43 X; R51–53 |
Xi; 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 S: (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; X50–53 |
X X: 50/53 X: 60-61 |
|||
|
608–024–00–9 |
2-{4-[butyl(fenethyl)amino]fenyl}ethen-1,1,2-trikarbonitril |
407–650–8 |
97460–76–9 |
R53 |
R:53 X: 61 |
|||
|
608–025–00–4 |
[2-xxxxx-4,5-xxx(xxxxxxxxx)xxxxx]xxxxxxxxxxx |
410–970–0 |
117568–27–1 |
X53 |
X:53 S: 61 |
|||
|
609–053–00-X |
xxxxxxxxxxx-xxxxxxxxxxxxxxxx |
414–850–9 |
— |
X; X3 X; X8 Xxxx. xxx. 2; X45 T; X23/25 R43 |
E; X 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 C; X34 X43 N; X50–53 |
X; X X: 22–34–43–48/22–50/53 X: (1/2-)22–26–36/37/39–45–60–61 |
|||
|
611–043–00–5 |
Směs (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, [bis{6-[(2-amino-4-hydroxyfenyl)azo]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx trisodný 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 trisodný |
402–850–1 |
Xi 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 xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(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 x[(4(5)-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx) (3-xxxxx-5-xxxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx |
403–720–7 |
117527–94–3 |
X; X51–53 |
Xx; X41 X52–53 |
|||
|
611–045–00–6 |
2-({4-[(4-xxxxxxxxxxxx)xxxxxxxxxx]-2-xxxxxxxxxxx}xxx)-3-xxxxxx-5-xxxxxxxxxxxx |
404–830–8 |
— |
X53 |
X:53 S: 61 |
X X: 51/53 S: 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 N; X50–53 |
X; N X: 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 S: 61 |
|||
|
611–048–00–2 |
Xxxx (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[bis(2-acetoxyethyl)amino]fenyl}azo)-6,7-dichlorbenzothiazol |
407–900–6 |
111381–12–5 |
R53 |
R: 53 S: 61 |
|||
|
611–049–00–8 |
Směs (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, kyselina octová x xxxxxx xxxxxxxx (2:1:1) |
408–000–6 |
118658–98–3 |
Xx; X48/22 R43 X52–53 |
Xx X: 43–48/22–52/53 X: (2-(22–36/37–61 |
|||
|
611–051–00–9 |
2-({4-[ethyl(2-hydroxyethyl)amino]-2-methylfenyl}azo)-6-methoxy-3-methylbenzothiazolium-chlorid |
411–110–7 |
136213–74–6 |
N; X50–53 |
X X: 50/53 X: 60-61 |
|||
|
611–052–00–4 |
[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) azo]-6-[(6-sulfonato-1-naftyl)azo]benzen-1,3-diolato}]železnatý xxxxxxx, xxxxx xxx |
400–720–9 |
— |
X52–53 |
X: 52/53 X: 61 |
|||
|
612–156–00–2 |
Xxxx:xxxxxxxxxxxx(xxxxxx)xxxxxxx-xxxxxxx x xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx |
405–620–9 |
— |
Xx; X41 X; X50–53 |
Xx; X X: 41–50/53 S: (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 Xx; R41 X43 N; R51–53 |
Xn; X R: 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 a 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx komplex a 4-xxxxxxxxxxxxxxxxxxxxx |
410–820–4 |
— |
X53 |
X: 53 X: 61 |
|||
|
612–159–00–9 |
xxxxxxx xxxxxxxx xxxxx 2,2,4-xxxxxxxxx- x 2,4,4-trimethylhexan-1,6-diaminu (x seznamu EINECS), xxxxxxxx [(alkyl(C10-C16)oxy)methyl]oxiranu (Xxxxxx 8) x 4-methylbenzen-1-sulfonové xxxxxxxx |
410–880–1 |
— |
Xx; R22 C; X34 X; R50–53 |
C; X X: 22–34–50/53 X: (1/2-)23–26–36/37/39–45–60–61 |
|||
|
613–149–00–7 |
2-xxxx-xxxxx-5-[(4-xxxx-xxxxxxxxxxx)xxxxxxxx]-4-xxxxxxxxxxxxxx-3(2X)-xx |
405–700–3 |
96489–71–3 |
X; R23/25 X; X50–53 |
X; N 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 S: 61 |
|||
|
613–152–00–3 |
xxxxx-X-(4,6-xxxxxxxxxxxxxxxxxx-2-xx)xxxxxxxx |
406–600–2 |
89392–03–0 |
X43 X; R51–53 |
Xi; X X: 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 X: 61 |
|||
|
613–154–00–4 |
2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx |
410–050–9 |
5734–64–5 |
Xx; R22 |
Xn X: 22 X: (2-)22 |
|||
|
613–155–00-X |
5-chlor-2,3-difluorpyridin |
410–090–7 |
89402–43–7 |
R10 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-butyl-5-chlorimidazol-4-karbaldehyd |
410–260–0 |
83857–96–9 |
R43 X; X51–53 |
Xx; N X: 43–51/53 S: (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; R41 X43 X; X51–53 |
Xx; N 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; X25 Xn; X20 N; 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 X: (2-)22–30–35–36/37 |
|||
|
615–023–00–7 |
xxxxxxxxxxx 2-[(isokyanatosulfonyl)methyl]benzoové kyselinymethyl-2-[(isokyanatosulfonyl)methyl]benzoát |
410–900–9 |
83056–32–0 |
R10 X14 Muta. xxx. 3; X40 Xx; X20–48/22 Xx; X41 X42 |
Xx R: 10–14–20–40–41–42–48/22 X: (2-)23–26–36/37/39 |
|||
|
616–044–00–4 |
N-(3,5-dichlor-4-ethyl-2-hydroxyfenyl)-2-(3-pentadecylfenoxy)butanamid |
402–510–2 |
— |
N; 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 X53 |
Xx X: 43-53 X: (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; X50–53 |
X X: 50/53 X: 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′′′-(ethylendinitrilo)tetraacetamid |
406–640–0 |
— |
R43 |
Xi R: 43 X: (2-)24-37 |
|||
|
616–048–00–6 |
3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx |
406–740–4 |
1939–27–1 |
Xx; X48/22 N; X51–53 |
Xx; 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 X: 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'-bis(4-methylfenyl)-1,1'-(2-methyl-1,3-fenylen)dimočovina Směs:2,4-bis[3-(4-methylfenyl)ureido]toluen x 2,6-xxx[(3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx |
411–070–0 |
— |
X53 |
X: 53 X: 61 |
|||
|
617–015–00–9 |
xxx(4-xxxxxxxxxxxxx)xxxxxxx |
407–950–9 |
895–85–2 |
X; R2 X; R7 X; X50–53 |
X; X R: 2–7–50/53 X: (2-)7–14–36/37/39–47–60–61 |
|||
|
650–032–00-X |
xxxxxxxxxxxx (XXX) (2X, 3X)-, (2 X, 3 X)-, (2 X, 3 X)-, (2 X, 3 X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxx-1-(1X- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx |
— |
94361–06–5 |
Xxxx. kat. 3; X63 Xx; X22 X; X50–53 |
Xx; X X: 22–50/53–63 X: (2-)36/37–60–61 |
XXXXXXX 2
XXXXXX SPECIFICKÝCH XXXXX SPOJENÝCH X XXXXXXXXXXXX LÁTKAMI A XXXXXXXXX
Xxx směrnice Xxxxxx 2001/59/XX,
Xx. xxxx. L 332, 28.12.2000, x. 81.
XXXXXXX 3A
STANDARDNÍ XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI X PŘÍPRAVKY
Viz xxxxxxxx Xxxxxx 2001/59/ES,
Úř. xxxx. X 332, 28.12.2000, x. 81.
XXXXXXX 3X
XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X NEBEZPEČNÝMI XXXXXXX X XXXXXXXXX
Xxx xxxxxxxx Xxxxxx 2001/59/ES,
Úř. xxxx. X 332, 28.12.2000, x. 81.
XXXXXXX 4A
"B.10 XXXXXXXXXX — XXXXXXX XX XXXXXXXXXXXX XXXXXXX U XXXXX XX VITRO
1. XXXXXX
Xxxx xxxxxx xx xxxxxxxx metody OECD XX 473 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx u savců xx xxxxx (1997).
1.1 XXXX
Xxxxxxx xx chromozomové xxxxxxx x xxxxx xx xxxxx xx xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx savců (1, 2, 3). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx aberací: xxxxxxxxxxxx x chromatidové. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx látka xx schopnost xxxxxxxxx xxxxxxxxx xxxxxxx. Tato xxxxxx xxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxx xxxx jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx a xxxxxxxx xxxxx důkazů x xxx, xx xxxxxxxxxxxx xxxxxx a x xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx změny x xxxxxxxxxx x v xxxxxx somatických xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx u xxxxxxx x x xxxxxxxxx xxxxxx.
Xx zkoušce xx xxxxxxxxxxxx aberace xx xxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx, xxxxxxx kmeny xxxx primární xxxxxxx xxxxxxx. Xxxxxxx buňky xxxx vybrány xx xxxxxxx schopnosti xxxxx x kultuře, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx četnosti xxxxxxxxxxxxxx xxxxxxx.
Xxxxxxx xxxxxxxxx in xxxxx xxxxxx vyžadují xxxxxxx vnějšího xxxxxx xxxxxxxxxxx aktivace. Tento xxxxxxxxxxx xxxxxxxxx systém xxxxxx xxxxx xxxxxxxxx xxxxxxxx in xxxx x savců. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx výsledkům, xxx xxxxxxxxxx vlastní xxxxxxxxxx x xxxx k xxx xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).
Tato xxxxxxx xx xxxxxxx ke xxxxxxxx možných mutagenů x xxxxxxxxxxx xxx xxxxx. Mnoho xxxxxxxxx, xxx xxx je xxxx zkouška xxxxxxxxx, xxxx pro savce xxxxxxxxxxx; xxxx xxxxx xxxxxxxx a xxxxxxxxxxxxxx xxxx není xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx chemické xxxxx x xxxxxxxxx důkazy x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx touto xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx mechanismy xxx xxxxxx poškozením XXX.
Xxx xxxx Xxxxxx xxxx, část B.
1.2 XXXXXXXX
Xxxxxxxxxxxx aberace : xxxxxxxxxx poškození xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxxx chromatid nebo xxxxx x xxxxxxxx xxxxxxx chromatid.
Chromozomová aberace : strukturní xxxxxxxxx xxxxxxxxxx x podobě xxxxx xxxx xxxxx x xxxxxxx obou xxxxxxxxx x xxxxxx xxxxx.
Xxxxxxxxxxxxxxx : xxxxxx, xxx xxxxxx x xxxxx xx X-xxxx xxxxxxxxx DNA xxxxxxx x xxxxxx, xxxxx xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx xxxx xxxxxxxxxx xx 4, 8, 16… xxxxxxxxxxxx.
Xxx : xxxxxxxxxxxx léze xxxxx xxx šířka jedné xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.
Xxxxxxxxx xxxxx : xxxxx xxxxx, xxxxx xx xxxxxxxxx x metafázi, x xxxxxxxxx xxxxx xxxxx x xxxxxxxx; xxxxx stupeň proliferace xxxx xxxxxxxx.
Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx xxxxxxxxxx od normálního xxxxx xxxxxxxxx x xxxxxxxxx xxxx xxxxx.
Xxxxxxxxxxx : xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxxx sad (x), jiný xxx xxxxxxxxx (xx. 3 x, 4 x xxx.).
Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx dělení ve xxxxxx metafáze; jeví xx xxxx xxxxxx x fragmenty, intrachromozomální xxxx xxxxxxxxxxxxxxxxxx xxxxx.
1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX
Xxxxxxx xxxxxxx jsou xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. X předem xxxxxxxxxxx xxxxxxxxxxx po xxxxxxxx látce xx xx xxxxxxxxx kultur xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx kolchicin), xxxxxxx xx xxxxxx, xxxxxx x xxxxxxxxxx chromozomových xxxxxxx se xxxxxx xxxxxxxxxxxxxx pozorováním buněk.
1.4 XXXXX XXXXXXXX METODY
1.4.1 Xxxxxxxxx
1.4.1.1 Buňky
Mohou být xxxxxxx xxxxx buněčné xxxxx, kmeny nebo xxxxxxxx buněčné xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (např. fibroblasty xxxxxx xxxxxxxx, xxxxxxxxx xxxxxxxxx xxxx člověka xxxx jiných xxxxx).
1.4.1.2 Xxxxx x kultivační xxxxxxxx
Xxx xxxxxxxxx kultur xx měla xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x vlhkost). U xxxxxxxxxxxxxxx xxxxxxxxx linií x kmenů by xxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxx x mělo xx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx mykoplasmaty; x případě xxxxxxxxxxx xx xxxxxx být xxxxxxx. Pro použité xxxxx x inkubační xxxxxxxx xx měla xxx xxxxx xxxxxxxx xxxxx buněčného xxxxx.
1.4.1.3 Xxxxxxxx xxxxxx
Xxxxxxxxxxxxx xxxxxxx xxxxx a xxxxx: xxxxx se pomnoží x xxxxxxxxx kultur, xxxxxx xx xx xxxxxxxxxxxx xxxxx x xxxxxx hustotě, xxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx, x xxxxxxxx xx xxx 37 °X.
Xxxxxxxxx: krev ošetřená xxxxxxxxxxxxxxx (xxxx. heparinem) xxxx oddělené xxxxxxxxx xxxxxxxx probandů se xxxxxxx do xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. xxxxxxxxxxxxxxxx) x xxxxxxxx xx xxx 37 °C.
1.4.1.4 Xxxxxxxxxxx xxxxxxxx
Xxxxx xx měly xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx metabolickou xxxxxxxx a xxx xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je kofaktorem xxxxxxxx postmitochondriální frakce (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx indukujícím enzymy, xxxx je Xxxxxxx 1254 (6, 7, 8 x 9), xxxx směs xxxxxxxxxxxxx x β-xxxxxxxxxxxx (10, 11 x 12).
Postmitochondriální xxxxxx xx v xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % obj. Xxxx xxxxxxxxxxxxx aktivačního xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxx, která je xxxxxxxx. V xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.
Xxxx xxxxxxxx xxxxxx, xxxxxx přípravy xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx endogenní xxxxxxxx. Xxxxx použitých xxxxxxxxx linií xx xxxx být vědecky xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx P450 xxx metabolismus xxxxxxxx xxxxx).
1.4.1.5 Xxxxxxxx látka/příprava
Pevné xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou xxx přidány přímo x xxxxxxxxxx systémům x/xxxx xxxxx xxx xxxx aplikací xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx možnost skladování.
1.4.2 Xxxxxxxx podmínky
1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx
Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxx x s xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Vodu xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.
1.4.2.2 Xxxxxxxxx koncentrace
Mezi xxxxxxxx, která xxxx xxx zohledněna xxx xxxxxxxxx nejvyšší koncentrace, xxxxx cytotoxicita, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x změny xX xxxx xxxxxxxxxx.
Xxxxxxxxxxxx by xxxx být stanovena x xxxxxxxxxxxx xxxxxxxx x bez ní x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x růstu, xxxx xxxx xxxxxx xxxxxxxxxx, xxxxx životaschopných xxxxx xxxx mitotický xxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.
Xxxx by být xxxxxxx alespoň tři xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, xxx obvykle xxxxxxx, xx xx xx xxxxxxxxxxx xxxxxx xxxxx více xxxxx xxxxxxxx 2 xx Ö10. V xxxxxxxx xxxxxxx xx měla xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, xxxxx xxxxx xxxx xxxxxxxxxxx xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx je xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x xxxxxx xx xxxx, která xxxxxxxx xx xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx xxxxxxxxxx u xxxxxxxxxxx xxxxxx, u xxxxx xxxxx být xxxx xxxxxx xxxxxxxxx xxxxxxxx obtížné a xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx buněčného cyklu, xxxxxxxxx xxxxxxxx generační xxxx (XXX), xxxxx xxx xxxxxxx jako xxxxxxxxx xxxxxxxxx. X xxxxxxx XXX však xxx x celkovou xxxxxxxxx hodnotu, x xxx xxxxx usoudit xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, x x xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx xxxx xxx za následek xxxxx xxxxxxxxx oddálení xxxxxxxx optimálního xxxxxxx xxxxxxx.
X případě xxxxxxxxx xxxxxxxxxxxxxxx látek xx xxxx xxx maximální xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 mg/ml xxxx 0,01 X, xxxxx xxxx, xxxxx x xxxx je xxxxxxxx.
X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx xxxxxxx xxx xxxxxxxxxxxxx nižších, xxx xx xxxxxx xxxxxxxxxxx, xx měla být xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxx, xxx xx nad xxxx xxxxxxxxxxxx v xxxxxxxx xxxxxxxxxxx xxxxx xx xxxxx doby xxxxxxxx. X xxxxxxxx xxxxxxxxx (xxxx. xxxxxxx-xx xx xxxxxxxx xxxxx xxx xxxxxxx koncentracích, xxx xx rozpustnost) se xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, xxx xxxxx xxxxxxx xx xxxxxxx. Xxxx být xxxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x na xxxxx expozice, xxxxx xxxxxxxxxxx x testovacím xxxxxxx xx xxxx x průběhu xxxxxxxx xxxxx v xxxxxxxx xxxxxxxxxxx buněk, xxxx X9 xxx. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.
1.4.2.3 Xxxxxxxxx x pozitivní xxxxxxxx
Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxx rozpouštědla xxxx vehikula). Při xxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxx xxx xxx xxxxxxxxx kontrolu xxxxxxx xxxxxxxx xxxxx, xxxxx k xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx.
X xxxxxxxxx xxxxxxxx xx xxx xxx použit xxxxx elastogen x xxxxxxxxxxx xxxxxxxxxxxxx, které xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx pozadí, xxxx xx xxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx.
Xxxxxxxxxxx pozitivních xxxxxxx xx xxxx xxx zvoleny tak, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Příklady xxxxxxxxxxx a negativních xxxxxxx:
|
Xxxx metabolické xxxxxxxx |
Xxxxx |
Xxxxx XXX |
Xxxxx podle XXXXXX |
|
Xxx xxxxxx xxxxxxxxxxx aktivace |
methyl-methansulfonát |
66–27–3 |
200–625–0 |
|
ethyl-methansulfonát |
62–50–0 |
200–536–7 |
|
|
1-ethyl-1-nitrosomočovina |
759–73–9 |
212–072–2 |
|
|
mitomycin 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 mohou být xxxxxxx x jiné xxxxxx látky. Pro xxxxxxxxx kontrolu by xxxx xxx pokud xxxxx vzato v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx.
X okamžiku xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx skládající xx xx samotného xxxxxxxxxxxx xxxx xxxxxxxx x xxxxxxxxxxx médiu x xxxxxxxxxx stejným xxxxxxxx xxxx xxxxxxx. Xxxxx xxxx by xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené rozpouštědlo xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.
1.4.3 Xxxxxx
1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx
Xxxxxxxxxxxxx xxxxx xx xxxxxxx xxxxxxxx xxxxx xxx za přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx bez xxxx. Xxxxxxxx xxxxxxxxx by xxxx xxx zahájena xxx 48 xxxxx xx xxxxxxxxx xxxxxxxxx.
1.4.3.2 Xxx xxxxxx xxxxxxxxxxx xx měly xxx xxxxxxx použity xxxxxxxxxx xxxxxxx, x xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx pro xxxxxxxxx kontrolu xxxx xxxxxxxx xxxxxxxxxxxx. Jestliže xxx na xxxxxxx xxxxxxxxxxx xxxxx prokázat (13, 14), že xxxx xxxxxxxxxxxx kulturami xx xxxxxxxxx xxxxxx, xxxx xxx přípustné xxxxxxx jediné xxxxxxx.
Xxxxxx xxxx těkavé látky xx xxxx xxx xxxxxxxx xxxxxxxx metodami, xxxx. x xxxxx xxxxxxxxxx kultivačních nádobách (15, 16).
1.4.3.3 Doba xxxxxxx xxxxxx
X prvním xxxxxxxxxxx xx xxxx xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, xx xxxx 3 — 6 xxxxx, x xxxx xx xxx xxxxxxxx po xxxxxx době od xxxxxxxx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (12). Xxxxxxxx xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx jak x xxxxxxxx, xxx xxx xxxxxxxx, xxx by xxx xxxxxxxx dodatečný xxxxxxxxxx bez xxxxxxxx x xxxxxxxxxxxx expozicí xx xx odběru x xxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného xxxxx. Xxxxxx xxxxxxxx xxxxx xxx snáze xxxxxxxxx xxx dobách xxxxxxxx xxxx xxxxxx xxxxxxx xxx 1,5xxxxxxx délky xxxxx. Negativní xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. X xxxxxxxxx, xxx xx xxxxxxxxxx potvrzení xxxxxxxxxxx xxxxxxxx za xxxxxxxx, xx xxxx xxx xxxxxx xxxxxxxxxx.
1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx
Xx xxxxxxx xxxxxxx xx xxxxxxx 1-3 hodiny před xxxxxxxxx xxxxx Xxxxxxxx® xxxx xxxxxxxxx. Xxx xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx se xxxxx buněčná kultura xxxxxx x xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx analýzu chromozomů xxxxxxxx xxxxxxxxxxxx buněk, xxxxxx x xxxxxxxx xxxxx.
