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Xxxxxxxx Komise 2000/32/XX

xx xxx 19. května 2000,

xxxxxx xx xx xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx pokroku směrnice Xxxx 67/548/XXX o xxxxxxxxxx xxxxxxxx a xxxxxxxxx předpisů xxxxxxxxxx xx klasifikace, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxx [1]

(Xxxx s xxxxxxxx xxx XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Smlouvu x xxxxxxxx Evropského xxxxxxxxxxxx,

x xxxxxxx na směrnici Xxxx 67/548/XXX xx xxx 27. xxxxxx 1967 o sbližování xxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx a xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], xxxxxxxxx pozměněnou xxxxxxxx Xxxxxxxxxx parlamentu x Rady 1999/33/ES [3], a xxxxxxx xx xxxxxx 28 xxxxxxx směrnice,

vzhledem k xxxxx xxxxxxx:

(1) Příloha X xxxxxxxx 67/548/EHS xxxxxxxx seznam xxxxxxxxxxxx xxxxx společně s xxxxxxxxxx xxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx a technické xxxxxxxx xxxxxxx, že xx xxx být xxxxxx xxxxxxxxxxxx látek x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx určitých xxxxxx xxxxxxxxx x tabulky X v xxxxxxx X.

(2) Příloha XXX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx a xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx s xxxxxxxxxxxxxx xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxx a xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/XXX xxxxxxxx xxxxx ke klasifikaci x k xxxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, IV x XX.

(3) X xxxxxxx V xxxxxxxx 67/548/XXX xx stanoví xxxxxx xxx stanovení xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, xxxxxxxx x xxxxxxxxxxx látek x xxxxxxxxx. Xx xxxxxxxx přizpůsobit xxxx xxxxxxx xxxxxxxxxxx xxxxxxx.

(4) Xxxxxxx XX směrnice 67/548/XXX obsahuje xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx. Xxxx xxxxxxxx xx xxxx xxx xxxxxxxxxxxx x xxxxxxxxxxxxx. Xx xxxxxxxx xxxxxxxx xxxxxx, xxx se xxxxxxx odolné xxxxx xxxxxxxx xxxxx xxxxxxxxx.

(5) Xxxxxxxx xxxx směrnice xxxx x xxxxxxx xx stanoviskem Výboru xxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx xxx xxxxxxxxxx xxxxxxxxxxx překážek xxxxxxx xx xxxxx xxxxxxxxxxxx látek a xxxxxxxxx,

XXXXXXX XXXX XXXXXXXX:

Xxxxxx 1

Směrnice 67/548/XXX xx xxxx xxxxx:

1. Xxxxxxx I xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxxxx x xxxxxxxxx xx xxxxxxxxx xxxxxxxxx X x xxxxxxx 1X xxxx xxxxxxxx;

x) xxxxxxxxxxxx řádky v xxxxxxx X xx xxxxxxxxx xxxxx x xxxxxxx 1B xxxx xxxxxxxx;

x) xxxxxxxxxxxx položky xx xxxxxxxxx xxxxxxxxx x xxxxxxx 1X xxxx xxxxxxxx;

x) vkládají xx xxxxxxx x xxxxxxx 1X této xxxxxxxx.

2. Xxxxxxxxxxxx věta x xxxxxxx XXX xx xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxx 2 této xxxxxxxx.

3. Xxxxxxx XX se xxxx xxxxx:

x) odpovídající xxxxxx v xxxxxxx XX xx xxxxxxxxx xxxxxxxxxxxx pokyny xxx xxxxxxxx xxxxxxxxx v xxxxxxx 3A xxxx xxxxxxxx;

x) odpovídající xxxxxx x příloze IV xx nahrazují kombinovanými xxxxxxxxxxxx xxxxxx xxx xxxxxxxx zacházení v xxxxxxx 3X této xxxxxxxx.

4. Část B xxxxxxx X se xxxx xxxxx:

x) kapitola X.10 xx nahrazuje xxxxxx x příloze 4X této xxxxxxxx;

x) xxxxxxxx X.11 xx xxxxxxxxx textem x xxxxxxx 4X xxxx xxxxxxxx;

x) xxxxxxxx B.12 xx xxxxxxxxx textem x xxxxxxx 4C xxxx xxxxxxxx;

x) xxxxxxxx X.13 x X.14 xx xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx xxxxxxxx;

x) kapitola X.17 xx xxxxxxxxx xxxxxx x příloze 4X této xxxxxxxx;

x) xxxxxxxx X.23 se xxxxxxxxx xxxxxx x xxxxxxx 4F této xxxxxxxx. Xxxxx xxxxxxxx X.23 ve xxxxxxxxxxx xx mění odpovídajícím xxxxxxxx;

x) xxxxxx se xxxx x příloze 4X této xxxxxxxx.

5. Xxxxxxx se xxxxxx xxxxxxx obecného úvodu x xxxxx X xxxxxxx X.

6. Odpovídající xxxxx v xxxxxxx XX xx nahrazují xxxxx x xxxxxxx 5 xxxx směrnice.

7. Xxxxxxx IX se xxxx xxxxxxxx uvedeným x xxxxxxx 6 xxxx směrnice.

Xxxxxx 2

1. Členské xxxxx xxxxxx x xxxxxxxx xxxxxx a xxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxxx souladu x touto xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x xxxx uvědomí Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx státy musí xxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxx xxxx xxxxxx odkaz xxx xxxxxx xxx xxxxxx úředním vyhlášení. Xxxxxx odkazu xx xxxxxxx xxxxxxx xxxxx.

2. Xxxxxxx xxxxx xxxxx Xxxxxx znění xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx přijmou x oblasti xxxxxxxxxx xxxx xxxxxxxx, a xxxxxxxxxx xxxxxxx mezi xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.

Xxxxxx 3

Xxxx xxxxxxxx xxxxxxxx x xxxxxxxx xxxxxx dnem xx xxxxxxxxx x Xxxxxxx xxxxxxxx Evropských xxxxxxxxxxxx.

Článek 4

Xxxx xxxxxxxx xx určena xxxxxxxx xxxxxx.

X Xxxxxxx xxx 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise

[1] Xxxxxxx xx xxxxxxxxxxxx xx dvacáté xxxxx.

[2] Xx. věst. 196, 16.8.1967, x. 1.

[3] Xx. xxxx. X 199, 30.7.1999, x. 57.

XXXXXXX 1A

PŘEDMLUVA X XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x označování xxxxx

(Xxxxxx xx českého xxxxx)

XXXXXXX 1X

"XXXXXXX A

Z

Symbol

ES

DA

DE

EL

EN

FI

FR

IT

NL

PT

SV

18

Ar

Argón

Argon

Argon

Αργό

Argon

Argon

Argon

Argon

Argon

Árgon

Argon

64

Gd

Gadolinio

Gadolinium

Gadolinium

Γαδολίνιο

Gadolinium

Gadolinium

Gadolinium

Gadolinio

Gadolinium

Gadolínio

Gadolinium"

PŘÍLOHA 1C

Indexové xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační limity

Poznámky x xxxxxxxxxx

006–011–00–7

xxxxxxxx (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

Xxxx. xxx. 3; X40 Xx; X22 X; X50

Xx; X X: 22–40–50 X: (2-)22–24–36/37–46–61

006–013–00–8

xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx

205–293–0

137–42–8

Xx; X22 R31 X; X34 R43 X; X50–53

X; N X: 22–31–34–43–50/53 X: (1/2-)26–36/37/39–45–60–61

006–015–00–9

xxxxxx (XXX) 3-(3,4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx

206–354–4

330–54–1

Xxxx. xxx. 3; X40 Muta. xxx. 3; X40 Xx; X22–48/22 X; X50–53

Xx; X R: 22–40–48/22–50/53 S: (2-)13–22–23–37–46–60–61

006–016–00–4

xxxxxxxx (XXX) 2- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

204–043–8

114–26–1

X; X25 N; X50–53

X; X R: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

xxxxxxxx (XXX) 2-xxxxxx-2-(xxxxxxxxxxxxxx)xxxxxxxx-X-(X-xxxxxxxxxxxxxxx)xxxx

204–123–2

116–06–3

X+; X26/28 X; X24 X; X50–53

X+; X X: 24–26/28–50/53 X: (1/2-)22–36/37–45–60–61

006–018–00–5

aminokarb (XXX) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx

217–990–7

2032–59–9

X; X24/25 N; X50–53

X; N R: 24/25–50/53 X: (1/2-)28–36/37–45–60–61

006–019–00–0

xx-xxxxx (XXX) X-(2,3-xxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx

218–961–1

2303–16–4

Xxxx. xxx. 3; X40 Xx; X22 X; X50–53

Xx; X X: 22–40–50/53 X: (2-)25–36/37–60–61

006–020–00–6

xxxxxx (XXX) 4-xxxxxxxx-2-xx-1-xx-X -(3-chlorfenyl)karbamát

202–930–4

101–27–9

Xn; X22 X43 X; X50–53

Xx; X X: 22–43–50/53 X: (2-)24–36/37–60–61

006–023–00–2

xxxxxxxxxxxxxxxx (XXX) xxxxxxxxxx 3,5-xxxxxxxx-4-(xxxxxxxxxxxxxx)xxxxx-X -xxxxxxxxxxxxxx

217–991–2

2032–65–7

X; X25 X; R50–53

T; X R: 25–50/53 X: (1/2-)22–37–45–60–61

006–024–00–8

xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx

205–443–5

140–93–2

Xx; R22 Xx; X38 X; X51–53

Xx; X X: 22–38–51/53 X: (2-)13-61

006–026–00–9

karbofuran (XXX) 2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx-X-xxxxxxxxxxxxxx

216–353–0

1563–66–2

X+; R26/28 N; X50–53

X+; N X: 26/28–50/53 X: (1/2-)36/37–45–60–61

006–028–00-X

dinobuton (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; X50–53

X; X R: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

dioxakarb (ISO) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx

230–253–4

6988–21–2

X; X25 X; X51–53

X; X X: 25–51/53 S: (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; R50–53

N X: 5 0/ 5 3 S: 60-61

006–034–00–2

xxxxxxx (ISO) X-xxxxxx-X-xxxxx-X-xxxxxxxxxxxxxxxxx

214–215–4

1114–71–2

Xx; X22 N; X51–53

Xx; X R: 22–51/53 X: (2-)23-61

006–035–00–8

xxxxxxxxxx (XXX) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx pyrimidin-4-yl-N,N-dimethylkarbamát

245–430–1

23103–98–2

T; X25 X; X50–53

X; 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

sulfallát (XXX) 2-chlorallyl-N,N-dimethyldithiokarbamát

E

202–388–9

95–06–7

Karc. xxx. 2; X45 Xx; X22 X; 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; R22–48/22 R43 X; X50–53

Xx; N X: 22–43–48/22–50/53 S: (2-)24–37–60–61

006–042–00–6

xxxxxxx (ISO) 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx

205–766–1

150–68–5

Xxxx. xxx. 3; X40 Xx; X22 X; X50–53

Xx; N X: 22–40–50/53 X: (2-)36/37–60–61

006–043–00–1

xxxxxxx-XXX 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx

—

140–41–0

Xx; R36/38 Xxxx. xxx. 3; R40 X; X50–53

Xx; N X: 36/38–40–50/53 X: (2-)36/37–60–61

006–045–00–2

xxxxxxxx (ISO) 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

bendiokarb (XXX) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx

245–216–8

22781–23–3

X; R23/25 Xx; X21 X; X50–53

X; X X: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61

006–047–00–3

bufenkarb (ISO) xxxx: 3-(1-methylbutyl)fenyl-N-methylkarbamátu a 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx

—

8065–36–9

X; R24/25 N; X50–53

X; N X: 24/25–50/53 S: (1/2-)28–36/37–45–60–61

006–048–00–9

xxxxxxxxxxxx (XXX) 2-[(ethylsulfanyl)methyl]fenyl-N-methylkarbamát

249–981–9

29973–13–5

Xn; R22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–050–00–X

xxxxxxx-XXX 3-xxxxx-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx

—

4482–55–7

Xx; X38 X; X50–53

Xx; X X: 38–50/53 S: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-isopropylfenyl-N-methylkarbamát

220–114–6

2631–40–5

Xn; X22 N; 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 Xx; X21 X; 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 X; X51–53

Xx; X X: 22–51/53 X: (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; R22 X52–53

Xx R:22–52/53 X: (2-)61

006–069–00–3

xxxxxxxxx-xxxxxx (ISO) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx

245–740–7

23564–05–8

Xxxx. xxx. 3; X40 X; X50–53

Xx; X X: 40–50/53 X: (2-)36/37–60–61

006–070–00–9

xxxxxxxxxxx N-cyklohexyl-N-methoxy-2,5-dimethyl-3-furamid

262–302–0

60568–05–0

Karc. xxx. 3; X40 X; X50–53

Xx; X X: 40–50/53 X: (2-)36/37–60–61

006–088–00–7

benfurakarb (XXX) ethyl-N -[({[(2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx)xxx]xxxxxxxx}xxxxxxxxxxx)xxxxxxxx]-X-xxxxxxxxx-β-xxxxxxxx(2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx)-X-({[2-(xxxxxxxxxxxxxx)xxxxx]xxxxxxxxxxxxxx}xxxxxxxx)-X-xxxxxxxxxxxxxx

—

82560–54–1

X; X23/25 X; R50–53

T; X X: 23/25–50/53 X: (1/2-)36/37–45–60–61

007–012–00–5

N,N-dimethylhydrazin 1,1-dimethylhydrazin

E

200–316–0

57–14–7

F; X11 Xxxx. xxx. 2; R45 X; X23/25 C; X34 X; X51–53

X; X; X R: 45–11–23/25–34–51/53 X: 53–45–61

007–013–00–0

X,X-xxxxxxxxxxxxxxxx 1,2-xxxxxxxxxxxxxxxx

X

—

540–73–8

Xxxx. xxx. 2; X45 X; X23/24/25 X; X51–53

X; X R: 45–23/24/25–51/53 S: 53–45–61

X ≥ 25 %: X; X45–23/24/25 3 % &xx; X &xx; 25 %: X; X45–20/21/22 0,01 % < X &xx; 3 %: X; X45

009–003–00–1

xxxxxxxx xxxxxxxxxxxxxx … %

B

231–634–8

7664–39–3

T+; X26/27/28 X; X35

X+; X X: 26/27/28–35 X: (1/2-)7/9–26–36/37–45

X ≥ 7 %: X+; X; X26/27/28–35 1 % ≤ X &xx; 7 %: X; X23/24/25–34 0,1 % ≤ X &xx; 1 %: Xx; X20/21/22–36/37/38

015–039–00–9

xxxxxxx-xxxxxx (XXX) X,X-xxxxxxxx-X -[(4(3 H)-oxo-1,2,3-benzotriazin-3-yl)methyl]-fosforodithioát

201–676–1

86–50–0

T+; R26/28 X; R24 X43 X; X50–53

X+; N X: 24–26/28–43–50/53 S: (1/2-)28–36/37–45–60–61

015–048–00–8

xxxxxxxx (ISO) X,X-xxxxxxxx-X-[3-xxxxxx-4-(xxxxxxxxxxxxxx)xxxxx]-xxxxxxxxxxxxx

200–231–9

55–38–9

Xxxx. xxx. 3; R40 X; R23–48/25 Xn; X21/22 X; X50–53

X; X R: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61

015–056–00–1

xxxxxxx-xxxxx (ISO) X,X-xxxxxxx-X-[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx

220–147–6

2642–71–9

X+; X28 X; R24 X; X50–53

X+; X R: 24–28–50/53 S: (1/2-)28–36/37–45–60–61

015–140–00–8

xxxxxxxxx (XXX) O,O-diethyl-O-(1-fenyl-1 H- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx

245–986–5

24017–47–8

X; R23/25 Xx; X21 N; R50–53

T; X X: 21–23/25–50/53 X: (1/2-)36/37–45–60–61

016–013–00-X

xxxxxxx xxxxxxx

234–129–0

10545–99–0

X14 X; R34 N; X50

X; X R: 14–34–50 S: (1/2-)26–36/37/39–45–61

C ≥ 10 %: X; R34 5 % ≤ C &xx; 10 %: Xx; X36/37/38

016–014–00–5

xxxxxxx xxxxxxxx

—

13451–08–6

X14 X; X34 N; X50

X; X X: 14–34–50 X: (1/2-)26–36/37/39–45–61

X ≥ 10 %: X; R34 5 % ≤ X &xx; 10 %: Xx; R36/37/38

016–023–00–4

dimethyl-sulfát

E

201–058–1

77–78–1

Karc. xxx. 2; X45 Xxxx. xxx. 3; X40 X+; X26 X; X25 C; R34 X43

X+ R: 45–25–26–34–43 X: 53-4 5

X ≥ 25 %: X+; X45–25–26–34–43 10 % ≤ C &xx; 25 %: X+; X45–22–26–34–43 7 % ≤ C &xx; 10 %: X+; X45–22–26–36/ 37/38–43 5 % ≤ X &xx; 7 %: T; R45–22–23–36/37/38–43 3 % ≤ X < 5 %: X; R45–22–23–43 1 % ≤ X < 3 %: X; R45–23–43 0,1 % ≤ X &xx; 1 %: X; X45–20 0,01 % ≤ X &xx; 0,1 %:X; X45

016–024–00-X

xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

X,X′-xxxxxxxx-xxxxxxxxxxx(xxxxxxxxxxx)215–993–8

1468–37–7

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

016–071–00–6

3-xxxxx-6,13-xxxxxxx-10-[(3-{[4-xxxxx-6-(2-xxxxxxxxxxxxxxxx)- 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 R: 43 X: (2-)22–24–37

022–001–00–5

xxxxxxx xxxxxxxxxx

231–441–9

7550–45–0

X14 X; R34

C X: 14-34 X: (1/2-)7/8–26–36/37/39–45

X ≥ 10 %: X; 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; R17 X; X34 X; R50–53

F; X; X R: 14–17–34–50/53 X: (1/2-)16–43–45–60–61

050–002–00–0

xxxxxxxxx (XXX) xxxxxxxxxxxxx(xxxxxxx)xxxxxxx xxxxxxxxxxxxxxxxxxxxx-xxxxxxxx

236–049–1

13121–70–5

Xx; X20/21/22 X; R50–53

Xn; X X: 20/21/22–50/53 X: (2-)13–60–61

050–012–00–5

tetracyklohexylstannan [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] butyl(tricyklohexyl)stannan [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; X20/21/22

1

050–017–00–2

xxxxxxxxxxxxxx (XXX) 1,1,1,3,3,3-xxxxxxx(2-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxxxx

236–407–7

13356–08–6

X+; R26 Xx; R36/38 X; X50/53

X+; X X: 26–36/38–50/53 S: (1/2-)28–36/37–45–60–61

082–009–00–X

žluť (xxxxxxxxxxxx xxxxxxxx) XX Xxxxxxx Yellow 34 (XX 77603) CI xxxxxxxxxx xxxx 34 (XX 77603)

215–693–7

1344–37–2

Xxxx. kat. 3; X40 Xxxx. xxx. 1; X61 Xxxx. kat. 3; X62 X33 X; X50–53

X; X X: 61–33–40–50/53–62 X: 53–45–60–61

1

082–010–00–5

xxxxxx (xxxxxxx-xxxxxxxxxx-xxxxx olovnatý) XX Xxxxxxx Xxx 104 (XX 77605) XX xxxxxxxxxx xxxxxx 104 (XX 77605)

235–759–9

12656–85–8

Xxxx. kat. 3; R40 Repr. xxx. 1; R61 Xxxx. kat. 3; X62 R33 X; X50–53

X; X X: 61–33–40–50/53–62 X: 53–45–60–61

1

601–024–00-X

xxxxx [1] propylbenzen [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

R10 Xx; X65 Xx; X37 X; X51–53

Xx; 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; X45 Muta. xxx. 2; X46 Xxxx. xxx. 2; X60–61 X; X50–53

X; X R: 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. xxx.2; X45 N; R50–53

T; X X: 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; X50–53

Xx; X X: 36–50/53 X: (2-)24/25–46–60–61

602–054–00–6

3-xxxxxxx-1-xx allyljodid

209–130–4

556–56–9

R10 X; R34

C X: 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; R21–48/22 X; X34

X X: 21–23/25–34–48/22 S: (1/2-)26–36/37/39–45

X ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ X &xx; 50 %: X; X21–23/25–36/38–48/22 10 % ≤ C &xx; 25 %: Xx; X20/22–48/22 3 % ≤ X &xx; 10 %: Xx; X20/22

603–091–00–0

xxx-4-xxxxxxxxx-1-xxxxxx-7-xxxxxxxxxx[2.2.1]xxxxxx-2-xx

402–470–6

87172–89–2

X; X8 Xx; X22 Xi; X36

X; Xx R: 8–22–36 X: (2-)26

603–093–00–1

exo-(±)-4-isopropyl-1-methyl-2-[(2-methylbenzyl)oxy]-7-oxabicyklo[2.2.1]heptan

402–410–9

87818–31–3

Xn; X20 X; X51–53

Xx; X X: 20–51/53 X: (2-)23-61

603–097–00–3

1,1', 1′′-xxxxxxxxxxxxxxxx-2-xx xxxxxxxxxxxxxxxxxx

204–528–4

122–20–3

Xx; X36 R52–53

Xi 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; X36 X67

X; Xx X: 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, xxxxx xxx xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx xxxxx xxxxxxx-xxxxxxx-2-xxxx

205–055–6

132–27–4

Xx; R22 Xi; X37/38–41 X; X50

Xx; X R: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

4,4'-(4-xxxxxxxxxxxx-2,2-xxxx)xxxxxxx 2,2-xxx(4-xxxxxxxxxxxx)-4-xxxxxxxxxxxx

401–720–1

6807–17–6

Xxxx. xxx. 2; X60 Xx; X36 X; X50–53

X; X R: 60–36–50/53 S: 53–45–60–61

604–041–00–0

xxxxxxxxxxx [1] xxxxxxxxxxx-xxxxxxx [2] 5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxxx xxxxxxxx [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]

Xn; X22 Xx; X38–41 N; X50–53

Xx; X X: 22–38–41–50/53 S: (2-)24–39–60–61

604–043–00–1

xxxxxxxxxxxxxxxx (4-xxxxxxxxxxxx)xxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx 4-(benzyloxy)fenol

203–083–3

103–16–2

Xi; X36 X43

Xx R: 36-43 S: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; R22 Xx; R36 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. xxx. 3; X40 Xn; X20 Xx; R36/38 X43

Xx X: 20–36/38–40–43 X: (2-)36/37

X ≥ 10 %: Xx; R20–36/38–40–43 1 % ≤ X &xx; 10 %: Xn; R40–43

606–016–00-X

pindon (XXX) 2-(xxxxxxxxxxxxxxx)xxxxx-1,3-xxxx

201–462–8

83–26–1

X; X25–48/25 X; X50–53

X; X X: 25–48/25–50/53 X: (1/2-)37–45–60–61

606–018–00–0

xxxxxxx (ISO) 2,3-xxxxxxx-1,4-xxxxxxxxxxx

204–210–5

117–80–6

Xx; X22 Xx; X36/38 X; X50–53

Xx; N X: 22–36/38–50/53 X: (2-)26–60–61

606–019–00–6

xxxxxxxxxx (XXX) xxxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx xxxxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx 1,2,4,5,6,7,8,8,9,10-dekachlorpentacyklo[5.3.0.02,6.04,10.05,9]dekan-3-on

205–601–3

143–50–0

Karc. xxx. 3; R40 X; X24/25 X; X50–53

X; X R: 24/25–40–50/53 X: (1/2-)22–36/37–45–60–61

606–034–00–8

metribuzin (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 X)-xx 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-4,5-xxxxxxx-1,2,4-xxxxxxx-5-xx

244–209–7

21087–64–9

Xx; X22 X; X50–53

Xx; X R: 22–50/53 X: (2-)60-61

606–035–00–3

chloridazon (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 X-[1,3]xxxxxxxx[4,5-x]xxxxxxxxxx-2-xx

219–455–3

2439–01–2

Xxxx. xxx. 3; X62 Xx; R20/21/22–48/22 Xx; X36 X43 X; X50–53

Xx; X R: 20/21/22–36–43–48/22–50/53–62 X: (2-)24–37–60–61

606–037–00–4

triadimefon (XXX) 1-(4-chlorfenoxy)- 3,3-xxxxxxxx-1-(1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

256–103–8

43121–43–3

Xx; X22 X; R51–53

Xn; X X: 22–51/53 X: (2-)61

606–044–00–2

2,4,6-xxxxxxxxxxxxxxxxxxx xxxxx(2,4,6-xxxxxxxxxxxxxx)xxxxxxxx

403–150–9

954–16–5

Xx; X22 Xi; X36 X; X50–53

Xx; X X: 22–36–50/53 S: (2-)26–60–61

607–043–00-X

xxxxxxx (XXX) 3,6-xxxxxxx-2-xxxxxxxxxxxxxxx xxxxxxxx

217–635–6

1918–00–9

Xx; X22 Xi; X41 R52–53

Xn; N X: 22–41–52/53 X: (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 X52–53

