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Xxxxxxxx Xxxxxx 2000/32/XX

xx xxx 19. xxxxxx 2000,

xxxxxx xx xx xxxxxxx šesté přizpůsobuje xxxxxxxxxxx xxxxxxx směrnice Xxxx 67/548/EHS x xxxxxxxxxx právních x xxxxxxxxx předpisů xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx nebezpečných xxxxx [1]

(Xxxx s xxxxxxxx pro XXX)

XXXXXX XXXXXXXXXX SPOLEČENSTVÍ,

s xxxxxxx xx Xxxxxxx x xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx xx směrnici Xxxx 67/548/XXX ze xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], xxxxxxxxx xxxxxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Xxxx 1999/33/XX [3], x zejména xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx x xxxxx důvodům:

(1) Xxxxxxx X xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx nebezpečných xxxxx xxxxxxxx s xxxxxxxxxx xxxxx x xxxxxxxxxxx x označování xxxxx xxxxx. Xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxx, xx xx xxx xxx xxxxxx nebezpečných látek x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx jazykové xxxxx směrnice xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxxxxx x xxxxxxx X v xxxxxxx X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/EHS obsahuje xxxxxx xxx xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx x přípravky. Xxxxxxx XX směrnice 67/548/XXX xxxxxxxx xxxxxx xxx x bezpečnostními xxxxxx týkajícími se xxxxxxxxxxxx xxxxx x xxxxxxxxx. Příloha XX xxxxxxxx 67/548/XXX obsahuje xxxxx xx xxxxxxxxxxx x k xxxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Některé xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, IV x VI.

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

(4) Xxxxxxx XX směrnice 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx xxxxx otevření xxxxx. Xxxx předpisy xx xxxx být xxxxxxxxxxxx x xxxxxxxxxxxxx. Xx nezbytné xxxxxxxx xxxxxx, xxx se xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxxxx.

(5) Xxxxxxxx této směrnice xxxx v xxxxxxx xx xxxxxxxxxxx Výboru xxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx směrnic xxx xxxxxxxxxx technických překážek xxxxxxx xx xxxxx xxxxxxxxxxxx látek x xxxxxxxxx,

XXXXXXX XXXX XXXXXXXX:

Článek 1

Směrnice 67/548/XXX xx xxxx xxxxx:

1. Xxxxxxx X xx xxxx xxxxx:

x) odpovídající xxxxxxxx x xxxxxxxxx xx xxxxxxxxx xxxxxxxxx X x příloze 1X xxxx xxxxxxxx;

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

x) xxxxxxxxxxxx xxxxxxx xx nahrazují položkami x xxxxxxx 1X xxxx směrnice;

d) xxxxxxxx xx xxxxxxx v xxxxxxx 1X xxxx xxxxxxxx.

2. Odpovídající věta x xxxxxxx III xx nahrazuje standardní xxxxx xxxxxxxxxx specifickou xxxxxxxxxx x xxxxxxx 2 této xxxxxxxx.

3. Xxxxxxx XX xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx x příloze XX xx xxxxxxxxx xxxxxxxxxxxx pokyny pro xxxxxxxx zacházení v xxxxxxx 3A této xxxxxxxx;

x) xxxxxxxxxxxx xxxxxx x xxxxxxx XX xx nahrazují xxxxxxxxxxxxx xxxxxxxxxxxx pokyny xxx xxxxxxxx xxxxxxxxx x xxxxxxx 3B xxxx xxxxxxxx.

4. Xxxx X xxxxxxx V xx xxxx xxxxx:

x) kapitola X.10 se nahrazuje xxxxxx v xxxxxxx 4X této směrnice;

b) xxxxxxxx X.11 se xxxxxxxxx xxxxxx v xxxxxxx 4X této xxxxxxxx;

x) xxxxxxxx B.12 xx xxxxxxxxx xxxxxx x příloze 4C xxxx směrnice;

d) xxxxxxxx X.13 a B.14 xx xxxxxxxxx textem x xxxxxxx 4D xxxx směrnice;

e) xxxxxxxx X.17 xx xxxxxxxxx xxxxxx x xxxxxxx 4X této směrnice;

f) xxxxxxxx B.23 xx xxxxxxxxx xxxxxx x xxxxxxx 4X této xxxxxxxx. Název xxxxxxxx X.23 xx xxxxxxxxxxx xx xxxx xxxxxxxxxxxxx xxxxxxxx;

x) vkládá xx xxxx v xxxxxxx 4X xxxx xxxxxxxx.