1.4.3.5 Xxxxxxx
Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx být xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx ke xxxxx části xxxxx x xxxxxxxx x xx xxxxxx xxxxxxxxxx, xxxx xx vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxx xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx buněk. Xx xxxxxx xxxxxxxxxxx a xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxx 200 dobře xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx mezi xxxxxxxxxx xxxxxxx. Xxxxx xxxxx 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 xxxxxxxxx je xxxxx a xxxx xx xxxx být xxxxxxxxxxx množství xxxxx xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx strukturních chromozomových xxxxxxx x jejich xxxxxx x četností. Xxxx xx zaznamenávají xxxxxxxx a uvádějí xx, xxx xxxxxxxxxx xx xx xxxxxxx xxxxxxxx xxxxxxx.
Xxxx xx xxx xxxx xxxxxxxxxxx xxxxxxxx, která xxxx xxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxx u xxxxx xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx kultur x xxxxxxxx experimentech s xxxxxxxxx.
Xxxx by xxx xxxxxxx údaje pro xxxxxxxxxx kultury. Xxxx xx xxxx xxx xxxxxxx xxxxx xxxxxxx xx xxxxx xxxxxxx.
Xxxxxxx xxxxx pozitivní xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxxx potvrdit negativní xxxxxxxx xxxx xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx parametrů studie x cílem rozšířit xxxxxx xxxxxxxxxxxx podmínek xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X parametrům xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x podmínky xxxxxxxxxxx xxxxxxxx.
2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX
Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx xxxxxx počtu. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.
Xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx mitotické xxxxxxx a indukovat xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx počtu xxxxx x endoreduplikovanými chromozomy xxxx znamenat, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx progresi xxxxxxxxx xxxxx (17, 18).
Xxxxxxxx xxxxx, xxxxx xxxxxxxx nesplňují výše xxxxxxx xxxxxxxx, xx x xxxxx xxxxxxx xxxxxxxx xx xxxxxxxxxxx.
Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo sporné xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx opakován.
Pozitivní xxxxxxxx xx zkoušky xx xxxxxxxxxxxx xxxxxxx in xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx savců xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.
3. XXXXXX
XXXXXXXX X XXXXXXX
Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx informace:
Rozpouštědlo/vehikulum:
- xxxxxxxxxx xxxxx vehikula,
- xxxxxxxxxxx x xxxxxxx zkoušené xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.
Xxxxx:
- xxx x xxxxx buněk,
- xxxxxxxxxx karyotypu x xxxxxxxx xxxxxxxxx typu xxxxx,
- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,
- xxxxxxxxx x xxxxx buněčného xxxxx,
- xxxxxxx dárce xxxx, xxx byla xxxxxxx xxxx krev nebo xxxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx,
- xxxxxxxx xxxxx xxxxxx,
- případně xxxxxx xxxxxxxxx buněčné kultury,
- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.
Xxxxxxxx podmínky:
- xxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxxxx, xxxx xxxxxxxxxxx x xxxxx xxxxxxxx buněk,
- xxxxxxxxxx výběru koncentrací x xxxxx xxxxxx, xxxxxx xxxx. xxxxx x xxxxxxxxxxxx a xxxxxx rozpustnosti, xxxx-xx x dispozici,
- xxxxxxx xxxxx, xxxxxxxx koncentrace XX2,
- xxxxxxxxxxx zkoušené xxxxx,
- objem xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,
- inkubační xxxxxxx,
- xxxxxxxxx xxxx,
- délka xxxxxxxx,
- xxxxxxxx xxxxxxx xxxxx při xxxxxxxx,
- xxx a xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxxxxxx,
- xxxxxxxxx x xxxxxxxxx xxxxxxxx,
- xxxxxx xxxxxxxx preparátů,
- kritéria xxxxxxxxx xxxxxxx,
- xxxxx xxxxxxxxxxxxx xxxxxxxx,
- metody xxxxxxxxx toxicity,
- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.
Xxxxxxxx:
- známky xxxxxxxx, xxxx. xxxxxx xxxxxxxxxx, xxxxx x buněčném xxxxx, počty xxxxx, xxxxxxxxx xxxxx,
- xxxxxx xxxxxxx,
- xxxxx x xX a osmolalitě xxxxxxxxxxx média, xxxxx xxxx xxxxxxxxx,
- xxxxxxxx xxxxxxx, včetně gapů,
- xxxxx buněk x xxxxxxxxxxxxxx aberacemi x xxxx xxxxxxx xxxxxx xxx xxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxxxx,
- xxxxx xxxxxxx, xxxxx xxxx pozorovány,
- podle xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,
- xxxxxxxx xxxxxxxxxxx xxxxxxx,
- xxxxx x xxxxxxxx negativní (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní xxxxxxxx,
- xxxxxxxxx xxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní xxxxxxxx x xxxxxxxxx, středními xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx.
Xxxxxx xxxxxxxx.
Xxxxxx.
4. XXXXXXXXXX
1) Xxxxx, X. X. (1976), Xxxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, xx: Chemical Xxxxxxxx, Xxxxxxxxxx xxx Xxxxxxx xxx xxxxx Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, X. (xx) Xxxxxx Xxxxx, New Xxxx xxx Xxxxxx, 1-29.
2) Ishidate, M. Xx., Xxxxxx, X. (1985), The Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Xxxxx Chinese Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Cells xx Xxxxxxx, xx: Progress xx Xxxxxxxxxx Research, Xxx. 5, Xxxxx, X. xx xx., (xxx) Xxxxxxxx Science Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.
3) Xxxxxxxx, S. X., Xxxxxxxxx, X. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxxxx, C., Xxxxx, A. D., Xxxxxxxx, X., Ahmed, X., Xxx, X., Xxxxx, X., Margolin, X. H., Xxxxxxx, X. A., Xxxxxxxx, X., Xxxxxx X. (1978), Chromozome aberration xxx xxxxxx chromatic xxxxxxxxx xx Xxxxxxx xxxxxxx ovary cells: Xxxxxxxxxx of 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.
4) Xxxxx, X., Xxxxxxxx, X. X., Marshall, X. X., Xxxxxxxx, X. Xx., Xxxxxxx, X., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx xxxxx Extreme Xxxxxxx Conditions. X xxxxxx from XXXXXX Xxxx Xxxxx 9, Xxxxxxxxxx Xxx., 257, 147-204.
5) Morita, X., Xxxxxx, T., Xxxxxx, X., Xxxxxxx, X., (1992), Xxxxxxxxxxxxxx xx xxx pH to Xxxxxxx Xxxxxxxx Xxxxxxxxx Xxxxx, Xxxxxxxxxx Res., 268, 297-305.
6) Xxxx, X. X., McCann, X., Yamasaki, X. (1975), Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx with xxx Xxxxxxxxxx/Xxxxxxxxx Microsome Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 31, 347-364.
7) Maron, X. M., Xxxx, X. N. (1983), Xxxxxxx Xxxxxxx xxx xxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 113, 173-215.
8) Natarajan, X. X., Tates, X. X., xxx Xxxx, P. P. X., Xxxxxxx, M., xx Xxxxx, X. (1976), Xxxxxxxxxxx Xxxxxxx xx Xxxxxxx/Xxxxxxxxxxx xxxxx Xxxxxxxxxx xx a Xxxxxxxxxxx Xxxxxx Xx xxxxx, X. Xxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xxx Xxxxxx Chromatid Xxxxxxxx xx Diethylnitrosamine (XXX) xxx Xxxxxxxxxxxxxxxxxxx (XXX) in XXX Xxxxx in the Xxxxxxxx xx Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.
9) Xxxxxxxx, X., Hayashi, M., Xxxxxxxx, X. Jr. (1979), Chromozomal Xxxxxxxxxx Xxxxx xx 29 Xxxxxxxxx Xxxxxxxx with X9 Xxx In xxxxx, Mutation Xxx., 66, 277-290.
10) Xxxxxx, X. X., Combes, X. X., Xxxxxxx, X. R., Xxxxxxxxx, X. X., Xxxxxx, X. G., Xxxxxx, X. M., Wolf, X. X. (1992), Xxxxxx of UK Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Party. Alternative xx Xxxxxxx 1254-induced X9 in Xx xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 175-177.
11) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), X. Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, xx: xx Xxxxxx, X. X., Xxxxx, J. X. Bend, J. X., Philpot, X. X. (eds), Xx xxxxx Xxxxxxxxx Activation xx Mutagenesis Testing, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.
12) Xxxxxxxx, X. X., Xxxxxxx, X. J., Xxxxxxxx, X. Jr., Xxxxx, J. L., Xxxxxxxx, X. J., Xxxxxx, X., Xxxxxxx, X., Xxxxxx, X. (1994), Xxxxxx xxxx Xxxxxxx Xxxxx on Xx xxxxx Xxxxx xxx Xxxxxxxxxxx Aberrations, Xxxxxxxxxx Xxx., 312, 241-261.
13) Xxxxxxxxxx, C., Xxxxxxxx, X. X., Xxxxx, X. A., Xxxxxxxx, G., Xxxxxxx, X. X., Xxxxxxxx, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx xxxxx Cytogenetic Xxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Kirkland, X. X., (xx) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 141-154.
14) Xxxxx, X. A., Xxxxxxxx, X. X. (1994), Xxxxxxxxx Xxxxxx xxx xxx Xxxxxxxxx xxx Xx xxxxx Xxxxxxxxxx Xxxxxxxxxx Xxxxxx xx XXX Xxxxx, Mutatation Xxx., 312, 139-149.
15) Xxxxx, X. F., Xxxxxx, X. X., XxXxxxx, K. X. (1982), CHO/HGPRT Mutation Xxxxx: Xxxxxxxxxx xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Xxxxx, X. X., Schaich, X. M. (eds), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.
16) Xxxxxx, P. O., Xxxxxx, J. X., Xx, X. X., Xxxxxx, A. X. (1983), Evaluation xx xx Xxxxxxxx System Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Highly Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxx., 5, 795-801.
17) Xxxxx-Xxxxx, X. (1983), Endoreduplication xx Chinese xxxxxxx xxxxx xxxxxx xxxxx-xxxxxxxxx xxxxxxx X2 arrest, Xxxxxxxxxx Xxx., 119, 403-413.
18) Xxxxx, X., Xxxxxx, X., Trosko, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx in Xxxxxxx xxxxxxx xxxxx, Xxxxxx Res., 43, 1362-1364."
XXXXXXX 4X
"X.11 MUTAGENITA–ZKOUŠKA XX XXXXXXXXXXXX XXXXXXX X BUŇKÁCH XXXXXX XXXXX XXXXX IN XXXX
1. XXXXXX
Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX TG 475 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx v xxxxxxx xxxxxx xxxxx xxxxx (1997).
1.1 XXXX
Xxxxxxx xx chromozomové aberace x savců xx xxxx je používána xxx xxxxxxx strukturních xxxxxxxxxxxxxx aberací xxxxxxxxxxxx xxxxxxxxx látkou v xxxxxxx xxxxxx dřeně xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx — xxxxxxxxxxxx x xxxxxxxxxxxx. Nárůst xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. V xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované xxxxxxx chromatidového xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxx xxxx xxxxxxxx xxxxx geneticky xxxxxxxxxxx chorob x xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, že chromozomové xxxxxx x xxxxxxxxxxx xxxx způsobující xxxxx x onkogenech x x genech xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxxxxxxxxx xxxxxxxxx.
Xxx xxxx xxxxxxx jsou rutinně xxxxxxxxx hlodavci. Xxxxxxx xxxxx je v xxxx xxxxxxx kostní xxxx, poněvadž xx xxxxxx xxxxxxxxxxxxxxxx xxxxx x xxxxxxxx populaci xxxxx s rychlým xxxxxx, které xx xxxxxx xxxxxxx x xxxxxxxxxxxx. Jiné xxxxx x xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxx.
Xxxx zkouška xx xxxxxxxxxxxx aberace je xxxxxxx xxxxxx k xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx DNA, xxxxxxx xx xxxxx x xxxxxxx druhů x xxxxx xxxxx. Xxxxxxx xx xxxx xx xxxxxx xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx xxxxxx zjištěných xxxxxxxx in xxxxx.
Xxxxxxxx xxxxxxxx xxxxx o xxx, xx se xxxxxxxx látka xxxx xxxxxxxxx xxxxxxxxxx nedostanou xx cílové xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.
Xxx také Xxxxxx úvod, xxxx X.
1.2 XXXXXXXX
Xxxxxxxxxxxx xxxxxxx : strukturní xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxxx chromatid xxxx zlomu a xxxxxxxx xxxxxxx chromatid.
Chromozomová xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu v xxxxxx xxxxx xxxx xxxxx a xxxxxxx xxxx chromatid x xxxxxx místě.
Endoreduplikace : xxxxxx, xxx xxxxxx x xxxxx xx X-xxxx xxxxxxxxx XXX xxxxxxx k xxxxxx, xxxxx následuje xxxxx X-xxxx. Výsledkem xxxx xxxxxxxxxx xx 4, 8, 16,… chromatidami.
Gap : xxxxxxxxxxxx léze xxxxx xxx xxxxx xxxxxxx chromatidu x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.
Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx xxxxxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx x xxxxxxxxx xxxxx.
Xxxxxxxxxxx : xxxxxxx xxxxxxxxxxx počtu xxxxxxxxxxxxxx xxx (x), xxxx xxx xxxxxxxxx (xx. 3 n, 4 x atd.).
Strukturní aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx buněčném dělení xx xxxxxx xxxxxxxx; xxxx xx jako xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx interchromozomální xxxxx.
1.3 PODSTATA XXXXXXXX XXXXXX
Xxxxxxx jsou vystavena xxxxxxxx xxxxx xxxxxxx xxxxxxxx x ve xxxxxxx xxxxxxxx xx xxxxxxxx xx xxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx metafázi (např. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx xxxxxx xxxxx xx xxxx xxxxxxxx preparáty xxxxxxxxxx, xxxxxx xx x xxxxxxxxx se xxxxxxxxxxxx xxxxxxx buněk x xxxxxxxx.
1.4 POPIS ZKUŠEBNÍ XXXXXX
1.4.1 Xxxxxxxxx
1.4.1.1 Xxxxx xxxxx xxxxxxx
Xxxxx xx xxxxxxxx potkan, xxx x křeček čínský, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx savčí xxxx. Xxxx xx xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx kmeny xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx studie xx měla xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx by u xxxx xxxxxxx překročit ± 20 % xxxxxxx hodnoty hmotnosti.
1.4.1.2 Xxxxxxxx xxxxx a xxxxxx
Xxxxx xxxxxx podmínky xxxxx xxxxxxxx úvodu x části B, xxxxxxx by xxxx xxx dosaženo xxxxxxxx xxxxxxx 50 – 60 %.
1.4.1.3 Příprava xxxxxx
Xxxxxx xxxxx pohlavně xxxxxxx xxxxxxx se xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx skupinu x skupinu, xxxxx xx xxxxxxx xxxxxxxx xxxxx. Xxxxx by xxxx xxx uspořádány xxx, xxx xxx xxxx jejich polohy xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Nechají xx x laboratorních xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat.
1.4.1.4 Xxxxxxxx xxxxx
Xxxxx xxxxxxxx xxxxx xx měly být xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx být xxxx xxxxxxx zředěny. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx údaje o xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.
1.4.2 Xxxxxxxx xxxxxxxx
1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx
Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx použitých xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx látkou. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx možno xxxxxxxx xxxxxx použití vodných xxxxxxxxxxxx/xxxxxxx.
1.4.2.2 Xxxxxxxx
Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx pozitivní a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx obě pohlaví. X xxxxxxxx xxxxxxxx xxxxxxxx látky xx xxxx zvířata xxxxxxxxx xxxxxxx podstoupit xxxxxxxxx xxxxxx jako xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx k xxxxxxxx.
Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx strukturní xxxxxxx xx xxxx xxx expozičních xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx preparátu. Je xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx xxxxx x xxx xxx xxxxx x jejím xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxx xxxxx ze xxxxxx xxxxxxxx třídy, xxxx-xx k dispozici. Xxxxxxxx xxxxx xxx 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 C |
50–07–7 |
200–008–6 |
|
cyklofosfamid |
50–18–0 |
200–015–4 |
|
cyklofosfamid 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 proveden xxxxx x xxxxxxxxxxx xxxxxxx, xxxx je xxxxxxxxxx pouze rozpouštědlo xxxx xxxxxxxxx a xxx xxxxx podstupují xxxxxx proces xxxx xxxxxxxxxx xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx údajů x xxxxxxxxx přijatelné údaje x xxxxxxxxxxx xxxxxx x četnosti xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx kontrolu xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx prvního xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.
1.5 POSTUP
1.5.1 Počet x xxxxxxx xxxxxx
Xxxxx xxxxxxxxxx x kontrolní xxxxxxx se skládá x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx. Xxxxxxxx xxxx x xxxx xxxxxx x dispozici xxxxx ze studií xx xxxxxxx xxxxxx x za xxxxxxx xxxxxxxx způsobu expozice, xxx xxxxxxxxx, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx v xxxxxxxx, xxxx postačující zkoušení xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx určité xxxxxxx, xxxx xx tomu xxxxxxxxx x některých xxxxxxxxxxxxxxx látek, xxxx xx xxx xxxxxxx xxxxxxxxx se xxxxxxx xxxxxxxxxxxxxx xxxxxxx.
1.5.2 Xxxx xxxxxxxx
Xxxxxxxx látky xx xxxx xxx xxxxx xxxxx podávány jednorázově. Xxxxxxxx látky xxxxx xxx xxxxxxxx xxxx xx dvou dávkách, xxx. xxx dávky x xxx xxx x rozmezí xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx podávání xxxxxxx xxxxxx materiálu. Xxxx xxxxxx podávání by xxxx xxx xxxxxxx xxxxxxxxxx.
Xxxxxx xx xxxx xxx odebrány ve xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxx podané x xxxxxx xxx. X xxxxxxxx xx xxxxx xxxxxxx xx xxxxxx xxxx xx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu (xxxx xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx a xxxxxxxxxxxx zkoušené xxxxx x xxxxxx xxx xxxxxx na xxxxxxxx xxxxxxxxx xxxxx xxxx xxx xxxx xx xxxxxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx xx provést xxxxx xxxxx xx 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxx xxx, měl xx xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx aplikace, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného xxxxx.
Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx podá xxxxxx dávka xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx x zvířat odběr. X myši xx xxxx doba xxxxxxxxx 3 — 5 x; u křečka xxxxxxxx xx xxxx xxxx přibližně 4 — 5 h. X xxxxxx xxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xx xx chromozomové xxxxxxx.
1.5.3 Xxxxxxxxx
Xxxxxxx-xx se xxxxx xxxxxxxxxxx vhodných dostupných xxxxx studie xxx xxxxxxxx rozsahu dávek, xxxx by xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, pohlavím x xx stejného xxxxxx xxxxxxxx, xxx xx použijí x xxxxxx xxxxxx (5). X případě toxicity xx xxx první xxxxx použijí xxx xxxxxx xxxxx. Tyto xxxxxx dávky xx xxxx pokrývat xxxxxxx xxxx maximální a xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx je xxxxxxxxxx jako dávka xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že xxxxx xxxxx xx xxxxx xxx stejném xxxxxx xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a mitogeny) xxxxxx xxxxxxxxx stanovení xxxxx vyhovovat a xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx být xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x xxxxxx xxxxx některé známky xxxxxxxx (např. více xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).
1.5.4 Xxxxxxx xxxxxxx
Xxxxxxxx xxxxxxx x jednou dávkou xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx xxxx dávkách v xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx údajů x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx studie xx třemi úrovněmi xxxxx xx xxxxxxxxx. X xxxx trvajících xxxxxx je xxxxxxx xxxxxx pro 14denní xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den a xxx delší než 14xxxxx aplikaci je xxxxxxx xxxxxx 1000 xx/xx tělesné hmotnosti/den. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx potřebu xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.
1.5.5 Xxxxxxxx xxxxx
Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx xxxxxxxx jsou x odůvodněných případech xxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx najednou podán xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx neměl xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx objem, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích vykazují xxxxxxxx xxxxxx, by xxxx xxx variabilita xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx při xxxxx úrovních xxxxx.
1.5.6 Xxxxxxxx xxxxxxxxx pro xxxxxxx xxxxxxxxxx
Xxxxx xx xxxxxxxx xx odebere xxxxxx dřeň, hypotonizuje xx x fixuje. Xxxxx se xxxxxxx xx xxxxxxxx sklíčka x xxxxxx xx.
1.5.7 Xxxxxxx
Xxxx měřítko xxxxxxxxxxxx xx měl být x xxxxx exponovaných xxxxxx (včetně pozitivních xxxxxxx) x x xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx, x xx xxxxxxx u 1000 buněk na xxxxx xxxxx.
X každého xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx. Xxxxx xxxxx lze snížit, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx zlomům xxxx ke ztrátě xxxxxxxxxx u části xxxxx x xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.
2. ÚDAJE
2.1 XXXXXXXXXX VÝSLEDKŮ
Údaje xxx xxxxxxxxxx zvířata xx xxxx xxx zpracovány xx xxxxx tabulky. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Pro xxxxx xxxxx xx xxx xxx vyhodnocen xxxxx xxxxx, xxxxx xxxxxxx xx xxxxx x xxxxx buněk x xxxxxxxxxxxxx aberací (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx xxxxx typy xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx obecně xx xxxxxxxxxx xx celkové xxxxxxxx xxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx mezi xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.
2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX
Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx buněk x xxxxxxxxxxxxxx aberacemi v xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx buněk s xxxxxxxxx xxx xxxxxxx x určitou xxxxxx x x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx xxxx xxx xxxxxxx biologická relevance xxxxxxxx. Při hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným určujícím xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx výsledky xx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravami xxxxxxxxxxxxxxxx podmínek.
Nárůst xxxxxxxxxxx xxxx xxxxxxxx, že xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxx xxxxx buněk s xxxxxxxxxxxxxxxxxxx xxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxx xxxxxxxx buněčného xxxxx (7, 8).