Xx X:48/22–52/53 X: (2-)37-61

607–058–00–1

kumafuryl (XXX) fumarin (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 X -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) ethyl-4-oxo-5-(perchlor-5-hydroxypentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-yl)pentanoát xxxxx-5-(1,2,3,5,6,7,8,9,10,10-xxxxxxxxx-4-xxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx)-4-xxxxxxxxxxxx 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 X: 22–24–51/53 X: (1/2-)36/37–45–61

607–097–00–4

xxxxxx-1,2,4-xxxxxxxxx-1,2-xxxxxxxx 1,2-anhydrid xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx trimellitanhydrid

209–008–0

552–30–7

Xi; X37–41 X42/43

Xx R: 37–41–42/43 X: (2-)22–26–36/37/39

607–143–00–3

xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx

203–677–2

109–52–4

X; X34 X52–53

X X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

2,3,6-TBA (ISO) 2,3,6-xxxxxxxxxxxxxxxx kyselina

200–026–4

50–31–7

Xn; R22 X; X51–53

Xx; X X: 22–51/53 S: (2-)61

607–153–00–8

xxxxxxxxx (ISO) (4-xxxxx-2-xxx-2,3-xxxxxxx-1,3-xxxxxxxxxxxx-3-xx)xxxxxx xxxxxxxx

223–297–0

3813–05–6

Xx; R36/38 X52–53

Xx 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; X22 Xx; R38 N; X50–53

Xx; X X: 22–38–50/53 S: (2-)37–60–61

607–158–00–5

xxxxx xxx chloroctové xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; X25 Xx; X38 X; X50

X; X X: 25–38–50 S: (1/2-)22–37–45–61

607–159–00–0

xxxxxxxxxxxxxx (XXX) xxxxx-2,2-xxx(4-xxxxxxxxxx)-2-xxxxxxxxxxxxx ethyl-4,4'-dichlorbenzilát

208–110–2

510–15–6

Xn; X22 N; R50–53

Xn; X X: 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 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-({3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}xxx)xxxx(xxxxxxxxxx)

400–830–7

—

X43 X; X51–53

Xx; N X: 43–51/53 X: (2-)36/37–61

607–188–00–9

xxxxxxx-xxxxxxxx-X-(2-xxxxxxxxxxxx)-X-(xxxxxxx-9-xx-1-xx)xxxxxxxxxx

402–970–4

—

X43 X; R51–53

Xi; X R: 43–51/53 X: (2-)24/37–61

607–209–00–1

Směs: O,O′-diisopropyl-trisulfanbis(karbothioát); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); O,O′-diisopropyl-pentasulfanbis(karbothioát)

403–030–6

—

Xn; X22 X43 N; X50–53

Xx; X X: 22–43–50/ 53 X: (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 N; X51–53

X; X R: 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 R53

Xi X: 43-53 S: (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-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [3]

217–846–3 [1] 246–590–5 [2] 258–527–9 [3]

1982–69–0 [1] 25059–78–3 [2] 53404–28–7 [3]

X52–53

X: 52/53 S: 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 TPGDA

256–032–2

42978–66–5

Xi; X36/37/38 R43 X; X51–53

Xx; X X:36/37/38–43–51/53 X: (2-)24–37–61

X ≥ 10 %: Xi; X36/37/38–43 1 % ≤ X &xx; 10 %: Xx; X43

607–252–00–6

λ-xxxxxxxxxxx (XXX) Xxxx (1:1): (X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx

415–130–7

91465–08–6

X+; R26 X; X25 Xn; X21 X; X50–53

X+; X X: 21–25–26–50/53 X: (1/2-)28–36/37/39–38–45–60–61

607–255–00–2

xxxxxxxxxx (XXX) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx xxxxxxxx

—

69377–81–7

X52–53

X: 52/53 X: 61

608–003–00–4

xxxxxxxxxxxx

X E

203–466–5

107–13–1

F; Xxx Xxxx. kat. 2; X45 X; X23/24/25 Xx; X37/38–41 X43 N; R51–53

F; X; N X: 45–11–23-/24/25–37/38–41–43–51/53 X: 9–16–53–45–61

X ≥ 20 %: X; R45–23/24/25–37/38–41–43 10 % ≤ C &xx; 20 %: X; X45–23/24/25–41–43 5 % ≤ C &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ X &xx; 5 %:X; X45–23/24/25–43 0,2 % ≤ C &xx; 1 %:X; X45–20/21/22 0,1 % ≤ X &xx; 0,2 %: X; X45

43

608–016–00–5

2,3,5,6-xxxxxxxxxx-1,4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxx

401–550–8

1897–41–2

X43 N; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

xxxxxxxx (ISO) 2-xxxx-xxxxx-4,6-xxxxxxxxxxxx

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 X+; R28 X; R24 R44 X; X50–53

X+; X X: 61–24–28–44–50/53 S: 53–45–60–61

609–040–00–9

xxxxxxxx (ISO) (2,4-xxxxxxxxxxxx)(4-xxxxxxxxxx)xxxxx

X

217–406–0

1836–75–5

Xxxx. xxx. 2; X45 Xxxx. xxx. 2; X61 Xx; R22 X; X50–53

X; X X: 45–61–22–50/53 X: 53–45–60–61

609–044–00–0

xxxxxxxx (ISO) 1,2,4,5-xxxxxxxxxx-3-xxxxxxxxxxx

204–178–2

117–18–0

Xx; X22 X43 X; X50–53

Xx; X X: 22–43–50/53 X: (2-)24–37–60–61

611–008–00–4

4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. xxx. 2; X45 N; R50–53

T; X R: 45–50/53 X: 53–45–60–61

611–013–00–1

4-xxxxxxx-3-{4-[2-xxxxxxx-4-(3-xxxxxxxxxxxxxxxxx)xxxxxxxx]-3-xxxxxxxxxxxxxx}-6-(3-xxxxxxxxxxxxxxxx)xxxxxxxx-2-xxxxxxxx xxxxxxxxx

403–650–7

117409–78–6

X; X2 X; R51–53

E; X X: 2–51/53 X: (2-)35-61

611–031–00-X

4,4'-[(4-xxxxxxxxxxxxxx-2,5-xxxx-1-xxxxxx)xxxxxxxx]xxxxxxxx-xxxxxxxxxxxx CI Xxxxx Xxx 9 XX basická xxxxxx 9

209–321–2

569–61–9

Xxxx. kat. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-methoxyanilin x-xxxxxxxx

X

201–963–1

90–04–0

Xxxx. xxx. 2; R45 Xxxx. kat. 3; X40 T; X23/24/25

X X: 45–23/24/25 X: 53-45

612–042–00–2

xxxxxxxx xxxxxxx-4,4'-xxxxxx 4,4'-xxxxxxxxxxxxxx xxxxxxx-4,4'-xxxxxxxxxx

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; X22 X; R50–53

T; X X: 45–22–50/53 X: 53–45–60–61

X ≥ 25 %: X; R45–22 0,01 % ≤ X < 25 %: X; X45

612–051–00–1

4,4'-xxxxxxxxxxxxxxxxxxxx xxx(4-xxxxxxxxxx)xxxxxx 4,4'-methylendianilin

E

202–974–4

101–77–9

Karc. xxx. 2; X45 Xxxx. xxx. 3; X40 X; X39/23/24/25Xx; R48/20/21/22 X43 X; R51–53

T; X X: 45–39/23/24/25–43–48/20/21/22–51/53 X:53–45–61

612–081–00–5

3,3'-xxxxxxxxxxxxxxxx, xxxx x-xxxxxxx, xxxx

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; X45 Xx; R22 X; X51–53

X; 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 Xx; X36 X43 N; X51–53

X; X R: 45–21–25–36–43–51/53 X: 53–45–61

612–105–00–4

2-(piperazin-1-yl)ethylamin2-(piperazin-1-yl)ethan-1-amin

205–411–0

140–31–8

Xn; X21/22 X; R34 X43 X52–53

X R: 21/22–34–43–52/53 X: (1/2-)26–36/37/39–45–61

612–111–00–7

2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,3-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,3-xxxxxx 2,6-xxxxxxxxxxxx

212–513–9

823–40–5

Xxxx. xxx. 3; X40 Xn; X21/22 X43 X; X51–53

Xx; X 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-xxxxxxxxxxxx

202–442–1

95–70–5

X; X25 Xn; X20/21 X43 X; X51–53

X; X X: 20/21–25–43–51/53 X: (1/2-)24–37–45–61

612–144–00–7

xxxxxxxxxxx (XXX) X-(2-xxxxx-6-xxxxxxxxxxx)-X-xxxxx-2,6-xxxxxxx-4-(xxxxxxxxxxxxxx)xxxxxx

—

62924–70–3

Xx; X36/38 R4 3 N; R50–53

Xi; X R: 36/38–43–50/53 X: (2-)36/37–60–61

612–151–00–5

xxxxxxxxxxxxx toluendiamin xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. xxx. 2; R45 X; X25 Xx; X20/21 Xx; X36 X43 X; X51–53

X; X X: 45–20/21–25–36–43–51/53 X: 53–45–61

613–018–00–4

xxxxxxxxxx (XXX) 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx

—

7411–47–4

Xx; X22 Xi; 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-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5H)-trion

201–782–8

87–90–1

O; X8 Xx; X22 R31 Xx; X36/37 X; X50–53

X; Xx; 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-fenyl-1,3,5-triazin-2,4-diamin xxxxxxxxxxxxx

202–095–6

91–76–9

Xx; 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 N; X41 X; X50–53

Xx; X 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; X20/22 Xi; X41 X; X50–53

Xx; X X: 20/22–41–50/53 X: (2-)26–39–60–61

613–066–00–6

xxxxxxxxxx (ISO) 2-(xxxx-xxxxxxxxxx)-4-(xxxxxxxxxx)-6-xxxxxxx-1,3,5-xxxxxxx

251–637–8

33693–04–8

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

613–091–00–2

xxxxxxxxxx-xxxxxxxxx [1] morfamkvat-sulfát [2] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx-xxxxxxxxx [1] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxx-xxxxxxxx [2]

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; X22 Xx; X36/37/38 X52–53

Xx; X: 22–36/37/38–52/53 X: (2-)22–36–61

613–098–00–0

1-xxxxxxxxxxxxxxx-2-xx 1-xxxxx-2-xxxxxxxxxx

403–700–8

2687–94–7

X; X34 X; X51–53

X; X X: 34–51/53 S: (1/2-)23–26–36/37/39–45–61

613–130–00–3

xxxxxxxxxxx (ISO) (XX)-2-(2,4-xxxxxxxxxxxx)-1-(1X-1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

—

79983–71–4

X43 X; X51–53

Xx; X X: 43–51/53 S: (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 R52–53

Xn X:22–52/53 X: (2-)61

613–134–00–5

xxxxxxxxxxxx (XXX) 2-(4-chlorfenyl)-2-[(1 H-1,2,4-triazol-1-yl)methyl]hexannitril

—

88671–89–0

Repr. xxx. 3; R63 Xx; X22 Xi; X36 X; X51–53

Xx; X X: 22–36–51/53–63 X: (2-)36/37–46–61

613–137–00–1

methabenzthiazuron (XXX) 1-(1,3-xxxxxxxxxxxx-2-xx)-1,3-xxxxxxxxxxxxxxxx

242–505–0

18691–97–9

X; R50–53

N X: 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; X50–53

X X: 50/53 S: 60-61

614–001–00–4

xxxxxxx (ISO) 3-(1-xxxxxxxxxxxxxxxx-2-xx)xxxxxxx

200–193–3

54–11–5

X+; X27 T; X25 X; R51–53

T+; N X: 25–27–51/53 X: (1/2-)36/37–45–61

614–006–00–1

xxxxxx 2,3-xxxxxxxxxxxxxxxxxxxx-10-xx

206–614–7

357–57–3

X+; X26/28 X52–53

X+ X:26/28–52/53 X: (1/2-)13–45–61

614–007–00–7

xxxxxx-xxxxxx [1] xxxxxx-xxxxxx [2] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [3] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [4]

225–432–9 [1] 227–317–9 [2] 269–439–5 [3] 269–710–8 [4]

4845–99–2 [1] 5786–97–0 [2] 68239–26–9 [3] 68310–42–9 [4]

X+; X26/28 R52–53

T+ X: 26/28–52/53 X: (1/2-)13–45–61

615–006–00–4

2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-methyl-m-fenylendiisokyanát [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] x-xxxxxxxxxxxxxxxxxxxx [3] 5-methyl-1,3-fenylendiisokyanát [3] xxxxxx-2,6-xxxxxxxxxxx [1] toluen-2,4-diisokyanát [2] xxxxxx-3,5-xxxxxxxxxxx [3]

X

202–039–0 [1] 209–544–5 [2] 247–722–4 [3]

91–08–7 [1] 584–84–9 [2] 26471–62–5 [3]

Xxxx. kat. 3; X40 X+; R26 Xx; X36/37/38 R42/43 X52–53

X+ R: 26–36/37/38–40–42/43–52/53 X: (1/2-)23–36/37–45–61

C320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; R26–40–42/43 1 % ≤ C &xx; 7 %: X; X23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42

2

616–010–00–9

xxxxxxx-xxxxxxxxxxxxxx N-chlor-4-methylbenzen-1-sulfonamid, sodná 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

xxxxxxxxx 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 N; X50–53

Xx; N X: 22–43–50/53 X: (2-)36/37–60–61

617–004–00–9

(1,2,3,4-xxxxxxxxxx-1-xxxxxx)xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxx

212–230–0

771–29–9

X; R7 Xx; X22 X; R34 X; R50–53

O; C; X X: 7–22–34–50/53 X:(1/2-)3/7–14–26–36/37/39–45–60–61

X325 %: X; X22–34 10 % ≤ C < 25 %: X; X34 5 % ≤ C &xx; 10 %: Xx; X36/37/38

617–006–00-X

xxx(α, α-xxxxxxxxxxxxxx)xxxxxxx xxx(2-xxxxxxxxxxx-2-xx)xxxxxxx xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx xxxxxxxxxxxxxx

201–279–3

80–43–3

X; X7 Xx; X36/38 X; X51–53

X; Xi; X X: 7–36/38–51/53 X: (2-)3/7–14–36/37/39–61

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xx; X36 X43

X; Xx; X: 2–36–43 X: (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. kat. 3; X40 Xx; X21/22 X; R50–53

Xn; X X: 21/22–40–50/53 X: (2-)22–36/37–60–61

650–008–00–9

xxxxxxxxxx (XXX) 4-[(2-xxxxxxxxxx)xxxxxxxxx]-3-xxxxxxxxxxxxxx-5(4 X)-xx

227–197–8

5707–69–7

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)22–24–36/37–45–60–61

650–009–00–4

xxxxxxxxxxxxx-xxxxxxxxxxxx X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx N2-(4-chlor-2-methylfenyl)-N1,N1-dimethylformimidamid-hydrochlorid X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx

243–269–1

19750–95–9

Xxxx. xxx. 3; R40 Xx; X22 X; X50–53

Xx; X R: 22–40–50/53 X: (2-)22–36/37–60–61

650–033–00–5

xxxxxxxxxxxx (XXX) [(S)-(3-fenoxyfenyl)kyanmethyl]-(S)-2-(4-chlorfenyl)-3-methylbutanoát (X)-3-xxxxxx-α-xxxxxxxxxx-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx

—

66230–04–4

X; X23/25 X43 X; X50–53

X; X R: 23/25–43–50/53 X: (1/2-)24–36/37/39–45–60–61

650–041–00–9

xxxxxxxxxxxx (XXX) 1-[2-(2-chlorethoxy)benzen-1-sulfonyl]-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)močovina

—

82097–50–5

N; R50–53

N X: 50/53 S: 60-61

PŘÍLOHA 1D

Indexové číslo

Chemický xxxxx

Xxxxxxxx k xxxxxx

Xxxxx XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx limity

Poznámky x xxxxxxxxxx

006–090–00–8

2-[(3-xxxxxxx-2-xx-1-xx)xxx]xxxxx-X-xxxxxxxxxxxxx

408–010–0

88558–41–2

Xx; X20 Xx; X41 R52–53

Xn X: 20–41–52/53 X: (2-)22–26–39–61

014–016–00–0

Xxxx: 1,3-di(hex-5-en-1-yl)- 1,1,3,3-tetramethyldisiloxan x 1,3-xx(xxx-x-xx-1-xx)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx

406–490–6

—

X; X51–53

X R: 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

Xxxx: X, X, X', X''-xxxxxxxxxx-4,4'-xxxxxxxxxxxxx(xxxxxxxxxxxxxx)-xxx(xxxxxxxxxxxxxxxx) x difenyl[4-(fenylsulfanyl)fenyl]sulfonium-hexafluorofosfát

404–986–7

—

Xi; X41 X; R50–53

Xi; N X: 41–50/53 X: (2-)15–26–39–60–61

015–166–00-X

3,9-xxx(2,6-xx-xxxx-xxxxx-4-xxxxxxxxxxxx)-2,4,8,10-xxxxxxxx-3,9-xxxxxxxxxxxx[5.5]xxxxxxx

410–290–4

80693–00–1

X53

X:53 S: 61

015–167–00–5

3-[hydroxy(fenyl)fosfinoyl]propanová xxxxxxxx

411–200–6

14657–64–8

Xx; X41

Xx R: 41 S: (2-)26-39

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; R50

N X: 50 S: 61

601–051–00–7

4-fenylbut-1-en

405–980–7

768–56–9

Xi; X38 X; X51–53

Xx; X R: 38–51/53 X: (2-)37-61

602–083–00–4

pentabromderivát xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; X48/21/22 X64 X; X50–53

Xx; N 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 X: 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

Směs xxxxxxx: α-(xxxxxxxxxxxxxxxxx)-ω-xxxxxxxxxxx(xxxxxxxxxx)

406–325–8

—

Xx; R22 X52–53

Xx X:22–52/53 S: (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 S: (2-)26–37/39–61

603–133–00–8

Xxxx:3-(4-xxxxx-2-xxxxx-5-xxxxxxxxxxxx)xxxxxx-1,2-xxxx x 3,3'-[(2-chlor-5-nitro-1,4-fenylen)diimino]di(propan-1,2-diol)

408–240–1

—

Xn; X22 X52–53

Xx R:22–52/53 X: (2-)22–36–61

603–134–00–3

Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx x xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (xxxxxxx x xxxxxxxxxx xxxxxxxxxxxx)

410–450–3

—

X53

X: 53 X: 61

603–135–00–9

xxx[2-(2-xxxxxxxxxxxxx)xxxxxxxxxx]xxx(2,2', 2-nitrilotriethan-1-olato-N,O)titaničitý xxxxxxx

410–500–4

—

Xx; R41 X; X51–53

Xx; N X: 41–51/53 S: (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 R: 41 X: (2-)26-39

603–138–00–5

3-(2,2-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-dimethyl-3-(3-methylfenyl)propan-1-ol

403–140–4

103694–68–4

R52–53

R:52/53 X: 61

604–050–00-X

4-chlor-o-kresol 4-chlor-2-methylfenol

216–381–3

1570–64–5

T; X23 X; X 35 N; R50

T; X; N R: 23–35–50 X: (1/2-)26–36/37/39–45–61

X ≥ 25 %: X; X; R23–35 10 % ≤ X < 25 %: C;R20–35 5 % ≤ C &xx; 10 %: X;X20–34 3 % ≤ X &xx; 5 %: Xx;X20–36/37/38 1 % ≤ X &xx; 3 %:Xx;X36/37/38

604–051–00–5

3,5-xxx(3,5-xx-xxxx-xxxxx-4-xxxxxxxxxxxxx)-2,4,6-xxxxxxxxxxxxxx

401–110–5

87113–78–8

X52–53

X:52/53 X: 61

604–052–00–0

2,2'-xxxxxxxxxxx[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -benzotriazol-2-yl)- 4,4'-xxx(1,1,3,3-xxxxxxxxxxxxxxxx)- 2,2'-xxxxxxxxxxxxxxx

403–800–1

103597–45–1

X53

X:53 X: 61

604–053–00–6

4-terc - xxxxx-2-xxxxxx-6-(1-xxxxxxxxxxxxxxxx)xxxxx

410–760–9

157661–93–3

Xx; R38 X43 N; X50–53

Xx; 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 x 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -pyran-2-yl)fenol

412–020–0

—

R43 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; X40

Xx X: 40 S: (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; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-xxxxxxxxxxxxxxxxxx pentylcyklohexan-1-on

4–406–670–4

61203–83–6

N; X51–53

X X: 51/53 X: 61

606–052–00–6

4-(X, X-xxxxxxxxxxxx)-2-xxxxxxx-2'-xxxxxxxxxxxxxxxxx 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx kyselina

410–410–5

54574–82–2

R52–53

R:52/53 X: 61

607–272–00–5

xxxxxxxxxxx-xxxxxx (XXX) [1] xxxxxxxxxx-xxxxxxxxx (XXX) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-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]

X; X50–53

X X: 50/53 X: 60-61

607–273–00–0

xxxxxxx-7-{2,6-xxxxxxxx-8-[(2,2-xxxxxxxxxxxxxxxx)xxx]- 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; X X: 43–51/53 S: (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 R43 X; X51–53

Xx; N R: 22–41–43–51/53 S: (2-)24–26–37/39–61

607–278–00–8

Xxxx:xxxxx(X7-X9 xxxxxxxxxx a nerozvětvené)-3-[3-(2 X - xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx

405–760–0

—

Xx; X41 R43 X52–53

Xx X: 41–43–52/53 X: (2-)24–26–37/39–61

607–279–00–3

Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) x (oktadecylimino)diethylen-(hydrogen-ftalát)-(hydrogen-maleinát)

405–960–8

—

R43 X; X51–53

Xx; 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; R36 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; X51–53

X X: 51/53 X: 61

607–282–00-X

2-(xxxxxxxxxxxxx)-4-(xxxxxxxxx)xxxxx-xxxxxx

407–140–5

131266–10–9

X52–53

X: 52/53 S: 61

607–283–00–5

xxxxx-(X)-4-xxxxx-4-xxxxxx-2-xxxxxxxxxx-(X)-4-xxxxx-4-xxxxxxxxxxx

408–040–4

15121–89–8

Xx; R21/22 Xx; X38–41 R43 N; X50–53

Xx; X X: 21/22–38–41–43–50/53 X: (2-)26–36/37/39–60–61

607–284–00–0

Xxxx (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) a xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx)

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

Xxxx:7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxxx xxxxxxxx, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx a 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 X: (2-)22–24–37–61

607–287–00–7

xxxxxx-[1-xxxxxx-2-(xxxxxxxxxxxxxxx)xxxxx]-1,2,3,6-xxxxxxxxxxxxxxxx

410–140–8

—

X52–53

X:52/53 X: 61

607–288–00–2

[x-(X -{3-[(1-{3-[(2,6(4,6)-xxxxxxx-5-xxxxxxxxxxxxx-4(2)-xx)xxxxxxxxxxx]xxxxxx}-2-xxxxxxx-4-xxxxxx-6-xxx-1,6-xxxxxxx-3-xxxxxxx)xxx]-4-xxxxxxxxxxxxxx}xxxxxxxxx)-x,x,x -xxxxxxxxxxxxxxxxxxxxxxx]xxxxxxxxx xxxxxxx, xxxxxxxxxx xxx; c = 15, 16, 17 xxxx 18, x = 1, 2, 3 xxxx 4, b = 8, 9, 10 xxxx 11, x = 22, 23, 24 xxxx 25

410–160–7

148732–74–5

Xi; X36 X43 X52–53

Xx X: 36–43–52/53 X: (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 kyselina

410–370–9

105488–33–3

R53

R:53 X: 61

607–290–00–3

Xxxx (o xxxxxxxx xxxxxx):xxxxxxx-1-xxxxx(X14-X18)-4-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx x xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx

410–540–2

—

Xx; X38 X43 X; X50–53

Xx; X X: 38–43–50/53 X: (2-)24–37–60–61

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx cyklohexyl)alkanoát

410–630–1

104051–92–5

R53

R: 53 X: 61

607–292–00–4

Směs:[2-(alkyl(C12)oxy)-1-(methoxymethyl)ethoxy]octová kyselina x [2-(xxxxx(X14)xxx)-1-(xxxxxxxxxxxxx)]xxxxxx xxxxxxxx

410–640–6

—

Xx; X38–41 N; X50–53

Xx; X R: 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 a 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx

410–650–0

—

Xx; X41 X43 X; X51–53

Xx; N X: 41–43–51/53 X: (2-)26–36/37/39–61

607–294–00–5

xxxxxxx-2-(xxxxxxxxxx)-1-xxxxxxxxxxxx-1-xxxxxxxx

410–680–4

—

X43

Xx X: 43 X: (2-)24-37

607–295–00–0

Směs:tetranatrium-fosfonobutandioát a xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx

410–800–5

—

X43 N; R51–53

Xi; X R: 43–51/53 X: (2-)24–37–61

607–296–00–6

Směs:tetraestery xxxxxxxxxxxxxxxx, xxxxxxxxx kyselina x 2-xxxxxxxxxxxxx xxxxxxxx

410–830–9

—

X53

X: 53 X: 61

607–297–00–1

3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(2-xxxxxxxxx-10-xxxxxxxxx xxxxxxxx)2,2'-xxxxx-3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(1,7,7-xxxxxxxxxxxxxxxx[2.2.1]xxxxxx-1-xxxxxxxxxxxxxxx xxxxxxxx)