5. Xxxxxxx xx čtvrtá xxxxxxx obecného úvodu x xxxxx X xxxxxxx X.

6. Xxxxxxxxxxxx xxxxx v xxxxxxx XX xx xxxxxxxxx xxxxx x xxxxxxx 5 xxxx xxxxxxxx.

7. Xxxxxxx XX se xxxx xxxxxxxx xxxxxxxx x xxxxxxx 6 xxxx směrnice.

Článek 2

1. Xxxxxxx xxxxx xxxxxx x xxxxxxxx právní a xxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxxx xxxxxxx x touto xxxxxxxx xxxxxxxxxx do 1. xxxxxx 2001. Neprodleně x nich uvědomí Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx na xxxx xxxxxxxx nebo xxxx xxxxxx odkaz xxx xxxxxx xxx xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx xxxxxx si xxxxxxx xxxxxxx xxxxx.

2. Xxxxxxx státy xxxxx Xxxxxx xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx xxxxxxx x xxxxxxx xxxxxxxxxx xxxx xxxxxxxx, x xxxxxxxxxx xxxxxxx mezi xxxxxxxx x přijatými xxxxxxxxxxxxxx ustanoveními.

Xxxxxx 3

Tato xxxxxxxx xxxxxxxx x xxxxxxxx xxxxxx dnem xx xxxxxxxxx v Xxxxxxx xxxxxxxx Xxxxxxxxxx společenství.

Xxxxxx 4

Xxxx xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.

V Xxxxxxx dne 19. xxxxxx 2000.

Za Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise


[1] Xxxxxxx po xxxxxxxxxxxx xx xxxxxxx xxxxx.

[2] Xx. xxxx. 196, 16.8.1967, x. 1.

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


PŘÍLOHA 1A

PŘEDMLUVA X XXXXXXX I

Vysvětlení xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx se xxxxxxx xxxxx)


PŘÍLOHA 1B

"TABULKA 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"


XXXXXXX 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x látkám

Číslo 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) natrium-N-methyldithiokarbamát

205–293–0

137–42–8

Xn; X22 X31 X; X34 X43 X; X50–53

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

006–015–00–9

diuron (XXX) 3-(3,4-dichlorfenyl)-1,1-dimethylmočovina

206–354–4

330–54–1

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

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

006–016–00–4

xxxxxxxx (XXX) 2- isopropoxyfenyl-N-methylkarbamát

204–043–8

114–26–1

T; X25 N; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

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

204–123–2

116–06–3

X+; X26/28 X; X24 X; X50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; X24/25 X; X50–53

X; X X: 24/25–50/53 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 N; R50–53

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

006–020–00–6

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

217–991–2

2032–65–7

T; X25 N; R50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; X22 Xx; X38 X; R51–53

Xn; X X: 22–38–51/53 X: (2-)13-61

006–026–00–9

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

216–353–0

1563–66–2

X+; X26/28 N; X50–53

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

006–028–00-X

xxxxxxxxx (XXX) 2-(1-methylpropyl)-4,6-dinitrofenyl-isopropyl-karbonát 2-xxx-xxxxx-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx

213–546–1

973–21–7

X; X25 N; X50–53

X; X R: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

xxxxxxxxx (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 X: (1/2-)37–45–61

006–033–00–7

xxxxxxxxx (XXX) 3-(3-chlor-4-methoxyfenyl)-1,1-dimethylmočovina

243–433–2

19937–59–8

N; X50–53

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

006–034–00–2

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

214–215–4

1114–71–2

Xx; X22 N; R51–53

Xn; X R: 22–51/53 X: (2-)23-61

006–035–00–8

xxxxxxxxxx (XXX) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx xxxxxxxxx-4-xx-X,X-xxxxxxxxxxxxxxxx

245–430–1

23103–98–2

X; X25 N; R50–53

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

006–037–00–9

xxxxxxxxx (ISO) 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. kat. 2; X45 Xx; X22 N; R50–53

T; X X: 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 X43 X; X50–53

Xx; X X: 22–43–48/22–50/53 X: (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; X 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; X36/38 Xxxx. xxx. 3; R40 X; X50–53

Xx; X 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; R50–53

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

006–046–00–8

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

245–216–8

22781–23–3

X; R23/25 Xx; X21 N; R50–53

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

006–047–00–3

xxxxxxxxx (XXX) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx

8065–36–9

X; X24/25 X; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xn; R22 X; R50–53