Zkoušená xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx uvedená xxxxxxxx, se xxxxxxxx x xxxxx xxxxxxx xx xxxxxxxxxxx.
Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx látky. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx na to, xxxxxxxx je xxxxxxxxxx xxxxxxxx.
Xxxxxxxxx výsledky xxxxxxx xx chromozomové aberace xx xxxx xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx v xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx aberace. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx neindukuje x xxxxxx xxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.
Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx xxxxxxxx xxxxx nebo její xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, nebo xxxxxxxxxx xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).
3. XXXXXX
XXXXXXXX X XXXXXXX
Xxxxxxxx x xxxxxxx xxxx obsahovat tyto xxxxxxxxx:
Xxxxxxxxxxxx/xxxxxxxxx:
- xxxxxxxxxx xxxxx xxxxxxxx,
- xxxxxxxxxxx x xxxxxxx zkoušené látky x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.
Xxxxxxxxx xxxxxxx:
- použitý xxxx/xxxx,
- xxxxx, stáří x xxxxxxx xxxxxx,
- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,
- xxxxxxxxxxxx xxxxxxxx zvířat na xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx pro xxxxxx skupinu.
Zkušební xxxxxxxx:
- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,
- údaje xx studie pro xxxxxxxx xxxxxxx, xxxxx xxxx provedena,
- zdůvodnění xxxxxxxxx úrovní xxxxx,
- xxxxx x přípravě xxxxxxxx xxxxx,
- údaje x podávání xxxxxxxx xxxxx,
- xxxxxxxxxx způsobu xxxxxxxx,
- popřípadě xxxxxx xxxxxxx, xxx xx xxxxxxxx látka dostala xx xxxxxxxx xxxxx xxxx xx xxxxxx xxxxx,
- případně přepočet xxxx xxxxxxxxxxx xxxxxxxx xxxxx x krmivu xxxx xxxx (xxx) xx odpovídající dávku (xx/xx tělesné hmotnosti/den),
- xxxxxxxx xxxxx o xxxxxxx xxxxxx x xxxx,
- xxxxxxxx popis xxxxxxx expozice x xxxxxx,
- xxxxxx xxxxxxxxx xxxxxxxx,
- xxxxxxxxxxxx xxxxx xxxxxxxxxxx metafázi, xxxx xxxxxxxxxxx x xxxxx xxxxxxxx,
- xxxxxx xxxxxxxx xxxxxxxxx,
- kritéria xxxxxxxxx xxxxxxx,
- xxxxx xxxxxxxxxxxxx xxxxx na jedno xxxxx,
- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou.
Výsledky:
- xxxxxx toxicity,
- xxxxxxxxx xxxxx,
- typ x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,
- celkový počet xxxxxxx xx xxxxxxx xx xxxxxxxxx hodnotami x xxxxxxxxxxxx xxxxxxxxxx,
- xxxxx xxxxx x xxxxxxxxx ve xxxxxxx xx xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx,
- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,
- podle xxxxxxxx závislost xxxxxxxx xx dávce,
- xxxxxxxx xxxxxxxxxxx xxxxxxx,
- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,
- xxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,
- xxxxx x xxxxxxxx xxxxxxxxx kontrole.
Rozbor xxxxxxxx.
Xxxxxx.
4. XXXXXXXXXX
1) Adler, X. D. (1984), Xxxxxxxxxxx Xxxxx in Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, S. Xxxxxx, X. M. Parry (xxx), XXX Xxxxx, Xxxxxx, Xxxxxxxxxx D. X., 275-306.
2) Xxxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, X., Xxxxxx, H., XxXxx, X. X., Xxxxxx, M. (1987), Xxxxxxxxx Xx xxxx Xxxxxxxxxxx Xxxxxx: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xx Xxxx Marrow Xxxxx, Xxxxxxxxxx Res., 189, 157-165.
3) Richold, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxxxxx, X. G., Xxxxxxx, X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Assays, xx: X. J. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx I xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.
4) Xxxx, X. R., Hayashi, X., XxxXxxxxxx, X. X., Xxxxxxxx, D., Xxxxxx, X. H., Xxxxxx, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx Xx., X. B., Xxxxxxxxxxxx, X., Xxxxxxx, X. J., Xxxxxxx, X., Shimada, X., Xxxxx, S., Xxxxxxx, X. (1994), Report xxxx xxx Working Xxxxx xx xxx xx vivo Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.
5) Xxxxxxx, R. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, P. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, D. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.
6) Xxxxxx, X. X., Xxxxxxxx, D., Xxxxxxxx, X., Amphlett, X. X., Xxxxx, G., Xxxxxxxx, X., Richold, X., Xxxxxxxx, X. X., Xxxxxx, J. X. K. (1989), Xxxxxxxxxxx Analysis of Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, X. X. Xxxxxxxx (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.
7) Xxxxx-Xxxxx, C. (1983), Xxxxxxxxxxxxxxxxx in Chinese xxxxxxx cells xxxxxx xxxxx-xxxxxxxxx-xxxxxxx X2 xxxxxx, Xxxxxxxxxx Res., 119, 403-413.
8) Xxxxx, X., Xxxxxx, C., Trosko, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx xx Xxxxxxx hamster xxxxx, Xxxxxx Xxx., 43, 1362-1364."
XXXXXXX 4C
"B.12 XXXXXXXXXX–XXXX XXXXXXX XXXXXXXXXXXXXXX XXXXXXXXXX XX XXXX
1. METODA
Tato xxxxxx xx xxxxxxxx xxxxxx OECD XX 474 — Test xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx (1997).
1.1 XXXX
Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxx poškození chromozomů xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, které je xxxxxxxxxx zkoušenou xxxxxx, x xx pomocí xxxxxxx erytrocytů xxxxxxxxxx x kostní xxxxx x/xxxx buněk periferní xxxx, xxxxxxx xxxxxxxx.
Xxxxxx xxxxx savčích erytrocytárních xxxxxxxxxx xx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxx je tvorba xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxx xxxxxxxxx nebo xxxx xxxxxxxxxx.
Xxxx xx xxxxxxxxxxx xxxxxx xxxxx xxxx xx xxxxxxxxxxxxxxx erytrocyt, xxxxxx jádro xx xxxxxxxx x mikrojádra, xxxxx při xxx xxxxx xxxxxxxxx, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx mikrojader je x těchto xxxxxxx xxxxxxxxx tím, že xxxxxxxxxx xxxxxx xxxxx. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx s mikrojádry x exponovaných zvířatech xx xxxxxxx indukovaného xxxxxxxxxxxxxx xxxxxxxxx.
X xxxxx xxxxx je xxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxxxx xxxx xxxx xxxxxxxxx polychromatické xxxxxxxxxx. Xxxxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx v periferní xxxx xx rovnocenně xxxxxxxxxx x kteréhokoli xxxxx, u něhož xxxx prokázána neschopnost xxxxxxx odstraňovat xxxxxxxxxx x mikrojádry, xxxx xxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, které xxxxxxxxx xxxxxxxxxx nebo xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxxxxx xxx xxxxxxxx řadou xxxxxxxx. Ta xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx centromerní (xxxxxxxxxxxx) XXX x xxxxxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx. Xxxxx zralých (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx x periferní xxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxxxxxxxx na xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx xxxx xxxxxxx xxxxxxxx xxxxxxx, jestliže xxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxx xxxx.
Xxxxx test savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx a procesy xxxxxxxx XXX, xxxxxxx xx mohou lišit x xxxxxxx xxxxx x xxxxx, xxxxx x x xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxx je xxxxxx xxxxxxxx pro xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx v xxxxxxxxx xx xxxxx.
Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx zkoušená xxxxx xxxx reaktivní xxxxxxxxxx nedostanou xx xxxxxx xxxxx, není xxxxxx tuto xxxxxxx xxxxxx.
Xxx také Xxxxxx xxxx, část B.
1.2 XXXXXXXX
Xxxxxxxxxx (kinetochor) : xxxxxx (xxxxxxx) xxxxxxxxxx, x níž (x xxxx) xx xxxxx xxxxxx xxxxx xxxxxxx xxxxxx vřeténko xxxxxxxxxx xxxxxxxxxx pohyb xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxx xxxxx.
Xxxxxxxxxx : xxxx xxxxx existující xxxxxxxx xx hlavních xxxxx a vedle xxxx, vytvářená během xxxxxxxx mitosy (xxxxxx) xxxxxxxxxxxxxxx se (lagging) xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxx xxxxxxxxxx.
Xxxxxxxxxxxxxxxx xxxxxxxxx : xxxxx xxxxxxxxx xxxxxxxxxxxx ribozomy, xxxxx xxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx selektivním xxx xxxxxxxx.
Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx erytrocyt ve xxxxxxxxx mezistadiu, xxxxx xxxxx xxxxxxxx ribozomy, x xxxx xxx xxxx rozlišen od xxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx selektivním xxx xxxxxxxx.
1.3 XXXXXXXX XXXXXXXX XXXXXX
Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Xxx použití xxxxxx xxxxx se xxxxxxx xx xxxxxxx xxxxxxxx po xxxxxxxx xxxxxx, odebere xx xxxxxx xxxx, xxxxxxxx xx xxxxxxxxx x xxxxxx se (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx xxxxxxxxx xxxx se xxxx xx vhodném xxxxxxxx xx xxxxxxxx xxxxxxx, xxxxxxxxxx se připraví xxxxxxxx a xxxxxx xx (4, 8, 9, 10). Xxx xxxxxxxx s periferní xxxx xx měla xxxx poslední xxxxxxxx x sklizením xxxxx xxxxxxxx xx nejkratší xxxx. Xxxxxxxxx xxxx xxxxxxxxxxx na xxxxxxxxxx xxxxxxxxxx.
1.4 XXXXX ZKUŠEBNÍ XXXXXX
1.4.1 Xxxxxxxxx
1.4.1.1 Xxxxx xxxxx xxxxxxx
Xxx použití xxxxxx dřeně xx xxxx xxxxxxxxx xxxxx xxxxxxxxxx xxx nebo xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxx xxxxxxx periferní krve xx xxxxxxxxxx xxx. Xxx však xxxxxx xxxxxxxx vhodný druh xxxxx xx xxxxxxxxxxx, xx xxx x xxxx, u xxxxx xxxxxxx xxxxxxxxxxxx erytrocyty x xxxxxxxxxx, xxxx xxxx xxxxxxxxxx dostatečnou xxxxxxxxx xxxxxxxxx činitele, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx xxxxx xxxxxxx laboratorní kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx zahájení xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx u xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.
1.4.1.2 Xxxxxxxx chovu a xxxxxx
Xxxxx xxxxxx xxxxxxxx xxxxx obecného xxxxx x části X, xxxxxxx xx xxxx xxx dosaženo xxxxxxxx xxxxxxx 50 – 60 %.
1.4.1.3 Xxxxxxxx xxxxxx
Xxxxxx mladá pohlavně xxxxxxx xxxxxxx se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x skupinu, x xxx xx xxxxxxx xxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx. Klece xx xxxxxxxxxx tak, xxx xxx vliv xxxxxx polohy minimalizován.
1.4.1.4 Xxxxxxxx xxxxx
Xxxxx zkoušené xxxxx xx měly xxx xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx být podávány xxxxx xxxx xxxxx xxx xxxx podáním xxxxxxx. Xxxx xx xxx použity xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.
1.4.2 Xxxxxxxx podmínky
1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx
Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx mít xxx xxxxxxxxx xxxxxxxx xxxxx toxické účinky x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx látkou. Xxxx-xx xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx být jejich xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul.
1.4.2.2 Xxxxxxxx
Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx měla xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx identický proces xxxx zvířata xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.
Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xx xxxx při expozičních xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx detekovatelný xxxxxx xxx pozadí. Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxx, aby byl xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx identifikace xxxxxxxxx. Xx přijatelné, xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx jiným způsobem xxx zkoušená xxxxx x aby xxx xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx navíc může xxx xxxxx x xxxxx použití xxxxxxxxxx xxxxx ze stejné xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx pro pozitivní 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 měl xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a která xxxxx podstupuje stejný xxxxxx jako xxxxxxxxxx xxxxxxx, xxxxx nejsou x dosavadních xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx x xxxxxxxxxx. Provádí-li xx xxx negativní xxxxxxxx xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx doba xxxxxxx xxxxxx. Xxxxx xxxx xx měly xxx neexponované xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx rozpouštědlo/vehikulum xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.
Při xxxxxxx xxxxxxxxx krve xxxx xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxx krve odebraný xxxx expozicí, xxxxx xxxx u krátkých xxxxxx s periferní xxxx (xxxx. 1 — 3 aplikace) xx předpokladu, že xxxxxxxx údaje budou x rozpětí, xxxxx xx na základě xxxxxxxxxxx kontrol očekává.
1.5 XXXXXX
1.5.1 Xxxxx a xxxxxxx xxxxxx
Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx xxxxxxx x alespoň xxxx xxxxxxxxxxxxxxxx zvířat pro xxxxx xxxxxxx (11). Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx se xxxxxxx xxxxxx a xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx xxxxxxx pohlaví. Xx-xx expozice xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx například u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by být xxxxxxx provedena xx xxxxxxxx odpovídajícího pohlaví.
1.5.2 Xxxx xxxxxxxx
Xxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxx (xx. xxxxx, dvě xxxx xxx xxxxxxxx x xxxxxxxxx 24 xxxxx). Vzorky xx xxxxxx s xxxxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxxx xx x xxxxxx studií xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –v xxxxxxx xxxxxxxxxxx studií — xxxxx xxxx prokázána xxxxxxxx nebo byla xxxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxxx xx xx xxxxxxxx xxxxxx. Zkoušené xxxxx xxxxx být xxxxxxxx xxxx ve xxxx xxxxxxx, xxx. xxx xxxxx v xxx xxx x xxxxxxx xx xxxx než xxxxxxxx hodin, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx objemů xxxxxxxxx.
Xxxx xxxx xxx xxxxxxxx xxxxx xxxxxxx:
x) xxxxxxxx xxxxx se xxxxxxxx xxxxxxxx jednou. Xxxxxx xxxxxx xxxxx xx xxxxxxxx alespoň xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 24 hodin xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 hodin xx xxxxxxxx a x xxxxxxxxxx xxxxxxxx xxxx odběry. Xxxxx xxxxx než 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx periferní xxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx první xxxxx xx provede xxxxxxxx 36 xxxxx xx xxxxxxxx a xxxxxxxx xxxxxxxxxx 72 xxxxx xx xxxxxxxx x xx prvnímodběru xx dodrží xxxxxxxxxxxx xxxxxx. Je-li xx xxxxxx odběru xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx odběr nutný;
b) xxxx-xx xxxxxxxx dvě xxxx xxxx dávek xxxxx (xxxx. xxx xxxx více xxxxx x xxxxxxxxx 24 xxxxx), měly xx xxx vzorky xxx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx xx 18 až 24 xxxxxxxx xx xxxxxxxx xxxxxxxx a při xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).
Xxxxx xxxxxxx mohou xxx xxxxx xxxxxxx xxxx xxxx xxxxxx.
1.5.3 Xxxxxxxxx
Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx studie xxx xxxxxxxx xxxxxxx dávek, xxxx xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, xxxxxxxx x xx stejného xxxxxx expozice, jež xx použijí v xxxxxx studii (13). X případě xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx xxxxxx známky xxxxxxxx, že xxxxx xxxxx xx xxxxx xxx stejném xxxxxx xxxxxxxxx podle xxxxxxxxx x letalitě. Látky xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx případ xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx erytrocytů x celkového množství xxxxxxxxxx x xxxxxx xxxxx xxxx x xxxxxxxxx krvi).
1.5.4 Limitní xxxxxxx
Xxxxxxxx zkouška x xxxxxx dávkou x xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo ve xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx údajů x látkách, které xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, není xxxxxxxxxx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X déle xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den x xxx xxxxx než 14xxxxx xxxxxxxx xx xxxxxxx dávkou 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx potřebu xxxxxx x limitní xxxxxxx xxxxx úroveň xxxxx.
1.5.5 Xxxxxxxx xxxxx
Xxxxxxxx xxxxx xx xxxxxxx xxxxxx nitrožaludečně, žaludeční xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx podávání jsou xxxxxxxxxx v odůvodnitelných xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx podán xxxxxxxxx xxxxxx nebo xxxxxxxx, závisí na xxxxxxxxx testovacího zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx xx uvedený xxxxx, xxxx být xxxxxxxxxx. Až xx xxxxxxxx a xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx měla xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx všech xxxxxxxx xxxxx.
1.5.6 Příprava xxxxxx xxxxx xxxx krve
Buňky xxxxxx xxxxx se xxxxxxx xxxxxxxxx z xxxxxx nebo xxxxx xxxxx xx xxxxxxxx. Xxxxx xx xxxxxxxx x femuru xxxx xxxxx a xxxxxxxxxx xxxxxxxx xx xxxxxxxxx x xxxxxx. Periferní xxxx xx xxxxxxx x ocasní xxxx xxxx jiné xxxxxx xxxxxx xxxx. Krevní xxxxx se xxxxx xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx připraví xxxxxxxxx xxxxxxxx a poté xx xxxxxx. Xxxxxxxx xxxxxxx xxxxxxxxxxxx xxx XXX (např. xxxxxxxxxx xxxxx (14) nebo Xxxxxxx 33258 a xxxxxxx-X (15)) xx xxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx x xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxx XXX. Tato xxxxxx nebrání xxxxxxx xxxxxxxxxxx xxxxxx (např. Xxxxxx). Xxxxxxxx systémy (xxxx. celulosová xxxxxx x xxxxxxxxxx buněk xxxxxxxxxxxx xxxxx (16)) xxx použít xx xxxxxxxxxxx, že xx xxxxxxxxx odpovídající xxxxxxxxx xxxxxx xxxxxxx xxx xxxxxxxxx mikrojader x xxxxxxxxxx.
1.5.7 Xxxxxxx
Xxx každé xxxxx xx xxxxxxx xxxxx xxxxxxxxx erytrocytů x xxxxxxxxx (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, přičemž xx x xxxxxxx kostní xxxxx xxxxxxx celkově xxxxxxx 200 xxxxxxxxxx x v xxxxxxx xxxxxxxxx krve alespoň 1000 xxxxxxxxxx (17). Xxxxxxx preparáty xxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx kontrol, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. U xxxxxxx xxxxxxx se xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx mikrojader v xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xx výskyt mikrojader. Xxx xxxxxxxxxxxxx analýze xx xxxxx xxx xxxxx nezralých xxxxxxxxxx x celkového množství xxxxxxxxxx menší xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx exponována xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxx xxxx xxxxxxxx xx výskyt xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx na xxxxx xxxxx. Xxxxxxx xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx a xxxxxxxxx cytometrická xxxxxxx xxxxxxx suspenze) xxxx xx xxxxxxxxxxxxx zdůvodnění x xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.
2. XXXXX
2.1 XXXXXXXXXX XXXXXXXX
Xxxxx xxx xxxxxxxxxx zvířata xx xxxx xxx xxxxxxxxxx ve formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Pro xxxxx xxxxxxxxxxx xxxxx xx xxx xxx xxxxxx počet xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, počet xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx a xxxxx xxxxxxxxx erytrocytů z xxxxxxxxx množství xxxxxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx nebo xxxx, xxxx by xxx xxxx uvedeny údaje x xxxxxxx xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Pro xxxxx xxxxx xx xxxxx podíl xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx erytrocytů x xxxxxxxx xxxxxxxx xxxxxxxxxx x mikrojádry xxxxxxxxx x procentech. Neexistuje-li xxxxx o xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, xxxxx být xxx xxxxxxxxxxxx xxxxxxx xxxxx pro obě xxxxxxx zkombinována.
2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX
Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x mikrojádry x xxxxxxxxxx xx xxxxx nebo jasný xxxxxx xxxxx buněk x xxxxxxxxxx pro xxxxxxx x určitou xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx výsledků zkoušky xxxxx být použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Statistická xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx odpověď. Xxxxxxxxxx xxxxxxxx by xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe x xxxxxxx experimentálních xxxxxxxx.
Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, se xxxxxxxx v xxxxx xxxxxxx za xxxxxxxxxxx.
Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů vyslovit xxxxxxx xxxxx x xxxxxxxx zkoušené látky. Xxxxxxxx mohou zůstat xxxxxxxxxx nebo sporné xxx xxxxxx xx xx, xxxxxxxx je xxxxxxxxxx opakován.
Pozitivní xxxxxxxx xxxxx na xxxxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx indukuje mikrojádra, xxx xxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxxxxx mitotického xxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx výsledky znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx v xxxxxxxxx xxxxxxxxxxxx testovacího xxxxx.
Xxxx xx xxx xxxxxxxxxxx pravděpodobnost, x xxxxx xx xxxxxxxx xxxxx nebo xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).
3. XXXXXX
XXXXXXXX X XXXXXXX
Xxxxxxxx o zkoušce xxxx obsahovat xxxx xxxxxxxxx:
Xxxxxxxxxxxx/xxxxxxxxx:
- zdůvodnění xxxxx xxxxxxxx,
- rozpustnost x xxxxxxx xxxxxxxx xxxxx x rozpouštědle/vehikulu, xx-xx xxxxx.
Xxxxxxxxx zvířata:
- xxxxxxx xxxx/xxxx,
- xxxxx, stáří x xxxxxxx zvířat,
- xxxxx, podmínky xxxxx, xxxxxx atd.,
- xxxxxxxxxxxx xxxxxxxx zvířat na xxxxxxx xxxxxxx, včetně xxxxxxx tělesné hmotnosti, xxxxxxx xxxxxxx a xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.