410–960–6

92761–26–7

Xx; X41

Xx X: 41 S: (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 xxxxxxx, xxxxxxxx xxx; a = 1,2,3 xxxx 4, b = 8, 9, 10 xxxx 11, c = 15, 16, 17 xxxx 18, x = 22, 23, 24 xxxx 25

411–430–7

—

X43

Xx R: 43 X: (2-)22–24–37

607–301–00–1

Xxxx:xxxxxxxxxx kyselina x xxxxxxxxxxx xxxxx(1-7)xxxxxxx

411–860–5

—

Xx; X38–41 X43 N; X51–53

Xx; X R: 38–41–43–51/53 X: (2-)24–26–37/39–61

607–302–00–7

Směs:tetradekanová xxxxxxxx a xxxxxxxxxxxxxx xxxxx(1-7)xxxxxxx

411–910–6

—

Xx; X38–41 R43 X; X51–53

Xx; X X: 38–41–43–51/53 X: (2-)24–26–37/39–61

607–303–00–2

1-xxxxxxxxxxx-6,7-xxxxxxx-4-xxx-1,4-xxxxxxxxxxxxxxx-3-xxxxxxxxxxx xxxxxxxx

413–760–7

93107–30–3

Xxxx. xxx.3; X62 X52–53

Xx X: 62–52/53 X: (2-)22–36/37–61

608–023–00–3

4-(4-xxxxxxxxxx)-2-xxxxx-2-[(1X- 1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx

406–140–2

114369–43–6

X; X50–53

X R: 50/53 X: 60-61

608–024–00–9

2-{4-[xxxxx(xxxxxxxx)xxxxx]xxxxx}xxxxx-1,1,2-xxxxxxxxxxxxxx

407–650–8

97460–76–9

X53

X:53 X: 61

608–025–00–4

[2-xxxxx-4,5-xxx(xxxxxxxxx)xxxxx]xxxxxxxxxxx

410–970–0

117568–27–1

X53

X:53 X: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

—

X; X3 X; X8 Xxxx. kat. 2; X45 X; X23/25 X43

X; T X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

1-xxxx-2-(2-xxxxx)-1-xxxxxxxxxx

406–110–9

35950–52–8

Xx; R22–48/22 X; X34 X43 X; X50–53

X; N R: 22–34–43–48/22–50/53 X: (1/2-)22–26–36/37/39–45–60–61

611–043–00–5

Xxxx (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx, [bis{6-[(2-amino-4-hydroxyfenyl)azo]- xxxx 6-[(2-amino-6-hydroxyfenyl)azo]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx xxxxxxxx x[{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-amino-6-hydroxyfenyl)azo]- 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 R: 41–52/53 X: (2-)26–39–61

611–044–00–0

Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [bis(4-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx 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 X: 61

N X: 51/53 X: 61

611–046–00–1

4,4'-xxxxxxx-2-xxxxxxxxxxxxxxx2-xxxxxxxxxxxxxxx-4,4'-xxxxxx

407–590–2

43151–99–1

X; R25 Xx; X48/22 X43 N; X50–53

X; N R: 25–43–48/22–50/53 X: (1/2-)22–28–36/37–45–60–61

611–047–00–7

Xxxx (1:1):2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx

407–890–3

111381–11–4

X53

X: 53 X: 61

611–048–00–2

Směs (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[bis(2-acetoxyethyl)amino]fenyl}azo)-6,7-dichlorbenzothiazol

407–900–6

111381–12–5

R53

R: 53 X: 61

611–049–00–8

Xxxx (2:1:1)7-[(4-{[3-(xxxxxxxxxxxx)xxxxxx]xxxxx}-6-{[3-(xxxxxxxxxxxxx)xxxxxx]xxxxx}-1,3,5-xxxxxxx-2-xx)xxxxx]-3-{[4-(xxxxxxxx)xxxxx]xxx}-4-xxxxxxxxxxxxxxx-2-xxxxxxxx, kyselina xxxxxx x mléčná kyselina (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-[xxxxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxx}xxx)-6-xxxxxxx-3-xxxxxxxxxxxxxxxxxxxxx-xxxxxxx

411–110–7

136213–74–6

X; 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 komplex, 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; R41 X; X50–53

Xx; X X: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

(X)-1-(1-xxxxxxxxxxxx-2-xx)xxxxx-1-xx-xxxx-xxxxxxxxxxxx

410–780–8

—

Xx; X22–48/22 Xx; X41 X43 X; X51–53

Xx; X X: 22–41–43–48/22–51/53 X: (2-)22–26–36/37/39–61

612–158–00–3

Směs:[bis(5-alkyl(rozvětvený X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx a 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx komplex x 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

—

X53

X: 53 X: 61

612–159–00–9

xxxxxxx produkty směsi 2,2,4-xxxxxxxxx- a 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x xxxxxxx XXXXXX), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Xxxxxx 8) a 4-xxxxxxxxxxxx-1-xxxxxxxxx xxxxxxxx

410–880–1

—

Xx; X22 X; X34 X; X50–53

X; X X: 22–34–50/53 X: (1/2-)23–26–36/37/39–45–60–61

613–149–00–7

2-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 X: 61

613–151–00–8

1-(2-xxxxx-3-X-xxxxx-5-X-xxxxxx-β-X-xxxxx-xxxxxxxxxxxxxx)-5-xxxxxxxxxxxxxxx-2(1X), 4(3 X)-xxxx

406–360–9

104218–44–2

X53

X:53 X: 61

613–152–00–3

xxxxx-X-(4,6-xxxxxxxxxxxxxxxxxx-2-xx)xxxxxxxx

406–600–2

89392–03–0

X43 X; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-xxxxxxxxxxxxxxx

407–270–2

16063–70–0

X52–53

X:52/53 S: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; R22

Xn X: 22 S: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; X22 X52–53

Xx X: 10–22–52/53 X: (2-)23–36–61

613–156–00–5

2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-xxxxx-5-xxxxxxxxxxxxx-4-xxxxxxxxxxx

410–260–0

83857–96–9

X43 N; X51–53

Xx; X 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 X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

2,3-dichlor-5-(trifluormethyl)pyridin

410–340–5

69045–84–7

Xn; R20/22 Xx; X41 X43 X; R51–53

Xn; X X: 20/22–41–43–51/53 X: (2-)24–26–37/39–61

613–159–00–1

4-[2-(4-xxxx-xxxxxxxxxx)xxxxxx]xxxxxxxxxx

410–580–0

120928–09–8

X; X25 Xn; X20 N; R50–53

T; X R: 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 R: 43 X: (2-)24-37

615–022–00–1

xxxxxx-3-(xxxxxxxxxxxxxxxxxx)xxxxxxx-2-xxxxxxxxxx

410–550–7

79277–18–2

X; X2 X14 Xx; X48/22 X42/43

X; Xx X: 2–14–42/43–48/22 S: (2-)22–30–35–36/37

615–023–00–7

xxxxxxxxxxx 2-[(isokyanatosulfonyl)methyl]benzoové kyselinymethyl-2-[(isokyanatosulfonyl)methyl]benzoát

410–900–9

83056–32–0

R10 X14 Muta. xxx. 3; X40 Xn; X20–48/22 Xx; R41 X42

Xx X: 10–14–20–40–41–42–48/22 X: (2-)23–26–36/37/39

616–044–00–4

X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)-2-(3-xxxxxxxxxxxxxxxx)xxxxxxxxx

402–510–2

—

X; X51–53

X X: 51/53 S: 61

616–045–00-X

2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(diethylamino)-2-methoxyacetanilid

405–190–2

122371–93–1

R43 R53

Xi X: 43-53 X: (2-)22–24–37–61

616–046–00–5

X -[2-(6-chlor-7-methylpyrazolo[1,5-b][1,2,4]triazol-4-yl)propyl]-2-(2,4-di-terc-pentylfenoxy)oktanamid

406–390–2

—

N; X50–53

X X: 50/53 X: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x N, N′,N″,N′′′ - xxxxxxxxxx(X18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx

406–640–0

—

X43

Xx R: 43 X: (2-)24-37

616–048–00–6

3'-(trifluormethyl)isobutyranilid

406–740–4

1939–27–1

Xn; X48/22 X; 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

Směs:3,3'-bis(4-methylfenyl)- 1,1'-(4-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx x 3,3'-bis(4-methylfenyl)-1,1'-(2-methyl-1,3-fenylen)dimočovina Xxxx:2,4-xxx[3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx x 2,6-bis[(3-(4-methylfenyl)ureido]toluen

411–070–0

—

R53

R: 53 X: 61

617–015–00–9

xxx(4-xxxxxxxxxxxxx)xxxxxxx

407–950–9

895–85–2

X; X2 X; X7 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 S)-, (2 X, 3 X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxx-1-(1X- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

—

94361–06–5

Xxxx. xxx. 3; X63 Xn; R22 X; R50–53

Xn; N X: 22–50/53–63 X: (2-)36/37–60–61

PŘÍLOHA 2

POVAHA SPECIFICKÝCH XXXXX SPOJENÝCH S XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Komise 2001/59/XX,

Xx. xxxx. X 332, 28.12.2000, x. 81.

XXXXXXX 3A

STANDARDNÍ POKYNY XXX BEZPEČNÉ ZACHÁZENÍ X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES,

Úř. xxxx. X 332, 28.12.2000, x. 81.

XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/XX,

Xx. xxxx. X 332, 28.12.2000, x. 81.

XXXXXXX 4X

"X.10 XXXXXXXXXX — ZKOUŠKA XX XXXXXXXXXXXX XXXXXXX X XXXXX XX XXXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX XX 473 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx u xxxxx xx xxxxx (1997).

1.1 XXXX

Xxxxxxx na xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxxx xx xxxxxxxxxxxxx činitele, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx v xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Rozlišují xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx chemických xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx vyskytují. Xxxxxx xxxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. Tato xxxxxx xxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx k xxxxxx xxxxx xxxxxxx používána. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx mnoha geneticky xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx xxxxx důkazů o xxx, xx chromozomové xxxxxx x s xxxx související jevy xxxxxxxxxxx xxxxx x xxxxxxxxxx x v xxxxxx xxxxxxxxxxx buněk xxxxxxxxx nádory, mají xxxxx xx xxxxxxx xxxxxxxx x člověka x u pokusných xxxxxx.

Xx zkoušce xx xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx buněčné xxxxx, buněčné xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx. Použité buňky xxxx xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxx x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx chromozomů a xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx prováděné xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx aktivace. Xxxxx xxxxxxxxxxx xxxxxxxxx systém xxxxxx zcela napodobit xxxxxxxx in xxxx x savců. Xx xxxxx xx xxxxx xxxxxxxxx podmínek, které xx vedly x xxxxxxxxxx výsledkům, jež xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx x xxx xxxxx xxxxxx xX, xxxxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxx xxxxx. Mnoho xxxxxxxxx, xxx něž je xxxx xxxxxxx pozitivní, xxxx xxx xxxxx xxxxxxxxxxx; xxxx touto xxxxxxxx a xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Korelace xxxxxx xx xxxxxxxx třídě x přibývají xxxxxx x xxx, xx xxxxxxxx karcinogeny, které xxxxxx zjištěny xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx mechanismy xxx xxxxxx xxxxxxxxxx XXX.

Xxx xxxx Obecný xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození chromozomu x xxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx a xxxxxxxx xxxxxxx chromatid.

Chromozomová xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x podobě xxxxx nebo zlomu x spojení xxxx xxxxxxxxx x xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : xxxxxx, xxx xxxxxx v xxxxx po X-xxxx xxxxxxxxx DNA nedojde x xxxxxx, xxxxx xxxxxxxxx xxxxx S-fáze. Xxxxxxxxx xxxx xxxxxxxxxx xx 4, 8, 16… xxxxxxxxxxxx.

Xxx : xxxxxxxxxxxx xxxx xxxxx xxx šířka jedné xxxxxxxxxx x x xxxxxxxxx odchylkou xxxxxxxxx.

Xxxxxxxxx xxxxx : xxxxx xxxxx, které xx xxxxxxxxx x xxxxxxxx, x celkového počtu xxxxx x xxxxxxxx; xxxxx xxxxxx proliferace xxxx xxxxxxxx.

Xxxxxxxxx aberace : xxxxxxxx počtu xxxxxxxxxx od normálního xxxxx obvyklého x xxxxxxxxx xxxx buněk.

Polyploidie : xxxxxxx haploidního xxxxx xxxxxxxxxxxxxx sad (x), xxxx xxx xxxxxxxxx (xx. 3 x, 4 x xxx.).

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx xxxxxx ve xxxxxx xxxxxxxx; xxxx xx xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, a xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. V předem xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxx xx xx xxxxxxxxx kultur xxxxx látka zastavující xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx), xxxxxxx xx sklidí, obarví x xxxxxxxxxx chromozomových xxxxxxx se xxxxxx xxxxxxxxxxxxxx xxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx xxxxx xxxxxxx xxxxx, kmeny nebo xxxxxxxx xxxxxxx xxxxxxx, xxxxxx lidských buněčných xxxxx (xxxx. fibroblasty xxxxxx čínského, xxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx x kultivační xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x inkubační xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x vlhkost). U xxxxxxxxxxxxxxx xxxxxxxxx xxxxx x kmenů xx xxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxxx chromozomů x xxxx xx xxx kontrolováno, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx neměly xxx xxxxxxx. Pro xxxxxxx xxxxx a xxxxxxxxx xxxxxxxx by měla xxx xxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx a xxxxx: xxxxx xx xxxxxxx x kmenových xxxxxx, xxxxxx xx xx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxxx, aby xxxxxxxxx konfluence před xxxxxxxxx, x inkubují xx při 37 °X.

Xxxxxxxxx: xxxx xxxxxxxx xxxxxxxxxxxxxxx (xxxx. xxxxxxxxx) xxxx xxxxxxxx lymfocyty xxxxxxxx probandů xx xxxxxxx xx xxxxxxxxxxxx xxxxx xxxxxxxxxxxx mitogen (xxxx. xxxxxxxxxxxxxxxx) x xxxxxxxx se při 37 °X.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x to x xxxxxxx metabolickou xxxxxxxx a bez xx. Nejčastěji xxxxxxxxxx xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx frakce (X9) xxxxxxxxxx x xxxxx hlodavců zpracovaná xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (6, 7, 8 x 9), xxxx směs fenobarbitonu x β-naftoflavonu (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx v xxxxxxxx testovacím médiu xxxxxxx xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % obj. Xxxx xxxxxxxxxxxxx aktivačního xxxxxxx xxxx xxxxxxx xx třídě xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. V xxxxxxxxx xxxxxxxxx xxxx být xxxxxx xxxxxx více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx výsledků xxxxxx, včetně xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx linií xx xxxx xxx vědecky xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx P450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx přidány xxxxx x testovacím xxxxxxxx x/xxxx xxxxx xxx xxxx aplikací xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x přežitím buněk x x xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx xx vodě xx xxxx být použita xxxxxxxxx rozpouštědla neobsahující xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx zohledněna xxx xxxxxxxxx xxxxxxxx koncentrace, xxxxx cytotoxicita, xxxxxxxxxxx x testovacím xxxxxxx x změny xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx integrity x xxxxx, jako xxxx stupeň xxxxxxxxxx, xxxxx xxxxxxxxxxxxxxx xxxxx xxxx mitotický xxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx by být xxxxxxx alespoň xxx xxxxxxxxxxxxxx xxxxxxxxxxx. V xxxxxxx xxxxxxxxxxxx by xxxx xxxx koncentrace xxxxxxxx xxxxxxx xxxx xxxxxxxxx až xxxxxxxxx xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, xxx xxxxxxx xxxxxxx, xx xx xx xxxxxxxxxxx xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. X xxxxxxxx xxxxxxx xx xxxx xxxxxxxx koncentrace vykazovat xxxxxxxx xxxxxxx stupně xxxxxxxxxx, xxxxx xxxxx xxxx mitotického xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx je xxxxx nepřímým měřítkem xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x xxxxxx xx xxxx, xxxxx xxxxxxxx od xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx přijatelný x xxxxxxxxxxx xxxxxx, x xxxxx xxxxx xxx xxxx metody stanovení xxxxxxxx obtížné x xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx buněčného cyklu, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (XXX), mohou xxx použity xxxx xxxxxxxxx xxxxxxxxx. V xxxxxxx XXX xxxx xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx xxxxx xxxxxxx xx xxxxxxxxx zpožděných xxxxxxxxxxx, a x xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx xxxx xxx za xxxxxxxx xxxxx xxxxxxxxx oddálení xxxxxxxx xxxxxxxxxxx výtěžku xxxxxxx.

X případě xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx maximální xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, která x xxxx je xxxxxxxx.

X případě xxxxxxxxx xxxxxxxxxxxxx látek, xxxxx xxxxxx xxxxxxx xxx xxxxxxxxxxxxx nižších, xxx xx xxxxxx rozpustnost, xx xxxx být xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxx, xxx xx xxx mezí xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx médiu xx xxxxx doby aplikace. X určitých xxxxxxxxx (xxxx. projeví-li xx xxxxxxxx xxxxx při xxxxxxx xxxxxxxxxxxxx, xxx xx xxxxxxxxxxx) se xxxxxxxxxx vyzkoušet xxxx xxxxxxxxxxx, při nichž xxxxxxx xx xxxxxxx. Xxxx xxx užitečné xxxxxxxx rozpustnost na xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx v xxxxxxxxxx xxxxxxx xx může x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, séra X9 atd. Xxxxxxxxxxxxx xxx zjistit vizuálně. Xxxxxxxxx by xxxxxx xxxxx při vyšetřování.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxx rozpouštědla xxxx xxxxxxxx). Xxx xxxxxxx metabolické aktivace xx xxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx, xxxxx x mutagenní xxxxxx xxxxxxxx aktivaci.

K xxxxxxxxx kontrole xx xxx být použit xxxxx xxxxxxxxx v xxxxxxxxxxx koncentracích, které xxxxxxxx xxxxxxxxx reprodukovatelný x detekovatelný xxxxxx xxx xxxxxx, xxxx xx prokáže xxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx by měly xxx zvoleny xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx:

Xxxx metabolické xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxx xxxxxx metabolické xxxxxxxx

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X xxxxxx xxxxxxxxxxxx xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Pro pozitivní xxxxxxxx xxxxx xxx xxxxxxx x jiné xxxxxx látky. Xxx xxxxxxxxx kontrolu by xxxx být xxxxx xxxxx vzato x xxxxx použití xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx třídy.

V okamžiku xxxxxxxx by měly xxx xxxxxxx negativní xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula x xxxxxxxxxxx médiu x xxxxxxxxxx stejným způsobem xxxx kultury. Xxxxx xxxx by xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx dosud xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx rozpouštědlo xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Expozice zkoušené xxxxx

Xxxxxxxxxxxxx buňky xx xxxxxxx xxxxxxxx xxxxx xxx xx přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx něho. Xxxxxxxx lymfocytů xx xxxx xxx xxxxxxxx xxx 48 xxxxx xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx xxxxxx koncentraci xx xxxx být xxxxxxx použity duplicitní xxxxxxx, a xxxxx xx xxxxxxx doporučuje x xxxxxx xxx xxxxxxxxx kontrolu nebo xxxxxxxx xxxxxxxxxxxx. Jestliže xxx na základě xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx kulturami xx minimální xxxxxx, xxxx xxx xxxxxxxxx xxxxxxx jediné xxxxxxx.

Xxxxxx xxxx xxxxxx xxxxx xx xxxx xxx xxxxxxxx xxxxxxxx metodami, xxxx. x těsně xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (15, 16).

1.4.3.3 Xxxx xxxxxxx xxxxxx

X xxxxxx xxxxxxxxxxx xx xxxx xxx buňky xxxxxxxxx xxxxxxxx látce, xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, xx xxxx 3 — 6 xxxxx, x xxxx xx xxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx normální xxxxx buněčného cyklu (12). Jestliže xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx jak s xxxxxxxx, xxx xxx xxxxxxxx, měl xx xxx proveden dodatečný xxxxxxxxxx bez xxxxxxxx x xxxxxxxxxxxx xxxxxxxx xx xx xxxxxx x době, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx chemické xxxxx xxx xxxxx xxxxxxxxx xxx dobách xxxxxxxx xxxx xxxxxx xxxxxxx xxx 1,5násobek xxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx být potvrzeny xxxxxx od případu. X případech, kdy xx xxxxxxxxxx potvrzení xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, xx xxxx xxx podáno xxxxxxxxxx.

1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů

Do buněčné xxxxxxx xx xxxxxxx 1-3 xxxxxx xxxx xxxxxxxxx přidá Xxxxxxxx® xxxx xxxxxxxxx. Pro xxxxxxxx xxxxxxxxx pro xxxxxxx chromozomů xx xxxxx xxxxxxx xxxxxxx xxxxxx x xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxx hypotonizaci buněk, xxxxxx x obarvení xxxxx.

1.4.3.5 Analýza

Všechny xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx xxx xxxxxx xxxxx dochází xx xxxxx části xxxxx x xxxxxxxx x xx xxxxxx xxxxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx obsahovat xxxxxxxxxx x xxxxx rovném xxxxxxx xxxxxxx ± 2 xxx xxxxxxx xxxx xxxxx. Na xxxxxx xxxxxxxxxxx x xxxxxxxx xx xxxx xxx xxxxxxxxx alespoň 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxx duplicitní xxxxxxx. Xxxxx xxxxx xxx xxxxxx, je-li xxxxxxxxx xxxxx xxxxx xxxxxxx.

Xxxxxx xx xxxxxx xxxxxxx detekovat strukturní xxxxxxxxxxxx xxxxxxx, je xxxxxxxx xxxxxxxxxx xxxxxxxxxxx x endoreduplikace, xxxx-xx xxxxxxxxxx.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx x mělo xx tedy být xxxxxxxxxxx xxxxxxxx xxxxx xx strukturní chromozomovou xxxxxxx (aberacemi) xxxxxxxxx x xxxxxxxxxx. Pro xxxxxxxxx x experimentální xxxxxxx xx měly xxx xxxxxxx různé xxxx xxxxxxxxxxxx chromozomových xxxxxxx s xxxxxx xxxxxx x xxxxxxxx. Xxxx se xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, ale xxxxxxxxxx xx xx celkové xxxxxxxx xxxxxxx.

Xxxx xx xxx xxxx zaznamenána xxxxxxxx, která xxxx xxxxxxxxx xxx stanovení xxxxxxxxxxxx u xxxxx xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxx. Xxxx xx xxxx xxx xxxxxxx údaje xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx potvrdit xxxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx x bodu 1.4.3.3. Xxxxx parametrů xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x následných xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx změněny, xxxxx xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje xxxxxxx kritérií, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x závislosti xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx tohoto xxxxx. Xxxxxxxx xx xxxx xxx uvážena biologická xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxx polyploidie xxxxx xxxx znamenat, xx xxxxxxxx xxxxx má xxxxxxxxx potlačit xxxxxxxxx xxxxxxx a xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x endoreduplikovanými xxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx xx xxxxxxxxx potlačit xxxxxxxx xxxxxxxxx xxxxx (17, 18).

Xxxxxxxx xxxxx, jejíž xxxxxxxx nesplňují xxxx xxxxxxx xxxxxxxx, xx x xxxxx xxxxxxx xxxxxxxx za nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx in xxxxx znamenají, že xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxxx somatických xxxxxxx savců strukturní xxxxxxxxxxxx aberace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx vehikula,

- xxxxxxxxxxx x xxxxxxx zkoušené xxxxx x rozpouštědle/vehikulu, xx-xx xxxxx.

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxx xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- informace x xxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxx krve, xxx byla xxxxxxx xxxx xxxx xxxx xxxxxxxxxx lymfocyty, xxxxxxx xxxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx kultury,

- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

- identifikace xxxxx xxxxxxxxxxx xxxxxxxx, xxxx koncentrace x xxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x xxxxx xxxxxx, xxxxxx např. xxxxx x cytotoxicitě x xxxxxx xxxxxxxxxxxx, xxxx-xx x dispozici,

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x přidané xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx při xxxxxxxx,

- xxx x složení xxxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, xxxxxx kritérií xxxxxxxxxxxxx,

- xxxxxxxxx x xxxxxxxxx kontroly,

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx metafází,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx, xxxx. stupeň xxxxxxxxxx, xxxxx o xxxxxxxx xxxxx, xxxxx xxxxx, xxxxxxxxx index,

- xxxxxx xxxxxxx,

- údaje x xX a xxxxxxxxxx xxxxxxxxxxx xxxxx, pokud xxxx stanoveny,

- xxxxxxxx xxxxxxx, xxxxxx gapů,

- xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi x xxxx xxxxxxx zvlášť xxx xxxxxx xxxxxxxxxxx x xxxxxxxxx kulturu,

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

- údaje x souběžné xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx,

- dosavadní xxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X. (1976), Xxxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, xx: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx xxx Xxxxxxx xxx xxxxx Xxxxxxxxx, Vol. 4, Xxxxxxxxxx, A. (xx) Xxxxxx Press, Xxx Xxxx xxx London, 1-29.

2) Xxxxxxxx, X. Xx., Sofumi, X. (1985), The Xx xxxxx Xxxxxxxxxxx Aberration Xxxx Xxxxx Xxxxxxx Xxxxxxx Xxxx (CHL) Xxxxxxxxxx Cells xx Xxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Xxxxx, X. xx xx., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Amsterdam-New Xxxx-Xxxxxx, 427-432.