Xn; 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 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 N; R50–53

Xn; X X: 22–50/53 X: (2-)60-61

006–054–00–1

xxxxxxxxxx (ISO) 4-(xxxxxxxxxxxxx)-3,5-xxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

206–249–3

315–18–4

X+; R28 Xn; X21 X; X50–53

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

006–057–00–8

nitrapyrin (XXX) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; N 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; X22 X52–53

Xx X:22–52/53 X: (2-)61

006–069–00–3

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

245–740–7

23564–05–8

Xxxx. xxx. 3; X40 X; X50–53

Xx; X X: 40–50/53 X: (2-)36/37–60–61

006–070–00–9

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

262–302–0

60568–05–0

Karc. xxx. 3; X40 N; X50–53

Xx; X X: 40–50/53 X: (2-)36/37–60–61

006–088–00–7

benfurakarb (XXX) xxxxx-X -[({[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]karbonyl}methylamino)sulfanyl]-N-isopropyl-β-alaninát(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)-N-({[2-(ethoxykarbonyl)ethyl]isopropylamino}sulfanyl)-N-methylkarbamát

82560–54–1

T; X23/25 X; X50–53

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

007–012–00–5

N,N-dimethylhydrazin 1,1-xxxxxxxxxxxxxxxx

X

200–316–0

57–14–7

X; X11 Xxxx. xxx. 2; X45 T; X23/25 X; X34 X; X51–53

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

007–013–00–0

N,N-dimethylhydrazin 1,2-xxxxxxxxxxxxxxxx

X

540–73–8

Xxxx. xxx. 2; X45 X; R23/24/25 X; X51–53

X; N X: 45–23/24/25–51/53 S: 53–45–61

X ≥ 25 %: X; X45–23/24/25 3 % < X &xx; 25 %: X; R45–20/21/22 0,01 % &xx; X &xx; 3 %: X; R45

009–003–00–1

kyselina fluorovodíková … %

B

231–634–8

7664–39–3

T+; X26/27/28 X; X35

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

X ≥ 7 %: X+; C; 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 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx

201–676–1

86–50–0

X+; X26/28 X; X24 X43 X; X50–53

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

015–048–00–8

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

200–231–9

55–38–9

Xxxx. xxx. 3; R40 X; X23–48/25 Xx; X21/22 X; R50–53

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

015–056–00–1

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

220–147–6

2642–71–9

T+; R28 X; R24 X; X50–53

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

015–140–00–8

xxxxxxxxx (XXX) X,X-xxxxxxx-X-(1-xxxxx-1 X- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx

245–986–5

24017–47–8

X; X23/25 Xn; X21 X; R50–53

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

016–013–00-X

chlorid xxxxxxx

234–129–0

10545–99–0

X14 X; X34 X; X50

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

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

016–014–00–5

chlorid xxxxxxxx

13451–08–6

X14 X; X34 X; X50

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

C ≥ 10 %: X; X34 5 % ≤ C &xx; 10 %: Xx; X36/37/38

016–023–00–4

xxxxxxxx-xxxxxx

X

201–058–1

77–78–1

Xxxx. kat. 2; X45 Xxxx. xxx. 3; R40 X+; X26 X; X25 X; X34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; R22 X; X50–53

Xx; X R: 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 X: 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 S: (1/2-)7/8–26–36/37/39–45

X ≥ 10 %: C; X34 5 % ≤ X &xx; 10 %: Xx; R36/37/38

030–004–00–8

dimethylzinek [1] xxxxxxxxxxxx [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

X14 X; X17 C; X34 X; R50–53

F; X; N 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; X50–53

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

050–012–00–5

tetracyklohexylstannan [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] xxxxx(xxxxxxxxxxxxx)xxxxxxx [3]

215–910–5 [1] 221–437–5 [2] 230–358–5 [3]

1449–55–4 [1] 3091–32–5 [2] 7067–44–9 [3]

Xx; X20/21/22 X; R50–53

Xn; N X: 20/21/22–50/53 X: (2-)26–28–60–61

X ≥ 1 %: Xx; R20/21/22

1

050–017–00–2

fenbutatinoxid (XXX) 1,1,1,3,3,3-hexakis(2-fenyl-2-methylpropyl)distannoxan

236–407–7

13356–08–6

T+; R26 Xx; R36/38 N; X50/53

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

082–009–00–X

xxxx (xxxxxxxxxxxx olovnatý) XX Xxxxxxx Yellow 34 (XX 77603) CI xxxxxxxxxx xxxx 34 (XX 77603)