Xxxxxxxx xxxxxxxx:
- xxxxx k pozitivní x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,
- xxxxx xx xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx byla xxxxxxxxx,
- xxxxxxxxxx xxxxxxxxx xxxxxx dávek,
- údaje x přípravě xxxxxxxx xxxxx,
- xxxxx x xxxxxxxx xxxxxxxx xxxxx,
- xxxxxxxxxx xxxxxxx xxxxxxxx,
- xxxxxxxxx xxxxxx xxxxxxx, xxx se xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx xx cílové xxxxx,
- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx látky x krmivu xxxx xxxx (xxx) xx xxxxxxxxxxxx xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),
- podrobné xxxxx o kvalitě xxxxxx a vody,
- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,
- xxxxxx přípravy xxxxxxxxx,
- xxxxxx stanovení xxxxxxxx,
- xxxxxxxx hodnocení xxxxxxxxxx x nezralých xxxxxxxxxxxx,
- xxxxx analyzovaných xxxxx xx xxxxx xxxxx,
- xxxxxxxx klasifikace studie xx xxxxxxxxx, negativní xxxx xxxxxxxxxxx.
Xxxxxxxx:
- xxxxxx xxxxxxxx,
- xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx,
- xxxxx xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx xxxxxxx xxxxxxxxxx xxx každé xxxxx,
- xxxxxxx xxxxxxx ± xxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx xx xxxxxxx,
- xxxxx xxxxxxxx závislost xxxxxxxx na xxxxx,
- xxxxxxxx xxxxxxxxxxx analýzy x xxxxxx,
- údaje x xxxxxxxx x xxxxxxxxx negativní xxxxxxxx,
- xxxxx o xxxxxxxx xxxxxxxxx xxxxxxxx.
Xxxxxx xxxxxxxx.
Xxxxxx.
4. XXXXXXXXXX
1) Xxxxxx, X. X. (1973), X Xxxxx In vivo Xxxx xxx Chromozomal Xxxxxx, Xxxxxxxxxx Xxx., 18, 187-190.
2) Xxxxxx, X. (1975), Xxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx., 31, 9-15.
3) Xxxxxx, J. X., Xxxxxxxx, M. X., Xxxx, M., Xxxxxxxx, X., Mavournin, X., XxxXxxxxx, X. G., Xxxxxx, X. X. (1983), Xxx Xxxxxxxxx xx Xxxxxxxxxxx a. x. x Xxxxxxx xx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx. 123, 61-118.
4) Xxxxxxxxx, X. H., Xxxxxx, D. H., Xxxxxx, M. X., Xxxxxxxx, X. X., Xxxxxx, X. A. (1990), Xxx Xx xxxx Xxxxxxxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxxxx xxx Peripheral Xxxxx. X xxxxxx xx xxx U. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 239, 29-80.
5) XxxXxxxxx, J. X., Xxxxxxxx, R., Xxxx, X. X., Xxxx, X. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Erythrocytes: X Xxxxx Screen xxx Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Toxicity Xxxxxxx xx Mice, xx: Xxxxxxxxxxxx in Xxxxxxx xxx Practice xx Xxxxxxxxxx, xx. X. X. Xxxxx, X. X. Xxxxxxx, X. X. Miya. Xxxxxxxx, Xxxxxxxxx, 555-558.
6) XxxXxxxxx, X. T., Xxxxxx, X. X. Xxxx, X., Xxxxxxxx, G. X., Xxxxx, C., Xxxxxxxx, M. X., Xxxx, X. R., Xxxx, X. (1987), Xxxxxxxxxx xxx xxx Xxxxxxx of Xxxxxxxxxxxx Xxxxxx xx Xxxxxxxxx Xxxx Marrow Xxxxxxxxxxxx, Xxxxxxxxxx Res., 189, 103-112.
7) MacGregor, X. X., Xxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X. (1990), The xx vivo Xxxxxxxxxxx Xxxxxxxxxxxx Xxxx: Measurement xx Steady Xxxxx Xxxxxxxxx Assay Efficiency xxx Xxxxxxx Xxxxxxxxxxx xxxx Toxicity Xxxxxxx, Xxxxxx. Appl. Xxxxxxx. 14, 513-522.
8) Xxxxxxx, X., Xxxxxx, X., Xxxxxx, Y., Xxxxxx, X., Xxxxxxxx, M. Xx. (1990), Xxx Xxxxxxxxxxxx Xxxxx xxxx Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxxx Using Xxxxxxxx Xxxxxx-Xxxxxx Slides, Xxxxxxxxxx Xxx., 245, 245-249.
9) Xxx Xxxxxxxxxxxxx Study Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (1992). Xxxxxxxxxxxx Xxxx with Xxxxx Peripheral Xxxxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx Supravital Staining: Xxx Xxxxxxx Report xx xxx 5xx Xxxxxxxxxxxxx Xxxxx xx XXXXX/XXXXX, XXX, Mutatation Xxx., 278, 83-98.
10) Xxx Xxxxxxxxxxxxx Study Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: Xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxx Xxxxx xx the Environmental Xxxxxxx Xxxxxxx of Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx xxx xxx xxxxx-xxxx mouse xxxxxxxxxx xxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 53-159.
11) Xxxxxxx, X., Tice, X. X., XxxXxxxxx, X. T., Xxxxxxxx, X., Xxxxxxx, X. X., Kirsch-Volders, M., Xxxxxx, Jr. F. X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, B. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Micronucleus Xxxxx, Xxxxx. Xxx., 312, 293-304.
12) Higashikuni, N., Xxxxx, S. (1995), Xx xxxxxxx, xxxxxxxxxxx xxxxxxxx xxxx of 30 ± 6 x after xxxxxx xxxxxx xx xxx xxxxx peripheral xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 313-319.
13) Xxxxxxx, R. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, P. X., Doe, J., Xxxxxxx, D. J., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, G., Xxxxxx, X. X., Xxxxxxxx, X. X., Rochold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Working Group: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.
14) Xxxxxxx, X., Xxxxxx, T., Xxxxxxxx, X. Jr. (1983), Xx Xxxxxxxxxxx xx Xxxxxxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxx xx the Xxxxxxxxxxxx Xxxx, Mutation Xxx., 120, 241-247.
15) XxxXxxxxx, J. X., Xxxx, X. X., Xxxxxxxx, X. X. (1983), A Xxxxxx Xxxxxxxxxxx Xxxxxxxx Procedure xxx Xxxxxxxxxxx xxx XXX in Erythrocytes Xxxxx Hoechst 33258 xxx Xxxxxxx Y, Xxxxxxxx Res., 120, 269-275.
16) Xxxxxxx, X., Xxxxxxxxxx, X. X. (1989), The xxxxxxxxx xxxx xxxxxx micronucleus xxxx, Xxxxxxxxxx Xxx., 213, 91-104.
17) Gollapudi, X., McFadden, L. X. (1995), Sample Xxxx for xxx Xxxxxxxxxx of Xxxxxxxxxxxxx xx Normochromatic Xxxxxxxxxxx Xxxxx xx the Xxxx Xxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 347, 97-99.
18) Xxxxxxx, X., Ashby, J., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxxx Assay, xx: X. X. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx, XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.
19) Xxxxxx, X. X., Anderson, X., Albanese, R., Xxxxxxxx, X. E., Xxxxx, X., Xxxxxxxx X., Xxxxxxx, X., Xxxxxxxx, D. G., Xxxxxx, X. R. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx on Guidelines xxx Mutagenicity Xxxxxxx. Xxxxxx, Part XXX, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."
XXXXXXX 4X
"X.13/14 XXXXXXXXXX — XXXXXXX XX XXXXXXXX XXXXXX X XXXXXXXXXX
1. XXXXXX
Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX TG 471 — Zkouška na xxxxxxxx mutace x xxxxxxxxxx (1997).
1.1 ÚVOD
Při xxxxxxx na reverzní xxxxxx x xxxxxxxxxx xx používají xxxxxxxxxxx xxxxx xxxxxxx na xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Xxxxxxxxxxx xxxx, x detekci xxxxxxxx xxxxxx, které zahrnují xxxxxxxxxx, xxxxx x xxxxxx xxxxxxx xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxx x detekci xxxxxx, xxxxx revertují xxxxxx obsažené v xxxxxxxxxxx xxxxxxx a xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx aminokyseliny. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx díky xxx xxxxxxxxxx xxxx x xxxxxxxxxxxxx xxxxxxxxxxxx, xxxxx xxxx xxxxxxxxxx mateřským xxxxxxxxxx kmenem.
Bodové xxxxxx x podobné jevy xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx a xxxxxxxx mnoho důkazů x xxx, že xxxxxx xxxxxx x xxxxxxxxxx a v xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxx xx tvorbě xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx. Zkouška na xxxxxxxx xxxxxx s xxxxxxxxxx xx rychlá, xxxxxxxxxx x xxxxxxxxx xxxxxx. Xxxxx testovacích xxxxx xx xxxx xxxxxxxxxx, xxxx nimž xxxx citlivější xx xxxxxxx xxxxxx, včetně xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx místech, xxxxxxx xxxxxxxxxxxx xxxxx xxx velké xxxxxxxx x eliminaci reparačních xxxxxxx XXX nebo xxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxxxxxxxx k xxxxxx. Xxxxxxxxxxxx testovacích xxxxx může xxxxxxxxxx xxxxxxx užitečné xxxxxxxxx x xxxxxx xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx k dispozici xxxxx rozsáhlá databáze xxxxxxxx pro širokou xxxxx xxxxxxxx x xxxx xxxx xxxxxxxx xxxxx xxxxxxxxxx metody xxxxxxxx chemických látek, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.
Xxx také xxxxxx xxxx, xxxx X.
1.2 XXXXXXXX
Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx x kmeni vyžadujícím xxxxxxxxxxxxx (xxxxxxxx xxxx. xxxxxxxxx), xxxxxxx vzniká xxxx nezávislý xx xxxxxxx xxxxxxx aminokyseliny.
Mutageny xxxxxxxxxx xxxx xxxx xxxx xxxxxxxx, jež xxxxxxxxx xxxxx x xxxxxx DNA. Xxx xxxxxxx xxxxxxxxxx xxxxxx xx mohou tyto xxxxx xxxxxxxxxx xx xxxxx xxxxxxx mutace xxxx xxxxx xxxxx xxxxxxxxxxxxx genomu.
Posunové mutageny xxxx xxxxxxxx, jež xxxxxxxxx adici xxxx xxxxxx jednoho xxxx xxxx xxxx xxxx XXX x xxxxxxxx xxx xxxxx xxxxx XXX.
1.3 XXXXXXX ÚVAHY
Při xxxxxxxxx na reverzní xxxxxx s xxxxxxxxxx xx xxxxxxxxx prokaryotické xxxxx, xxxxx xx xxxx xx xxxxx xxxxx xxxxxxx, xxxx xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx a xxxxxxxxx procesy XXX. Xxxxxxx prováděné in xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxxx in xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx informaci x xxxxxxxxxx a xxxxxxxxxxxxx xxxxxxxxxx xxxxx pro xxxxx.
Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx zpravidla využívána xxx počáteční vyšetření xxxxxxxxxxx aktivity, a xxxxxxx aktivity xxxxxxxxxxxx xxxxxx xxxxxx. Z xxxxxxxx databáze xxxxxxx, xx xxxxx xxxxxxxxxx xxxxx, xxxxx xxxx x xxxx xxxxxxx xxxxxxxxx, vykazuje xxxxxxxxx xxxxxxxx i x xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx činitelů, xxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx. Xxxxxxx xxxxxx xxxxxxxxxxx xxx xxxxxxxxx xx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx jevu, x xxxxxxxxx x xxxxxxxxxxx xxxxxxxx nebo x xxxxxxxxx v xxxxxxxxxx dostupnosti. Xx xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx xx xxxxxxxxxx, xxxxx vést x xxxxxxxxxxxx mutagenní xxxxxxxx.
Xxxxxxx xx reverzní mutace x xxxxxxxxxx nemusí xxx xxxxxx xxx xxxxxx xxxxx xxxxxxxxxx xxxxx, například vysoce xxxxxxxxxxxx sloučeniny (xxxx. xxxxxx xxxxxxxxxxx) a xxx xxxxxxxx xxxxx, x xxxxx xx xxxxxxxxxxx (nebo o xxxxx se xx), xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx xxxxx (např. xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx x některé xxxxxxx xxxxxxxxxx). X takových xxxxxxxxx mohou xxx xxxxxxxxx zkoušky xxxxxxxxxx x xxxxx.
Xxxxxxxx xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xx xxxxxxxxxxxx xxx xxxxx, xxxx xxxxxxxx absolutní. Xxxxxx xx xxxxxxxx xxxxx x existuje xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx jinými, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx buňkách neexistují.
1.4 XXXXXXXX XXXXXXXX XXXXXX
Xxxxxxxx xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx látce, x xx xx xxxxxxxxxxx vnějšího xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx x xxx něho. Ve xxxxxxxxxxx xxxxxxxx xxxxx xx suspenze xxxxxxxx x vrchním xxxxxx x xxxxx xx xxxxxxx xx minimální xxxx. X xxxxxxxxxxxx xxxxxx xx zkoušená xxxx xxxxxxxx x xxxx se před xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx s xxxxxxx xxxxxx. Při xxxx technikách xx xx xxxx nebo xxxxx xxxxx inkubace xxxxxxxxx kolonie xxxxxxxxxx x xxxxxxx xx xxxxxxxx x xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxx misce x rozpouštědlem.
Je popsáno xxxxxxx postupů provedení xxxxxxx na xxxxxxxx xxxxxx x bakteriemi. Xxxx běžně xxxxxxxxx xxxxx standardní xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx xxxx (9, 10) a xxxxxxxxx xxxxxx (11). Xxxxxx xxx xxxxxxxx xxxxx x xxx xxxx popsány (12).
Zde xxxxxxx postupy se xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxx a xxxxxxxxxxxxxx metod. Xxxxx x xxxx xx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx jak s xxxxxxxxxxxx xxxxxxxx, xxx xxx ní. Xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxx za xxxxxxx xxxxxxxxxxxx metody. Xxxx xxxxx xxxxx do xxxxxxxxxx xxxx, xx xxxxx xxxxx xxxx xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, dvojvazné xxxx, xxxxxxxx, xxxxxxxxxx a xxxxxxxxxx xxxxxxxxxx, pyrrolizidinové xxxxxxxxx, xxxxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx připouští, xx určité třídy xxxxxxxx xxxxx xxxx xxxxxxxxx standardními postupy, xxxx xx xxxxxxxxxx xxxxxxx xxxx nebo xxxxxxxxxxxx xxxxxx. Xxxx xx xxx považovány xx "xxxxxxxx xxxxxxx" x x jejich xxxxxxx se xxxxxxx xxxxxxxxxx použít alternativní xxxxxxx. Xx xxxxx xxxxxxxxxxxxx tyto "zvláštní xxxxxxx" (společně x xxxxxxxx xxxxxxx xxxxxx xxxxxxx): xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx látky (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx od xxxxxxxxxxxx postupu musí xxx xxxxxxx xxxxxxxxxx.
1.5 XXXXX ZKUŠEBNÍ METODY
1.5.1 Xxxxxxxxx
1.5.1.1 Xxxxxxxx
Xxxxxxx xxxxxxx xxxxxxxx by měly xxx xxxxxxxxxxx xx xxxxxx exponenciální fáze xxxx do xxxxx xxxxxxxxxxx xxxx růstu (xxxxxxxxx 109 xxxxx xx xx). Buňky x xxxxxx xxxxxxxxxxx xxxx by neměly xxx xxxxxxx. Xx xxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx vysoký xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx xxxx xxx xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, nebo pro xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx buněk xx xxxxxxx.
Xxxxxxxxxx inkubační xxxxxxx xx 37 °X.
Xxxx by xxx xxxxxxx xxxxxxx pět xxxxx xxxxxxxx. Xxxx xxxx xx měly xxx čtyři kmeny X. xxxxxxxxxxx (TA1535; XX1537 xxxx TA97a xxxx TA97; TA98 x TA100), xxxxxxx xxxxxxx xx ukázala x xxxxxxx laboratořích xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx čtyři xxxxx S. xxxxxxxxxxx xxxx pár xxxx XX xx xxxxxxxxx xxxxxxxxx xxxxx a xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx určité xxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx XXX x hydraziny. Xxxx xxxxx xxxxx xxx xxxxxxxxxx xxxxx X. xxxx XX2 xxxx X. xxxxxxxxxxx TA102 (19), které mají xx xxxxxxxxx xxxxxxxxx xxxxx pár xxxx XX. Doporučená kombinace xxxxx xx xxxx xxxx:
- S. xxxxxxxxxxx XX1535 x
- X. xxxxxxxxxxx XX1537 nebo XX97x x
- X. xxxxxxxxxxx TA98 x
- X. xxxxxxxxxxx XX100 x
- E. coli XX2 xxxX, nebo X. xxxx WP2 xxxX (pKM101), xxxx X. xxxxxxxxxxx XX102.
Xxx xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx DNA xxxx xxx xxxxxxxxx xxxxxxx TA102 xxxx xxxxxx kmen X. xxxx x vysokou xxxxxxxxxx xxxxxxxx DNA, (xxxx. X. xxxx XX2 (pKM101)).
Měly xx xxx xxxxxxx zavedené xxxxxxx přípravy kmenové xxxxxxx, verifikace xxxxxxx x skladování. Xxxxxxx xxxxxxxxxxxxx xxx xxxx xx xxxx xxx xxxxxxxxx xxx xxxxxx xxxxxxxxx kmenovou xxxxxxx (xxxxxxxx xxx xxxxx X. xxxxxxxxxxx x xxxxxxxxx pro X. xxxx). Podobně xx xxxx být xxxxxxxxxxxx xxxx xxxxxxxxxx charakteristiky, xxxxxxxxx podle xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (tj. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, XX100 x TA97a xxxx XX97, WP2 uvrA x XX2 uvrA (xXX101) x xxxxxxxxxxxx x xxxxxxxxxxxxxx rezistence x kmene TA102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. xxx mutací x X. xxxxxxxxxxx xxxxxxxxxx na xxxxxxxxxxx xxxxxx x xxxX xxxxxx x E. xxxx nebo xxxX xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx světlo) (2, 3). Xxxxx xx xxxx xxxxxx dávat xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxx četností xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx a xxxxxxx x xxxxxxx uvedeném x xxxxxxxxxx.
1.5.1.2 Médium
Použije xx xxxxxx xxxxxxxxx xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx E (Xxxxx-Xxxxxx) a xxxxxxx) x xxxxxx xxxx xxxxxxxxxx xxxxxxxx a xxxxxx xxxx xxxxxxxxx xxxxxxxxxx několik buněčných xxxxxx (1, 2, 9).
1.5.1.3 Xxxxxxxxxxx xxxxxxxx
Xxxxxxxx xx měly xxx xxxxxxxxx xxxxxxxx látce, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x bez xxxx. Nejčastěji používaným xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx ošetřených xxxxxxxxxxx indukujícím xxxxxx, xxxx je Xxxxxxx 1254 (1, 2) xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx frakce xx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx x xxxxxxx 5 až 30 % xxx. xx xxxxx X9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx aktivačního systému xxxx xxxxxxx xx xxxxx xxxxxxxx chemické xxxxx. V xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx koncentraci xxxxxxxxxxxxxxxxxxx xxxxxx. U xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).
1.5.1.4 Zkoušená xxxxx xxxx xxxxxxxxx
Xxxxx xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx na xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx systémům x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.
Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, a xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxxxxx x x xxxxxxxxx S9 (22). Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje se xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx zkoušení xxxxx nestálých ve xxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx.
1.5.2 Xxxxxxxx xxxxxxxx
1.5.2.1 Zkušební xxxxx (xxx 1.5.1.1)
1.5.2.2 Xxxxxxxxx koncentrace
Mezi kritéria, xxxxx mají xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxx xxxxxxxxxxxx x rozpustnost v xxxxxxx xxxxx xxx xxxxxxxx.
Xxxx být užitečné xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x předběžných xxxxxxxxxxxxx. Cytotoxicita xxxx xxx xxxxxxxxxx xxxxxxxx xxxxx kolonií revertantů, xxxxxxxxx nebo xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx kultur. Cytotoxicita xxxxx se může xxxxxx v přítomnosti xxxxxxxxxxxxx aktivačních xxxxxxx. Xxxxxxxxxxxxx by xxxx xxx posouzena xx xxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxxx xxxxx xx skutečných xxxxxxxxxx xxxxxxxx.
Xxxxxxxxxx maximální zkušební xxxxxxxxxxx xxx rozpustné xxxxxxxxxxxxx xxxxx xx 5 mg/misku xxxx 5 μl/misku. U xxxxxxxxxxxxxxx xxxxx nerozpustných xxx koncentracích 5 xx/xxxxx xxxx 5 μx/xxxxx by xxxx xxx xxxxx xxxx xxxx zkušebních koncentrací xxxxxxxx, aby xxxxx xxxx x xxxxxxx xxxxx xxx aplikaci xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx, xx xxxx xxx xxxxxxxx xx xx cytotoxické koncentrace. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.
Xxxx xx být použito xxxxxxx pět xxxxxxx xxxxxxxxxxxxxxxx koncentrací zkoušené xxxxx, xxxxxxx xxx xxxxxx experimentu xx xxxx xxx xxxxxxxxx xxxx zkušebními xxxx xxxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxx stupnice (xx. Ö10). Xxxxx xxxxxxxxx xxxx xxxxxx x xxxxxxx, kdy xx vyšetřuje křivka xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxx. Zkoušení xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx xxxx xxx xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx významné xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.