3) Galloway, S. X., Armstrong, X. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxxxx, C., Xxxxx, X. X., Xxxxxxxx, X., Xxxxx, X., Xxx, X., Xxxxx, J., Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X., Zeiger E. (1978), Xxxxxxxxxx aberration xxx xxxxxx xxxxxxxxx xxxxxxxxx in Chinese xxxxxxx ovary cells: Xxxxxxxxxx xx 108 xxxxxxxxx, Environ. Molec. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Xxxxx, X., Xxxxxxxx, S. X., Marshall, X. X., Xxxxxxxx, X. Xx., Brusick, X., Xxxxx, J., Xxxx, X. C. (1991), Xxxxxxxxxxxx xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. X xxxxxx from XXXXXX Xxxx Xxxxx 9, Xxxxxxxxxx Res., 257, 147-204.

5) Xxxxxx, T., Xxxxxx, T., Xxxxxx, X., Okumura, X., (1992), Xxxxxxxxxxxxxx xx xxx pH xx Xxxxxxx Xxxxxxxx Xxxxxxxxx Xxxxx, Mutatation Res., 268, 297-305.

6) Ames, X. N., McCann, X., Xxxxxxxx, E. (1975), Xxxxxxx for Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Mutation Res., 31, 347-364.

7) Xxxxx, X. M., Xxxx, X. N. (1983), Xxxxxxx Xxxxxxx xxx xxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 113, 173-215.

8) Natarajan, X. T., Xxxxx, X. X., van Xxxx, P. X. X., Xxxxxxx, X., xx Vogel, X. (1976), Cytogenetic Xxxxxxx xx Mutagen/Carcinogens xxxxx Xxxxxxxxxx in x Xxxxxxxxxxx Xxxxxx Xx xxxxx, I. Xxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xxx Sister Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Dimethylnitrosamine (XXX) xx XXX Xxxxx xx xxx Xxxxxxxx xx Xxx-Xxxxx Xxxxxxxxxx, Mutatation Xxx., 37, 83-90.

9) Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. Xx. (1979), Xxxxxxxxxxx Xxxxxxxxxx Xxxxx xx 29 Xxxxxxxxx Xxxxxxxx with X9 Xxx In xxxxx, Xxxxxxxx Xxx., 66, 277-290.

10) Xxxxxx, X. M., Xxxxxx, X. X., Xxxxxxx, X. R., Xxxxxxxxx, X. G., Xxxxxx, X. X., Mackay, X. M., Xxxx, X. X. (1992), Xxxxxx xx UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx Xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Sawamura, X., Xxxx, K., Xxxxxxxx, X. (1976), X. Xxxx Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. s. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: xx Xxxxxx, F. X., Xxxxx, X. X. Xxxx, J. X., Xxxxxxx, R. X. (xxx), Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Testing, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. Jr., Xxxxx, X. X., Xxxxxxxx, X. X., Xxxxxx, X., Xxxxxxx, X., Sofumi, X. (1994), Report xxxx Xxxxxxx Xxxxx xx Xx xxxxx Xxxxx xxx Chromozomal Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 312, 241-261.

13) Richardson, C., Xxxxxxxx, X. X., Xxxxx, X. X., Xxxxxxxx, G., Chanter, X. X., Phillips, X. (1989), Xxxxxxxx xx Data xxxx Xx vitro Xxxxxxxxxxx Xxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. J., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

14) Xxxxx, X. X., Xxxxxxxx, X. M. (1994), Xxxxxxxxx Xxxxxx xxx xxx Xxxxxxxxx xxx Xx xxxxx Xxxxxxxxxx Xxxxxxxxxx Xxxxxx in XXX Xxxxx, Xxxxxxxxxx Xxx., 312, 139-149.

15) Xxxxx, X. X., Xxxxxx, X. C., XxXxxxx, X. X. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Volatile Xxxxxxx, in: Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Xxxxxx, New Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, X. X., Xxxxxx, X. M., Xx, A. X., Xxxxxx, X. X. (1983), Xxxxxxxxxx of xx Exposure Xxxxxx Xxxxx Cells Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Mutation Xxxxx, Xxxxxxxxxxxxx Xxxxxxx., 5, 795-801.

17) Locke-Huhle, X. (1983), Xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx-xxxxxxxxx xxxxxxx X2 xxxxxx, Xxxxxxxxxx Res., 119, 403-413.

18) Xxxxx, Y., Xxxxxx, C., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx endoreduplication xx Xxxxxxx hamster cells, Xxxxxx Xxx., 43, 1362-1364."

PŘÍLOHA 4B

"B.11 XXXXXXXXXX–XXXXXXX XX CHROMOZOMOVÉ XXXXXXX X BUŇKÁCH KOSTNÍ XXXXX XXXXX IN XXXX

1. METODA

Tato xxxxxx xx replikou metody XXXX XX 475 — Xxxxxxx na xxxxxxxxxxxx aberace v xxxxxxx xxxxxx dřeně xxxxx (1997).

1.1 ÚVOD

Zkouška xx chromozomové xxxxxxx x xxxxx xx xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx aberací indukovaných xxxxxxxxx xxxxxx x xxxxxxx xxxxxx xxxxx xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx xx xxx typy strukturních xxxxxxx — xxxxxxxxxxxx x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx látka xx schopnost indukovat xxxxxxxxx xxxxxxx. X xxxxxxx většiny xxxxxxxxxx xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx aberace xx rovněž xxxxxxxxx. Xxxxxxxxxxxx mutace x xxxxxxxxxxx xxxx jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x existuje xxxxx xxxxxx x xxx, xx chromozomové xxxxxx x xxxxxxxxxxx xxxx způsobující změny x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx na xxxxxxx xxxxxxxx u xxxxxxx a x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx xxxx rutinně xxxxxxxxx hlodavci. Xxxxxxx xxxxx xx v xxxx xxxxxxx xxxxxx xxxx, xxxxxxxx xx xxxxxx vaskularizovanou tkání x obsahuje xxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxxx xx xxxxxx izolují a xxxxxxxxxxxx. Jiné druhy x cílové tkáně xxxxxx předmětem xxxx xxxxxx.

Xxxx zkouška xx xxxxxxxxxxxx xxxxxxx je xxxxxxx xxxxxx k xxxxxxxxx nebezpečí mutagenese, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx metabolismu xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx se mohou x různých druhů x xxxxx xxxxx. Xxxxxxx in vivo xx xxxxxx užitečná xxx další výzkum xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx xx vitro.

Jestliže xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx metabolity nedostanou xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxxx chromatid xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : strukturní xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx x xxxxxxx xxxx xxxxxxxxx x xxxxxx místě.

Endoreduplikace : xxxxxx, při xxxxxx x xxxxx po X-xxxx replikace XXX xxxxxxx x xxxxxx, xxxxx následuje další X-xxxx. Výsledkem xxxx xxxxxxxxxx se 4, 8, 16,… chromatidami.

Gap : achromatická xxxx xxxxx xxx šířka xxxxxxx xxxxxxxxxx x x xxxxxxxxx odchylkou xxxxxxxxx.

Xxxxxxxxx xxxxxxx : xxxxxxxx počtu chromozomů xx xxxxxxxx xxxxxxx xxxxxxx u xxxxxxxxx xxxxx.

Xxxxxxxxxxx : xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxxx xxx (x), xxxx xxx xxxxxxxxx (tj. 3 x, 4 x xxx.).

Xxxxxxxxxx xxxxxxx : mikroskopicky pozorovatelné xxxxx struktury chromozomů xxx buněčném xxxxxx xx stadiu xxxxxxxx; xxxx se xxxx xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xx xxxxxxx okamžiku po xxxxxxxx se xxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx chromozomů, xxxxxx se x xxxxxxxxx xx chromozomové xxxxxxx buněk v xxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx je xxxxxxxx potkan, myš x xxxxxx xxxxxx, xxxxxx lze použít xxxxxxxx vhodný savčí xxxx. Měly xx xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx zahájení xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx by u xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx hodnoty hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

Xxxxx obecné xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx B, xxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx zvířata se xxxxxxxx xxxxxxx rozdělí xx kontrolní skupinu x xxxxxxx, xxxxx xx vystaví xxxxxxxx xxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, xxx byl xxxx jejich xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Nechají xx v xxxxxxxxxxxxx xxxxxxxxxx alespoň pět xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly být xxxx xxxxxxxx zvířatům xxxxxxxxxx xxxx suspendovány xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky mohou xxx xxxxxxxx přímo xxxx mohou být xxxx podáním xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx dávek xxxxxxx xxxxxx a mělo xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx zařazení podloženo xxxxx o jejich xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx použití vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí každého xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx pohlaví. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx zvířata xxxxxxxxx xxxxxxx xxxxxxxxxx identický xxxxxx jako xxxxxxx xx skupinách, x xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx kontroly xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx se xxxxxxx, xx poskytnou xxxxxxxxxxxxx nárůst xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx xx měly xxx zvoleny xxx, xxx xxx účinek xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby byla xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx xxx odběr x jejím xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx xxx použity xxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx 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 okamžiku xxxxxxx xxxxxx by xxx být xxxxxxxx xxxxx u xxxxxxxxxxx xxxxxxx, xxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx vehikulum x xxx xxxxx podstupují xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, pokud xxxxxx z dosavadních xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx údaje x variabilitě zvířat x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx kontrolu xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx toho xx xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx nebo mutagenní xxxxxx.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx se xxxxxx x alespoň pěti xxxxxxxxxxxxxxxx xxxxxx pro xxxxx pohlaví. Jestliže xxxx x xxxx xxxxxx x dispozici xxxxx ze xxxxxx xx stejným xxxxxx x za xxxxxxx xxxxxxxx xxxxxxx expozice, xxx xxxxxxxxx, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x toxicitě, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx pohlaví. Xx-xx xxxxxxxx xxxxxxx specifická xxx xxxxxx pohlaví, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx zkouška xxxxxxxxx xx zvířaty xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx by xxxx xxx pokud xxxxx xxxxxxxx jednorázově. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx xxxx dávkách, xxx. xxx xxxxx x xxx xxx x xxxxxxx xx xxxx než xxxxxxxx xxxxx, aby bylo xxxxxxxxx podávání xxxxxxx xxxxxx materiálu. Xxxx xxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx xxxxxxxx xx xxxx různých intervalech xx aplikace xxxxxx x xxxxxx xxx. X hlodavců xx xxxxx xxxxxxx po xxxxxx xxxx xx xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx normální xxxxx xxxxxxxxx xxxxx (xxxx xxxx obvykle 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx příjem x xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxx xxxxxx na kinetiku xxxxxxxxx cyklu xxxx xxx vliv xx xxxxxxxxx xxxxxxx xxx xxxxxxxxx chromozomových xxxxxxx, xxxxxxxxxx se xxxxxxx xxxxx xxxxx xx 24 x xx xxxxxxx xxxxxx. Je-li xxxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xx xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx poslední xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx xxxxxxxx délky buněčného xxxxx.

Xxxx usmrcením xx xxxxxxxx intraperitoneálně xxxx xxxxxx dávka xxxxx xxxxxxxxxxx metafázi (např. Xxxxxxxx® xxxx kolchicin). Xxxx xx xx xxxxxx xxxx provede x xxxxxx xxxxx. X myši xx xxxx xxxx xxxxxxxxx 3 — 5 x; x xxxxxx xxxxxxxx je xxxx xxxx přibližně 4 — 5 x. X xxxxxx xxxxx xx xxxxxxxx xxxxx x analyzují xx xx xxxxxxxxxxxx xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx xxxxxxx dávek, xxxx by xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, xxxxxxxx x xx xxxxxxxx xxxxxx expozice, xxx xx použijí v xxxxxx studii (5). X případě xxxxxxxx xx xxx první xxxxx xxxxxxx xxx xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx xxxxxxxx rozpětí xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, případně xxxxxx toxicitou. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx nejvyšší xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx dávka xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách v xxxxxx dni xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx základě xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx xxxxxx xx třemi úrovněmi xxxxx za xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx než 14xxxxx aplikaci je xxxxxxx xxxxxx 1000 xx/xx tělesné hmotnosti/den. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx potřebu xxxxxx x limitní xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx se obvykle xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx x odůvodněných případech xxxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx při xxxxxxx koncentracích vykazují xxxxxxxx xxxxxx, by xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx minimalizována xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem při xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů

Ihned xx xxxxxxxx xx odebere xxxxxx xxxx, hypotonizuje xx a xxxxxx. Xxxxx xx xxxxxxx xx podložní sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx měřítko xxxxxxxxxxxx xx měl xxx x xxxxx xxxxxxxxxxxx xxxxxx (xxxxxx xxxxxxxxxxx xxxxxxx) x x xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx, x xx alespoň x 1000 buněk xx xxxxx xxxxx.

X každého xxxxxxx xx mělo xxx xxxxxxxxxxx xxxxxxx 100 xxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx pozorován xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx xx xxxx být xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx zlomům xxxx xx ztrátě xxxxxxxxxx u části xxxxx x metafázi, xxxx by xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x počtu odpovídajícímu xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx jednotkou je xxxxx. Pro každé xxxxx by xxx xxx xxxxxxxxxx xxxxx xxxxx, počet xxxxxxx xx xxxxx a xxxxx buněk x xxxxxxxxxxxxx aberací (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx v xxxxxxxxxx. Xxx exponované x xxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich xxxxxx x xxxxxxxx. Gapy xx xxxxxxxxxxxxx odděleně x uvádějí xx, xxx xxxxxx xx xxxxxxxxxx do xxxxxxx xxxxxxxx aberací. Xxxxxxxxxx-xx xxxxx o rozdílu x xxxxxxxx xxxx xxxxxxxxx, xxxxx xxx xxx statistickou xxxxxxx xxxxx pro xxx xxxxxxx zkombinovány.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi v xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx buněk x xxxxxxxxx pro xxxxxxx x určitou xxxxxx x x určitému xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx by neměla xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx podmínek.

Nárůst xxxxxxxxxxx xxxx znamenat, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxx xxxxx xxxxx s xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx má potenciál xxxxxxxx xxxxxxxx buněčného xxxxx (7, 8).

Xxxxxxxx xxxxx, jejíž xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, se xxxxxxxx x xxxxx xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx soubor xxxxx vyslovit konečný xxxxx x aktivitě xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx chromozomové xxxxxxx xx xxxx xxxxxxxxx, xx zkoušená látka xxxxxxxx v kostní xxxxx testovacího xxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx x kostní xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx by xxx xxxxxxxxxxx pravděpodobnost, x xxxxx xx zkoušená xxxxx nebo její xxxxxxxxxx dostanou xx xxxxxxxx oběhu, nebo xxxxxxxxxx xx cílové xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL O XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- rozpustnost a xxxxxxx zkoušené xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, stáří x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx hodnoty a xxxxxxxxxx xxxxxxxx pro xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- xxxxx xx xxxxxx xxx xxxxxxxx rozsahu, pokud xxxx provedena,

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxx x přípravě xxxxxxxx látky,

- údaje x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, xxx se xxxxxxxx látka xxxxxxx xx krevního xxxxx xxxx do cílové xxxxx,

- xxxxxxxx přepočet xxxx xxxxxxxxxxx xxxxxxxx xxxxx x krmivu xxxx xxxx (ppm) xx odpovídající xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx údaje o xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx xxxxx xxxxxxxxxxx metafázi, xxxx xxxxxxxxxxx a délka xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx hodnocení xxxxxxx,

- xxxxx analyzovaných xxxxx na xxxxx xxxxx,

- kritéria klasifikace xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxx toxicity,

- mitotický xxxxx,

- xxx x xxxxx aberací xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- celkový xxxxx xxxxxxx xx skupině xx středními hodnotami x směrodatnými xxxxxxxxxx,

- xxxxx buněk x xxxxxxxxx xx skupině xx středními hodnotami x směrodatnými odchylkami,

- xxxxx ploidie, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx analýzy,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx x rozpětími, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X. (1984), Xxxxxxxxxxx Xxxxx in Xxxxxxx, in: Xxxxxxxxxxxx Xxxxxxx: x Practical Xxxxxxxx, X. Venitt, X. X. Parry (xxx), XXX Press, Xxxxxx, Xxxxxxxxxx X. X., 275-306.

2) Preston, X. X., Xxxx, X. J., Xxxxxxxx, X., Xxxxxx, H., XxXxx, X. F., Xxxxxx, X. (1987), Xxxxxxxxx Xx xxxx Xxxxxxxxxxx Assays: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xx Bone Marrow Xxxxx, Xxxxxxxxxx Xxx., 189, 157-165.

3) Richold, X., Xxxxxxxx, X., Xxxxx, J., Gatehouse, X. X., Xxxxxxx, X., Henderson, L. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx I xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. X., Hayashi, X., MacGregaro, X. X., Anderson, X., Xxxxxx, X. X., Xxxxxx, X. E., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., F. B., Xxxxxxxxxxxx, X., Preston, X. J., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xxxxxx xxxx xxx Xxxxxxx Xxxxx xx xxx xx vivo Xxxxxxxxx Xxxx Xxxxxx Chromozomal Xxxxxxxxxx Test, Mutatation Xxx., 312, 305-312.

5) Xxxxxxx, X. J., Xxxxx, X. A., Xxxxxx, X. X., Xxxxxx, P. X., Xxx, X., Xxxxxxx, X. X., Gatehouse, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, D. X., Kirkland, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Amphlett, X. X., Xxxxx, X., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, X. X., Savage, J. X. X. (1989), Xxxxxxxxxxx Analysis of Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxxxx Xxxx III. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Test Data, X. J. Kirkland (xx.) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 184-232.

7) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx during xxxxx-xxxxxxxxx-xxxxxxx X2 xxxxxx, Xxxxxxxxxx Xxx., 119, 403-413.

8) Xxxxx, X., Xxxxxx, C., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx endoreduplication in Xxxxxxx xxxxxxx cells, Xxxxxx Xxx., 43, 1362-1364."

PŘÍLOHA 4X

"X.12 XXXXXXXXXX–XXXX XXXXXXX XXXXXXXXXXXXXXX MIKROJADER XX VIVO

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX XX 474 — Test xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx vivo (1997).

1.1 XXXX

Xxxx xxxxxxx erytrocytárních xxxxxxxxxx xx vivo xx xxxxxxxx pro xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx látkou, x xx xxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx x/xxxx xxxxx periferní xxxx, obvykle xxxxxxxx.

Xxxxxx xxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx poškození, jehož xxxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxxxxxxx nereplikující xx (lagging) xxxxxxxxxxxx xxxxxxxxx xxxx celé xxxxxxxxxx.

Xxxx xx xxxxxxxxxxx xxxxxx dřeně xxxx xx xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxx xxxxx je xxxxxxxx x xxxxxxxxxx, xxxxx při xxx xxxxx xxxxxxxxx, xxxxxxxxx x xxxxxxxxxx, která xxxxx jádra xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx je x těchto xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx hlavní xxxxx. Xxxxxx xxxxxxx polychromatických xxxxxxxxxx s mikrojádry x exponovaných zvířatech xx xxxxxxx indukovaného xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx je xxxxxxx xxxxxxxxx kostní xxxx xxxxxxxx, poněvadž xxxx xxxx produkuje xxxxxxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) erytrocytů s xxxxxxxxxx x periferní xxxx je xxxxxxxxxx xxxxxxxxxx x kteréhokoli xxxxx, x něhož xxxx prokázána xxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, nebo xxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx způsobují xxxxxxxxxx xxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxxxxxxxx xxx xxxxxxxx řadou xxxxxxxx. Ta xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX x xxxxxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx v xxxxxxxxx xxxx, xxxxx xxxxxxxx xxxxxxxxxx, připadající xx xxxxxx xxxxx zralých xxxxxxxxxx xxx xxxxxx xxxxxx xxxx konečný xxxxxxxx zkoušky, xxxxxxxx xxxx xxxxxxx exponována xxxxx xxxxx nebo xxxx.

Xxxxx test xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx xx zvláště xxxxxx x posouzení xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx DNA, třebaže xx xxxxx xxxxx x různých xxxxx x xxxxx, xxxxx x z xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxx je xxxxxx xxxxxxxx xxx další xxxxxx mutagenních xxxxxx xxxxxxxxxx x xxxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx zkoušku xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (oblasti) chromozomu, x xxx (x xxxx) xx xxxxx xxxxxx buněk xxxxxxx xxxxxx vřeténko xxxxxxxxxx xxxxxxxxxx xxxxx dceřiných xxxxxxxxxx k xxxxx xxxxxxxxx buněk.

Mikrojádra : xxxx jádra existující xxxxxxxx od xxxxxxxx xxxxx x vedle xxxx, xxxxxxxxx xxxxx xxxxxxxx xxxxxx (xxxxxx) xxxxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxxxx fragmenty nebo xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx xxxxxxxxx : xxxxx erytrocyt xxxxxxxxxxxx xxxxxxxx, který xxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx xxxxxxxxx ve xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx xxxxxxxx ribozomy, x může xxx xxxx xxxxxxxx xx xxxxxxx normochromatických xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx vhodným xxxxxxxx vystaví zkoušené xxxxx. Xxx použití xxxxxx xxxxx xx xxxxxxx xx vhodném xxxxxxxx po expozici xxxxxx, xxxxxxx se xxxxxx xxxx, xxxxxxxx xx preparáty x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx použití xxxxxxxxx xxxx se krev xx xxxxxxx xxxxxxxx xx xxxxxxxx odebere, xxxxxxxxxx xx připraví xxxxxxxx a xxxxxx xx (4, 8, 9, 10). Při xxxxxxxx s periferní xxxx xx xxxx xxxx xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxx xxxxxxxx xx xxxxxxxxx xxxx. Xxxxxxxxx jsou xxxxxxxxxxx na xxxxxxxxxx xxxxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx xxxxxxx xxxxxx xxxxx xx xxxx xxxxxxxxx xxxxx xxxxxxxxxx xxx nebo xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxxx xxxx. Xxx xxxxxxx periferní krve xx xxxxxxxxxx xxx. Xxx xxxx použít xxxxxxxx xxxxxx druh xxxxx za xxxxxxxxxxx, xx jde x xxxx, x něhož xxxxxxx xxxxxxxxxxxx erytrocyty x mikrojádry, xxxx xxxx vykazující dostatečnou xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx strukturní xxxx xxxxxxxxx chromozomové xxxxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. V xxxxxxxx zahájení xxxxxx xx xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx x xxxx xxxxxxx překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu a xxxxxx

Xxxxx obecné xxxxxxxx xxxxx xxxxxxxx xxxxx x části X, xxxxxxx by xxxx xxx dosaženo xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx zvířata xx xxxxxxxx výběrem rozdělí xx xxxxxxxxx skupinu x xxxxxxx, x xxx se xxxxxxx xxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Nechají xx v laboratorních xxxxxxxxxx alespoň pět xxx xxxxxxxxxxxxx. Xxxxx xx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx podávány xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx použity xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo mít xxx použitých úrovních xxxxx toxické xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx experimentu xx měly xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx pro xxx xxxxxxx. X xxxxxxxx aplikace zkoušené xxxxx xx xxxx xxxxxxx kontrolní skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx mikrojádra in xxxx xxx expozičních xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx pozadí. Xxxxx xxxxxxxxx kontroly by xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, ale xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx identifikace xxxxxxxxx. Xx xxxxxxxxxx, aby xxxxxxxxx kontrola xxxx xxxxxxxx jiným způsobem xxx zkoušená látka x aby byl xxxxx x tomto xxxxxxx xxxxxxxx xxx xxxxxx. Pro pozitivní xxxxxxxx xxxxx může xxx xxxxx x xxxxx použití xxxxxxxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx, xxxx-xx x dispozici. Xxxxxxxx xxxxx xxx pozitivní xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx podle 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 xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx je aplikováno xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxx xxxxx podstupuje xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx s xxxxxxxxxx. Xxxxxxx-xx xx xxx negativní kontrolu xxxxx xxxxx, je xxxxxxxxxxxxx okamžikem doba xxxxxxx xxxxxx. Xxxxx xxxx xx měly xxx neexponované xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx dosud xxxx xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx krve xxxx xxx jako xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx x xxxxxxxx xxxxxx x xxxxxxxxx xxxx (xxxx. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, že xxxxxxxx xxxxx budou x rozpětí, xxxxx xx xx základě xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx musí skládat x xxxxxxx pěti xxxxxxxxxxxxxxxx zvířat xxx xxxxx pohlaví (11). Xxxxxxxx xxxx x xxxx studie x xxxxxxxxx xxxxx ze xxxxxx xx stejným xxxxxx x za xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx mezi xxxxxxxxx xxxxxx v xxxxxxxx, bude postačující xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx xx xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx aplikace

Nelze doporučit xxxxx xxxxxxxxxx xxxx (xx. jednu, xxx xxxx xxx aplikace x intervalu 24 xxxxx). Xxxxxx ze xxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxxx xx x xxxxxx xxxxxx xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –x xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx byla prokázána xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxx dávka x xxxxxxxx xxxxxxxxx xx xx xxxxxxxx xxxxxx. Zkoušené xxxxx xxxxx být xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. dvě xxxxx x xxx xxx x rozmezí xx xxxx xxx xxxxxxxx hodin, aby xxxx usnadněno podávání xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx být xxxxxxxx xxxxx xxxxxxx:

x) zkoušená xxxxx xx aplikuje xxxxxxxx jednou. Xxxxxx xxxxxx dřeně xx xxxxxxxx xxxxxxx dvakrát, xxxxxxx xxxxx xxxxx xx provede nejdříve 24 xxxxx po xxxxxxxx a poslední xxxxxxxxxx 48 hodin xx aplikaci a x xxxxxxxxxx xxxxxxxx xxxx xxxxxx. Xxxxx xxxxx xxx 24 xxxxx xx aplikaci xxxx xxx xxxxxxxxx. Xxxxxx xxxxxxxxx krve xx odeberou xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx provede xxxxxxxx 36 xxxxx xx xxxxxxxx a xxxxxxxx nejpozději 72 xxxxx xx xxxxxxxx x xx xxxxxxxxxxxx xx dodrží xxxxxxxxxxxx xxxxxx. Je-li po xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx xxxxx xxxxx;

x) xxxx-xx podávány xxx xxxx více dávek xxxxx (xxxx. xxx xxxx xxxx xxxxx x intervalu 24 xxxxx), xxxx xx xxx xxxxxx xxx xxxxxxx kostní xxxxx xxxxxxxx xxxxxx po 18 xx 24 xxxxxxxx po xxxxxxxx xxxxxxxx a při xxxxxxx periferní xxxx xxxxxx po 36 xx 48 xxxxxxxx xx xxxxxxxx aplikaci (12).