215–693–7

1344–37–2

Karc. xxx. 3; X40 Repr. xxx. 1; X61 Xxxx. xxx. 3; X62 R33 N; X50–53

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

1

082–010–00–5

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

235–759–9

12656–85–8

Xxxx. xxx. 3; R40 Xxxx. xxx. 1; X61 Xxxx. kat. 3; X62 X33 X; X50–53

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

1

601–024–00-X

xxxxx [1] xxxxxxxxxxxx [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

R10 Xx; R65 Xx; X37 X; R51–53

Xn; X X: 10–37–51/53–65 X: (2-)24–37–61–62

4

601–032–00–3

xxxxx[x]xxxxx benzo[def]chrysen

200–028–5

50–32–8

Karc. xxx.2; R45 Muta. xxx. 2; X46 Xxxx. xxx. 2; X60–61 N; X50–53

X; X X: 45–46–60–61–50/53 X: 53–45–60–61

601–034–00–4

xxxxx[x]xxxxxxxxxxxxxxx

205–911–9

205–99–2

Xxxx. xxx.2; X45 X; X50–53

X; X R: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-dichlorbenzen p-dichlorbenzen

203–400–5

106–46–7

Xi; X36 X; X50–53

Xx; X R: 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; X34

X 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; X21–48/22 X; X34

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

C ≥ 50 %: X; R21–23/25–34–48/22 25 % ≤ C &xx; 50 %: X; X21–23/25–36/38–48/22 10 % ≤ X &xx; 25 %: Xx; R20/22–48/22 3 % ≤ C &xx; 10 %: Xx; R20/22

603–091–00–0

exo-4-isopropyl-1-methyl-7-oxabicyklo[2.2.1]heptan-2-ol

402–470–6

87172–89–2

O; X8 Xx; R22 Xx; X36

X; Xn X: 8–22–36 X: (2-)26

603–093–00–1

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

402–410–9

87818–31–3

Xn; X20 X; X51–53

Xx; X R: 20–51/53 X: (2-)23-61

603–097–00–3

1,1', 1′′-nitrilotripropan-2-ol xxxxxxxxxxxxxxxxxx

204–528–4

122–20–3

Xx; X36 R52–53

Xi X:36–52/53 S: (2-)26-61

603–117–00–0

propan-2-ol xxxxxxxxxxxxxxxx xxxxxxxxxxx

200–661–7

67–63–0

X; X11 Xx; X36 R67

F; Xx X: 11–36–67 X: (2-)7–16–24/25–26

604–020–00–6

xxxxxxx-2-xx 2-hydroxybifenyl 2-xxxxxxxxxx (ISO)

201–993–5

90–43–7

Xi; R36/37/38 X; R50

Xi; X X: 36/37/38–50 X: (2-)22-61

604–021–00–1

2-xxxxxxxxxx, xxxxx sůl xxxxxxx-2-xxxxxxxxxxxx 2-bifenylát xxxxx xxxxxxx-xxxxxxx-2-xxxx

205–055–6

132–27–4

Xx; X22 Xx; X37/38–41 N; X50

Xx; X X: 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; N X: 60–36–50/53 X: 53–45–60–61

604–041–00–0

acifluorfen [1] xxxxxxxxxxx-xxxxxxx [2] 5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxxx kyselina [1] xxxxxxx-5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxx [2]

256–634–5 [1] 263–560–7 [2]

50594–66–6 [1] 62476–59–9 [2]

Xn; R22 Xx; R38–41 X; X50–53

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

604–043–00–1

xxxxxxxxxxxxxxxx (4-xxxxxxxxxxxx)xxxxx hydrochinonmonobenzylether 4-(xxxxxxxxx)xxxxx

203–083–3

103–16–2

Xx; X36 X43

Xx X: 36-43 X: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; X22 Xx; X36 X43

Xx X: 22–36–43 X: (2-)24/25–26–37/39–46

605–016–00–7

xxxxxxx… % ethandial… %

X

203–474–9

107–22–2

Xxxx. kat. 3; X40 Xx; R20 Xx; X36/38 R43

Xn X: 20–36/38–40–43 S: (2-)36/37

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

606–016–00-X

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

201–462–8

83–26–1

X; R25–48/25 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; R50–53

Xn; 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-xxxxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx

205–601–3

143–50–0

Xxxx. xxx. 3; X40 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

xxxxxxxxxx (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 X)-xx 4-amino-6-terc-butyl-3-(methylsulfanyl)-4,5-dihydro-1,2,4-triazin-5-on