1.5.2.3 Negativní a xxxxxxxxx xxxxxxxx
Xxxxxxxx xxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx a negativní (xxxxxxxxxxxx nebo vehikulum) xxxxxxxx s metabolickou xxxxxxxx x xxx xx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx vybrány xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.
X xxxxxxx zkoušek x použitím metabolického xxxxxxxxxxx xxxxxxx by xxxx xxx xxxxx (xxxxx) xxx xxxxxxxxx xxxxxxxx xxxxxxx (vybrány) xx xxxxxxx typu xxxxxxxxx kmene xxxxxxxx.
Xxxxxxxxx xxxxxx pozitivní xxxxxxxx x xxxxxxx s xxxxxxxxxxxx aktivací jsou xxxx látky:
|
Látka |
Číslo CAS |
Číslo 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 monohydrát |
6055–19–2 |
Tato xxxxx je xxxxxxx xxxxxxxxx kontrolou pro xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx:
|
Xxxxx |
Xxxxx CAS |
Číslo xxxxx XXXXXX |
|
XX Direct Xxx 28 |
573–58–0 |
209–358–4 |
2-xxxxxxxxxxxxxx xx neměl xxx použit xxxx xxxxxx indikátor xxxxxxxxx xxxxx S9. Při xxxxxxx 2-aminoanthracenu xx xxxx xxx každá xxxxx X9 charakterizována xxxxxxxxx, xxxxx vyžaduje xxxxxxxxxxxx aktivaci mikrosomálními xxxxxx, xxxxxxxxx xxxxx[x]xxxxx xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.
Xxxxxxxxx kmenověspecifické xxxxxxxxx kontroly x xxxxxxx xxx xxxxxx xxxxxxxxxxx aktivace xxxx xxxx xxxxx:
|
Xxxxx |
Xxxxx XXX |
Xxxxx xxxxx XXXXXX |
Xxxx |
|
xxxx xxxxx |
26628–22–8 |
247–852–1 |
XX1535 x XX100 |
|
2-xxxxxxxxxxxx |
607–57–8 |
210–138–5 |
XX98 |
|
9-xxxxxxxxxxxx |
90–45–9 |
201–995–6 |
XX1537, TA97 x TA97a |
|
ICR 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 x TA102 |
|
1-methyl-3-nitro-1-nitrosoguanidin |
70–25–7 |
200–730–1 |
WP2, XX2 uvrA x XX2 xxxX (xXX101) |
|
4-xxxxxxxxxxxxx-1-xxxx |
56–57–5 |
200–281–1 |
XX2, XX2 uvrA x XX2 uvrA (xXX101) |
|
α-[(5-xxxxx-2-xxxxx)xxxxxxxxxx]xxxxx-2-xxxxxxxx (XX2) |
3688–53–7 |
xxxxx xxxxxxxxxx plasmidy |
Pro xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxx referenční xxxxx. Xxx pozitivní xxxxxxxx xx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx li x xxxxxxxxx.
Xxxx xx xxx použity xxxxxxxxx xxxxxxxx xxxxxxxxxx se xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx rozpouštědlo xxxxxxxxxx žádné zhoubné xxxx xxxxxxxxx xxxxxx.
1.5.3 Xxxxxx
X xxxxxxxxxx xxxxxxx xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,05 xx nebo 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x 0,5 xx sterilního pufru x 2,0 xx xxxxxxxx xxxxx. X xxxxxxx xxxxxxx s xxxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x rozmezí 5 xx 30 % xxx. x metabolické xxxxxxxxx xxxxx) x xxxxxxx agarem (2,0 xx) a zároveň x bakteriemi x xxxxxxxxx xxxxxx nebo xxxxxxxxx xxxxxxxx. Xxxxx xxxxx xxxxxxxx se xxxxxxxx a xxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx xxxxx. Xxxx inkubací xx xxxxx xxxxxx xxxx xxxxxxxx.
X preinkubační xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx zkoušený xxxxxx xxxx xxxxxxxxx x vrchním agarem x přelitím xxxx xxxxxx minimálního xxxxx xx xxxxx xxxxxxx 20 xxxxx nebo xxxx xxxxxxxxxxx s xxxxxxxxxx xxxxxx (obsahujícím xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a xxxxxxxxx xxxxxx xxxx metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx xx smíchá 0,05 nebo 0,1 xx xxxxxxxx xxxxx xxxx xxxxxxxxxx roztoku, 0,1 ml bakterií x 0,5 xx xxxxx X9 xxxx xxxxxxxxxx xxxxx x 2,0 ml xxxxxxxx xxxxx. Xxxxxxxx by xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx na xxxxxxxx.
X xxxxxxxxxxxx xxxxxx xxxxxxxx by xxxx xxx při xxxxx xxxxxx xxxxx použity 3 xxxxx. Xxxxxxx xxxx misek je xxxxxxxxxx po vědeckém xxxxxxxxxx. Xxxxxxxx xxxxxx xxxxx nemusí znamenat xxxxxxxxxxxx zkoušky.
Plynné nebo xxxxxx xxxxx xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, např. x těsně uzavřených xxxxxxxxxxxx nádobách (12, 14, 15, 16).
1.5.4 Xxxxxxxx
Xxxxxxx xxxxx x xxxx zkoušce xx xxxx xxx xxxxxxxxxx xxx 37 °X xx 48 –72 xxxxxxxx. Xx xxxxxxxx xxxxxxxxx xxxx se xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx.
2. XXXXX
2.1 ZPRACOVÁNÍ VÝSLEDKŮ
Předloženými xxxxx xx xxxx xxx xxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xx xxxxx. Xxx xx xxx xxxxxx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx na xxxxxxx x xxxxxxxxx xxxxxxxxx (xxxxxxxx rozpouštědla x xxxxxxxx neexponovaná xxxxxxxx), xxx xx xxxxxxx x xxxxxxxxx xxxxxxxxx. Xxxxx na jednotlivých xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx revertantů xx xxxxx a xxxxxxxxxx xxxxxxxx xx xxxx být předloženy xxx zkoušenou xxxxx x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx a/nebo xxxxxxxx xxxxxxxxxxxx).
Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx se nepožaduje. Xxxxxxxxxx xxxxxxxx by xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx xxx potvrzeny xxxxxx xx xxxxxxx. Xxxxxxxx se xxxxxxxxx xxxxxxxxxxx výsledků xxxxxxxxxx xx xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxxxx. Změna xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx, metoda xxxxxxxxxx (xxxxxxxxxx misková xxxxxx xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) x xxxxxxxx metabolické aktivace.
2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX
Xxx stanovení xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx xxx xxxxxxxxx xxxxxx u xxxxxxx jednoho kmene x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxx bez xxxx, x to x závislosti xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx tohoto xxxxx xxx xxxxx nebo xxxx xxxxxxxxxxx (23). Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx faktorem pro xxxxxxxxx xxxxxxx.
Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx uvedená xxxxxxxx, xx xxxxxxxx v xxxxx systému za xxxxxxxxxxx.
Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx to, xxxxxxxx xx experiment xxxxxxxx.
Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxxxx xxxxxx s xxxxxxxxxx znamenají, že xxxxxxxx xxxxx indukuje x genomu xxxxx Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx xxxxxx xxxxxx xxxxxxxxxx xxxx xxxx posunem xxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxx xx xxxxxxxx xxxxxxx pro xxxxxxxxx xxxxx xxxxxxxxx.
3. XXXXXX
XXXXXXXX X XXXXXXX
Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:
Rozpouštědlo/vehikulum:
- xxxxxxxxxx xxxxx rozpouštědla/vehikula,
- xxxxxxxxxxx a xxxxxxx xxxxxxxx látky x xxxxxxxxxxxx/xxxxxxxx, xx-xx známa.
Kmeny:
- xxxxxxx kmeny,
- xxxxx xxxxx x xxxxxxx,
- xxxxxxxxxxxxxxx kmene.
Zkušební podmínky:
- xxxxxxxx xxxxxxxx xxxxx xx misku (mg/misku xxxx μx/xxxxx) x xxxxxxxxxxx xxxxxx xxxxx x xxxxx xxxxx xx koncentraci,
- xxxxxxx xxxxx,
- xxx x xxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxxxxx kritérií xxxxxxxxxxxxx,
- xxxxxx xxxxxxxx.
Xxxxxxxx:
- xxxxxx xxxxxxxx,
- xxxxxx xxxxxxx,
- xxxxx xx xxxxxxxxxxxx miskách,
- střední xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxx,
- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,
- xxxxxxxx xxxxxxxxxxx xxxxxxx,
- xxxxx x xxxxxxxx xxxxxxxxx (rozpouštědlo/vehikulum) x xxxxxxxxx xxxxxxxx x xxxxxxxxx, středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,
- xxxxxxxxx xxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx.
Xxxxxx xxxxxxxx.
Xxxxxx.
4. XXXXXXXXXX
1) Xxxx, X. X., McCann, X., Xxxxxxxx X. (1975), Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx with xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 31, 347-364.
2) Maron, X. X., Xxxx, X. X. (1983), Xxxxxxx Xxxxxxx for the Xxxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Res., 113, 173-215.
3) Xxxxxxxxx, D., Xxxxxxx, S., Xxxxxx, X., Xxxxx, E., Xxxx, X., Matsushima, X., Xxxxxxx, X., Xxxxx, X., Venitt, X., Xxxxxx, E. (1994), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx of Xxxxxxxxx Xxxxxxxx Assays, Xxxxxxxxxx Res., 312, 217-233.
4) Xxxx, L. X., Xxxxxxx X. X., Xxxxxxx, X. X., Xxx Halle, X. S., Brown, X. X., Xxxxxx, X. F., Xxxxxx, X., XxXxxx, X., Xxxxxxxxxx, K., Xxxxxx, X., Rao, X. X., Xxx X. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Xxxxxx xx xxx U. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 168, 69-240.
5) Xxxxxx, X., Xxxxxx, X., Seino, X. X., Xxxxxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. (1975), Xxxxxxxxxxxx xx Xxxxxxxxxx Xxx Xxxx xxx xxxxx Derivatives, Xxxxxx Xxxx. 1, 91-96.
6) Xxxxxxxxxx, M., Xxxxxxxx, X., Xxxxx, X., Yahagi, X., Xxxxxx, X., Xxxxxxxx, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxx, in: Xxxxx-xxxx Xxxx Systems xxx Xxxxxxxxx Carcinogens, xx. Xxxxxxx K. X., Xxxxxx, X. C., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.
7) Xxxxxxxxx, D. X., Rowland, X. X., Wilcox, P., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Mutation Assays, xx: Xxxxx Xxxxxxxxxxxx Xxxxx: XXXXX Xxxx 1 Xxxxxxx, xx. X. X. Xxxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, 13-61.
8) Xxxxxxxxxx, H. X., Xxxxxx, U., Xxxxxxx, X. (1987), Xxxxxx Xxxxxxxxxxxxx Mutagenicity Xxxx for Xxxxx, X. Food Safety., 8, 167-177.
9) Xxxxx, X. X. L., Xxxxxx, X. X., Xxxxxxx, B. A. (1976), Xxx of x simplified xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxx of xxxxxxxx, Mutatation Res., 38, 33-42.
10) Xxxxxxx, X. X., Xxxxx, X. H. X., Xxxxxxxxx, D., Xxxxxxx, X. X. (1984), Xxx Xxxxxxxxxxx Test xx Bacteria, in: Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, 2. xxx., Kilbey, X. X., Xxxxxxx, M., Xxxxxxx, X., Xxxxx, X. (xxx.), Xxxxxxxx, Xxxxxxxxx-Xxx York-Oxford, 141-161.
11) Xxxxxxxx, X. X., Xxxxxxx, X. X. (1981), Xx Xxxxxxxxxxx xx xxx Quantitative Xxxxxxxxxx Assay xxx Xxxxxxxxxxx with Strains xx Salmonella xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.
12) Araki, A., Xxxxxxx, T., Kato, X., Xxxxxxxxxx, T. (1994), Xxxxxxxx Method xxx Mutagenicity Xxxxxxx xx Xxxxxxx Xxxxxxxxx xx Xxxxx x Xxx Sampling Bag, Xxxxxxxxxx Res., 307, 335-344.
13) Prival, X. X., Xxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxx, X. X. (1984), Xxxxxxxxxxxx xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Xxxx xx x Modified Xxxxxxxxxx Assay, Xxxxxxxxxx Xxx., 136, 33-47.
14) Xxxxxx, X., Xxxxxxxx, X. E., Xxxxxxx, X., Xxxxxx, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Mutagenicity Xxxxx. X. Xxxxxxx from xxx Xxxxxxx xx 311 Xxxxxxxxx, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.
15) Xxxxxx, V., Xxxxxxxx, X., Xxxxxxx, X. G. (1977), Xxxxxxxxx Xxxxxxxx of Xxxxxxxxx Identified xx Xxxxxxxx Water, xx Xxxxxxxx in Genetic Xxxxxxxxxx, X. Xxxxx, X. Xxxxxxx, X. Xxxxxx (xxx.) Xxxxxxxx, Xxxxxxxxx, 249-258.
16) Hughes, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Xxxxxxxxx xx Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxxxxx Xxxxxxx Xxxxxxxxx xx xxx Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.
17) Xxxxxxxxxx, X., Xxxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx the Xxxxxxxxx Xxxxxxxxx Carcinogen Cycasin xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxxxx Xxxxxxxxxx in Xxxxxxxxxx xxxxxxxxxxx, Xxxxxx Xxx., 39, 3780-3782.
18) Xxxxxx, X., Xxxx, X., Xxxxx-Xxxxx, X., Xxxx, B. X. (1980), Xxxxxxxx: A Xxxxx xxx Xxxxxxxxxx xx Xxxxxxx Xxxxxxxxxx xx Xxxxxxxx by Xxxxxxxxxx Flora, Proc. Xxxx. Acad. Xxx. X. X. X, 77, 4961-4965.
19) Wilcox, X., Naidoo, X., Xxxx, D. X., Xxxxxxxxx, X. X. (1990), Xxxxxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx XX 102 with Escherichia xxxx WP2 Tester xxxxxxx, Mutagenesis, 5, 285-291.
20) Matsushima, T., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X Safe Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx a. x. xx Inducer xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: In vitro Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xxx. X. X. de Xxxxxx xx xx. Xxxxxxxx, North Xxxxxxx, 85-88.
21) Elliot, B. X., Combes, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Mackay, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 in xx xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx, 7, 175-177.
22) Xxxxx, X., Xxxxxxxxxxxxxxxx, X., Xxxx, B. X. (1981), Xxxxxxxxxxxxx xx Xxxxxxx Solvents xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 88, 343-350.
23) Xxxxxxx, X. D., Xxxxx, X., Xxxxxxx, A., Xxxxxxxxxx, K., Nestmann, X., Xxxxxx, E. (1987), Guide xxx xxx Salmonella typhimurium/Mammalian Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Xxxxxxxxxxxx, Mutatation Xxx., 189, 83-91.
24) Xxxxx, X. X. X., Green, X. X. X., Xxxxxxxxx, X., Mitchel, X., Xxxxxxxx, W. X., Xxxxxx, X. X. (1989), Xxxxxxxx xx Xxxx from Microbial Xxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Xxxx XX. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Test Data, xx. Kirkland, X. X., Cambridge Xxxxxxxxxx Xxxxx, 28-65."
XXXXXXX 4X
"X.17 MUTAGENITA — XXXXXXX XX XXXXXX XXXXXX X XXXXXXX XXXXX IN XXXXX
1. XXXXXX
Xxxx metoda xx xxxxxxxx xxxxxx XXXX XX 476 — Xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx (1997).
1.1 ÚVOD
Zkoušku xx genové xxxxxx x buňkách xxxxx xx xxxxx xxx xxxxxx xxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxx. Mezi xxxxxx xxxxxxx linie xxxxx buňky xxxxxxx X5178X xxxx, xxxxxxx xxxxx CHO, CHO-AS52 x X79 xxxxxx xxxxxxxx x xxxxxxxxxxxxxxx xxxxx XX6 člověka (1). U xxxxxx xxxxxxxxx linií jsou xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx xxxxxx xxxx xxx thymidinkinasu (XX) x hypoxanthin-guaninfosforibosyltransferasu (XXXX) x xxxxxxxx xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx xx xxxxxx TK, XXXX x XPRT xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX x XXXX xxxx xxxxxxx detekci xxxxxxxxxxx xxxxxxxx (např. xxxxxxxx delece), které xxxxx xxxxxxxxx v XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).
Xx xxxxxxx xx xxxxxx xxxxxx v xxxxxxx xxxxx xx xxxxx xxx použít xxxxxxx xxxxxxxxxx xxxxx xxxxx nebo buněčné xxxxx. Xxxxx xx xxxxxxxx xxxxx xxxxxxxxxx xxxxx x xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx mutací.
Zkoušky prováděné xx vitro obecně xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x savců. Xx xxxxx se xxxxx xxxxxxxxx xxxxxxxx, xxxxx by vedly x pozitivním výsledkům, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, jež neodrážejí xxxxxxx xxxxxxxxxx, může xxxxx změnou xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (7).
Xxxx xxxxxxx se xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx je xxxx xxxxxxx xxxxxxxxx, xxxx xxxxxxxxxxx savců; xxxx xxxxx zkouškou x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx závisí xx xxxxxxxx xxxxx a xxxxxxxxx xxxxxx o xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx působí xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, které x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx (6).
Xxx xxxx xxxxxx úvod, xxxx X.
1.2 XXXXXXXX
Xxxxx mutace : xxxxxx xxxxxx xxxxxxxxx xxxx mutované xxxxx, xxxxx způsobuje xxxxx xxxx xxxxxx xxxxxxxxxxx aktivity kódovaných xxxxxxxx.
Xxxxxxxx xxxxxxxxxx xxxx xxxx : látky, xxxxx způsobují substituci xxxxxxx xxxx více xxxx xxxx x XXX.
Xxxxxxxx mutageny : xxxxx, které xxxxxxxxx xxxxx nebo xxxxxx xxxxxxx xxxx xxxx xxxx xxxx x xxxxxxxx XXX.
Xxxx exprese xxxxxxxx : doba, xxxxx xxx xxxxxx x xxxx mutovaných xxxxx nezměněné genové xxxxxxxx.
Xxxxxxx mutantů : xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxxxxx xxxxxxxxxxxxxxx xxxxx.
Xxxxxxxxx xxxxxxx xxxx : xxxxxx xxxxx xxxxx x xxxx xx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx xx xxxx xxxxxx poměru xxxxxxxxx růstu v xxxxxxxx x v xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx k negativní xxxxxxxx.
Xxxxxxxxx xxxx x xxxxxxxx : nárůst xxxxx xxxxx x xxxxxxx exprese xxxxxxxx x xxxxxxxxx kontrole.
Životaschopnost : účinnost xxxxxxxxx xxxxx v okamžiku xxxxxxxx xx misku xx xxxxxxxxxxxx xxxxxxxx xx xxxxxxx.
Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx xx xxxxx xx xxxxx xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx xxxxxxxxx x xxxxxx x xxxxxxx xxxxxxxxx xxxxxxxx xxxxx.
1.3 PODSTATA ZKUŠEBNÍ XXXXXX
Xxxxx, xxxxx x xxxxxxxx mutace TK+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) xxxx xxxxxxxxxxx x cytotoxickým xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxxxxxx (XXX). Buňky xxxxxxxxxxx xxxxxxxxxxxxxx jsou xxxxxxx xx XXX, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxx xxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxx tedy schopny xxxxxxxxxxx xx přítomnosti XXX, zatímco normální xxxxx, xxxxx xxxxxxxx xxxxxxxxxxxxxx tuto xxxxxxxxx xxxxxx. Podobně lze x buněk x xxxxxxxxxxxx XXXX xxxx XXXX xxxxxxx selekci xxxxxxxxxxxxxxx rezistence x 6-xxxxxxxxxxx (XX) nebo 8-xxxxxxxxxx (AG). Xxxxxxxxxx xxxxxxxx látky by xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx xx xx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xxxxxxx xxxxxx báze xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx by xxx xxxxxxxxx xxxxxxxxx xxxxxxxx podezření xx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx pro mutantní xxxx nemutantní buňky. Xxx zkoušení xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, xxxx xxxx být xxxxxxxxx xxxxxxxx systému xxxx xxxxxxx xxx xxxxxxx (8).
Xxxxx x xxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxx xxxx vhodnou xxxx xxxxxxxxx xxxxxxxx látce xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, x xxxxxxxxxxxxxx xx účelem stanovení xxxxxxxxxxxx a za xxxxxx exprese fenotypu xxxx xxxxxxx mutantů (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx zjistí xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx xxxxxxxxxxx celkového xxxxx xxxxxx xx xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx x xxxxxxxx xxxxx xx xxxxxxx xxxx charakteristickou pro xxxxx zvolený xxxxx x typ xxxxx, xxx nastala přibližně xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx mutací. Xxxxxxx xxxxxxx xx stanoví xxx, xx xx xxxxxx xxxxx počet xxxxx do média xxxxxxxxxxxx selekční činidlo xxx xxxxxxx mutantních xxxxx x xx xxxxx xxx xxxxxxxxxx xxxxxxx, aby xxxx xxxxxxxxx účinnost xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx se xxxxxxxxx kolonie. Četnost xxxxxxx xx vypočte x počtu mutantních xxxxxxx x selekčním xxxxx x xxxxx xxxxxxx v xxxxx xxx selekčního xxxxxxx.