Xxxxx xxxxxxx xxxxx xxx xxxxx xxxxxxx xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx kvůli xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx studie xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, jež xx použijí v xxxxxx xxxxxx (13). X xxxxxxx xxxxxxxx xx xxx první xxxxx xxxxxxx xxx xxxxxx dávky. Xxxx xxxxxx dávky xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx xxxxxx stačí, xxxx bude xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx je xxxxxxxxxx jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že xxxxx xxxxx by xxxxx xxx xxxxxxx režimu xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx být xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx být xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx známky xxxxxxxx (xxxx. xxxxxxx xxxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx x xxxxxxxxx xxxx).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx xxxxxx o xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx xxxx ve xxxx dávkách v xxxxxx xxx nevykazuje xxxxx pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx údajů x xxxxxxx, xxxxx xxxx xxxxxxxx strukturu, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx nezbytnou. X déle trvajících xxxxxx xx xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx než 14xxxxx aplikaci xx xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx obvykle xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx podávání xxxx xxxxxxxxxx x xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx najednou podán xxxxxxxxx xxxxxx nebo xxxxxxxx, závisí xx xxxxxxxxx testovacího xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, musí být xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx obvykle xxx xxxxxxx koncentracích xxxxxxxx zesílené účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx všech xxxxxxxx xxxxx.

1.5.6 Příprava xxxxxx xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx se xxxxxxx získávají x xxxxxx xxxx xxxxx xxxxx xx xxxxxxxx. Xxxxx xx odeberou x xxxxxx xxxx xxxxx x zavedenými xxxxxxxx se xxxxxxxxx x xxxxxx. Xxxxxxxxx xxxx se získává x ocasní žíly xxxx xxxx vhodné xxxxxx xxxx. Krevní xxxxx xx xxxxx xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx xxxxxxxx preparáty xxxxxxxx x poté xx xxxxxx. Xxxxxxxx xxxxxxx xxxxxxxxxxxx pro XXX (např. akridinová xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) se xxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx x xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxx XXX. Xxxx xxxxxx nebrání xxxxxxx xxxxxxxxxxx xxxxxx (např. Xxxxxx). Přídavné systémy (xxxx. xxxxxxxxxx kolona x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx za xxxxxxxxxxx, xx xx xxxxxxxxx odpovídající xxxxxxxxx xxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxx v xxxxxxxxxx.

1.5.7 Analýza

Pro každé xxxxx xx stanoví xxxxx xxxxxxxxx erytrocytů x celkového (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx se x xxxxxxx xxxxxx xxxxx použije xxxxxxx xxxxxxx 200 xxxxxxxxxx x v případě xxxxxxxxx xxxx xxxxxxx 1000 xxxxxxxxxx (17). Xxxxxxx preparáty včetně xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by xxxx být xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxx xxxxxxx 2000 xxxxxxxxx erytrocytů xx xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Další xxxxxxxxx xxxxx být získány xxxxxxxxxx zralých xxxxxxxxxx xx xxxxxx xxxxxxxxxx. Xxx xxxxxxxxxxxxx xxxxxxx xx xxxxx být xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx xxxxx než 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx jsou xxxxxxx exponována nepřetržitě xxxxx týdny xxxx xxxx, lze také xxxxxxxx xx xxxxxx xxxxxxxxxx alespoň 2000 xxxxxxx erytrocytů na xxxxx zvíře. Xxxxxxx xxx automatickou xxxxxxx (xxxxxxx xxxxxx a xxxxxxxxx cytometrická xxxxxxx xxxxxxx suspenze) xxxx xx xxxxxxxxxxxxx zdůvodnění x xxxxxxxx přijatelnými xxxxxxxxxxxxx manuálního hodnocení.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx analyzované xxxxx xx měl xxx xxxxxx xxxxx vyšetřených xxxxxxxxx erytrocytů, počet xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx erytrocytů. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx xxxx déle, xxxx xx xxx xxxx xxxxxxx údaje x xxxxxxx xxxxxxxxxxxx, xxxx-xx shromažďovány. Xxx xxxxx zvíře xx xxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x odpovědi xxxx xxxxxxxxx, xxxxx xxx xxx statistickou xxxxxxx xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního výsledku xxxxxxxx několik kritérií, xxxx. xxxxxx počtu xxxxx s xxxxxxxxxx x závislosti xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x mikrojádry pro xxxxxxx x určitou xxxxxx a x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (18, 19). Statistická významnost xx xxxxxx xxx xxxxxxx určujícím faktorem xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx vyjasněny xxxxxx zkoušením, xxxxxxx x xxxxxxx experimentálních xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx kritéria, xx xxxxxxxx x xxxxx xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx poskytne xxxxx pozitivní xxxx xxxxxxxxx výsledky, v xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx sporné xxx xxxxxx xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx xx mikrojádra xxxxxxxxx, že zkoušená xxxxx xxxxxxxx mikrojádra, xxx jsou xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxx aparátu xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xx xxxxxxxx zkoušky xxxxxxxxxxx mikrojádra v xxxxxxxxx erytrocytech xxxxxxxxxxx xxxxx.

Xxxx xx být xxxxxxxxxxx pravděpodobnost, s xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx do cílové xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

- xxxxxxxxxxx a xxxxxxx zkoušené xxxxx x xxxxxxxxxxxx/xxxxxxxx, je-li xxxxx.

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- počet, stáří x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx zkoušky, včetně xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx a xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxx x xxxxxxxxx x xxxxxxxxx (vehikulum/rozpouštědlo) xxxxxxxx,

- xxxxx ze xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx xxxx xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x přípravě zkoušené xxxxx,

- údaje o xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx způsobu podávání,

- xxxxxxxxx xxxxxx xxxxxxx, xxx xx xxxxxxxx xxxxx xxxxxxx do xxxxxxxx xxxxx nebo xx xxxxxx xxxxx,

- xxxxxxxx xxxxxxxx mezi xxxxxxxxxxx zkoušené látky x krmivu xxxx xxxx (ppm) xx xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a odběru,

- xxxxxx přípravy preparátů,

- xxxxxx xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx buněk xx jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- podíl xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx,

- xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx uvedený xxxxxxxxxx xxx xxxxx zvíře,

- xxxxxxx xxxxxxx ± xxxxxxxxxx odchylka počtu xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxx,

- xxxxx x xxxxxxxx a xxxxxxxxx negativní xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxxx, J. X. (1973), X Xxxxx Xx xxxx Xxxx for Chromozomal Xxxxxx, Xxxxxxxxxx Xxx., 18, 187-190.

2) Xxxxxx, X. (1975), The Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 31, 9-15.

3) Xxxxxx, X. A., Xxxxxxxx, M. F., Xxxx, M., Kirkhart, X., Mavournin, X., XxxXxxxxx, J. X., Xxxxxx, X. X. (1983), The Xxxxxxxxx xx Xxxxxxxxxxx a. x. x Xxxxxxx xx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx. 123, 61-118.

4) Xxxxxxxxx, X. X., Xxxxxx, X. H., Xxxxxx, X. C., Xxxxxxxx, M. X., Xxxxxx, X. A. (1990), Xxx Xx xxxx Micronucleus Xxxxx xx Xxxxxxxxx Xxxx Xxxxxx xxx Xxxxxxxxxx Xxxxx. X xxxxxx xx the U. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 239, 29-80.

5) MacGregor, X. X., Xxxxxxxx, R., Xxxx, W. N., Xxxx, X. X. (1983), Xxxxxxxxxxx in Xxxxxxxxxxx Xxxxxxxxxxxx: A Xxxxx Xxxxxx xxx Xxxxxxxxxxx Xxxxxx During Xxxxxxx Xxxxxxxx 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., Margolin, X. X., Xxxxx, X., Xxxxxxxx, M. F., Xxxx, R. X., Xxxx, D. (1987), Xxxxxxxxxx xxx xxx Xxxxxxx of Xxxxxxxxxxxx Xxxxxx in Mammalian Xxxx Xxxxxx Erythrocytes, Xxxxxxxxxx Xxx., 189, 103-112.

7) MacGregor, X. X., Xxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X. (1990), Xxx xx xxxx Xxxxxxxxxxx Xxxxxxxxxxxx Test: Xxxxxxxxxxx xx Xxxxxx State Xxxxxxxxx Xxxxx Xxxxxxxxxx xxx Xxxxxxx Xxxxxxxxxxx xxxx Xxxxxxxx Xxxxxxx, Xxxxxx. Xxxx. Toxicol. 14, 513-522.

8) Xxxxxxx, X., Xxxxxx, T., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, M. Xx. (1990), The Xxxxxxxxxxxx Assay with Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxxx Xxxxx Acridine Xxxxxx-Xxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 245, 245-249.

9) Xxx Collaborative Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (1992). Xxxxxxxxxxxx Test xxxx Xxxxx Peripheral Blood Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx Xxxxxxxxxx Staining: Xxx Xxxxxxx Xxxxxx xx the 5xx Xxxxxxxxxxxxx Xxxxx xx XXXXX/XXXXX, XXX, Xxxxxxxxxx Xxx., 278, 83-98.

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: Xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxx Xxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx xx Xxxxx) (1995), Protocol xxxxxxxxxxx xxx xxx xxxxx-xxxx xxxxx peripheral xxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, M., Tice, X. X., XxxXxxxxx, X. X., Xxxxxxxx, X., Blackey, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx, Jr. F. X., Pacchicrotti, X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xx vivo Xxxxxx Xxxxxxxxxxx Xxxxxxxxxxxx Assay, Xxxxx. Xxx., 312, 293-304.

12) Higashikuni, N., Xxxxx, X. (1995), Xx xxxxxxx, generalised xxxxxxxx time xx 30 ± 6 x xxxxx xxxxxx xxxxxx xx xxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 313-319.

13) Xxxxxxx, X. X., Xxxxx, J. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Xxxxxx xx British Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Mutagenicity Xxxxxx, Mutagenesis, 7, 313-319.

14) Xxxxxxx, X., Xxxxxx, T., Ishidate, X. Xx. (1983), Xx Xxxxxxxxxxx of Xxxxxxxx Orange Xxxxxxxxxxx Xxxxxxxx xx xxx Xxxxxxxxxxxx Test, Xxxxxxxx Xxx., 120, 241-247.

15) XxxXxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, R. G. (1983), X Xxxxxx Xxxxxxxxxxx Xxxxxxxx Procedure xxx Xxxxxxxxxxx xxx XXX xx Xxxxxxxxxxxx Xxxxx Xxxxxxx 33258 xxx Xxxxxxx Y, Xxxxxxxx Xxx., 120, 269-275.

16) Xxxxxxx, X., Xxxxxxxxxx, C. X. (1989), The xxxxxxxxx xxxx xxxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxx Xxx., 213, 91-104.

17) Xxxxxxxxx, X., McFadden, L. X. (1995), Sample Xxxx for xxx Xxxxxxxxxx of Xxxxxxxxxxxxx xx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxx xx xxx Xxxx Marrow Xxxxxxxxxxxx Xxxx, Mutatation Xxx., 347, 97-99.

18) Richold, X., Ashby, J., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, D. X., Xxxxxxxxx, L. (1990), Xx xxxx Xxxxxxxxxxxx Xxxxx, xx: X. X. Kirkland (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, UKEMS Sub-Committee xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, revised, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Lovell, X. X., Anderson, X., Albanese, X., Xxxxxxxx, X. E., Xxxxx, X., Xxxxxxxx X., Xxxxxxx, M., Xxxxxxxx, X. X., Xxxxxx, X. X. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. J. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Part XXX, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."

XXXXXXX 4X

"X.13/14 XXXXXXXXXX — XXXXXXX XX XXXXXXXX XXXXXX X XXXXXXXXXX

1. XXXXXX

Xxxx metoda xx xxxxxxxx metody XXXX XX 471 — Zkouška na xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx na xxxxxxxx xxxxxx x bakteriemi xx xxxxxxxxx bakteriální xxxxx závislé xx xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Xxxxxxxxxxx coli, x xxxxxxx xxxxxxxx xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, adici x xxxxxx jednoho xxxx xxxxxxxx párů bází XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxx x xxxxxxx xxxxxx, xxxxx xxxxxxxxx xxxxxx xxxxxxxx v xxxxxxxxxxx xxxxxxx x xxxxxxxx tak xxxxxxx xxxxxxxxx bakterií xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx xxxx xxx xxxxxxxxxx růst x xxxxxxxxxxxxx xxxxxxxxxxxx, které xxxx vyžadovány mateřským xxxxxxxxxx kmenem.

Bodové xxxxxx x podobné xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x xxxxxxxx xxxxx xxxxxx x tom, že xxxxxx xxxxxx v xxxxxxxxxx a x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx mají xxxxx xx tvorbě xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx. Xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xx rychlá, xxxxxxxxxx x relativně xxxxxx. Xxxxx testovacích xxxxx xx xxxx xxxxxxxxxx, xxxx nimž xxxx xxxxxxxxxx xx xxxxxxx xxxxxx, včetně xxxxxxxxxxxxx sekvencí XXX xx xxxxxxxxxx místech, xxxxxxx xxxxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx x xxxxxxxxx reparačních xxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxx XXX náchylných x xxxxxx. Xxxxxxxxxxxx xxxxxxxxxxx xxxxx xxxx poskytnout xxxxxxx xxxxxxxx informace x typech mutací, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xx x xxxxxxxxx xxxxx xxxxxxxx databáze xxxxxxxx pro širokou xxxxx xxxxxxxx a xxxx xxxx xxxxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx chemických xxxxx, xxxxxx xxxxxxxx sloučenin, x různými xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx Xxxxxxxxxx typhimurium xxxx Xxxxxxxxxxx xxxx slouží x xxxxxxx xxxxxx x xxxxx vyžadujícím xxxxxxxxxxxxx (histidin xxxx. xxxxxxxxx), přičemž xxxxxx xxxx nezávislý xx xxxxxxx přísunu xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx bází xxxx xxxxxxxx, jež xxxxxxxxx změny x xxxxxx XXX. Při xxxxxxx reverzních mutací xx xxxxx xxxx xxxxx vyskytnout xx xxxxx původní mutace xxxx xxxxx místě xxxxxxxxxxxxx genomu.

Posunové xxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx xxxx xxxxxx jednoho xxxx xxxx xxxx xxxx XXX x posunují xxx xxxxx xxxxx XXX.

1.3 XXXXXXX XXXXX

Xxx xxxxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xx xxxx od buněk xxxxx xxxxxxx, xxxx xxxx xxxxxx, metabolismus, xxxxxxxxxxxx struktura x xxxxxxxxx procesy XXX. Xxxxxxx prováděné xx xxxxx obecně xxxxxxxx xxxxxxx vnějšího zdroje xxxxxxxxxxx aktivace. Xxxxxxxxxxx xxxxxxxxx systémy xx xxxxx xxxxxxx xxxxx xxxxxxxxx podmínky xx xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx o xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx látky xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxx xxx počáteční xxxxxxxxx xxxxxxxxxxx aktivity, x xxxxxxx xxxxxxxx vyvolávající xxxxxx xxxxxx. X xxxxxxxx databáze xxxxxxx, xx xxxxx xxxxxxxxxx xxxxx, xxxxx xxxx x xxxx xxxxxxx xxxxxxxxx, vykazuje xxxxxxxxx xxxxxxxx x v xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx mutagenních xxxxxxxx, xxxxx nejsou detekovány xxxxx xxxxxxxx. Příčiny xxxxxx skutečností lze xxxxxxxxx xx specifické xxxxxx xxxxxxxxxxxxxxxxxxxxx xxxx, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx nebo x xxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx straně faktory, xxxxx xxxxxxx citlivost xxxxxxx xx reverzní xxxxxx na bakteriích, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx aktivity.

Zkouška xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxx xxx xxxxxx xxx xxxxxx xxxxx chemických xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (např. xxxxxx xxxxxxxxxxx) x xxx xxxxxxxx látky, x xxxxx se xxxxxxxxxxx (xxxx o xxxxx se xx), xx xxxxxxxxxx zasahují xx replikačního xxxxxxx xxxxx xxxxx (xxxx. xxxxxxx xxxxxxxxxx topoisomerasy x xxxxxxx analogy xxxxxxxxxx). V xxxxxxxx xxxxxxxxx xxxxx být xxxxxxxxx xxxxxxx xxxxxxxxxx x savců.

Přestože mnoho xxxxxxxxx, xxx něž xx xxxx xxxxxxx xxxxxxxxx, je karcinogenní xxx xxxxx, xxxx xxxxxxxx xxxxxxxxx. Závisí xx xxxxxxxx xxxxx x existuje mnoho xxxxxxxxxxx, xxx nejsou xxxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx jinými, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx buňkách xxxxxxxxxx.

1.4 XXXXXXXX ZKUŠEBNÍ METODY

Suspenze xxxxxxxxxxxxx xxxxx jsou xxxxxxxxx xxxxxxxx xxxxx, x to za xxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému x xxx xxxx. Xx xxxxxxxxxxx miskovém xxxxx xx suspenze xxxxxxxx x xxxxxxx xxxxxx x xxxxx se xxxxxxx xx minimální xxxx. V xxxxxxxxxxxx xxxxxx se zkoušená xxxx inkubuje x xxxx xx xxxx xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx. Xxx xxxx xxxxxxxxxx xx xx dvou xxxx xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx revertantů x provede se xxxxxxxx x xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

Xx popsáno xxxxxxx xxxxxxx xxxxxxxxx xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx. Xxxx xxxxx používané xxxxx xxxxxxxxxx xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), fluktuační xxxx (9, 10) a xxxxxxxxx xxxxxx (11). Xxxxxx pro xxxxxxxx xxxxx a par xxxx xxxxxxx (12).

Xxx xxxxxxx xxxxxxx xx xxxxxx xxxxxx standardního xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Xxxxx x nich xx xxxxxxxxxx xxx provádění xxxxxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Některé xxxxx xxx xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx metody. Tyto xxxxx xxxxx do xxxxxxxxxx xxxx, xx xxxxx xxxxx xxxx xxxxx xxxxxx alifatické xxxxxxxxxxx, xxxxxxxxx xxxx, xxxxxxxx, xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, allylové xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx xxxxxxxxx, xx xxxxxx xxxxx xxxxxxxx xxxxx vždy xxxxxxxxx xxxxxxxxxxxx postupy, xxxx je xxxxxxxxxx xxxxxxx xxxx xxxx xxxxxxxxxxxx metoda. Xxxx xx být xxxxxxxxxx xx "zvláštní xxxxxxx" x x jejich xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Je xxxxx xxxxxxxxxxxxx tyto "zvláštní xxxxxxx" (xxxxxxxx x xxxxxxxx xxxxxxx jejich xxxxxxx): xxxxxxxxxx x xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx xxxxx (12, 14, 15, 16), x glykosidy (17, 18). Xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxx xxx xxxxxxx xxxxxxxxxx.

1.5 XXXXX XXXXXXXX METODY

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx měly xxx xxxxxxxxxxx xx xxxxxx xxxxxxxxxxxxx xxxx xxxx xx časné xxxxxxxxxxx fáze xxxxx (xxxxxxxxx 109 xxxxx xx ml). Buňky x xxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxxx. Je xxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx vysoký xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx xxxx být xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, nebo xxx xxxxxx xxxxxxx stanovením xxxxx životaschopných buněk xx xxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxx xx 37 °X.

Xxxx xx xxx xxxxxxx alespoň pět xxxxx xxxxxxxx. Mezi xxxx xx xxxx xxx xxxxx xxxxx X. typhimurium (XX1535; XX1537 xxxx TA97a xxxx XX97; XX98 x TA100), xxxxxxx xxxxxxx se xxxxxxx x různých laboratořích xxxx xxxxxxxxxx a xxxxxxxxxxxxxxxx. Tyto xxxxx xxxxx S. xxxxxxxxxxx xxxx xxx xxxx XX xx xxxxxxxxx xxxxxxxxx xxxxx a xx xxxxx, že xxxxxx prostřednictvím xxxxx xxxxxxxxx určité xxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx DNA x xxxxxxxxx. Tyto xxxxx mohou xxx xxxxxxxxxx kmeny X. xxxx XX2 xxxx X. xxxxxxxxxxx XX102 (19), xxxxx xxxx xx primárním xxxxxxxxx xxxxx pár xxxx XX. Doporučená xxxxxxxxx xxxxx xx xxxx xxxx:

- X. typhimurium XX1535 x

- X. xxxxxxxxxxx XX1537 xxxx XX97x x

- S. xxxxxxxxxxx XX98 x

- X. typhimurium TA100 x

- X. coli XX2 uvrA, xxxx X. xxxx XX2 xxxX (xXX101), xxxx X. xxxxxxxxxxx TA102.

Pro xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx XXX xxxx xxx vhodnější xxxxxxx TA102 xxxx xxxxxx xxxx X. xxxx s vysokou xxxxxxxxxx reparace XXX, (xxxx. X. xxxx XX2 (xXX101)).

Xxxx xx xxx použity zavedené xxxxxxx přípravy xxxxxxx xxxxxxx, xxxxxxxxxx markeru x skladování. Potřeba xxxxxxxxxxxxx xxx xxxx xx xxxx xxx xxxxxxxxx pro každou xxxxxxxxx kmenovou kulturu (xxxxxxxx xxx xxxxx X. xxxxxxxxxxx x xxxxxxxxx xxx X. xxxx). Podobně xx xxxx xxx xxxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxxxx podle xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, XX100 x TA97a xxxx XX97, XX2 uvrA x XX2 uvrA (xXX101) a xxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxx x kmene XX102), xxxxxxxxxx charakteristických xxxxxx (xx. rfa mutací x S. xxxxxxxxxxx xxxxxxxxxx xx krystalovou xxxxxx x uvrA xxxxxx x X. xxxx xxxx xxxX xxxxxx x X. xxxxxxxxxxx citlivostí na xxxxxxxxxxxx xxxxxx) (2, 3). Kmeny xx xxxx rovněž xxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx na xxxxx x xxxxxxx četností xxxxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx a nejlépe x xxxxxxx xxxxxxxx x literatuře.

1.5.1.2 Xxxxxx

Xxxxxxx xx vhodný minimální xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx E (Xxxxx-Xxxxxx) x glukosu) x vrchní agar xxxxxxxxxx histidin a xxxxxx xxxx tryptofan xxxxxxxxxx několik buněčných xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx měly být xxxxxxxxx xxxxxxxx látce, x to x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx hlodavců xxxxxxxxxx xxxxxxxxxxx indukujícím xxxxxx, xxxx xx Xxxxxxx 1254 (1, 2) xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx xxxxxx xx xxxxxxx xxxxxxxxx x koncentracích x xxxxxxx 5 xx 30 % xxx. xx xxxxx X9. Xxxxx x podmínky xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx xxxxxxx xx xxxxx zkoušené xxxxxxxx xxxxx. V xxxxxxxxx xxxxxxxxx může být xxxxxx použít xxxx xxx xxxxx koncentraci xxxxxxxxxxxxxxxxxxx frakce. U xxxxxxxxx a diazoniových xxxxxxxxx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému (6, 13).