244–209–7

21087–64–9

Xn; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

xxxxxxxxxxx (ISO) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx xxxxxxx

216–920–2

1698–60–8

X43 X; X50–53

Xx; N X: 43–50/53 S: (2-)24–37–60–61

606–036–00–9

xxxxxxxxxxxxxx (XXX) 6-xxxxxx-2 H-[1,3]dithiolo[4,5-b]chinoxalin-2-on

219–455–3

2439–01–2

Repr. xxx. 3; X62 Xx; R20/21/22–48/22 Xi; X36 R43 X; X50–53

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

606–037–00–4

xxxxxxxxxxx (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; X51–53

Xx; X X: 22–51/53 X: (2-)61

606–044–00–2

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

403–150–9

954–16–5

Xx; X22 Xx; R36 X; X50–53

Xx; X X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; X22 Xi; X41 X52–53

Xx; X X: 22–41–52/53 X: (2-)26-61

607–057–00–6

xxxxxxxxx (ISO) 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

xxxxxxxxx (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 H -chromen-2-on 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-furyl)-3-oxobutyl]-4-hydroxy-2 X -xxxxxxx-2-xx

204–195–5

117–52–2

X; R25–48/25 X52–53

X X:25–48/25–52/53 S: (1/2-)37–45–61

607–079–00–6

xxxxxxx (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx ethyl-5-(1,2,3,5,6,7,8,9,10,10-dekachlor-4-hydroxypentacyklo[5.2.1.02,6.03,9.05,8]dekan-4-yl)-4-oxopentanoát xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx

4234–79–1

X; X24 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-xxxxxxxx xxxxxx-1,2,4-xxxxxxxxxxxxxx kyseliny xxxxxxxxxxxxxxxxx

209–008–0

552–30–7

Xx; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx xxxxxxxx kyselina

203–677–2

109–52–4

C; X34 X52–53

X R:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xn; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

607–153–00–8

xxxxxxxxx (XXX) (4-chlor-2-oxo-2,3-dihydro-1,3-benzothiazol-3-yl)octová xxxxxxxx

223–297–0

3813–05–6

Xx; R36/38 R52–53

Xi X:36/38–52/53 X: (2-)22-61

607–156–00–4

xxxxxxxxxxx (XXX) 4-xxxxxxxxxx-4-xxxxxxxxxxx-1-xxxxxxxx

201–270–4

80–33–1

Xx; X22 Xx; X38 N; X50–53

Xx; N X: 22–38–50/53 S: (2-)37–60–61

607–158–00–5

sodná xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; R25 Xx; X38 X; X50

X; N X: 25–38–50 X: (1/2-)22–37–45–61

607–159–00–0

xxxxxxxxxxxxxx (XXX) ethyl-2,2-bis(4-chlorfenyl)-2-hydroxyacetát xxxxx-4,4'-xxxxxxxxxxxxxxx

208–110–2

510–15–6

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

607–176–00–3

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

400–830–7

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24/37–61

607–209–00–1

Xxxx: X,X′-xxxxxxxxxxx-xxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx)

403–030–6

Xx; X22 X43 X; X50–53

Xx; X R: 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; R7 X10 X; X51–53

X; X X: 2–7–10–51/53 X: (2-)3/7–14–33–36/37/39–61

607–217–00–5

2-xxxxxxxxxxx-[4-(7-xxxxx-2,6-xxxxx-2,6-xxxxxxx-1,5-xxxxx-x-xxxxxxx-3-xx)xxxxxx]xxxxxx

403–960–2

X43 X53

Xx X: 43-53 X: (2-)24–37–61

607–243–00–7

xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-hydroxyethyl)amonium-3,6-dichlor-2-methoxybenzoát [3] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [3]

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

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

X52–53

X: 52/53 X: 61

607–248–00–4

Xxxxxxxx-xxxxxxx Natrium-N-(1-naftyl)ftalamát

205–073–4

132–67–2

Xn; R22

Xn X: 22 X: (2)

607–249–00-X

(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx tripropylenglykol-diakrylát TPGDA