1.4 XXXXX XXXXXXXX XXXXXX
1.4.1 Xxxxxxxxx
1.4.1.1 Buňky
Pro použití x xxxx xxxxxxx xxxx k xxxxxxxxx xxxxx xxxx xxxxx, xxxxxx xxxxxxxx xxxxx X5171X, XXX, CHO-AS52, X79 xxxx XX6. Xxxx xxxxx x xxxx zkoušce by xxxx xxxxxxxxx citlivost x xxxxxxxxx mutagenům, xxxxxxx xxxxxxxxx xxxxxxxxx x stabilní xxxxxxxxx xxxxxxxxxxx mutací. Xxxxx xx měly xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx mykoplasmaty, x x xxxxxxx kontaminace xx neměly xxx xxxxxxx.
Xxxxxxx xx měly xxx xxxxxxxx xxx, xxx xxxx předem xxxxxxxxxx xxxxxxxxx x xxxx. Xxxxx xxxxxxxxx xxxxx, xxxxxx x xxxxxxxxxxx xxxxxxxx xxxxx xx měl xxxx xxxxxxxxxx xxxxxxxxx xxxxxxx (14). Xxxxxxxxx xxxxx xxxxx, xxxxx xxxxxxx xxxxxxxx x které xxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx, xx xxx xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx xx, aby xxx xxxxxx xxxxx xxxxx, který xx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx spontánních mutací. Xx xxxx doporučeno, xxx xxxx xxxxxxx xxxxxxx 106 xxxxx. Xxxx by být x xxxxxxxxx xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.
1.4.1.2 Média x xxxxxxxxxx xxxxxxxx
Xxx xxxxxxxxx xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx média x xxxxxxxxx xxxxxxxx (kultivační xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). Xxxxx xx měla xxx xxxxxxx podle xxxxxxxxxx systémů x xxxx xxxxx použitých xxx zkoušce. Je xxxxxxx důležité, xxx xxxxxxxxxx xxxxxxxx byly xxxxxxx xxx, aby xxxx xxxxxxxxx xxxxxxxxx xxxx buněk xxxxx xxxxxx xxxxxxx a xxxxxxxxx xxx mutovaných, xxx xxxxxxxxxxxx buněk xxxxxx xxxxxxx.
1.4.1.3 Xxxxxxxx xxxxxx
Xxxxx xx xxxx xxx získávány x xxxxxxxxx xxxxxx, xxxxxxxx xx kultivačního xxxxx x xxxxxxxxxx xxx 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx může xxx xxxxxxxx xxxxxxxxx x xxxxxxx xxx xxxxxxxx xxxxxxxx buňky.
1.4.1.4 Metabolická xxxxxxxx
Xxxxx xx xxxx xxx vystaveny xxxxxxxx xxxxx, x xx x xxxxxxx systémem xxxxxxxxxxx aktivace x xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx dotovaná xxxxxxxxxxxxxxxxxxx xxxxxx (S9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx činidlem xxxxxxxxxxx xxxxxx, jako xx Xxxxxxx 1254 (15, 16, 17 a 18), xxxx xxxx xxxxxxxxxxxxx a β-naftoflavonu (19, 20).
Postmitochondriální xxxxxx xx v xxxxxxxx xxxxxxxxxx médiu obvykle xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Volba x xxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx zkoušena. X xxxxxxxxx xxxxxxxxx xxxx xxx vhodné použít xxxx než xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.
Xxxx xxxxxxxx vývoje, včetně xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx linií exprimujících xxxxxxxxxx aktivační enzymy, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx aktivaci. Xxxxx xxxxxxxxx buněčných xxxxx xx měla být xxxxxxx zdůvodněna (např. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).
1.4.1.5 Xxxxxxxx xxxxxxxx xxxxx
Xxxxx zkoušené xxxxx xx měly xxx před xxxxxxxx xx buňky xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx xxx xxxxxxx přímo k xxxxxxxxxx systémům x/xxxx xxxxx být xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.
1.4.2 Xxxxxxxx xxxxxxxx
1.4.2.1 Rozpouštědlo/vehikulum
Rozpouštědlo/vehikulum xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxx x x xxxxxxxxx X9. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx zařazení xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx látek xxxxxxxxx xx xxxx xx xxxx xxx použitá xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.
1.4.2.2 Expoziční xxxxxxxxxxx
Xxxx xxxxxxxx, xxxxx xxxx xxx zohledněna xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x xxxxx xX xxxx xxxxxxxxxx.
Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x metabolickou xxxxxxxx x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, xxxx xxxx relativní xxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxx xxxxxxx růst. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x předběžném xxxxxxxxxxx.
Xxxx xx xxx xxxxxxx xxxxxxx čtyři xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx toxicity xx xxxx tyto xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a minimální xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx xxxx xxxxxxx znamenat, xx xx xx xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. Xx-xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx, xxxx xx xxx xxxxxxxxx přibližně 10 — 20 % (xxx xxxxxxx 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx by xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, která x xxxx je xxxxxxxx.
Xxxxxxxxx xxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxx xx x xxxx rozpustnosti za xxxxxxxxxxxx podmínek, xxxx xx za xxxx xxx. Xxxx xx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxx v xxxxxxxx xxxxx, ve kterému xxxx buňky exponovány. Xxxx být výhodné xxxxxxxx xxxxxxxxxxx xx xxxxxxx a na xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx xx xxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx xxxxxxx xxxxx v xxxxxxxx xxxxxxxxxxx xxxxx, S9 xxxx, xxx. Nerozpustnost xxx zjistit xxxxxxxx. Xxxxxxxxx xx neměla xxxxx při vyšetřování.
1.4.2.3 Xxxxxxxx
Xxxxxxxx každého xxxxxxxxxxx xx měly xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx nebo vehikulum) xxxxxxxx jak x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Xxx xxxxxxx metabolické aktivace xx měla xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, xxxxx k xxxxxxxxx xxxxxxxx vyžaduje xxxxxxxx.
Xxxxxxxxx xxxxxxxxx kontroly xxxxx být tyto xxxxx:
|
Xxxx metabolické xxxxxxxx |
Xxxxx |
Xxxxx |
Xxxxx XXX |
Xxxxx podle Xxxxxx |
|
Xxx xxxxxx metabolické 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 metabolickou 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 a xxxxx kolonie) |
cyklofosfamid |
50–18–0 |
200–015–4 |
|
|
cyklofosfamid 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 xxxxxx xxxxxx X9) |
62–75–9 |
200–549–8 |
|
|
xxxxx[x]xxxxx |
50–32–8 |
200–028–5 |
Xxxxx xxx použity xxxx jiné referenční xxxxx pro xxxxxxxxx xxxxxxxx, xxxx. xx-xx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxx x 5-brom-2′-deoxyuridinu (XXX 59–14–3, XXXXXX 200–415–9), xxxx xxx xxxx xxxxxxxxxx xxxxx xxxxxx xxxxxxx. Xxx xxxxxxxxx kontrolu xx xxxx xxx xxxxx x úvahu použití xxxxxxxxxx látek xxxxx xxxxx xx xxxxxx xxxxxxxx třídy.
Měly by xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx médiem xxxxxxxxxxx samotné rozpouštědlo xxxx xxxxxxxxx x xxxxxxxxxx jinak stejným xxxxxxxx jako xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.
1.4.3 Postup
1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx
Xxxxxxxxxxxxx buňky xx xxxx xxx xxxxxxxxx zkoušené xxxxx xxx xx přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx systému, xxx bez xxxx. Xxxxxxxx xx xxxx xxxxx vhodnou xxxx (xxxxxxx je xxxxxx xxxx 3 až 6 hodin). Expoziční xxxx xxxx xxx xxxxxxxxxxx xx xxxxx xxxx xxxx buněčných xxxxx.
Xxx každou zkušební xxxxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx kultury xxxx xxxxx exponovaná xxxxxxx. Xx-xx použita xxxxx xxxxxxx, xxx xx xxx xxxxx xxxxxxxxxxx xxxxxx xxx, xxx byl xxxxxxxx xxxxxxxxxxxx počet kultur xxx xxxxxxx (např. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx by xxx použity xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx xxxxxxxxxxxx).
Xxxxxx xxxx xxxxxx xxxxx xx xxxx být xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x těsně uzavřených xxxxxxxxxxxx nádobách (21, 22).
1.4.3.2 Stanovení přežití, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx
Xx xxxxx expoziční xxxx se xxxxx xxxxxxx x xxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxx x za xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Xx xxxxxxxxxx cytotoxicity xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (přežití) xxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx se xxxxxxx xxxxxxx xx xxxxxxxxx xxxx.
Xxxxx xxxxx xx xxxxxxxxxx minimální časové xxxxxx, aby xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (XXXX x XXXX vyžadují xxxxxxx 6 xx 8 xxx, XX xxxxxxx xxx xxx). Xxxxx xxxx xxxxxxxxxxx v xxxxx xx xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxxx) x xxx xxxx (xxx xxxx) za xxxxxx stanovení počtu xxxxxxx x klonovací xxxxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxxxxxx (použité pro xxxxxxx xxxxxxxx mutantů) xx xxxxxxx xx xxxxx doby exprese xxxxxxxxx xx xxxxx xxx xxxxxxxxxx činidla.
Je-li xxxxxxxx xxxxx xxxxxxxxx xx xxxxxxx X5178X XX+/-, xxxx xx xxx provedeno xxxxxxx xx jedné xx xxxxxxxxxx xxxxxx (x xxxxxxxx pozitivní koncentrací) x xx negativních x pozitivních kontrolách xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxx. Je-li xxxxxxxx xxxxx xx xxxxxxx X5178X TK+/- xxxxxxxxx, mělo by xxx rozdělení kultury xxxxx velikosti kolonií xxxxxxxxx xx xxxxxxxxxxx x xxxxxxxxxxx kontrolách. Xxx xxxxxxxx za xxxxxxx XX6 XX+/- xxxx xxx xxxx xxxxxxxxx xxxxxxxxx kultury xxxxx velikosti xxxxxxx.
2. XXXXX
2.1 XXXXXXXXXX VÝSLEDKŮ
Údaje xx xxxx zahrnovat xxxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x xxxxxxxx xxxxxxx xxx xxxxxxxxxx x xxxxxxxxx kultury. V xxxxxxx xxxxxxxxx odpovědi xx xxxxxxx X5178X XX+/- xx xxxxxxx xxxxxxxxx alespoň x xxxxx xxxxxxxxxxx xxxxxxxx xxxxx (xxxxxxxx pozitivní xxxxxxxxxxx) x u xxxxxxxxx x xxxxxxxxx xxxxxxxx xx použití xxxxxxxx malá xxxxxxx — xxxxx xxxxxxx. Xxxxxxxxxxx a xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxx xxxxxxx, xxx mutantů tvořících xxxx xxxxxxx byla xxxxxxxx xxxxxxxx (23, 24). Ve xxxxxxx XX+/- jsou kolonie xxxxxxxxxxx xx použití xxxxxxxx kolonie x xxxxxxxxx xxxxxx (xxxxx) x kolonie x xxxxxxx xxxxxx (malá) (25). X xxxxxxxxxx xxxxx, které xxxxxxx xxxxxxxxxxxxxx genetické xxxxxxxxx, xx prodloužily xxxx xxxxxxxx, a xxxxx xxxx malé kolonie. Xxxxxxxxx xx xxxxxxx xxxxxx xx ztrát xxxxxx xxxx xx xx xxxxxxxxxxxx viditelné xxxxxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx tvořících xxxx xxxxxxx xx xxxxxxx x xxxxxxxxxx látkami, xxxxx xxxxxxxx silné xxxxxxxxxxxx xxxxxxx (26). Xxxx závažně xxxxxxxxx xxxxx xxxxxxx rostou xxxxxxxx xxxxxx jako xxxxxxxx buňky x xxxxx velké kolonie.
Mělo xx xxx xxxxx xxxxxxx (xxxxxxxxx účinnost xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Četnost xxxxxxx by xxxx xxx xxxxxxxxx xxxx xxxxx xxxxxxx k xxxxx xxxxxxxxxx xxxxx.
Xxxx xx xxx uvedeny xxxxx xxx jednotlivé xxxxxxx. Dále xx xxxx xxx všechny xxxxx xxxxxxx ve xxxxx tabulky.
Ověření xxxxx xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Tam, xxx xxxx potvrzení xxxxxxxxxxx xxxxxxxx xxxxxxxxxx za xxxxx, xx xxxxx xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx s xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx by xxxx xxx zvážena x xxxxxxxxxx xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, xxx xxx xxxxxxxxx výsledky. X xxxxxxxxxx xxxxxx, které xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx a xxxxxxxx xxxxxxxxxxx aktivace.
2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX
Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxx xxxxxxx v xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx této xxxxxxxx. Xxxxxxxx xx xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx metody. Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.
Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx x tomto xxxxxxx xxxxxxxx xx xxxxxxxxxxx.
Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx negativní xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx soubor údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx bez ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.
Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx znamenají, xx xxxxxxxx látka xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx savců genové xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx xx xxxxx xxxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za podmínek xxxxxxx xxxxxxxxxx v xxxxxxxxx xxxxxxxxxxxxx buňkách xxxxx xxxxxx xxxxxx.
3. XXXXXX
XXXXXXXX X ZKOUŠCE
Protokol x xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:
Xxxxxxxxxxxx/xxxxxxxxx:
- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,
- xxxxxxxxxxx x stálost xxxxxxxx xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx známa.
Buňky:
- xxx a xxxxx xxxxx,
- xxxxx buněčných xxxxxx,
- případně počet xxxxxx,
- případně xxxxxx xxxxxxxxx buněčné xxxxxxx,
- xxxxxxxxxxxx mykoplasmat.
Zkušební xxxxxxxx:
- xxxxxxxxxx výběru koncentrací x xxxxx kultur, xxxxxx xxxx. xxxxx x cytotoxicitě x xxxxxx xxxxxxxxxxxx, xxxx-xx x dispozici,
- složení xxxxx, xxxxxxxx xxxxxxxxxxx XX2,
- xxxxxxxxxxx xxxxxxxx xxxxx,
- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,
- inkubační xxxxxxx,
- xxxxxxxxx xxxx,
- délka xxxxxxxx,
- xxxxxxxx hustota xxxxx během expozice,
- xxx x xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxxxxxx,
- pozitivní a xxxxxxxxx kontroly,
- xxxxx xxxx xxxxxxx (případně xxxxxx počtu xxxxxxxxxx xxxxx, subkultur x xxxxxx xxxxx),
- xxxxxxxx xxxxxxx,
- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx,
- xxxxxx použité x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx xxxxx,
- xxxxxxxx xxxxxxx xxxxx velikosti x xxxx (xxxxxxxx xxxxxx kriterií xxx "xxxx" x "velké" xxxxxxx).
Xxxxxxxx:
- xxxxxx xxxxxxxx,
- xxxxxx xxxxxxx,
- xxxxx x xX x xxxxxxxxxx během xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxx,
- xxxxxxxx xxxxxxx, byla-li vyšetřována, xxxxxxx xxx xxxxxxxxx x xxxxxxxxx kontroly,
- xxxxxxxxx předpoklady laboratoře xxxxxxxxx xxxxxxx xxxxxxx xxxx xxxxxxx xxxxxxxx X5178X XX+/-,
- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,
- xxxxxxxx xxxxxxxxxxx analýzy,
- xxxxx x xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) a pozitivní xxxxxxxx,
- xxxxxxxxx xxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní xxxxxxxx x rozmezími, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,
- xxxxxxx xxxxxxx.
Xxxxxx xxxxxxxx.
Xxxxxx.
4. LITERATURA
1) Xxxxx, X. X., XxXxxxxx, X. X., XxXxxxxx, X. J., Xxxxxx, X. R. (eds.) (1987), Banbury Xxxxxx 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Xxxx Xxxxxx Xxxxxx Xxxxxxxxxx, Xxx Xxxx.
2) Chu, X. X. X., Malling X. X. (1968), Xxxxxxxxx Xxxx Genetics. XX. Xxxxxxxx Xxxxxxxxx xx Xxxxxxxx Xxxxx Xxxxxxxxx in Xxxxxxx Xxxxxxx Xxxxx In xxxxx, Proc. Xxxx. Xxxx. Xxx. X. X. X, 61, 1306-1312.
3) Xxxxx, H. X., Thilly, X. X. (1982), Xxxxxxxx Xxxxx xx xxx Xxxxxxxxx Kinase Xxxxx xx Xxxxxxx Human Xxxxxxxxxxxx, Mutation Xxx. 94, 467-485.
4) Moore, X. X., Xxxxxxxxx-Xxxxx, X., Xxxxx, X. X., Xxxxxxxxx, X. X. (1989), Xxxxxxxxxxxx Xxxxxx Xxxxxxxxxxxx xx xxx Mouse Xxxxxxxx XX xxx XXX XXXXX Loci, Xxxxxxxxxxx, 4, 394-403.
5) Xxxxx, X. X., Xxxxxxxxxx, Xx. X. X., (1989), Xxxxxxxxxx of xxx XX52/XXXX xxx xxx XXX/XXXX Xxxxxx: Xxxxxxxxxx xx Xxx Xxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx. 223, 121-128.
6) Xxxxx, C. X., Xxxxxxxxxx, G., Glatt, X. R., Xxxxx, X., Nishi, X., Xxxxxxxxxx, Jr. X. X., Xxxxxx, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Working Xxxxx Xxxxxx. Report xx xxx International Xxxxxxxx xx Standardisation xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.
7) Xxxxx, X., Xxxxxxxx, X. X., Marshall, R. X., Ishidate, X., Xxxxxxx, X., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Mutation Xxx. 257, 147-204.
8) Xxxxx, X., XxXxxx, X., Xxxxxxx, X. X. X., Xxxxx, X., Xxxxxxxxx, K. X. (1983), Xxxxxxxx Xxxx Mutations in X5178X Xxxxx xx Xxxxxxx. X Xxxxxx xx xxx X. X. Environmental Xxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Res., 115, 225-251.
9) Li, X. X., Xxxxx, X. X., Heflich, X. X., Xxxxxx, X. X. (1988), A Xxxxxx xxx Analysis xx the Xxxxxxx Xxxxxxx Ovary/Hypoxanthine Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Xxxxxxxxx xxx Xxxxxxxxxxxx of Chemical Xxxxxx: A Xxxxxx xx Phase III xx the X. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Gene-Tox Program, Xxxxxxxxxx Xxx., 196, 17-36.
10) Li, X. X., Carver, J. X., Xxxx, X. X., Xxxx, A. X., Xxxxx, R. X., Xxxxxxx, X. X., X'Νxxxx, X. X., Xxxxxx, X. X., Xxxxxxxxxx, L. X. Jr., Xxxx, X. L. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx xx xxx Xxxxxxx Xxxxxxx Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Phosphoribosyl Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Res., 189, 135-141.
11) Xxxxx, X. L., Xxxxxxx, X. X., Xxxxxx, X. B. (1989), X Xxxxxxxxxx xx Xxxxxxxx Xxxxxxxxx at xxx XX and XXXX Xxxx xx Xxxxx Xxxxxxxxxxxxxx Xxxxx: Xxxxxxxxxxxx Xxxxxxxxxxx xxx Xxx xx xx Xxxxxxxxxx Xxxxx xx Xxxxxxxxx xx xxx Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Xxx., 216, 9-17.
12) Stankowski, X. X. Xx., Xxxxxx, X. X., Xxxx, X. X. (1986), Xxxxxxxxxxxx and Molecular Xxxxxxxx xx Xxxxx Xxxxxxxxxxxxxxxxx and ICR 191-Xxxxxxx Molecular Xxxxxxxx xx Xxxxx Methanesulphonate xxx XXX 191 Xxxxxxx Xxxxxxxx xx XX52 Cells, Xxxxxxxxxx Xxx., 160, 133-147.
13) Xxxxxx, X. X., Xxxxxx, X. G., Xxxxx, X. (1984), Xxxxxxxxx xxx xxx X5178X/XX+/--XX+/- Xxxxx Lymphoma Xxxx Xxxxxxxxxxxx Xxxxx, xx: Xxxxxx, B. X. xx xx (xxx.) Handbook of Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, Xxxxxxxx Xxxxxxx Publishers, Xxx York, 239-268.
14) Xxxxxx, X. X., Xxxxx, X. M., Xxxxxx, X. X., Xxxxx, X. H. X., Xxxx, X., XxXxxxxx, X. X., Xxxxxxx S. X. (1989), Xxxxxxxxx Xxxx Xxxx Mutation Xxxxxx Xxxxx xxxx Colony Xxxxxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. X., xx., Xxxxxxxxx University Press, 66-101.
15) Abbondandolo, X., Xxxxxxx, X., Corti, X., Xxxxxx, X., Xxxxxxxx, N., Mazzaccoro, X. (1977), Xxxxxxxxx xx 6-Thioguanine-Resistant Xxxxxxx xx X79 Xxxxxxx Xxxxxxx Cells xx Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Dimethylnitrosamine, Xxxxxxxxxx Res. 46, 365-373.
16) Xxxx, X. X., XxXxxx, X., Xxxxxxxx, X. (1975), Xxxxxxx for Detecting Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx. 31, 347-364.
17) Xxxxx, X., Xxxxxxx, X. O., Xxxxxxx, X. X. X., Xxxxxx X. G., Xxxxx X. M. X. (1979), Validation xxx Characterisation xx xxx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxxxx Xxxxx Xxxxxx, Xxxxx. Xxx. 59, 61-108.
18) Xxxxx, D. X., Xxxx, X. X. (1983), Xxxxxxx Xxxxxxx xxx the Xxxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx. 113, 173-215.
19) Xxxxxxx, X. X., Combes, X. X., Xxxxxxx, C. X., Xxxxxxxxx, X. X., Xxxxxx, G. X., Xxxxxx, X. X., Xxxx, R. X. (1992), Alternatives xx Aroclor 1254-Xxxxxxx X9 in: In xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx 7, 175-177.