1.5.1.4 Zkoušená xxxxx xxxx přípravek

Pevné xxxxxxxx xxxxx xx xxxx být xxxx xxxxxxxx xx bakterie xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky mohou xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx xxxxxxxxx, xx reaguje xx xxxxxxxxx xxxxxx, a xxxx by xxx xxxxxxxxxx s přežitím xxxxxxxx x x xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx xxxx xxx známá rozpouštědla/vehikula, xxxx by být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje se xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx zkoušení xxxxx xxxxxxxxx xx xxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx vodu.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Xxxxxxxx xxxxx (viz 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx mají xxx xxxxxxxxxx při xxxxxxxxx xxxxxxxxxx xxxxxxxx zkoušené xxxxx xxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx být užitečné xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx v předběžných xxxxxxxxxxxxx. Cytotoxicita xxxx xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx revertantů, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx xx xxxx xxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx xx xxxx xxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxxx směsi xx skutečných xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx zkušební xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx xx 5 xx/xxxxx nebo 5 μx/xxxxx. U xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx by xxxx xxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, xxx látky xxxx x xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx jsou xxxxxxxxxxx xxx při xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, by xxxx xxx xxxxxxxx xx xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

Mělo xx být xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, přičemž xxx xxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx xxxx xxxxxxxxxx body xxxxx přibližně polovině xxxxx logaritmické xxxxxxxx (xx. Ö10). Menší xxxxxxxxx xxxx xxxxxx x xxxxxxx, xxx xx vyšetřuje křivka xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Xxxxxxxx koncentrací xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx být xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx x negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx x metabolickou xxxxxxxx x xxx xx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx účinnost xxxxx xxxxxxx.

X xxxxxxx xxxxxxx x xxxxxxxx metabolického xxxxxxxxxxx systému xx xxxx být xxxxx (xxxxx) xxx pozitivní xxxxxxxx xxxxxxx (xxxxxxx) xx xxxxxxx typu xxxxxxxxx xxxxx xxxxxxxx.

Xxxxxxxxx xxxxxx xxxxxxxxx kontroly x xxxxxxx x xxxxxxxxxxxx aktivací jsou xxxx látky:

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Tato xxxxx xx vhodnou xxxxxxxxx kontrolou pro xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

XX Xxxxxx Xxx 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx by xxxxx xxx použit xxxx xxxxxx indikátor xxxxxxxxx xxxxx X9. Xxx xxxxxxx 2-xxxxxxxxxxxxxxx by xxxx xxx každá xxxxx S9 charakterizována xxxxxxxxx, který xxxxxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

Xxxxxxxxx kmenověspecifické xxxxxxxxx xxxxxxxx x xxxxxxx xxx xxxxxx xxxxxxxxxxx xxxxxxxx xxxx xxxx xxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxxx

xxxx sodný

26628–22–8

247–852–1

TA1535 x TA100

2-nitrofluoren

607–57–8

210–138–5

TA98

9-aminoakridin

90–45–9

201–995–6

TA1537, TA97 x TA97a

ICR 191

17070–45–0

241–129–4

TA1537, XX97 a TA97a

Kumenhydroperoxid

80–15–9

201–254–7

TA102

mitomycin X

50–07–7

200–008–6

XX2xxxX x XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 xxxX x XX2 xxxX (pKM101)

4-nitrochinolin-1-oxid

56–57–5

200–281–1

WP2, XX2 xxxX x XX2 xxxX (xXX101)

α-[(5-xxxxx-2-xxxxx)xxxxxxxxxx]xxxxx-2-xxxxxxxx (XX2)

3688–53–7

xxxxx xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx x úvahu xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou xx x xxxxxxxxx.

Xxxx by xxx použity negativní xxxxxxxx xxxxxxxxxx se xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx způsobem xxxx xxxxxxxxxx skupiny. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx prokazující, xx zvolené xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní účinky.

1.5.3 Xxxxxx

X xxxxxxxxxx xxxxxxx xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx xxxxxxxx se xxxxxxx smíchá 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 ml xxxxxxx xxxxxxxxxxx kultury (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x 0,5 xx sterilního pufru x 2,0 ml xxxxxxxx xxxxx. X xxxxxxx zkoušky x xxxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,5 xx xxxxxxxxxxx aktivační xxxxx xxxxxxxxxx přiměřené xxxxxxxx postmitochondriální xxxxxx (x xxxxxxx 5 xx 30 % xxx. v metabolické xxxxxxxxx xxxxx) x xxxxxxx agarem (2,0 xx) a xxxxxxx x bakteriemi x xxxxxxxxx xxxxxx nebo xxxxxxxxx xxxxxxxx. Xxxxx xxxxx xxxxxxxx xx xxxxxxxx a xxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx xxxxx. Xxxx xxxxxxxx xx xxxxx xxxxxx xxxx xxxxxxxx.

X preinkubační xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx nebo xxxxxxxx xxxxxx xxxx xxxxxxxxx x xxxxxxx xxxxxx x xxxxxxxx xxxx xxxxxx xxxxxxxxxxx agaru xx xxxxx xxxxxxx 20 xxxxx xxxx xxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxx (obsahujícím xxxxxxxxx 108 životaschopných xxxxx) x sterilním xxxxxx xxxx xxxxxxxxxxxx xxxxxxxxxx systémem (0,5 xx) xxx 30 — 37 °X. Xxxxxxx xx xxxxxx 0,05 nebo 0,1 xx zkoušené látky xxxx xxxxxxxxxx roztoku, 0,1 xx xxxxxxxx x 0,5 ml xxxxx X9 xxxx xxxxxxxxxx pufru x 2,0 xx xxxxxxxx xxxxx. Zkumavky by xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx xxxxxxxx by xxxx xxx při xxxxx xxxxxx xxxxx použity 3 xxxxx. Xxxxxxx xxxx xxxxx xx xxxxxxxxxx po vědeckém xxxxxxxxxx. Xxxxxxxx ztráta xxxxx nemusí znamenat xxxxxxxxxxxx zkoušky.

Plynné xxxx xxxxxx xxxxx xx xxxx xxx xxxxxxxx xxxxxxxx metodami, např. x xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (12, 14, 15, 16).

1.5.4 Xxxxxxxx

Xxxxxxx xxxxx x xxxx xxxxxxx by xxxx být xxxxxxxxxx xxx 37 °X xx 48 –72 xxxxxxxx. Xx xxxxxxxx xxxxxxxxx doby xx xxxxxx počet xxxxxxx xxxxxxxxxx xx xxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxx xxxxx xx xxxx xxx xxxxx kolonií xxxxxxxxxx xxxxxxxxxxx na xxxxx. Xxx xx xxx xxxxxx uveden xxxxx xxxxxxx revertantů xxx xx miskách x negativní xxxxxxxxx (xxxxxxxx rozpouštědla x xxxxxxxx xxxxxxxxxxxx xxxxxxxx), xxx na miskách x xxxxxxxxx kontrolou. Xxxxx xx xxxxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxx xxxxx kolonií xxxxxxxxxx xx misku a xxxxxxxxxx xxxxxxxx by xxxx xxx předloženy xxx xxxxxxxxx látku x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx nepožaduje. Xxxxxxxxxx výsledky by xxxx být xxxxxxxxx xxxxxx zkoušením, nejlépe x xxxxxxx experimentálních xxxxxxxx. Negativní xxxxxxxx xxxx xxx potvrzeny xxxxxx xx xxxxxxx. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx nepovažuje xx xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx rozsah posuzovaných xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx studie, xxxxx xx xxxxx být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx zpracování (xxxxxxxxxx xxxxxxx xxxxxx xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) a xxxxxxxx metabolické xxxxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx misku xxx xxxxxxxxx xxxxxx x xxxxxxx jednoho xxxxx x metabolickým aktivačním xxxxxxxx xxxx bez xxxx, x to x závislosti xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx tohoto počtu xxx xxxxx nebo xxxx xxxxxxxxxxx (23). Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx významnost by xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxxxx xxxxx, xxxxx výsledky xxxxxxxxx xxxx uvedená xxxxxxxx, xx považuje v xxxxx systému za xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx negativní xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx to, kolikrát xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx znamenají, xx xxxxxxxx látka indukuje x genomu kmenů Xxxxxxxxxx xxxxxxxxxxx a/nebo Xxxxxxxxxxx xxxx xxxxxx xxxxxx xxxxxxxxxx xxxx xxxx xxxxxxx xxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxx xx xxxxxxxx xxxxxxx xxx xxxxxxxxx druhy mutagenní.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x zkoušce musí xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

- xxxxxxxxxxx x xxxxxxx xxxxxxxx xxxxx v xxxxxxxxxxxx/xxxxxxxx, je-li xxxxx.

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx v kultuře,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxx xxxxxxxx látky xx xxxxx (mg/misku xxxx μl/misku) s xxxxxxxxxxx výběru xxxxx x xxxxx misek xx xxxxxxxxxxx,

- xxxxxxx xxxxx,

- typ a xxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, xxxxxx kritérií xxxxxxxxxxxxx,

- xxxxxx expozice.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- počty xx xxxxxxxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx odchylka,

- xxxxx možnosti xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx statistické analýzy,

- xxxxx x xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) a xxxxxxxxx xxxxxxxx s xxxxxxxxx, středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Ames, X. X., XxXxxx, X., Yamasaki X. (1975), Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx with xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 31, 347-364.

2) Xxxxx, X. X., Ames, B. X. (1983), Xxxxxxx Xxxxxxx xxx the Xxxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Res., 113, 173-215.

3) Gatehouse, D., Xxxxxxx, S., Cebula, X., Xxxxx, X., Xxxx, L., Xxxxxxxxxx, X., Melcion, X., Xxxxx, T., Xxxxxx, X., Zeiger, X. (1994), Xxxxxxxxxxxxxxx xxx xxx Performance of Xxxxxxxxx Mutation Assays, Xxxxxxxxxx Xxx., 312, 217-233.

4) Xxxx, X. X., Brusick X. X., Xxxxxxx, X. X., Xxx Xxxxx, X. X., Brown, X. M., Simmon, X. F., Dunkel, X., McCann, J., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, T. X., Xxx X. (1986), The Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Assay: X Report xx xxx X. S. Xxxxxxxxxxxxx Protection Agency Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, T., Xxxxxx, X., Seino, Y. X., Xxxxxxxxxx, X., Xxxxx, M., Sugimura, X., Xxxxxxxxx, X. (1975), Xxxxxxxxxxxx xx Xxxxxxxxxx Xxx Xxxx xxx xxxxx Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

6) Xxxxxxxxxx, X., Xxxxxxxx, T., Xxxxx, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Microbial Xxxxx, xx: Short-term Xxxx Xxxxxxx xxx Xxxxxxxxx Carcinogens, xx. Xxxxxxx X. H., Xxxxxx, X. C., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

7) Gatehouse, D. X., Rowland, X. X., Xxxxxx, X., Xxxxxxxxx, R. X., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Xxxxxx, xx: Xxxxx Mutagenicity Xxxxx: XXXXX Part 1 Xxxxxxx, xx. X. X. Xxxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, 13-61.

8) Xxxxxxxxxx, X. X., Xxxxxx, U., Xxxxxxx, X. (1987), Xxxxxx Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxx xxx Foods, X. Food Safety., 8, 167-177.

9) Xxxxx, X. X. X., Xxxxxx, X. X., Xxxxxxx, X. X. (1976), Use of x xxxxxxxxxx fluctuation xxxx xx xxxxxx xxx xxxxxx xx xxxxxxxx, Xxxxxxxxxx Xxx., 38, 33-42.

10) Xxxxxxx, X. X., Green, X. X. L., Xxxxxxxxx, X., Xxxxxxx, X. X. (1984), Xxx Xxxxxxxxxxx Xxxx xx Bacteria, xx: Xxxxxxxx xx Mutagenicity Xxxx Xxxxxxxxxx, 2. xxx., Xxxxxx, X. X., Legator, X., Xxxxxxx, X., Ramel, X. (eds.), Xxxxxxxx, Xxxxxxxxx-Xxx York-Oxford, 141-161.

11) Xxxxxxxx, X. X., Xxxxxxx, X. X. (1981), An Xxxxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxxx Xxxxx for Xxxxxxxxxxx with Xxxxxxx xx Xxxxxxxxxx typhimurium, Xxxxxxxxxxxxx Mutagenesis, 3, 453-465.

12) Xxxxx, X., Xxxxxxx, X., Xxxx, X., Xxxxxxxxxx, T. (1994), Xxxxxxxx Method xxx Mutagenicity Testing xx Gaseous Xxxxxxxxx xx Using a Xxx Sampling Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

13) Xxxxxx, M. X., Bell, X. X., Xxxxxxxx, V. X., Xxxxxxx, X. X., Xxxxxxx, X. X. (1984), Xxxxxxxxxxxx xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Monoazo Xxxx xx x Xxxxxxxx Xxxxxxxxxx Assay, Mutatation Xxx., 136, 33-47.

14) Xxxxxx, X., Anderson, X. X., Xxxxxxx, X., Xxxxxx, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Tests. X. Xxxxxxx from xxx Xxxxxxx xx 311 Chemicals, Environ. Xxx. Xxxxxxx., 19, 2-141.

15) Xxxxxx, V., Xxxxxxxx, X., Tardiff, X. G. (1977), Xxxxxxxxx Xxxxxxxx of Xxxxxxxxx Identified xx Xxxxxxxx Xxxxx, in Xxxxxxxx xx Xxxxxxx Xxxxxxxxxx, D. Xxxxx, X. Xxxxxxx, F. Xxxxxx (xxx.) Xxxxxxxx, Xxxxxxxxx, 249-258.

16) Hughes, X. J., Xxxxxxx, X. X., Monteith, X. X., Xxxxxxx, X. D. (1987), Xxxxxxxxxxxx Xxxxxxxxx xx Xxxxxxx Xxxxxxxxx Activity xx Volatile Xxxxxxx Xxxxxxxxx in xxx Xxxx/Xxxxxxxxxx Assay, Environmental Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, T., Xxxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx xxx Naturally Xxxxxxxxx Carcinogen Cycasin xxx Synthetic Methylazoxy Xxxxxxx Conjugates in Xxxxxxxxxx typhimurium, Xxxxxx Xxx., 39, 3780-3782.

18) Xxxxxx, G., Gold, X., Ferro-Luzzi, A., Xxxx, B. X. (1980), Xxxxxxxx: X Xxxxx for Xxxxxxxxxx xx Xxxxxxx Xxxxxxxxxx xx Xxxxxxxx xx Xxxxxxxxxx Xxxxx, Xxxx. Xxxx. Acad. Sci. X. S. X, 77, 4961-4965.

19) Xxxxxx, X., Naidoo, A., Xxxx, D. X., Xxxxxxxxx, X. G. (1990), Comparison of Xxxxxxxxxx xxxxxxxxxxx TA 102 xxxx Escherichia xxxx XX2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Xxxxxxxxxx, T., Xxxxxxxx, X., Hara, X., Sugimura, X. (1976), X Xxxx Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx a. x. xx Inducer xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: Xx vitro Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, eds. X. X. de Xxxxxx et al. Xxxxxxxx, North Xxxxxxx, 85-88.

21) Elliot, X. X., Combes, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Alternatives xx Xxxxxxx 1254-xxxxxxx X9 xx xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, X., Xxxxxxxxxxxxxxxx, X., Xxxx, B. X. (1981), Xxxxxxxxxxxxx xx Organic Solvents xxxx xxx Salmonella/Microsome Xxxx, Mutatation Xxx., 88, 343-350.

23) Claxton, X. X., Xxxxx, X., Auletta, X., Xxxxxxxxxx, K., Nestmann, X., Xxxxxx, X. (1987), Xxxxx xxx xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Tests xxx Xxxxxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, G. A. X., Green, X. X. X., Middleton, X., Mitchel, I., Xxxxxxxx, X. D., Xxxxxx, D. X. (1989), Xxxxxxxx xx Xxxx xxxx Xxxxxxxxx Xxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Part XX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxx, xx. Xxxxxxxx, D. X., Cambridge Xxxxxxxxxx Xxxxx, 28-65."

XXXXXXX 4X

"X.17 MUTAGENITA — XXXXXXX XX XXXXXX XXXXXX X XXXXXXX XXXXX XX XXXXX

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX XX 476 — Zkouška na xxxxxx xxxxxx x xxxxxxx xxxxx in xxxxx (1997).

1.1 XXXX

Xxxxxxx xx genové mutace x xxxxxxx xxxxx xx xxxxx xxx xxxxxx xxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxx. Mezi xxxxxx xxxxxxx xxxxx xxxxx xxxxx xxxxxxx X5178X myší, xxxxxxx xxxxx CHO, XXX-XX52 x X79 xxxxxx xxxxxxxx x lymfoblastoidní xxxxx XX6 xxxxxxx (1). U těchto xxxxxxxxx xxxxx jsou xxxxxxxxxxxxxxx xxxxx genetických xxxxxx xxxxxx xxxx xxx xxxxxxxxxxxxxx (TK) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (HPRT) x xxxxxxxx xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx na xxxxxx TK, HPRT x XPRT xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Autosomální xxxxxx XX a XPRT xxxx xxxxxxx xxxxxxx xxxxxxxxxxx událostí (xxxx. xxxxxxxx xxxxxx), xxxxx xxxxx xxxxxxxxx x XXXX xxxxxx xx X chromozomech (2, 3, 4, 5, 6).

Xx zkoušce xx xxxxxx xxxxxx x xxxxxxx savců in xxxxx xxx xxxxxx xxxxxxx zavedených xxxxx xxxxx xxxx xxxxxxx xxxxx. Buňky xx xxxxxxxx podle xxxxxxxxxx xxxxx v xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx vitro xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx nemůže zcela xxxxxxxxx xxxxxxxx in xxxx u xxxxx. Xx xxxxx xx xxxxx vyvarovat podmínek, xxxxx by xxxxx x pozitivním xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx neodrážejí xxxxxxx xxxxxxxxxx, může xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx a karcinogenů xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx zkouška xxxxxxxxx, xxxx karcinogeny xxxxx; xxxx touto xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx absolutní korelace. Xxxxxxxx xxxxxx xx xxxxxxxx třídě a xxxxxxxxx důkazy o xxx, že xxxxxxxx xxxxxxxxxxx, xxxxx nejsou xxxxxxxx touto xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, které x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx (6).

Xxx také xxxxxx xxxx, část X.

1.2 DEFINICE

Přímá xxxxxx : xxxxxx xxxxxx xxxxxxxxx typu xxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxx nebo xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx : xxxxx, xxxxx xxxxxxxxx substituci xxxxxxx nebo xxxx xxxx xxxx x XXX.

Xxxxxxxx xxxxxxxx : xxxxx, xxxxx způsobují xxxxx nebo xxxxxx xxxxxxx xxxx xxxx xxxx xxxx v xxxxxxxx XXX.

Xxxx xxxxxxx xxxxxxxx : xxxx, xxxxx níž xxxxxx x nově xxxxxxxxxx xxxxx nezměněné genové xxxxxxxx.

Xxxxxxx xxxxxxx : xxxxx xxxxxxxxxxxx mutantních xxxxx xxxxxx xxxxxx xxxxxxxxxxxxxxx buněk.

Relativní xxxxxxx xxxx : xxxxxx xxxxx xxxxx x xxxx xx xxxxxxxx x xxxxxxxxx populací xxxxx; xxxxxxx se xxxx xxxxxx xxxxxx xxxxxxxxx růstu v xxxxxxxx x x xxxxxxxxx xxxxxxxx a xxxxxxxxx účinnosti xxxxxxxxx xxxxxxxx x negativní xxxxxxxx.

Xxxxxxxxx xxxx x xxxxxxxx : xxxxxx xxxxx xxxxx x xxxxxxx xxxxxxx xxxxxxxx x negativní xxxxxxxx.

Xxxxxxxxxxxxxxx : xxxxxxxx xxxxxxxxx xxxxx v xxxxxxxx xxxxxxxx xx misku xx selektivních podmínek xx expresi.

Přežití : xxxxxxxx klonování xxxxx xxx xxxxxxxx xx xxxxx na xxxxx xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx vyjádřeno x poměru k xxxxxxx xxxxxxxxx populace xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx XX+/-® XX— /- neobsahují xxxxxxxxxxxxxx (XX) xxxx xxxxxxxxxxx x cytotoxickým xxxxxxx xxxxxxx pyrimidinu xxxxxxxxxxxxxxxxx (XXX). Xxxxx xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx na XXX, xxx xxxxxxxxx inhibici xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxx buněčné xxxxxx. Xxxxxxxx xxxxx xxxx xxxx schopny xxxxxxxxxxx xx přítomnosti XXX, xxxxxxx xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxxxxxxx tuto schopnost xxxxxx. Xxxxxxx lze x buněk s xxxxxxxxxxxx HPRT xxxx XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx k 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (AG). Vlastnosti xxxxxxxx xxxxx xx xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx je xx zkoušce xx xxxxxx xxxxxx x xxxxxxx xxxxx zkoušen xxxxxx xxxx xxxx xxxxxxxxxx podobná selekčnímu xxxxxxx. Xxxx by xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx pro xxxxxxxx xxxx xxxxxxxxxx buňky. Xxx xxxxxxxx chemických xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx jako xxxxxxxx činidlo, xxxx xxxx xxx xxxxxxxxx xxxxxxxx systému xxxx xxxxxxx xxx selekci (8).

Xxxxx v suspenzní xxxx xxxxxxxxxxxxx kultuře xxxx vhodnou xxxx xxxxxxxxx xxxxxxxx látce xxx x xxxxxxxxxxxx xxxxxxxx, tak xxx xx, a xxxxxxxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxxxxxxx a xx xxxxxx xxxxxxx xxxxxxxx xxxx selekcí xxxxxxx (9, 10, 11, 12, 13). Cytotoxicita xx obvykle xxxxxx xxxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxx relativního xxxxxxxxx xxxxx xxxxxx po xxxxxxxx doby xxxxxxxx. Xxxxxxxxxx kultury xx xxxxxxx v xxxxxxxx xxxxx po xxxxxxx xxxx xxxxxxxxxxxxxxxxx xxx xxxxx zvolený xxxxx x xxx buněk, xxx nastala xxxxxxxxx xxxxxxxxx xxxxxxxxxx exprese xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx se stanoví xxx, xx se xxxxxx xxxxx počet xxxxx xx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx detekci mutantních xxxxx x xx xxxxx xxx xxxxxxxxxx xxxxxxx, aby xxxx xxxxxxxxx účinnost klonování (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx době xx xxxxxxxxx kolonie. Xxxxxxx xxxxxxx se xxxxxxx x xxxxx xxxxxxxxxx xxxxxxx x xxxxxxxxx xxxxx x xxxxx xxxxxxx x xxxxx xxx xxxxxxxxxx činidla.

1.4 XXXXX ZKUŠEBNÍ METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Pro xxxxxxx x xxxx zkoušce xxxx x dispozici xxxxx typy xxxxx, xxxxxx subklonů buněk X5171X, XXX, CHO-AS52, X79 xxxx XX6. Xxxx xxxxx x xxxx xxxxxxx by xxxx vykazovat xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxx klonovací xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxxxxxxxx mutací. Buňky xx xxxx být xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, x x xxxxxxx kontaminace xx neměly xxx xxxxxxx.

Xxxxxxx xx měly xxx navrženy tak, xxx xxxx předem xxxxxxxxxx xxxxxxxxx x xxxx. Počet xxxxxxxxx xxxxx, xxxxxx x xxxxxxxxxxx xxxxxxxx xxxxx xx měl xxxx xxxxxxxxxx xxxxxxxxx odrážet (14). Xxxxxxxxx xxxxx xxxxx, xxxxx přežijí xxxxxxxx x xxxxx xxxxx xxxxxxx v xxxxxx xxxxxx xxxxxxx, xx měl xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx xx, aby xxx xxxxxx xxxxx xxxxx, xxxxx xx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx však xxxxxxxxxx, xxx xxxx použito xxxxxxx 106 buněk. Xxxx xx být x dispozici xxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx systému, xxx xxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx měla xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx podmínky (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x vlhkost). Xxxxx xx xxxx xxx zvolena xxxxx xxxxxxxxxx xxxxxxx a xxxx xxxxx použitých xxx xxxxxxx. Xx xxxxxxx důležité, xxx xxxxxxxxxx xxxxxxxx byly xxxxxxx xxx, xxx xxxx xxxxxxxxx xxxxxxxxx xxxx xxxxx xxxxx xxxxxx exprese a xxxxxxxxx jak xxxxxxxxxx, xxx xxxxxxxxxxxx xxxxx xxxxxx kolonie.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx by měly xxx získávány x xxxxxxxxx xxxxxx, xxxxxxxx xx kultivačního xxxxx x inkubovány při 37 °C. Xxxx xxxxxxxx x této xxxxxxx xxxx být xxxxxxxx xxxxxxxxx z xxxxxxx xxx přítomné xxxxxxxx xxxxx.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x vhodným xxxxxxxx xxxxxxxxxxx aktivace x xxx xxxx. Nejčastěji xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx dotovaná xxxxxxxxxxxxxxxxxxx xxxxxx (S9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (15, 16, 17 a 18), xxxx směs xxxxxxxxxxxxx a β-naftoflavonu (19, 20).

Postmitochondriální frakce xx x konečném xxxxxxxxxx médiu xxxxxxx xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % xxx. Xxxxx x stav metabolického xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx vhodné xxxxxx xxxx než jednu xxxxxxxxxxx postmitochondriální frakce.

Řada xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx linií xxxxxxxxxxxxx xxxxxxxxxx aktivační xxxxxx, xxxxxxxxx možnosti xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx linií xx xxxx být xxxxxxx zdůvodněna (např. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 pro metabolismus xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx měly xxx před aplikací xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx přímo k xxxxxxxxxx systémům x/xxxx xxxxx xxx xxxx xxxxxxxx zředěny. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx mělo xxx xxxx podezření, xx xxxxxxx se xxxxxxxxx xxxxxx, a xxxx xx xxx xxxxxxxxxx x xxxxxxxx buněk x x xxxxxxxxx X9. Xxxx-xx použita xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, mělo by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx látek xxxxxxxxx xx xxxx by xxxx xxx xxxxxxx xxxxxxxxx rozpouštědla xxxxxxxxxxxx xxxx. Vodu lze xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx cytotoxicita, xxxxxxxxxxx x xxxxxxxxxx systému x xxxxx xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x bez ní x xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x růstu, xxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxx celkový xxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx alespoň čtyři xxxxxxxxxxxxxx xxxxxxxxxxx. V xxxxxxx toxicity xx xxxx xxxx xxxxxxxxxxx xxxxxxxx rozmezí xxxx xxxxxxxxx x minimální xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx, že xx xx xxxxxxxxxxx xxxx xxxxx faktorem 2 xx Ö10. Xx-xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx, xxxx xx xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx klonování) xxxx xxxxxxxxx xxxxxxx xxxx. X xxxxxxx relativně xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx toho, která x xxxx xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxx až k xxxx rozpustnosti xx xxxxxxxxxxxx xxxxxxxx, xxxx xx xx xxxx xxx. Xxxx by xxx stanovena xxxxxxxx xxxxxxxxxxxxx x konečném xxxxx, xx xxxxxxx xxxx xxxxx xxxxxxxxxx. Xxxx xxx výhodné xxxxxxxx xxxxxxxxxxx na xxxxxxx a na xxxxx xxxxxxxx, neboť xxxxxxxxxxx xx xxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx systému xxxxx v xxxxxxxx xxxxxxxxxxx buněk, X9 xxxx, xxx. Nerozpustnost xxx zjistit xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx nebo vehikulum) xxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Při xxxxxxx metabolické aktivace xx měla xxx xxxxxxxxx kontrolou xxxxxxxx xxxxx, xxxxx x xxxxxxxxx odpovědi xxxxxxxx xxxxxxxx.

Xxxxxxxxx pozitivní xxxxxxxx xxxxx být tyto xxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Einecs

Bez xxxxxx xxxxxxxxxxx xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx x xxxxx 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 x xxxxx xxxxxxx)

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxx[x]xxxxx

50–32–8

200–028–5

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–5

XXXX

X-xxxxxxxxxxxxxxxxxxx (xxx 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, EINECS 200–415–9), xxxx xxx xxxx referenční látka xxxxxx použita. Xxx xxxxxxxxx xxxxxxxx xx xxxx být xxxxx x xxxxx xxxxxxx xxxxxxxxxx látek xxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx.

Xxxx by xxx xxxxxxx negativní xxxxxxxx tvořené xxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx vehikulum a xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx exponované xxxxxxx. Kromě toho xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx 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 xxxxxxxx látce xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx xx xxxx xxxxx xxxxxxx xxxx (xxxxxxx je xxxxxx xxxx 3 xx 6 xxxxx). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx na xxxxx xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx zkušební xxxxxxxxxxx mohou xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxx jedna exponovaná xxxxxxx. Xx-xx použita xxxxx xxxxxxx, měl xx xxx počet xxxxxxxxxxx zvýšen xxx, xxx xxx xxxxxxxx xxxxxxxxxxxx počet xxxxxx xxx xxxxxxx (např. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx by xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx xxxxxxxxxxxx).

Xxxxxx xxxx xxxxxx látky by xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, např. x xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Stanovení xxxxxxx, xxxxxxxxxxxxxxxx x četnosti xxxxxx

Xx konci xxxxxxxxx xxxx se xxxxx xxxxxxx a xxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxx x xx xxxxxx umožnění xxxxxxx xxxxxxxx xxxxxxx. Xx xxxxxxxxxx cytotoxicity xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxx xxxxxxx xx expoziční xxxx.

Xxxxx lokus xx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, aby umožnil xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx nově xxxxxxxxxxxx xxxxxxx (XXXX a XXXX vyžadují xxxxxxx 6 xx 8 xxx, XX xxxxxxx xxx dny). Xxxxx xxxx kultivovány x xxxxx xx xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxxx) x xxx něho (xxx xxxx) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx x klonovací xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx xxxxxxxx mutantů) xx xxxxxxx na xxxxx xxxx xxxxxxx xxxxxxxxx na misku xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx látka pozitivní xx xxxxxxx L5178Y XX+/-, xxxx xx xxx xxxxxxxxx xxxxxxx xx xxxxx xx xxxxxxxxxx kultur (s xxxxxxxx pozitivní xxxxxxxxxxx) x xx xxxxxxxxxxx x xxxxxxxxxxx kontrolách xxxxxxxxx xxxxxxx podle xxxxxxxxx kolonií. Xx-xx xxxxxxxx xxxxx xx xxxxxxx X5178X XX+/- xxxxxxxxx, mělo xx xxx rozdělení xxxxxxx xxxxx xxxxxxxxx kolonií xxxxxxxxx xx negativních x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx XX6 TK+/- xxxx xxx xxxx xxxxxxxxx xxxxxxxxx kultury xxxxx velikosti xxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xx xxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x xxxxxxxx xxxxxxx xxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. X xxxxxxx pozitivní xxxxxxxx xx xxxxxxx L5178Y XX+/- xx xxxxxxx xxxxxxxxx xxxxxxx x xxxxx xxxxxxxxxxx xxxxxxxx xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x x xxxxxxxxx x xxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxx xxxxxxx — velká xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx jak mutantů xxxxxxxxx xxxxx xxxxxxx, xxx xxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxxxx zkoumána (23, 24). Xx xxxxxxx XX+/- xxxx kolonie xxxxxxxxxxx xx použití xxxxxxxx kolonie s xxxxxxxxx xxxxxx (velká) x xxxxxxx s xxxxxxx xxxxxx (malá) (25). X mutantních xxxxx, které xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx doby xxxxxxxx, x xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx xx xxxxx xxxxxx genu až xx karyotypické xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Indukce xxxxxxx tvořících malé xxxxxxx xx spojuje x xxxxxxxxxx xxxxxxx, xxxxx indukují xxxxx xxxxxxxxxxxx aberace (26). Xxxx závažně postižené xxxxx xxxxxxx rostou xxxxxxxx xxxxxx jako xxxxxxxx xxxxx a xxxxx xxxxx kolonie.

Mělo xx xxx xxxxx xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx růst. Xxxxxxx xxxxxxx xx xxxx xxx vyjádřena jako xxxxx mutantů x xxxxx xxxxxxxxxx xxxxx.

Xxxx xx xxx uvedeny xxxxx pro xxxxxxxxxx xxxxxxx. Xxxx xx xxxx být xxxxxxx xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Xxxxxxxxxx výsledky xx měly být xxxxxxxxx dalším zkoušením, xxxxxxx s xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx musí být xxxxxxxxx případ od xxxxxxx. Tam, kde xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx za xxxxx, je xxxxx xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx s xxxxx xxxxxxxx rozsah xxxxxxxxxxxx xxxxxxxx xx xxxx xxx zvážena x následných experimentech xxx pro xxxxxxxxxx xxxxxxxx, xxx pro xxxxxxxxx xxxxxxxx. K xxxxxxxxxx studie, xxxxx xx xxxxx být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx a podmínky xxxxxxxxxxx xxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst četností xxxxxxx v závislosti xx koncentraci, nebo xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Nejdříve xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď.

Zkoušená xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx x xxxxx xxxxxxx považuje xx xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx experiment opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx savců xx xxxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x použitých xxxxxxxxxxxxx xxxxxxx savců genové xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx je xxxxx xxxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx zkoušená xxxxx za podmínek xxxxxxx neindukuje x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

- xxxxxxxxxxx a stálost xxxxxxxx látky v xxxxxxxxxxxx/xxxxxxxx, xx-xx známa.

Buňky:

- xxx x zdroj xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- xxxxxxxx počet xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx buněčné kultury,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxxx výběru xxxxxxxxxxx x xxxxx xxxxxx, xxxxxx např. xxxxx x cytotoxicitě x xxxxxx xxxxxxxxxxxx, xxxx-xx x xxxxxxxxx,

- xxxxxxx xxxxx, případně xxxxxxxxxxx XX2,

- xxxxxxxxxxx zkoušené xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxxxx xxxxxxxx,

- xxx x xxxxxxx xxxxxxxxx metabolického xxxxxxxxxxx xxxxxxx, xxxxxx kritérií xxxxxxxxxxxxx,

- pozitivní a xxxxxxxxx xxxxxxxx,

- xxxxx xxxx xxxxxxx (případně xxxxxx počtu nasazených xxxxx, xxxxxxxxx x xxxxxx xxxxx),

- xxxxxxxx xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxx xxxxx velikosti x typu (případně xxxxxx xxxxxxxx xxx "xxxx" a "velké" xxxxxxx).

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx srážení,

- xxxxx x xX x xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxx stanoveny,

- velikost xxxxxxx, xxxx-xx xxxxxxxxxxx, xxxxxxx xxx xxxxxxxxx x xxxxxxxxx kontroly,

- xxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx tvořící xxxx xxxxxxx systémem X5178X XX+/-,

- podle xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

- xxxxx x souběžné xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx,

- dosavadní údaje x negativní (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- četnost xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X., XxXxxxxx, X. X., XxXxxxxx, X. J., Xxxxxx, X. R. (xxx.) (1987), Xxxxxxx Report 28; Mammalian Xxxx Xxxxxxxxxxx, Cold Xxxxxx Xxxxxx Laboratory, New Xxxx.

2) Chu, X. X. Y., Xxxxxxx X. V. (1968), Xxxxxxxxx Cell Genetics. XX. Chemical Induction xx Specific Locus Xxxxxxxxx xx Xxxxxxx Xxxxxxx Xxxxx Xx xxxxx, Xxxx. Xxxx. Xxxx. Xxx. X. X. X, 61, 1306-1312.

3) Xxxxx, H. X., Thilly, X. X. (1982), Xxxxxxxx Xxxxx xx xxx Xxxxxxxxx Kinase Locus xx Diploid Xxxxx Xxxxxxxxxxxx, Xxxxxxxx Xxx. 94, 467-485.

4) Xxxxx, X. X., Xxxxxxxxx-Xxxxx, X., Xxxxx, X. X., Xxxxxxxxx, X. X. (1989), Xxxxxxxxxxxx Xxxxxx Xxxxxxxxxxxx xx xxx Xxxxx Lymphoma XX and CHO XXXXX Xxxx, Xxxxxxxxxxx, 4, 394-403.

5) Aaron, X. X., Xxxxxxxxxx, Xx. X. X., (1989), Comparison of xxx AS52/XPRT xxx xxx XXX/XXXX Assays: Xxxxxxxxxx of Xxx Xxxx Candidates, Mutatation Xxx. 223, 121-128.

6) Xxxxx, X. X., Xxxxxxxxxx, X., Xxxxx, X. R., Xxxxx, X., Xxxxx, X., Xxxxxxxxxx, Jr. X. X., Xxxxxx, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Working Xxxxx Xxxxxx. Xxxxxx xx the International Xxxxxxxx on Xxxxxxxxxxxxxxx xx Genotoxicity Test Xxxxxxxxxx. Mutation Xxx. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxxx, R. X., Ishidate, M., Xxxxxxx, D., Xxxxx, X., Myhr, X. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. X report xxxx XXXXXX Task Xxxxx 9, Mutation Xxx. 257, 147-204.

8) Xxxxx, X., XxXxxx, X., Xxxxxxx, J. X. S., Piper, X., Mavournin, X. X. (1983), Specific Xxxx Xxxxxxxxx in X5178X Xxxxx xx Xxxxxxx. A Report xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Res., 115, 225-251.

9) Xx, A. X., Gupta, R. X., Xxxxxxx, X. X., Xxxxxx, J. X. (1988), A Xxxxxx and Analysis xx xxx Chinese Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx System xx Xxxxxxxxx the Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx: X Report xx Xxxxx XXX xx xxx U. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, X. X., Carver, X. X., Xxxx, X. X., Hsie, A. X., Gupta, R. X., Xxxxxxx, X. X., O'Νeill, J. X., Xxxxxx, X. X., Xxxxxxxxxx, X. X. Jr., Xxxx, X. X. (1987), X Xxxxx for xxx Xxxxxxxxxxx xx xxx Xxxxxxx Xxxxxxx Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

11) Xxxxx, X. X., Xxxxxxx, X. X., Xxxxxx, X. X. (1989), X Xxxxxxxxxx xx Xxxxxxxx Xxxxxxxxx xx xxx XX xxx XXXX Loci in Xxxxx Lymphoblastoid Xxxxx: Xxxxxxxxxxxx Differences xxx Xxx to xx Xxxxxxxxxx Xxxxx of Xxxxxxxxx at the Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Res., 216, 9-17.

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13) Xxxxxx, N. X., Xxxxxx, X. X., Xxxxx, D. (1984), Xxxxxxxxx xxx xxx X5178X/XX+/--XX+/- Mouse Lymphoma Xxxx Xxxxxxxxxxxx Xxxxx, xx: Xxxxxx, X. X. et xx (xxx.) Handbook xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, Xxxxxxxx Xxxxxxx Publishers, Xxx Xxxx, 239-268.

14) Xxxxxx, X. X., Xxxxx, D. X., Xxxxxx, X. X., Xxxxx, M. H. X., Xxxx, X., XxXxxxxx, D. B., Xxxxxxx X. X. (1989), Xxxxxxxxx Cell Xxxx Xxxxxxxx Xxxxxx Xxxxx xxxx Xxxxxx Xxxxxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Data, Xxxxxxxx, X. J., xx., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 66-101.

15) Xxxxxxxxxxxx, X., Xxxxxxx, X., Corti, X., Xxxxxx, X., Xxxxxxxx, X., Mazzaccoro, X. (1977), Xxxxxxxxx xx 6-Thioguanine-Resistant Xxxxxxx xx X79 Xxxxxxx Xxxxxxx Cells by Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Dimethylnitrosamine, Xxxxxxxxxx Xxx. 46, 365-373.

16) Ames, X. X., XxXxxx, X., Xxxxxxxx, X. (1975), Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx xxxx xxx Salmonella/Mammalian-Microsome Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx. 31, 347-364.

17) Xxxxx, X., Johnson, X. O., Spector, X. F. X., Xxxxxx A. G., Xxxxx X. X. X. (1979), Xxxxxxxxxx xxx Characterisation xx xxx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxxxx Xxxxx Xxxxxx, Xxxxx. Res. 59, 61-108.

18) Xxxxx, D. X., Xxxx, B. X. (1983), Xxxxxxx Xxxxxxx xxx xxx Xxxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx. 113, 173-215.

19) Elliott, X. X., Xxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, J. X., Xxxx, X. X. (1992), Alternatives xx Aroclor 1254-Xxxxxxx X9 xx: Xx xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, T., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Biphenyls x. x. xx Xxxxxxx of Metabolic Xxxxxxxxxx Systems, V: Xx xxxxx Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xx Xxxxxx, X. X., Xxxxx, X. X., Xxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, X. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx and Volatile Xxxxxxx, in: Ticc, X. X., Xxxxx, X. X., Schaich, X. X. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

22) Xxxxxx, X. X., Xxxxxx, X. X., Xx, A. X., Xxxxxx, X. X. (1983), Xxxxxxxxxx of xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxx. Mutagenesis, 5, 795-801.

23) Xxxxxxxxx, X. X., Moore, X. X., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxx, X. X. (1990), Molecular Xxxxxxxxxx xx Mutations xx xxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Locus xx Mouse Xxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Xxx. U. X. A, 87, 51-55.

24) Xxxxx, X. X., Clive, X., Xxxxxx, X. C., Xxxxxx, B. X., Xxxxxx, A. G., Xxxxxx, X. X., Xxxxxx, X. (1985), Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (TFT+) Xxxxxxx xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Res. 151, 161-174.

25) Yandell, X. X., Dryja, X. X., Little, X. B. (1990), Xxxxxxxxx Xxxxxxx Analysis xx Xxxxxxxxx Mutations xx a Xxxxxxxxxxxx Xxxxxxxxx Locus xx Xxxxx Cells, Xxxxxxxxxx Xxx. 229, 89-102.

26) Xxxxx, X. X., Xxxxx, C. L. (1990), Xxxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxx Xxxxxxxxx xxx Small Xxxxxx XX-Xxxxxxxxx Xxxxxx Frequency xx X5178X/XX+/- 3.7.2X Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxxx, 5, 609-614."

XXXXXXX 4X

"X.23 ZKOUŠKA XX CHROMOZOMOVÉ ABERACE XX XXXXXXXXXXXXXXX SAVCŮ

1. XXXXXX

Xxxx metoda je xxxxxxxx xxxxxx XXXX XX 483 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1997).

1.1 ÚVOD

Účelem xxxxxxx xx xxxxxxxxxxxx xxxxxxx ve xxxxxxxxxxxxxxx xxxxx xx xxxx xx xxxxxxxxxxxxx xxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxx chromozomové xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Rozlišují xx dva xxxx xxxxxxxxxxxx aberací: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxx xxxxxx xx xxxxxxxxx numerických xxxxxxx x xxxx x tomuto xxxxx xxxxxxx používána. Chromozomové xxxxxx a xxxxxxx xxxx xxxx příčinou xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u xxxxxxx.

Xxxxx xxxxxxxx se stanovují xxxxxxxxxxxx xxxxx ve xxxxxxxxxxxxxxx a xxxxxxxxxxx xx xxxx, xx xxxx xxxxxxx xxxxxxxx xxxxxxxxx indukce xxxxxxxxx xxxxxx x germinálních xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx používáni xxxxxxxx. Touto xxxxxxxxxxxxxx xxxxxxxx xx xxxx xx xxxxxxxx xxxxxxxxxxxx xxxxxxx xxx xxxxxx xxxxxxxxxxxxx. Jiné xxxxxx xxxxx nejsou předmětem xxxx zkoušky.

Pro detekci xxxxxxx xxxxxxxxxxxxxx xxxx xx xxxxxxxxxxxxxxx xx xxxx být — xxxxx xxx xxxxx xx xxxxxx léze — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx xx xxxxxxxx. Xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx chromozomovou xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx x xxxxxxxxx-xxxxxxxx X, kdy xx xxxxxxxxxx buňky xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx je xxxxxxxx xxx vyšetření, xxx xxxx xxxxxxxx somatických xxxxx aktivní xxxx x germinálních xxxxxxx. Xxxxx xx xxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx xxx posouzení xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx xx vivo, xxxxxxxxxxxxxxx x procesy xxxxxxxx XXX.

Xx varlatech xx přítomna řada xxxxxxxx xxxxxxxxxxxxx x xxxxxx citlivostí xx xxxxxxxx chemické xxxxx. Xxxxxxxxxx aberace tedy xxxxxxxxxxx xxxxxxxxx odpověď xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X závislosti xx xxx xxxxxx xx varlatech, xxxxx xxxx xxxxxx být xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx celkovému xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx buněk x xxxxxxx xxxx xxxxxxx xxxxxx a xxxxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, že xx xxxxxxxx xxxxx xxxx reaktivní metabolity xxxxxxxxxx xx cílové xxxxx, není vhodné xxxx xxxxxxx xxxxxx.

Xxx xxxx xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx jednotlivých xxxxxxxxx xxxx xxxxx x opětného xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx chromozomu x xxxxxx xxxxx xxxx xxxxx a xxxxxxx xxxx xxxxxxxxx x xxxxxx xxxxx.

Xxx : achromatická xxxx xxxxx než xxxxx xxxxx xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx xxxxxxxxxx xx xxxxxxxx hodnoty x xxxxxxxxx xxxxx.

Xxxxxxxxxxx : násobek xxxxxxxxxxx xxxxx xxxxxxxxxxxxxx xxx (x), xxxx xxx xxxxxxxxx (tj. 3 x, 4 n xxx.).

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx změny xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx xxx xxxxxxxxxxx, xxxx xx xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx nebo xxxxxxxxxxxxxxxxxx xxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx jsou xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxx a xx vhodné xxxx xx xxxxxxxx xxxxxxxx. Xxxx usmrcením xx xxxxxxxx podá xxxxx xxxxxxxxxxx metafázi (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx připraví xxxxxxxxx chromozomů, xxxxxx xx a xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xxxx xxxxxxxxx xxxxx xxxxxx čínského x xxxx; xxx xxxx xxxxxx xxxxx jakéhokoli xxxxxx xxxxxxxx xxxxx xxxxx. Xxxx xx xxx použity běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx x xxxxxx by xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

Xxxxx xxxxxx podmínky xxxxx obecného xxxxx x xxxxx X, xxxxxxx xx xxxx xxx dosaženo xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladí pohlavně xxxxxxx xxxxx xx xxxxxxxx výběrem rozdělí xx xxxxxxxxx xxxxxxx x skupinu, která xx xxxxxxxx. Xxxxx xx xxxx být xxxxxxxxxx tak, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx jednoznačně xxxxxxxxxxxx. Xxxx započetím xxxxxx xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xxxxxxxx rozpuštěny xxxx xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx nebo mohou xxx xxxx podáním xxxxxxx. Měly xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx při xxxxxxxxx xxxxxxxxx dávek xxxxxxx účinky a xxxx by být xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by xxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly. S xxxxxxxx aplikace xxxxxxxx xxxxx xx měla xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx identický xxxxxx xxxx xxxxxxx ve xxxxxxxxx, x nichž xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx spermatogoniích in xxxx při xxxxxxxxxxx xxxxxxxx, u xxxxx xx xxxxxxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx xxxxx x xxx xxx odběr x jejím případě xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxx být navíc xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx chemické xxxxx, xxxx-xx x xxxxxxxxx. Příklady xxxxx xxx pozitivní xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx C

50–07–7

200–008–6

akrylamid (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 xxxxxxx odběru xx xxx xxx xxxxxxxx odběr x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x která xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx exponované xxxxxxx, pokud nejsou x dosavadních kontrolních xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx buněk s xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 POSTUP

1.5.1 Xxxxx zvířat

Každá exponovaná x xxxxxxxxx xxxxxxx xxxx zahrnovat alespoň xxx analyzovatelných xxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxx (xx. xxx xxxxx xxxxxxxx xxxx xxxx xxxxxxxxxx). Xxxxxxxx xxxxx xxxxx být xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. xxx xxxxx x týž xxx v xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx xxxxxx podávání xx měly xxx xxxxxxx xxxxxxxxxx.

Xx skupině x xxxxxxxx dávkou xx xxxx xxx xx xxxxxxxx xxxxxxxxx xxx xxxxxx. Poněvadž xxxxxxxx xxxxxxxxx xxxxx xxxx xxx zkoušenou xxxxxx xxxxxxxxx, provede xx jeden xxxxx xxxxx a xxxxx xxxxxxxx xxxxx xxxxxxxxx 24 x 48 xxxxx xx xxxxxxxx. X případě xxxx xxx xxxxxxxx xxxxx xx xxx být xxxxx proveden xx 24 hodin xxxx xx xxxxxx xxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx xxxx xxxxx xxxx vhodnější xxxx pro xxxxxxx xxxxxx (6).

Xxxxx mohou xxx xxxxxx provedeny xxxx v jiné xxxx. Například v xxxxxxx chemických xxxxx, xxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (lagging) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx S-nezávislé xxxxxx, xxxx být xxxxxxxxx xxxxxxxx odběr (1).

Vhodnost xxxxx opakované xxxxxxxx xxxx xxx určena xxxxxx xx případu. X xxxxxxx xxxxx x opakovanou expozicí xx xxxx xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx xxxxx xxxxx) po xxxxxxxx xxxxxxxx. Xxxxx xxxxxxx xxxxx xxx prováděny xxxxx xxxxxx x xxxx době.

Před xxxxxxxxx xx zvířatům intraperitoneálně xxxx xxxxxx xxxxx xxxxx zastavující xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Poté se xx xxxxxx xxxx xxxxxxx u xxxxxx xxxxx. U xxxx xx tato xxxx xxxxxxxxx 3 — 5 xxxxx; x xxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx zjištění xxxxxxx, xxxx xx xxx xxxxxxxxx xx stejné xxxxxxxxxx, se xxxxxxx xxxxxx a xxxxxx x xx stejného xxxxxx xxxxxxxx, xxxxx xx xxxxxxx x xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx xxx první xxxxx xxxxxxx xxx xxxxxx xxxxx. Tyto xxxxxx dávky by xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx odběru xxxxx, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx by xxxxx xxxxx xxxxx xxx stejném xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx nízkých netoxických xxxxxxx (xxxx. hormony x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx vyvolávající xx spermatogoniích některé xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxx xxxxxxxxxxxxx x mitose xxxxxxxx x první x xxxxx xxxxxxxxx metafázi; xxxx snížení xx xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx žádné pozorovatelné xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. Xxxxxxxxx expozice xxxxxxx může xxxxxxxx xxxxxxx xxxxxx x xxxxxxx zkoušce xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx intraperitoneální xxxxxxx. Xxxx způsoby podávání xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx může xxx xxxxxxxx podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, musí xxx xxxxxxxxxx. Xx xx xxxxxxxx x žíravé xxxxx, které xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx zkoušeného xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava xxxxxxxxx xx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx xx x xxxxxxx xxxx xxxx xxxxxx xxxxx xxxxxxx suspenze, hypotonizuje xx a fixuje. Xxxx se xxxxxx xx podložní sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

X každého xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx v xxxxx xxxxxxxxxxxx metafázi (tj. xxxxxxxxx 500 metafází xx xxxxxxx). Tento xxxxx lze xxxxxx, xx-xx pozorován xxxxx xxxxx xxxxxxx. Všechny xxxxxxxxx včetně preparátů xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx, xx xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx zlomům xxxx xxxxxx chromozomů u xxxxx xxxxxxxx, měly xx xxxxxxxxxxx buňky xxxxxxxxx xxxxxxxxxx v xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx zpracovány xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx je zvíře. Xxx xxxxx xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx a počet xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx exponované x xxxxxxxxx skupiny xx xxxx být xxxxxxx různé xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx aberací x xxxxxx xxxxxx x četností. Xxxx xx zaznamenávají odděleně x uvádějí xx, xxx xxxxxx se xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx a také xxxxxx, xxx by xxx pro stanovení xxxxxxx xxxxxxxxxxxxx účinků xxxx xxxx xxxxxxxxxxxx xxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx jako xxxxxxxxx kontrola xxxxx xxxxxxxxxxxxx v xxxxxx xxxxxxxx k xxxxx x xxxxx meiotické xxxxxxxx, x xx x xxxxxxxx xxxxxx 100 dělících xx xxxxx xx jedno xxxxx. Xxxxx xx xxxxxxxxx pouze xxxxxx, xxxxxxx x 1000 xxxxxxx xx xxxxx xx xxx být xxxxxxxx xxxxxxxxx xxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. xxxxxx xxxxx buněk s xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx xx xxxxx xxxx jasný xxxxxx xxxxx xxxxx s xxxxxxxxx pro xxxxxxx x určitou dávkou x x určitému xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx (8). Statistická xxxxxxxxxx xx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx dalším zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx podmínek.