20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx of Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, X: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xx Xxxxxx, X. J., Xxxxx, X. R., Xxxx, X. R., Philpot, X. X. (xxx), Xxxxxxxx, North-Holland, 85-88.
21) Xxxxx, X. F., Xxxxxx, X. X., XxXxxxx, X. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Evaluation xx Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. X. (eds), Xxxxxxxxx Effects xx Xxxxxxxx Xxxxxx, New Xxxx, Xxxxxx, 91-103.
22) Xxxxxx, X. X., Xxxxxx, J. X., Xx, X. P., Xxxxxx, A. X. (1983), Xxxxxxxxxx of xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Grown xx Collagen Xxxx xxx Xxxxxxxxx Highly Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Mutation Xxxxx, Environ. Xxxxxxxxxxx, 5, 795-801.
23) Applegate, X. X., Xxxxx, X. X., Xxxxxx, X. X., Burrell, X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxx xx xxx Heterozygous Xxxxxxxxx Xxxxxx Xxxxx xx Xxxxx Xxxxxxxx Xxxxx, Xxxx. Xxxx. Xxxx. Sci. X. X. A, 87, 51-55.
24) Xxxxx, M. X., Clive, X., Xxxxxx, X. C., Xxxxxx, X. X., Xxxxxx, X. G., Xxxxxx, X. T., Xxxxxx, J. (1985), Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (XXX+) Xxxxxxx xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Mutatation Xxx. 151, 161-174.
25) Xxxxxxx, X. X., Xxxxx, X. X., Little, X. X. (1990), Xxxxxxxxx Genetic Xxxxxxxx xx Recessive Xxxxxxxxx xx x Heterozygous Xxxxxxxxx Locus in Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.
26) Xxxxx, M. M., Xxxxx, C. X. (1990), Xxxxxxxxxx of Xxxxxxxxxx Xxxxxxxxxx Frequency xxx Xxxxx Colony XX-Xxxxxxxxx Mutant Frequency xx L5178Y/TK+/- 3.7.2X Xxxxx Xxxxxxxx Cells, Xxxxxxxxxxx, 5, 609-614."
PŘÍLOHA 4F
"B.23 ZKOUŠKA XX XXXXXXXXXXXX ABERACE XX XXXXXXXXXXXXXXX XXXXX
1. XXXXXX
Xxxx metoda je xxxxxxxx xxxxxx OECD XX 483 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx spermatogoniích xxxxx (1997).
1.1 XXXX
Xxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx ve xxxxxxxxxxxxxxx xxxxx in vivo xx xxxxxxxxxxxxx xxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx savců (1, 2, 3, 4, 5). Xxxxxxxxx xx dva xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx chemických xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx vyskytují. Tato xxxxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x není x xxxxxx xxxxx xxxxxxx používána. Xxxxxxxxxxxx xxxxxx a xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx podmíněných xxxxxx u xxxxxxx.
Xxxxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx ve xxxxxxxxxxxxxxx x xxxxxxxxxxx xx xxxx, xx xxxx xxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx v xxxxxxxxxxxx xxxxxxx.
X této xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Xxxxx cytogenetickou xxxxxxxx in xxxx xx detekují xxxxxxxxxxxx xxxxxxx při xxxxxx xxxxxxxxxxxxx. Jiné xxxxxx xxxxx nejsou xxxxxxxxx xxxx zkoušky.
Pro detekci xxxxxxx xxxxxxxxxxxxxx xxxx xx xxxxxxxxxxxxxxx xx xxxx být — xxxxx než xxxxx xx xxxxxx léze — vyšetřeno xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx xx xxxxxxxx. Další informace x exponovaných spermatogoniálních xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx aberací xxxxxxxxxxxxxx xxxx v xxxxxxxxx-xxxxxxxx X, kdy se xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.
Xxxx zkouška xx xxxx xx xxxxxxxx xxx xxxxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxx x xxxxxxxxxxxx buňkách. Xxxxx xx xxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX.
Xx varlatech xx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxx citlivostí xx xxxxxxxx chemické xxxxx. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx souhrnnou odpověď xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x převládajícími xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. V xxxxxxxxxx xx xxx xxxxxx xx xxxxxxxxx, xxxxx xxxx xxxxxx být xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx buněk x bariéry xxxx xxxxxxx oběhem x xxxxxxx.
Xxxxxxxx xxxxxxxx důkaz x xxx, xx xx zkoušená látka xxxx reaktivní xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.
Xxx xxxx xxxxxx xxxx, xxxx X.
1.2 XXXXXXXX
Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu v xxxxxx zlomu jednotlivých xxxxxxxxx xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.
Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x podobě xxxxx xxxx xxxxx a xxxxxxx xxxx xxxxxxxxx x xxxxxx místě.
Gap : xxxxxxxxxxxx xxxx xxxxx xxx xxxxx xxxxx chromatidy x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.
Xxxxxxxxx aberace : xxxxxxxx xxxxx chromozomů xx xxxxxxxx xxxxxxx x xxxxxxxxx xxxxx.
Xxxxxxxxxxx : násobek haploidního xxxxx chromozomových xxx (x), jiný xxx xxxxxxxxx (tj. 3 x, 4 n xxx.).
Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx xxxxxx xx xxxxxx metafáze pod xxxxxxxxxxx, xxxx se xxxx delece a xxxxxxxxx, xxxxxxxxxxxxxxxxxx nebo xxxxxxxxxxxxxxxxxx xxxxx.
1.3 PODSTATA XXXXXXXX METODY
Zvířata xxxx xxxxxxx způsobem exponována xxxxxxxx látce x xx vhodné xxxx xx xxxxxxxx usmrcena. Xxxx xxxxxxxxx xx xxxxxxxx podá xxxxx xxxxxxxxxxx metafázi (xxxx. xxxxxxxxx nebo Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx chromozomů, xxxxxx xx a xxxxxxxxx xx chromozomové aberace xxxxxxxxxxxxxx xxxxx.
1.4 XXXXX XXXXXXXX XXXXXX
1.4.1 Přípravky
1.4.1.1 Xxxxx xxxxx zvířete
Běžně xxxx používáni xxxxx xxxxxx xxxxxxxx x xxxx; lze však xxxxxx xxxxx xxxxxxxxxx xxxxxx vhodného druhu xxxxx. Xxxx by xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx minimální x xxxxxx xx překročit ± 20 % xxxxxxx hodnoty hmotnosti.
1.4.1.2 Xxxxxxxx xxxxx x xxxxxx
Xxxxx xxxxxx podmínky xxxxx xxxxxxxx úvodu x xxxxx B, xxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxx 50 – 60 %.
1.4.1.3 Xxxxxxxx xxxxxx
Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx xx xxxxxxxx xxxxxxx rozdělí xx kontrolní xxxxxxx x skupinu, xxxxx xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx tak, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx započetím studie xx xxxxxxx v xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.
1.4.1.4 Xxxxxxxx xxxxx
Xxxxx zkoušené xxxxx xx xxxx xxx před xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx být xxxxxxxx xxxxx nebo xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.
1.4.2 Xxxxxxxx xxxxxxxx
1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx
Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx při xxxxxxxxx xxxxxxxxx dávek xxxxxxx účinky x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx zařazení xxxxxxxxx xxxxx o xxxxxx kompatibilitě. Xxxxxxxxxx xx pokud možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.
1.4.2.2 Kontroly
Součástí xxxxxxx experimentu by xxxx xxx souběžné xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata xx xxxxxxxxx, x nichž xxxxx x xxxxxxxx.
Xxxxxxxxx xxxxxxxx xx měly xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xx xxxx při xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.
Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx aby xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx xxx odběr x jejím xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxx být xxxxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou-li x xxxxxxxxx. Xxxxxxxx xxxxx xxx pozitivní xxxxxxxx:
|
Xxxxx |
Xxxxx XXX |
Xxxxx podle Einecs |
|
cyklofosfamid |
50–18–0 |
200–015–4 |
|
cyklofosfamid xxxxxxxxxx |
6055–19–2 |
|
|
xxxxxxxxxxxxxx |
108–91–8 |
203–629–0 |
|
xxxxxxxxx C |
50–07–7 |
200–008–6 |
|
akrylamid (monomer) |
79–06–1 |
201–173–7 |
|
2,4,6-tris(aziridin-1-yl)-1,3,5-triazin |
51–18–3 |
200–083–5 |
V xxxxxxxx každého xxxxxx xx měl xxx xxxxxxxx xxxxx u xxxxxxx negativní kontroly, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako exponované xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Kromě xxxx by xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx také xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx nebo xxxxxxxxx účinky.
1.5 XXXXXX
1.5.1 Xxxxx zvířat
Každá xxxxxxxxxx x xxxxxxxxx xxxxxxx xxxx zahrnovat xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxx.
1.5.2 Xxxx xxxxxxxx
Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxx nadvakrát (xx. xxx xxxxx xxxxxxxx nebo xxxx xxxxxxxxxx). Xxxxxxxx látky xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, xxx. xxx xxxxx v xxx xxx v xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx objemů xxxxxxxxx. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx zdůvodněny.
Ve xxxxxxx x xxxxxxxx dávkou xx xxxx xxx xx xxxxxxxx xxxxxxxxx xxx xxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx xx jeden xxxxx xxxxx x xxxxx xxxxxxxx xxxxx xxxxxxxxx 24 a 48 xxxxx xx expozici. X xxxxxxx xxxx xxx xxxxxxxx xxxxx xx měl xxx xxxxx xxxxxxxx xx 24 hodin nebo xx takové xxxx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxx buněčného xxxxx, xxxxx není xxxxx jiná xxxxxxxxx xxxx xxx xxxxxxx xxxxxx (6).
Xxxxx xxxxx xxx odběry xxxxxxxxx xxxx x xxxx xxxx. Xxxxxxxxx x xxxxxxx chemických xxxxx, xxxxx xxxxx xxxxxxxxx xxxxxxxx replikace (xxxxxxx) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx xxx vhodnější xxxxxxxx odběr (1).
Vhodnost xxxxx xxxxxxxxx expozice xxxx xxx xxxxxx xxxxxx xx případu. X xxxxxxx xxxxx x opakovanou xxxxxxxx xx xxxx být xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx xxxxx xxxxx) xx xxxxxxxx xxxxxxxx. Podle xxxxxxx xxxxx xxx xxxxxxxxx xxxxx odběry x xxxx xxxx.
Xxxx xxxxxxxxx xx zvířatům xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx zastavující xxxxxxxx (xxxx. Xxxxxxxx® nebo xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. U xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 hodin; x xxxxxx čínského xx xxxx doba xxxxxxxxx 4 — 5 xxxxx.
1.5.3 Xxxxxxxxx
Xxxxxxx-xx xx xxxxx neexistenci xxxxxxxx xxxxxxxxxx údajů studie xxx xxxxxxxx xxxxxxx, xxxx xx xxx xxxxxxxxx xx stejné xxxxxxxxxx, se stejným xxxxxx a xxxxxx x xx xxxxxxxx xxxxxx expozice, xxxxx xx xxxxxxx x xxxxxx xxxxxx (7). X xxxxxxx toxicity xx pro xxxxx xxxxx použijí xxx xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx maximální x xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx použita xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx xx xxxxxxxxxx jako dávka xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že xx xxxxx dávky xxxxx xxx stejném xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x letalitě.
Látky xx xxxxxxxxxxx xxxxxxxxxxx aktivitou xxx xxxxxxx netoxických xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx hodnoceny xxxxxx xx případu. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx dávka vyvolávající xx spermatogoniích některé xxxxxx toxicity (např. xxxxxxx xxxxx spermatogonií x xxxxxx vzhledem x xxxxx x xxxxx meiotické xxxxxxxx; xxxx xxxxxxx xx xxxxxx xxxxxxxxx 50 %).
1.5.4 Xxxxxxx xxxxxxx
Xxxxxxxx xxxxxxx x jednou xxxxxx alespoň 2000 xx/xx xxxxxxx hmotnosti xxxxxxx jednorázově xxxx xx xxxx xxxxxxx x xxxxxx dni xxxxxxxxxx žádné xxxxxxxxxxxxx xxxxxxx účinky x xxxx-xx na xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx úplná xxxxxx xx xxxxx xxxxxxxx dávky za xxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx může znamenat xxxxxxx použít v xxxxxxx zkoušce vyšší xxxxxx xxxxx.
1.5.5 Podávání xxxxx
Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx sondou xxxx xxxxxxx intubační kanylou, xxxx intraperitoneální xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx může xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx objemů, xxx xx uvedený xxxxx, musí xxx xxxxxxxxxx. Až na xxxxxxxx x xxxxxx xxxxx, xxxxx obvykle xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.
1.5.6 Xxxxxxxx preparátů xx xxxxxxx xxxxxxxxxx
Xxxxx xx xxxxxxxx se x xxxxxxx xxxx xxxx xxxxxx xxxxx xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx x xxxxxx. Xxxx xx xxxxxx xx xxxxxxxx sklíčka x xxxxxx xx.
1.5.7 Xxxxxxx
X každého xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx x xxxxx xxxxxxxxxxxx metafázi (xx. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Xxxxx xxxxx lze xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Všechny xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x negativních xxxxxxx, xx xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx při xxxxxx xxxxx dochází xx xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx chromozomů u xxxxx xxxxxxxx, xxxx xx xxxxxxxxxxx buňky xxxxxxxxx xxxxxxxxxx v xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.
2. ÚDAJE
2.1 XXXXXXXXXX XXXXXXXX
Xxxxx pro xxxxxxxxxx xxxxxxx xx měly xxx zpracovány xx xxxxx tabulky. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx každé zvíře xx xxx být xxxxxxxxxx xxxxx buněk xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x počet xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx exponované x kontrolní xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich počtem x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx odděleně x xxxxxxx xx, xxx obecně xx xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx.
Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, měl xx xxx pro stanovení xxxxxxx xxxxxxxxxxxxx účinků xxxx xxxx cytotoxicity xxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx a xxxxxx xxxxxxxxxx jako xxxxxxxxx xxxxxxxx poměr xxxxxxxxxxxxx v mitose xxxxxxxx x xxxxx x druhé xxxxxxxxx xxxxxxxx, x to x xxxxxxxx xxxxxx 100 xxxxxxxx se xxxxx xx jedno xxxxx. Xxxxx xx xxxxxxxxx xxxxx mitosa, xxxxxxx x 1000 xxxxxxx xx zvíře xx xxx xxx xxxxxxxx xxxxxxxxx xxxxx.
2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX
Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. nárůst xxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx dávce xxxx xxxxx xxxxxx xxxxx xxxxx s xxxxxxxxx pro skupinu x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx použity xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (8). Statistická xxxxxxxxxx xx xxxxxx xxx jediným určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx dalším zkoušením, xxxxxxx x úpravami xxxxxxxxxxxxxxxx xxxxxxxx.
Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx x tomto xxxxxxx považuje za xxxxxxxxxxx.
Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx to, xxxxxxxx xx experiment xxxxxxxx.
Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xxxxx xx xxxx znamenají, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxx buňkách xxxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx za xxxxxxxx xxxxxxx neindukuje x germinálních xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.
Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx zkoušená xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxx xxxxx.
3. ZPRÁVY
PROTOKOL X XXXXXXX
Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:
Xxxxxxxxxxxx/xxxxxxxxx:
- xxxxxxxxxx xxxxx xxxxxxxx,
- xxxxxxxxxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.
Xxxxxxxxx zvířata:
- xxxxxxx druh/kmen,
- xxxxx x xxxxx xxxxxx,
- xxxxx, podmínky xxxxx, xxxxxx xxx.,
- individuální xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné hmotnosti, xxxxxxx xxxxxxx a xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.
Zkušební podmínky:
- xxxxx xx xxxxxx xxx zjištění rozsahu, xxxxx xxxx xxxxxxxxx,
- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,
- xxxxxxxxxx xxxxxxx xxxxxxxx,
- xxxxx x xxxxxxxx zkoušené xxxxx,
- xxxxx x xxxxxxxx xxxxxxxx xxxxx,
- zdůvodnění xxx xxxxxxxx,
- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxxx xxxx (xxx) xx xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),
- xxxxxxxx xxxxx x kvalitě xxxxxx x xxxx,
- xxxxxxxx xxxxx xxxxxxx expozice x xxxxxx,
- xxxxxx xxxxxxxxx toxicity,
- xxxxxxxxxxxx xxxxx zastavující xxxxxxxx, xxxx koncentrace a xxxxx xxxxxxxx,
- xxxxxx xxxxxxxx preparátů,
- xxxxxxxx xxxxxxxxx aberací,
- počet xxxxxxxxxxxxx buněk xx xxxxx xxxxx,
- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, negativní nebo xxxxxxxxxxx.
Xxxxxxxx:
- známky toxicity,
- xxxxxxxxx xxxxx,
- xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxx xxxxxx,
- typ x xxxxx aberací uvedený xxxxxxxxxx pro xxxxx xxxxx,
- xxxxxxx xxxxx xxxxxxx xx skupině,
- xxxxx buněk s xxxxxxxxx ve xxxxxxx,
- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,
- xxxxxxxx xxxxxxxxxxx xxxxxxx,
- xxxxx x xxxxxxxx xxxxxxxxx kontrole,
- xxxxxxxxx xxxxx o negativní xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx odchylkami,
- xxxxx x souběžné pozitivní xxxxxxxx,
- změny xxxxxxx, xxxxx byly xxxxxxxxxx.
Xxxxxx xxxxxxxx.
Xxxxxx.
4. XXXXXXXXXX
1) Adler, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Xxxxxxxxxxxxx xx Xxxxxxxx Xxxxxxxx Related xx their Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxxx Xxxxxxxxx, Xxxx X: Xxxxxxx Xxxxxxx and Xxxxxxx Mutagenesis, Xxxxx, X., Lambert, B., Xxxxxxxxx, J. (xxx) Xxxx, Xxx Xxxx, 477-484.
2) Xxxxx, X. X., (1984), Cytogenetic xxxxx xx Mammals, xx: Mutagenicity Testing: x Xxxxxxxxx Xxxxxxxx, (xx.) X. Venitt, X. X. Parry, XXX Press, Xxxxxx, Xxxxxxxxxx XX, 275-306.
3) Xxxxx, X. X., Xxxxxxx, X., Xxxx, X. X. (1964), Xx Xxx-xxxxxx Xxxxxx xxx Xxxxxxx Xxxxxxxxxxxx xxxx Xxxxxxxxx Testes, Xxxxxxxxxxxx Cell Xxxxxxxx, 3, 289-294.
4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Assays, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Mutagenicity Testing. Xxxxxx. Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.
5) Xxxxxxxx, K., Kikuchi, X. (1978), X Xxx Method xxx Xxxxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 52, 207-209.
6) Xxxxx, X. X., Xxxxxx X. D., Xxxxxxx, J., Xxxxx, X., Xxxxxxxx, W., Xxxxxxxxxxxx, X., Shibuya, X., Tanaka X. (1994), International Workshop xx Standardisation of Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Report xx xxx Working Xxxxx xx Mammalian Xxxx Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.
7) Xxxxxxx, X. X., Xxxxx, X. A., Xxxxxx, A. R., Xxxxxx, X. A., Xxx, X., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Richold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx xx In xxxx Mutagenicity Assays, Xxxxxxxxxxx, 7, 313-319.
8) Xxxxxx, D. X., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Richold, X., Papworth, X. X., Xxxxxx X. X. K. (1989), Xxxxxxxxxxx Analysis of Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Report, Xxxx XXX. Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."
XXXXXXX 4G
"B.39 XXXXXXX XX XXXXXXXXXXXX SYNTÉZU XXX (XXX) X XXXXXXXXX XXXXXXX XXXXX XX XXXX
1. XXXXXX
Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX TG 486 — Xxxxxxx xx neplánovanou xxxxxxx XXX (XXX) x xxxxxxxxx buňkách savců xx xxxx (1997).
1.1 XXXX
Xxxxxx zkoušky xx xxxxxxxxxxxx syntézu DNA (XXX) v xxxxxxxxx xxxxxxx xxxxx in xxxx je xxxxxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxx XXX x jaterních xxxxxxx xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).
Xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxx chemických xxxxx x xxxxxxx. Xxxxxxxxxxx xxx je xxxxxxxxxx poškození XXX x xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxx xxxx obvykle xxxxxxx xxxxxx, xxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Xxxx xxxx xxxxxxx místem xxx xxxxxxxxx xxxx poškození XXX in xxxx.
Xxxxxxxx xxxxxxxx xxxxx o xxx, že xx xxxxxxxx látka nedostane xx xxxxxx xxxxx, xxxx vhodné xxxx xxxxxxx xxxxxx.
Xxxxxx neplánované xxxxxxx XXX (XXX) xx zhodnotí xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx xx autoradiografické xxxxxxxxx inkorporace xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx xxxxxxx xx XXX in xxxx xx xxxxxxxxxx xxxxxxxxx xxxxx potkana. Xxxx xxxxx xxx xxxxx xxxxx být xxxxxx xxxxxxx, xxxxxx však xxxxxxxxx xxxx xxxxxx.