Zkoušená látka, xxxxx xxxxxxxx xxxxxxxxx xxxx uvedená kritéria, xx x xxxxx xxxxxxx považuje xx xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx xx xxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx látka za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx xxxx její xxxxxxxxxx dostanou do xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

- xxxxxxxxxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.

Xxxxxxxxx xxxxxxx:

- xxxxxxx druh/kmen,

- počet x stáří xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné hmotnosti, xxxxxxx hodnoty x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxx xx xxxxxx xxx zjištění xxxxxxx, xxxxx xxxx xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxx xxxxxxxx,

- případně xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx nebo xxxx (xxx) xx odpovídající xxxxx (mg/kg tělesné xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x kvalitě xxxxxx x xxxx,

- podrobný xxxxx rozvrhu xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx xxxxx xxxxxxxxxxx metafázi, xxxx xxxxxxxxxxx x xxxxx xxxxxxxx,

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxx na xxxxx xxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxxxx xxxxxxxxxxxxx x mitose xxxxxxxx x xxxxx x xxxxx xxxxxxxx xxxxxx,

- xxx a xxxxx xxxxxxx uvedený xxxxxxxxxx pro každé xxxxx,

- xxxxxxx počet xxxxxxx ve xxxxxxx,

- xxxxx xxxxx x xxxxxxxxx xx skupině,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx kontrole,

- dosavadní xxxxx o negativní xxxxxxxx s rozpětími, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. D., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Xxxxxxxxxxxxx xx Xxxxxxxx Xxxxxxxx Related xx their Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxxx Xxxxxxxxx, Xxxx X: Xxxxxxx Xxxxxxx and Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Xxxxxxx, X., Xxxxxxxxx, X. (eds) Xxxx, Xxx Xxxx, 477-484.

2) Xxxxx, X. X., (1984), Xxxxxxxxxxx xxxxx in Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, (xx.) X. Venitt, X. X. Xxxxx, XXX Xxxxx, Oxford, Xxxxxxxxxx XX, 275-306.

3) Xxxxx, X. P., Xxxxxxx, X., Xxxx, X. E. (1964), Xx Xxx-xxxxxx Xxxxxx xxx Meiotic Xxxxxxxxxxxx xxxx Mammalian Testes, Xxxxxxxxxxxx Xxxx Xxxxxxxx, 3, 289-294.

4) Xxxxxxx, X., Ashby, X., Xxxxxxxx, A., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: D. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Part X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

5) Xxxxxxxx, K., Xxxxxxx, X. (1978), X Xxx Method xxx Xxxxxxxxxxx xx Mammalian Xxxxxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 52, 207-209.

6) Xxxxx, X. X., Xxxxxx X. X., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx X. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures. Xxxxxxx Report of xxx Working Xxxxx xx Mammalian Xxxx Xxxx Tests, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, X. J., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. A., Xxx, J., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Hodson-Walker, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Richold, X. (1992), Report xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, D. X., Xxxxxxxx, X., Xxxxxxxx, X., Amphlett, G. X., Clarc, G., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, X. X., Savage X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Kirkland (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."

XXXXXXX 4X

"X.39 XXXXXXX XX XXXXXXXXXXXX XXXXXXX XXX (UDS) V XXXXXXXXX XXXXXXX XXXXX XX XXXX

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx OECD TG 486 — Xxxxxxx xx neplánovanou syntézu XXX (UDS) x xxxxxxxxx buňkách savců xx xxxx (1997).

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx DNA (XXX) x xxxxxxxxx xxxxxxx xxxxx xx xxxx xx xxxxxxxxxxxxx xxxxxxxx látky, xxxxx xxxxxxxx xxxxxxxx XXX x xxxxxxxxx xxxxxxx xxxxxxxxxxxx zvířat (1, 2, 3, 4).

Xxxx xxxxxxx xx vivo xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx účinků chemických xxxxx v xxxxxxx. Xxxxxxxxxxx xxx xx xxxxxxxxxx xxxxxxxxx XXX x xxxxxxxx xxxxxxxx x jaterních buňkách. Xxxxx xxxx xxxxxxx xxxxxxx místem, xxx xxxx absorbované xxxxxxxxxx xxxxxxxxxxxxxx. Jsou xxxx xxxxxxx xxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx XXX xx xxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, xx xx xxxxxxxx xxxxx xxxxxxxxx xx xxxxxx xxxxx, xxxx vhodné xxxx xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx XXX (UDS) xx zhodnotí xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx buněk, které xxxxxxxx plánovanou syntézou XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx je autoradiografické xxxxxxxxx xxxxxxxxxxx thymidinu xxxxxxxxx tritiem (3X-XxX). Xxx xxxxxxx na XXX xx xxxx xx xxxxxxxxxx xxxxxxxxx xxxxx xxxxxxx. Xxxx xxxxx xxx xxxxx xxxxx xxx xxxxxx xxxxxxx, nejsou xxxx xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx XXX závisí xx počtu bází XXX xxxxxxxxxxx x xxxxxxxxxxx x xxxxx xxxxxxxxx. Zkouška xx XXX je xxxx xxxxxx zvláště pro xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 xxxx) xxxxxxxxxxxx xxxxxx. Krátké xxxxxx ("short-patch xxxxxx") (xxxxx xx xxx xxxx) jsou xxxxxxx xxxx xxxxxxxxxx x xxxxxx xxxxx citlivostí. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxxxx xxxx XXX xxxxx k xxxxxxxxxx xxxxxxxxx. Xxxxxx xxxxxxxx XXX xxxxxxxxxxx žádnou xxxxxxxxx o xxxxxxxx xxxxxxxxxxx procesů. Xxxxx xx xxxxx, xx xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxx, xxxxx xxxx zkouška xxxxxxxxx x xxxxxxxxx xxxxxxxx, xx vyvážen xxxxxxxxxxx xxxxxxxxxx xxxxxx jevu, xxxxx xx vyšetřován x xxxxx xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : xxxxx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX), xxxxx xxx xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx zkoušku.

Čistý xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx míra XXX xxxxxxxx buněk x xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxx xxx x cytoplasmatických oblastech (XX) xxxxxxxxxxxxxx xxxxxx xx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx jádrům (XX): XXX = XX — CG. Xxxxxxx NNG se xxxxxxx xxx jednotlivé xxxxx, poté společně xxx xxxxx x xxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxx.

Xxxxxxxxxxx syntéza XXX (UDS) : Xxxxxxx reparací XXX xx vyštěpení x xxxxxxxxxx úseku XXX xxxxxxxxxxxx region x xxxxxxxxxx xxxxxxxxxxx chemickými xxxxxxx nebo fyzikálními xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx XXX x jaterních xxxxxxx xxxxx xx vivo xxxxxxxx xxxxxxx reparací XXX po xxxxxxxxx x odstranění xxxxx XXX xxxxxxxxxxxx xxxxxx x poškozením indukovaným xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx xxxxxxxx xx xxxxxxxxxxx 3H-TdR xx XXX xxxxxxxxx xxxxx, kde xx xxxx četnost xxxxx x X-xxxx buněčného xxxxx. Xxxxxxxxxxx 3X-XxX xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx xxxx tak xxxxxxx xx xxxx X-xxxx xxxxx xxxx xxxx. kapalná xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 POPIS XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr druhu xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X okamžiku xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx by xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx pro obě xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x strava

Platí obecné xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx X, xxxxxxx by xxxx xxx xxxxxxxx xxxxxxxx vzduchu 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Klece xx xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx minimalizován. Xxxxxxx xx jednoznačně xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx xx nechají x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx xxxx xxxxxxxx zvířatům xxxxxxxxxx xxxx suspendovány xx vhodných rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx přímo xxxx xxxxx xxx xxxx podáním zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx xxxxxxxxx xxxxxxxx dávek xxxxxxx xxxxxx x xxxx xx xxx vyloučeno xxxxxxxxx, že xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx xxxxxx xxxxxxx xxxxx možno xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx prováděné části xxxxxxxxxxx by xxxx xxx xxxxxxxx pozitivní x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx zkoušené látky xx měla xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x nichž xxxxx x xxxxxxxx.

Xxxxxxxxxxx kontrolami xx xxxx xxx xxxxx, o nichž xx xxxxx, xx xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Pozitivní kontroly xxxxxxxxxx xxxxxxxxxxxx aktivaci xx měly xxx xxxxxxx v xxxxxxx xxxxxxxxxxxx mírnou xxxxxxx (4). Dávky mohou xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxx pro pozitivní xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx CAS

Číslo xxxxx Einecs

Časné xxxx xxxxxx (2 xx 4 h)

N-nitrosodimethylamin

62–75–9

200–249–8

Pozdní doby xxxxxx (12 až 16 x)

X-(xxxxxxx-2-xx)xxxxxxxx (2-XXX)

53–96–3

200–188–6

Xxxxx xxx xxxxxxx xxxx xxxx xxxxx xxx xxxxxxxxx kontrolu. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxx látka xxxxxxxx xxxxx xxxxxxxx, xxx zkoušená xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx xxxxxx

Xxx by xxx xxxxxx xxxxxxxxxx xxxxx zvířat, xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxx odpovědi xx xxxxxxx. Každá xxxxxxx by xx xxxx skládat xxxxxxx xx tří analyzovatelných xxxxxx. Xxxxxxxx jsou xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx xxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx skupiny xxxxxxxx xxxxx xxxxx xx xxx xxxxxxx.

Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx údaje xx xxxxxx se xxxxxxx druhem x xx xxxxxxx stejného xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x toxicitě, xxxx xxxxxxxxxxx xxxxxxxx jednoho xxxxxxx, xxxxxxx xxxxx. Xx-xx expozice člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx například x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by xxx xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx expozice

Zkoušené xxxxx xxxx xxxxxxxxx podávány xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx normálních xxxxxxxx se xxxxxxxxx xxxxxxx xxx úrovně xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx dávky xx xxxxx xxxxx xxxxxxxxx xxx xxxxxxx režimu xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx xx xxxx xxx xxxxxxxxx 50 % až 25 % xxxxx xxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky vyhovovat x xxxx xx xxx hodnoceny xxxxxx xx xxxxxxx. Xxxxxxx-xx xx kvůli neexistenci xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx xxxxxxx, měla xx xxx provedena xx xxxxxx xxxxxxxxxx, se xxxxxxx druhem, xxxxxx, xxxxxxxx a xx xxxxxxxx režimu xxxxxxxx, xxx xx xxxxxxx x xxxxxx studii.

Nejvyšší xxxxx může xxx xxxxxxxxxx xxxx xxxx xxxxx xxxxxxxxxxxx známky xxxxxxxx v játrech (xxxx. pyknotická jádra).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx x alespoň 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx x xxxx-xx na xxxxxxx xxxxx x látkách, xxxxx xxxx podobnou xxxxxxxxx, očekávána genotoxicita, xxxxxx být xxxxx xxxxxx xxxxxxxx. Očekávaná xxxxxxxx xxxxxxx xxxx xxxxxxxx potřebu použít x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxx, xxx-xx xx zdůvodnit. Xxxxxxxx xxxxxxxxxxxxxxxxx xx xxxx xxxxxxxxxxxx, xxxxx xx xxxxx xxxxx xxx xxxxxxxxxx zkoušené xxxxx xxxxx x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který může xxx xxxxxxxx podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x žíravé xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx úrovních xxxxx.

1.5.6 Příprava xxxxxxxxx xxxxx

Xxxxxxx xxxxx se xxxxxxxxxx z xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 hodin xx xxxxxx xxxxx. Xxxxxxxxxx dřívější xxxxxxxx xxxxxx (xxxxxx dvě xx čtyři xxxxxx xx expozici) xx xxxxxxxx, není-li xx 12 xx 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx xxxxxxx xxxx xxxx xxxxxx, jsou-li xxxxxxxxxx na xxxxxxx xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxxx xx xxxxxxxxx zakládají xxxxxxx jater xxxxxxxxxxx xx xxxx a xxxxxx xx, xxx xx xxxxxxx disociované xxxxxxx xxxxx xxxxxxxxx xx vhodném xxxxxxx. Xxxxxxx buňky x xxxxxxxxx kontroly by xxxx vykazovat životaschopnost (5) alespoň 50 %.

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxx xxxx, např. xxx xx xxx xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3X-XxX. Xx xxxxx xxxxxxxxx xxxx xx xxxx xxx xxxxxx z xxxxx odstraněno x xxxxx xxxx xxxxx xxx xxxxxxxxxx x xxxxxx obsahujícím přebytek xxxxxxxxxxx xxxxxxxxx, xxx xxxx xxxxxxx neinkorporovaná xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx xx xxxx xxxxxxx, xxxxxx a xxxxxx. Xxx xxxxx xxxxxxxxx době nemusí xxx snížení radioaktivity xxxxxxxx. Preparáty xx xxxxxx xx xxxxxxxxxxxxxxxxx xxxxxx, exponují xx x temnu (např. x xxxxxx 7 xx 14 xxx), xxxxxxxx se, xxxxxx x xxxxxxxxx xx xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx zvířete xx xxxxxxxx xxx xx tři preparáty.

1.5.8 Xxxxxxx

Xxxxxxxxx xx měly xxxxxxxxx xxxxxxxxxx počet xxxxxxxxxxxx normálních xxxxx, xxx xxxx xxxxxxxxx XXX výpovědní hodnotu. Xxxxxxxxx xx xxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxx cytotoxicity (xxxx. xx pyknosu, xxxxxxxx xxxxxx značení xxxxxxxxxxxxx izotopem).

Před xxxxxxxxx xxx xx xxxx xxx preparáty xxxxxxxx. Xxxxxxxxx se vyšetřuje 100 xxxxx na xxxxx zvíře alespoň xx xxxx xxxxxxxxx; xxxxxxxxx xxxx než 100 xxxxx/xxxxx xx xxxx xxx xxxxxxxxxx. Xxx xxxxxxxx xxx xx xxxxx v X-xxxx xxxxxxxxxxx, ale xxxxx xxxxx v X-xxxx xxxx xxx xxxxxxxxxx.

Xxxxxxxx 3H-TdR inkorporovaného xx xxxxx x xxxxxxxxxx morfologicky xxxxxxxxxx xxxxx doložené navrstvením xxx stříbra xx xxxx xxx stanoveno xxxxxxx xxxxxxx.

Xxxxx xxxxx xx xxxxxxx x xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (ng) x x xxŭxxxxxxx xxxxx xxx v xxxxxxxxxxxxxxxxx xxxxxxxxx (xx) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx xx xx xxxxxxx xxx xxxxx xxxxx pro nejsilněji xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx prŭměrná xxxxxxx xxxx až xxx xxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx jader. po xxxxxxxxxxxxx xxXxxxxxxx mohou xxx xxxxxxx x xxxx xxxxxxx stanovení xxxxx xxxxx (např. xxxxxxxx xxxxxx xxxxx) (6).

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx xx být xxxxxxx xxxxx pro xxxxxxxxxx preparáty x xxxxxxx. Xxxxx xx xxxx xxx dále xxxxxxx ve formě xxxxxxx. Xxxxxxxxx xxxxxxx XX xx xxxxxxx XX xx xxx xxx xxxxxxxx xxx xxxxxx buňku, pro xxxxx zvíře x xxx xxxxxx xxxxx x čas xxxxx xxxxx xxx odpovídajících xxxxxxxx jádrům (XXX). Xxxxxxxx jsou počítány "xxxxxxxxxx" buňky, xxxx xx xxx xxxxxxxx xxx xxxxxxxxxx "opravovaných" xxxxx xxxxxxxxxx a xxxxxxxx xx xxxxxxxxxxx xxxx souběžných údajích x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx mohou xxx zhodnoceny statistickými xxxxxxxx. Xxxx-xx xxx xxxxxxx, měly xx xxx xxxxxxxxxxx testy xxxxxxx x xxxxxxxxxx xxxx provedením xxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx

x)

xxxxxxx XXX xxxx xxx xxxxxxxx úrovní, která xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx;

xxxx

xx)

xxxxxxx XXX je xxxxxxxx xxxxx xxx xxxxxxx pro xxxxxxxxx xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx XXX xxxx xx xxxxxxxxx xxxxxxx xxxxxxx nebo pod xx;

xxxx

xx)

xxxxxxx XXX xxxx xxxxxxxx vyšší než xxxxxxx pro xxxxxxxxx xxxxxxxx.

Xxxx xx xxx xxxxxxxxx biologická relevance xxxxx, tj. měly xx být vzaty x xxxxx xxxxxxxxx, xxxx xxxx xxxxxxxxxxx xxxxxx, vztah xxxxx x xxxxxxxx x xxxxxxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx mohou xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx však xxxxxx xxx xxxxxxx určujícím xxxxxxxx pro xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na XXX v jaterních xxxxxxx xxxxx in xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x jaterních buňkách xxxxx in xxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxx neplánovanou xxxxxxxx XXX xx xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx neindukuje xxxxxxxxx XXX, které xxx xxxxxxxxx touto xxxxxxxx.

Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x jakou xx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx popř. xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- rozpustnost x xxxxxxx xxxxxxxx xxxxx v xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.

Xxxxxxxxx xxxxxxx:

- xxxxxxx druh/kmen,

- xxxxx, xxxxx x pohlaví xxxxxx,

- zdroj, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx zvířat xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, střední xxxxxxx x xxxxxxxxxx odchylky xxx každou xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

- xxxxx ze studie xxx xxxxxxxx xxxxxxx, xxxxx xxxx provedena,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x podávání xxxxxxxx látky,

- zdůvodnění xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx ověření, xxx xx zkoušená xxxxx xxxxxxx xx krevního xxxxx xxxx do xxxxxx xxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx nebo vodě (xxx) xx xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx údaje x xxxxxxx krmiva x vody,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- metody xxxxxxxx x kultivace xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- počet xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,

- kritéria xxxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxxx xxxxxxx počtu xxx xxxxxxxxxxxxxx buněčným xxxxxx a xxxxx xxx odpovídajících xxxxxxxxxx, x čistý počet xxx, xxxxxxxxxx pro xxxxxxxxx, zvířata x xxxxxxx,

- podle možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxx,

- xxxxx x souběžné xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) a xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxx "xxxxxxxxxxxx" xxxxx, xx-xx xxxxxxxx,

- xxxxx xxxxx x S-fázi, xx-xx xxxxxxxx,

- životaschopnost xxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, X. Lefevre, X. X., Burlinson, X., Penman, X. X. (1985), Xx Xxxxxxxxxx xx xxx Xx xxxx Xxx. Xxxxxxxxxx DNA Xxxxxx Xxxxx, Xxxxxxxxxx Res., 156, 1-18.

2) Xxxxxxxxxxx, X. X., Xxxxx, X., Bermudez, X., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1987), X Protocol and Xxxxx for xxx Xx vivo Xxx Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 123-133.

3) Xxxxxxxx, X. X., Xxxxxx, X., Ashby, X., Xxxxxxx, P. X., Xxxxxxxxx, X., Xxxxxxx, X. X., Dean, X. X., Xxxxxxxx, X. xx X. (1993), In xxxx Xxx Xxxxx XXX Xxxxx, xx: Kirkland X. J., Fox X., (xxx), Supplementary Xxxxxxxxxxxx Tests: XXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, New Xxxx, Xxxx Chester, Xxxxxxxxx, Sydney, 52-77.

4) Xxxxx, X., Xxxx, X. X., Andrac, X., Xxxxxxxxx. X., Xxxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, T., XxXxxxx, X. X., Xxxx, H. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx of XXX Xxxxx Xx xxxxx xxx Xx xxxx, Xxxxx. Res., 312, 263-285.

5) Xxxxx, R., Xxxxxxx, B., Efstathiou, X., Xxxxxxxxxxxx-Xxxxxx, C. (1993), Assessment xx xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Viability xxx xxx Attachment xx Xxxxxxx Isolated Xxx Xxxxxxxxxxx Xxxx xxx the In xxxx/Xx vitro XXX Xxxxxx Xxxxx (XXX), Xxxxxxxxxx Res., 291, 21-27.

6) Xxxxxxxx, X. X., Xxxxx, X. X., Xxxxxxxxxxx, B. X. (1982), Xxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xx the Xx xxxx/Xx xxxxx Hepalocyte XXX Xxxxxx Assay, Xxxxxxx.Xxxxxxx. 4, 553-562."

XXXXXXX 5

OBECNÉ XXXXXXXXX XX KLASIFIKACI X XXXXXXXXXX XXXXXXXXXXXX XXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES, Úř. xxxx. X 332, 28. 12. 2000, x. 81.

XXXXXXX 6

"

XXXXXXX IX

ČÁST X

xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx dětmi

Kromě ustanovení xx. 22 xxxx. 1 písm. x) xxxx xxxxxxxx, xxxx xxx xxxxx o xxxxxxxxx xxxxxx xxxxxxxxxx xxxxx, x xxxxx xx xxxxxxx riziko xxx xxxxxxxxxx (Xn; X 65) x xxxxx jsou klasifikovány x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX této xxxxxxxx, x xxxxxxxx látek xxxxxxxxx na xxx xx xxxxx xxxxxxxx xxxx x xxxxxxxx xxxxxxxxxx aerosolovým xxxxxxxxxxxxx, xxxxxxxx uzávěry xxxxxxxx xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx obaly

Uzávěry xxxxxx xxxxx xxxxxxxx xxxxx použité xx xxxxxxxxx xxxxxxxxxxxxxx obalech xxxx xxxxxxxx xxxxxxxxx xxxxx ISO 8317 (xxxxxx xx xxx 1. xxxxxxxx 1989) "Xxxxx odolné xxxxx — Xxxxxxxxx xx xxxxxxxxx uzavíratelné xxxxx x xxxxxx xxxxxx xxxxxxxx" xxxxxxxx Xxxxxxxxxxx xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Xxxxxxxxx neuzavíratelné xxxxx

Xxxxxxx odolné xxxxx xxxxxxxx xxxxx použité xx opakovaně xxxxxxxxxxxxxxxx xxxxxxx musí xxxxxxxx xxxxxxxxx xxxxx XXX XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Xxxxx xxxxxx dětem — Xxxxxxxxx x xxxxxxxx xxxxxxx xxx opakovaně xxxxxxxxxxxxxx obaly xxxxxx xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Evropským výborem xxx xxxxxxxxxxx (XXX).

3. Xxxxxxxx

1. Prokázání shody x xxxx xxxxxxxxx xxxxxxx mohou xxxxxxxxxx xxxxx xxxxxxxxxx, xxxxx xxxxxxx evropské xxxxx xxxx EN 45000.

2. Xxxxxxxxxx případy

Je-li xxxxxx, xx xxxx xx xxxxxxxxxx bezpečný xxx xxxx, xxxxx se xxxxxxx dostat x xxxxxx xxx pomoci xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxx xxxxxx x pochybám x bezpečnosti xxxxxxx xxx xxxx, xxxx xxxxxxxxxxxx orgán xxxxxxxxx, xxx osoba xxxxxxxxx xx xxxxxxx xxxxxxx xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx odst. 3 xxxx 1 konstatující, xx xxx

- xxx xxxxxxx xx xxxxxx, xx xxx není xxxxxxxx xxxxxxx xxxxx xxxx uvedených xxxxx XXX x CEN,

nebo

- xx uzávěr xxx xxxxxxx x xxx xxxxxxx xxxxxxxxxxx xxxxx xxxx uvedených xxxxx.

XXXX X

Xxxxxxxx týkající se xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx xxxxxxxxxxx xxx xxxxxxxxxx xxxxxxxx xxxx xxx x xxxxxxx s xxxxxx XX XXX 11683 (xxxxxx z xxxx 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Xxxxxxxxx".

"