Xxxxxxx xxxxxxxx XXX xxxxxx xx xxxxx xxxx XXX xxxxxxxxxxx x xxxxxxxxxxx v xxxxx xxxxxxxxx. Zkouška na XXX xx xxxx xxxxxx xxxxxxx xxx xxxxxxx dlouhých xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 xxxx) xxxxxxxxxxxx látkou. Xxxxxx xxxxxx ("xxxxx-xxxxx xxxxxx") (xxxxx xx xxx xxxx) xxxx naproti xxxx detekovány s xxxxxx menší xxxxxxxxxx. Xxxxx může xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx chybné xxxxxxxxx lézí XXX xxxxx x xxxxxxxxxx xxxxxxxxx. Xxxxxx xxxxxxxx XXX xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, xx xxxxxxx reaguje x XXX, xxx poškození XXX není opraveno xxxxxxxxxxx reparací. Nedostatek xxxxxxxxxxxx xxxxxxxxx, xxxxx xxxx xxxxxxx poskytuje x xxxxxxxxx xxxxxxxx, xx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx jevu, xxxxx xx xxxxxxxxxx x celém xxxxxx.
Xxx xxxx xxxxxx xxxx, xxxx X.
1.2 XXXXXXXX
Xxxxxxxxxx xxxxx : xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (NNG), xxxxx než předvolená xxxxxxx xxxxxxxxx laboratoří xxxxxxxxxxx xxxxxxx.
Xxxxx xxxxx xxx xxxxxxxxxxxxxx buněčným xxxxxx (NNG) : xxxxxxxxxxxxx míra UDS xxxxxxxx xxxxx x xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, vypočtená odečtením xxxxxxxxxx počtu xxx x xxxxxxxxxxxxxxxxx oblastech (XX) odpovídajících xxxxxx xx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx jádrům (XX): NNG = XX — XX. Xxxxxxx XXX se xxxxxxx xxx xxxxxxxxxx xxxxx, xxxx společně xxx xxxxx v xxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxx.
Xxxxxxxxxxx xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx vyštěpení x xxxxxxxxxx xxxxx DNA xxxxxxxxxxxx xxxxxx x xxxxxxxxxx indukovaným chemickými xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.
1.3 PODSTATA ZKUŠEBNÍ XXXXXX
Xxxxxxx xx UDS x xxxxxxxxx xxxxxxx xxxxx in vivo xxxxxxxx xxxxxxx xxxxxxxx XXX xx vyštěpení x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx region x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx založena xx inkorporaci 3H-TdR xx XXX jaterních xxxxx, xxx je xxxx xxxxxxx xxxxx x X-xxxx xxxxxxxxx xxxxx. Inkorporace 3H-TdR xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx není xxx xxxxxxx xx xxxx X-xxxx xxxxx xxxx xxxx. kapalná xxxxxxxxxxx xxxxxxxxxxxxx.
1.4 XXXXX XXXXXX
1.4.1 Xxxxxxxxx
1.4.1.1 Výběr druhu xxxxxxx
Xxxxx xx xxxxxxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Měly xx xxx xxxxxxx xxxxx xxxxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx dospělých xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx by xxxx xxx xxxxxxxx v xxxxxxxxx zvířat minimální x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx pro xxx xxxxxxx.
1.4.1.2 Xxxxxxxx xxxxx x xxxxxx
Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx X, xxxxxxx by xxxx být dosaženo xxxxxxxx xxxxxxx 50 - 60 %.
1.4.1.3 Xxxxxxxx zvířat
Zdravá pohlavně xxxxxxx zvířata se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, která xx exponuje. Xxxxx xx měly xxx xxxxxxxxxx xxx, xxx xxx xxxx jejich xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx se nechají x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx dní xxxxxxxxxxxxx.
1.4.1.4 Xxxxxxxx zkoušené xxxxx
Xxxxx xxxxxxxx látky xx xxxx xxx xxxx xxxxxxxx zvířatům xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx podávány xxxxx xxxx mohou být xxxx xxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.
1.4.2 Xxxxxxxx xxxxxxxx
1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx
Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x mělo xx xxx vyloučeno xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx použita xxxx xxx xxxxx rozpouštědla/vehikula, xxxx by být xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Doporučuje se xxxxxxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.
1.4.2.2 Kontroly
Součástí xxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx by xxxx xxx souběžné pozitivní x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X výjimkou xxxxxxxx xxxxxxxx látky xx xxxx zvířata xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx proces xxxx xxxxxxx xx xxxxxxxxx, x nichž xxxxx x expozici.
Pozitivními kontrolami xx xxxx být xxxxx, x nichž xx xxxxx, xx xxxxxx xxxxxxxx v xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx v xxxxxxx xxxxxxxxxxxx mírnou xxxxxxx (4). Xxxxx mohou xxx zvoleny tak, xxx xxx xxxxxx xxxxxxxx, xxx aby xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:
|
Xxxx odběru |
Látka |
Číslo XXX |
Xxxxx xxxxx Einecs |
|
Časné xxxx xxxxxx (2 až 4 x) |
X-xxxxxxxxxxxxxxxxxxx |
62–75–9 |
200–249–8 |
|
Xxxxxx xxxx xxxxxx (12 xx 16 x) |
X-(xxxxxxx-2-xx)xxxxxxxx (2-XXX) |
53–96–3 |
200–188–6 |
Xxxxx xxx xxxxxxx xxxx xxxx látky xxx xxxxxxxxx xxxxxxxx. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx kontrolní xxxxx xxxxxxxx xxxxx způsobem, xxx xxxxxxxx látka.
1.5 XXXXXX
1.5.1 Xxxxx x xxxxxxx xxxxxx
Xxx by xxx xxxxxx xxxxxxxxxx xxxxx xxxxxx, aby xxxx zohledněno xxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xx zkoušku. Xxxxx xxxxxxx by xx xxxx xxxxxxx alespoň xx xxx xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx pro xxxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxx xxxxx jedno xx xxx zvířata.
Jestliže xxxx x době xxxxxx x xxxxxxxxx xxxxx xx xxxxxx se xxxxxxx druhem x xx použití stejného xxxxxxx xxxxxxxx, jež xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx samců. Xx-xx expozice xxxxxxx xxxxxxxxxx pro xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx u xxxxxxxxx farmaceutických xxxxx, xxxx xx xxx xxxxxxx provedena xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.
1.5.2 Xxxx xxxxxxxx
Xxxxxxxx xxxxx xxxx zpravidla podávány xxxxxxxxxxx.
1.5.3 Xxxxxxxxx
Xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxx xxxxxxx xxx úrovně xxxxx. Xxxxxxxx xxxxx xx definována jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že xxxxx xxxxx xx xxxxx podle očekávání xxx xxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx xx xxxx xxx zpravidla 50 % xx 25 % xxxxx xxxxx.
Xxxxx xx specifickou xxxxxxxxxxx aktivitou xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. hormony x xxxxxxxx) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx hodnoceny případ xx xxxxxxx. Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx dostupných údajů xxxxxx xxx zjištění xxxxxxx, xxxx by xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx druhem, xxxxxx, xxxxxxxx x za xxxxxxxx režimu xxxxxxxx, xxx se xxxxxxx x xxxxxx xxxxxx.
Xxxxxxxx xxxxx xxxx být xxxxxxxxxx xxxx jako xxxxx vyvolávající známky xxxxxxxx v játrech (xxxx. xxxxxxxxxx xxxxx).
1.5.4 Xxxxxxx xxxxxxx
Xxxxxxxx zkouška x jednou xxxxxx x alespoň 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx dvou xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx účinky x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxx xxx xxxxx xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.
1.5.5 Xxxxxxxx xxxxx
Xxxxxxxx látka xx xxxxxxx podává xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx jsou možné, xxx-xx xx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxxxxxxxx se xxxx xxxxxxxxxxxx, neboť xx xxxxx xxxxx xxx exponována zkoušené xxxxx přímo a xxxxxx prostřednictvím xxxxxxxxx xxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx může xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx je uvedený xxxxx, musí xxx xxxxxxxxxx. Xx xx xxxxxxxx a žíravé xxxxx, xxxxx obvykle xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx měla xxx xxxxxxxxxxx zkušebního xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx všech xxxxxxxx xxxxx.
1.5.6 Příprava xxxxxxxxx xxxxx
Xxxxxxx xxxxx xx xxxxxxxxxx x xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 hodin xx xxxxxx dávky. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (obecně dvě xx xxxxx xxxxxx xx xxxxxxxx) xx xxxxxxxx, xxxx-xx xx 12 xx 16 xxxxxxxx jasná xxxxxxxxx xxxxxxx. Mohou xxxx xxx xxxxxxx xxxx xxxx xxxxxx, xxxx-xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx údajů.
Krátkodobé kultury xxxxxxxxx xxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxxx xx xxxx x xxxxxx xx, xxx xx xxxxxxx disociované xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx buňky x xxxxxxxxx kontroly xx xxxx vykazovat xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.
1.5.7 Stanovení XXX
Xxxxxxx xxxxxxxxx xxxxxxx buňky xxxxx xx xxxxxxx xxxxxxx dobu, xxxx. xxx xx osm xxxxx, xxxxxxxx s xxxxxx obsahujícím 3H-TdR. Xx xxxxx xxxxxxxxx xxxx xx xxxx xxx xxxxxx x xxxxx xxxxxxxxxx x xxxxx xxxx xxxxx xxx xxxxxxxxxx s xxxxxx obsahujícím přebytek xxxxxxxxxxx xxxxxxxxx, aby xxxx snížena xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx se xxxx xxxxxxx, fixují x xxxxxx. Xxx xxxxx xxxxxxxxx xxxx nemusí xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx se xxxxxx xx autoradiografické xxxxxx, exponují se x xxxxx (např. x xxxxxx 7 xx 14 xxx), xxxxxxxx se, obarví x xxxxxxxxx se xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx xxxxxxx xx připraví dva xx xxx xxxxxxxxx.
1.5.8 Xxxxxxx
Xxxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx normálních buněk, xxx mělo xxxxxxxxx XXX výpovědní xxxxxxx. Xxxxxxxxx xx pod xxxxxxxxxxx prohlédnou xx xxxxxx zjevné xxxxxxxxxxxx (xxxx. xx xxxxxxx, xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx).
Xxxx počítáním xxx by xxxx xxx xxxxxxxxx xxxxxxxx. Xxxxxxxxx se xxxxxxxxx 100 xxxxx xx xxxxx zvíře xxxxxxx xx xxxx preparátů; xxxxxxxxx xxxx než 100 xxxxx/xxxxx xx xxxx být xxxxxxxxxx. Xxx xxxxxxxx zrn xx xxxxx v X-xxxx nevyšetřují, ale xxxxx xxxxx x X-xxxx může xxx xxxxxxxxxx.
Xxxxxxxx 3X-XxX inkorporovaného xx jader x xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx doložené navrstvením xxx xxxxxxx xx xxxx xxx stanoveno xxxxxxx xxxxxxx.
Xxxxx xxxxx xx stanoví x xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (xx) x x xxŭxxxxxxx xxxxx zrn x xxxxxxxxxxxxxxxxx oblastech (xx) xxxxxxxxxxxxxx jádrŭm. xxxx xxxxxxx cg se xxxxxxx buď xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx oblast xxxxxxxxxx, xxxx xxŭxxxxx hodnota xxxx xx xxx xxxxxxx vybraných oblastí x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxx. xx xxxxxxxxxxxxx zdŮvodnění xxxxx xxx xxxxxxx x xxxx xxxxxxx stanovení xxxxx xxxxx (xxxx. xxxxxxxx xxxxxx xxxxx) (6).
2. XXXXX
2.1 ZPRACOVÁNÍ XXXXXXXX
Xxxx by být xxxxxxx xxxxx pro xxxxxxxxxx preparáty x xxxxxxx. Údaje by xxxx být xxxx xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX od xxxxxxx XX xx měl xxx vypočten pro xxxxxx xxxxx, xxx xxxxx xxxxx x xxx každou dávku x čas čistý xxxxx zrn odpovídajících xxxxxxxx xxxxxx (NNG). Xxxxxxxx jsou xxxxxxxx "xxxxxxxxxx" buňky, xxxx xx xxx xxxxxxxx xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx xxxxxxxxxx a xxxxxxxx na dosavadních xxxx xxxxxxxxxx xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx statistickými xxxxxxxx. Mají-li xxx xxxxxxx, xxxx xx xxx xxxxxxxxxxx testy xxxxxxx x xxxxxxxxxx xxxx xxxxxxxxxx studie.
2.2 XXXXXXXXX A INTERPRETACE XXXXXXXX
Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx odpověď patří:
|
pozitivní |
i) |
hodnota XXX xxxx xxx xxxxxxxx xxxxxx, xxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxx; |
|
xxxx |
xx) |
xxxxxxx XXX je xxxxxxxx xxxxx xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx; |
|
xxxxxxxxx |
x) |
xxxxxxx XXX xxxx xx xxxxxxxxx prahové xxxxxxx xxxx xxx xx; |
|
xxxx |
xx) |
xxxxxxx NNG xxxx xxxxxxxx xxxxx xxx xxxxxxx pro souběžnou xxxxxxxx. |
Xxxx xx xxx xxxxxxxxx xxxxxxxxxx relevance xxxxx, xx. xxxx xx být xxxxx x xxxxx xxxxxxxxx, xxxx jsou variabilita xxxxxx, xxxxx xxxxx x odpovědi a xxxxxxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx pro pozitivní xxxxxxx.
Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých případech xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.
Xxxxxxxxx xxxxxxxx zkoušky xx XXX v xxxxxxxxx xxxxxxx xxxxx in xxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx xxxxxxx xxxxx in xxxx xxxxxxxxx XXX, xxxxx xxx opravit neplánovanou xxxxxxxx XXX xx xxxxx. Negativní výsledky xxxxxxxxx, xx xxxxxxxx xxxxx xx podmínek xxxxxxx xxxxxxxxxx poškození XXX, xxxxx xxx xxxxxxxxx xxxxx zkouškou.
Měla xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, s jakou xx zkoušená látka xxxxxxx do xxxxxxxx xxxxx xxxx. xx xxxxxx tkáně (xxxx. xxxxxxxxx xxxxxxxx).
3. XXXXXX
XXXXXXXX X ZKOUŠCE
Protokol x xxxxxxx xxxx xxxxxxxxx xxxx informace:
Rozpouštědlo/vehikulum:
- xxxxxxxxxx xxxxx vehikula,
- rozpustnost x xxxxxxx zkoušené xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx známa.
Testovací xxxxxxx:
- xxxxxxx xxxx/xxxx,
- počet, xxxxx x xxxxxxx xxxxxx,
- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,
- xxxxxxxxxxxx xxxxxxxx xxxxxx xx počátku xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, střední xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.
Xxxxxxxx xxxxxxxx:
- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,
- xxxxx xx xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx xxxx provedena,
- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,
- xxxxx o xxxxxxxx xxxxxxxx látky,
- xxxxx o podávání xxxxxxxx látky,
- zdůvodnění xxxxxxx xxxxxxxx,
- xxxxxxxxx xxxxxx xxxxxxx, zda xx xxxxxxxx látka xxxxxxx xx krevního xxxxx xxxx xx xxxxxx xxxxx,
- případně xxxxxxxx mezi xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxxx vodě (xxx) xx xxxxxxxxxxxx xxxxx (xx/xx tělesné xxxxxxxxx/xxx),
- podrobné xxxxx x xxxxxxx xxxxxx x vody,
- podrobný xxxxx rozvrhu xxxxxxxx x odběru,
- metody xxxxxxxxx xxxxxxxx,
- xxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxx,
- použitá xxxxxxxxxxxxxxxxx xxxxxxxx,
- xxxxx xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,
- kritéria xxxxxxxxx,
- xxxxxxxx xxxxxxxxxxx xxxxxx xx pozitivní, xxxxxxxxx xxxx dvojznačnou.
Výsledky:
- xxxxxxx xxxxxxx xxxxx xxx xxxxxxxxxxxxxx buněčným xxxxxx a xxxxx xxx xxxxxxxxxxxxxx cytoplasmě, x xxxxx xxxxx xxx, jednotlivě pro xxxxxxxxx, xxxxxxx x xxxxxxx,
- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,
- xxxxxxxx statistické xxxxxxxxx,
- xxxxxx xxxxxxxx,
- xxxxx o xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx,
- xxxxxxxxx xxxxx o xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,
- xxxxx xxxxx "xxxxxxxxxxxx" buněk, xx-xx xxxxxxxx,
- xxxxx xxxxx x X-xxxx, xx-xx stanoven,
- xxxxxxxxxxxxxxx xxxxx.
Xxxxxx výsledků.
Závěry.
4. XXXXXXXXXX
1) Xxxxx, J. Xxxxxxx, X. X., Burlinson, X., Penman, X. X. (1985), Xx Xxxxxxxxxx of xxx Xx xxxx Xxx. Xxxxxxxxxx DNA Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.
2) Butterworth, X. E., Ashby, X., Xxxxxxxx, E., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxx, G., Xxxxxxxx, G. (1987), X Xxxxxxxx and Xxxxx xxx xxx Xx vivo Xxx Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 123-133.
3) Kennelly, X. C., Xxxxxx, X., Xxxxx, X., Xxxxxxx, X. A., Xxxxxxxxx, X., Xxxxxxx, X. J., Dean, X. X., Mitchell, X. xx X. (1993), Xx xxxx Xxx Xxxxx XXX Xxxxx, xx: Kirkland X. X., Xxx X., (eds), Supplementary Xxxxxxxxxxxx Xxxxx: XXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx. Xxxxxx. Xxxx XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Port Chester, Xxxxxxxxx, Xxxxxx, 52-77.
4) Xxxxx, S., Xxxx, X. W., Xxxxxx, X., Xxxxxxxxx. X., Xxxxxxxxx, X., Doolittle, X. X., Furihata, X., Xxxxxxx, X., XxXxxxx, X. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx XXX Xxxxx Xx xxxxx xxx Xx xxxx, Xxxxx. Res., 312, 263-285.
5) Xxxxx, X., Xxxxxxx, X., Efstathiou, X., Xxxxxxxxxxxx-Xxxxxx, C. (1993), Assessment xx xxx Xxxxxxxx Between xxx Xxxxxxx Viability xxx the Attachment xx Xxxxxxx Xxxxxxxx Xxx Xxxxxxxxxxx Xxxx xxx the Xx xxxx/Xx xxxxx DNA Xxxxxx Xxxxx (UDS), Xxxxxxxxxx Xxx., 291, 21-27.
6) Xxxxxxxx, X. X., Tyson, C. X., Xxxxxxxxxxx, X. X. (1982), Xxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xx the In xxxx/Xx xxxxx Xxxxxxxxxx XXX Xxxxxx Assay, Xxxxxxx.Xxxxxxx. 4, 553-562."
XXXXXXX 5
XXXXXX XXXXXXXXX XX XXXXXXXXXXX A XXXXXXXXXX NEBEZPEČNÝCH XXXXX X PŘÍPRAVKŮ
Viz xxxxxxxx Xxxxxx 2001/59/ES, Xx. xxxx. L 332, 28. 12. 2000, x. 81.
PŘÍLOHA 6
"
XXXXXXX XX
XXXX X
xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx proti xxxxxxxx xxxxx
Xxxxx xxxxxxxxxx xx. 22 odst. 1 xxxx. x) xxxx směrnice, musí xxx xxxxx x xxxxxxxxx objemu xxxxxxxxxx xxxxx, x nimiž xx xxxxxxx xxxxxx xxx vdechování (Xx; X 65) x xxxxx xxxx xxxxxxxxxxxxx x označeny xxxxx xxxx 3.2.3 xxxxxxx XX této xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx xx xxx xx xxxxx xxxxxxxx xxxx v xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx, xxxxxxxx uzávěry xxxxxxxx xxxxx otevření xxxxx.
1. Xxxxxxxxx xxxxxxxxxxxx xxxxx
Xxxxxxx xxxxxx proti otevření xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx obalech xxxx splňovat xxxxxxxxx xxxxx XXX 8317 (xxxxxx ze xxx 1. xxxxxxxx 1989) "Xxxxx xxxxxx xxxxx — Xxxxxxxxx xx xxxxxxxxx uzavíratelné obaly x metody xxxxxx xxxxxxxx" xxxxxxxx Xxxxxxxxxxx xxxxxxxxxx pro xxxxxxxxxxx (XXX).
2. Xxxxxxxxx neuzavíratelné xxxxx
Xxxxxxx odolné xxxxx xxxxxxxx dětmi xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxx xxxxxxx musí splňovat xxxxxxxxx normy CEN XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Obaly xxxxxx dětem — Xxxxxxxxx x zkušební xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxx xxxxxx xxx farmaceutických xxxxxxx" xxxxxxxx Xxxxxxxxx xxxxxxx xxx normalizaci (XXX).
3. Xxxxxxxx
1. Prokázání xxxxx x xxxx uvedenými xxxxxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxx, které xxxxxxx xxxxxxxx normy xxxx EN 45000.
2. Xxxxxxxxxx případy
Je-li xxxxxx, xx obal xx xxxxxxxxxx bezpečný xxx xxxx, xxxxx xx xxxxxxx xxxxxx x xxxxxx xxx pomoci xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.
Xx všech xxxxxxxxx xxxxxxxxx a xxxxx xxxxxxxx oprávněné xxxxxx x xxxxxxxx x xxxxxxxxxxx xxxxxxx xxx xxxx, xxxx xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx xxxxx odpovědná xx xxxxxxx xxxxxxx xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx odst. 3 xxxx 1 konstatující, xx xxx
- xxx xxxxxxx xx takový, xx jej xxxx xxxxxxxx xxxxxxx xxxxx xxxx xxxxxxxxx xxxxx XXX x XXX,
xxxx
- xx xxxxxx byl xxxxxxx a byl xxxxxxx xxxxxxxxxxx podle xxxx xxxxxxxxx xxxxx.
XXXX X
Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx
Xxxxxxxxx specifikace xxx hmatatelné xxxxxxxx xxxx být v xxxxxxx s xxxxxx XX ISO 11683 (xxxxxx x xxxx 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Požadavky".
"