256–032–2

42978–66–5

Xi; X36/37/38 R43 X; X51–53

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

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

607–252–00–6

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

415–130–7

91465–08–6

X+; X26 X; X25 Xn; X21 X; X50–53

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

607–255–00–2

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

69377–81–7

X52–53

X: 52/53 X: 61

608–003–00–4

akrylonitril

D X

203–466–5

107–13–1

X; Xxx Karc. kat. 2; X45 X; X23/24/25 Xi; X37/38–41 X43 N; X51–53

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

X ≥ 20 %: X; X45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; R45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ X &xx; 5 %:X; X45–23/24/25–43 0,2 % ≤ C &xx; 1 %:T; 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 R: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 X+; X28 X; X24 X44 X; X50–53

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

609–040–00–9

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

X

217–406–0

1836–75–5

Xxxx. xxx. 2; X45 Xxxx. kat. 2; X61 Xx; R22 X; R50–53

T; N X: 45–61–22–50/53 X: 53–45–60–61

609–044–00–0

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

204–178–2

117–18–0

Xx; X22 X43 N; X50–53

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

611–008–00–4

4-aminoazobenzen 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. xxx. 2; X45 N; X50–53

X; 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; X51–53

X; X X: 2–51/53 X: (2-)35-61

611–031–00-X

4,4'-[(4-iminocyklohexa-2,5-dien-1-yliden)methylen]dianilin-hydrochlorid XX Xxxxx Xxx 9 XX basická xxxxxx 9

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X R: 45 X: 53-45

612–035–00–4

2-xxxxxxxxxxxxx x-xxxxxxxx

X

201–963–1

90–04–0

Xxxx. xxx. 2; R45 Xxxx. xxx. 3; X40 X; R23/24/25

T X: 45–23/24/25 S: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. kat. 1; X45 Xn; R22 X; X50–53

X; N X: 45–22–50/53 X: 53–45–60–61

X ≥ 25 %: T; X45–22 0,01 % ≤ X &xx; 25 %: X; R45

612–051–00–1

4,4'-diaminodifenylmethan xxx(4-xxxxxxxxxx)xxxxxx 4,4'-xxxxxxxxxxxxxxxx

X

202–974–4

101–77–9

Xxxx. xxx. 2; R45 Xxxx. xxx. 3; X40 X; X39/23/24/25Xx; R48/20/21/22 X43 X; X51–53

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

612–081–00–5

3,3'-xxxxxxxxxxxxxxxx, xxxx o-tolidin, xxxx

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; R45 Xx; R22 X; X51–53

X; X R: 45–22–51/53 S: 53–45–61

612–099–00–3

4-methyl-m-fenylendiamin4-methyl-1,3-fenylendiamin4-methylbenzen-1,3-diamin 2,4-xxxxxxxxxxxx

X

202–453–1

95–80–7

Xxxx. kat. 2; X45 X; X25 Xx; R21 Xx; X36 X43 X; X51–53

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

612–105–00–4

2-(xxxxxxxxx-1-xx)xxxxxxxxx2-(xxxxxxxxx-1-xx)xxxxx-1-xxxx

205–411–0

140–31–8

Xx; X21/22 C; X34 X43 X52–53

X X: 21/22–34–43–52/53 S: (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 Xx; 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; R20/21 X43 N; 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 X4 3 X; X50–53

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

612–151–00–5

xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx methylbenzendiamin

E

246–910–3

25376–45–8

Karc. xxx. 2; X45 X; X25 Xx; X20/21 Xx; X36 R43 X; X51–53

X; X X: 45–20/21–25–36–43–51/53 S: 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; X36/37/38 X52–53

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

613–031–00–5

xxxxxxxxx trichlorisokyanurová xxxxxxxx xxxxxxxx-1,3,5-xxxxxxxxxxxx 1,3,5-trichlor-1,3,5-triazin-2(1H), 4(3X), 6(5X)-xxxxx

201–782–8

87–90–1

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

X; Xn; X X: 8–22–31–36/37–50/53 S: (2-)8–26–41–60–61

613–038–00–3

6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxx xxxxxxxxxxxxx

202–095–6

91–76–9

Xx; X22 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 H-imidazol

252–615–0

35554–44–0

Xn; X20/22 X; X41 X; X50–53

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

613–043–00–0

xxxxxxxx-xxxxxx (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1X -imidazol-1-ium-hydrogensulfát [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 N; X50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; X22 X; X50–53

Xx; N R: 22–50/53 X: (2-)60-61

613–091–00–2

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

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; R22 Xx; X36/37/38 R52–53

Xn; X: 22–36/37/38–52/53 S: (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; R51–53

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

613–130–00–3

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

79983–71–4

X43 X; X51–53

Xx; X X: 43–51/53 S: (2-)24–37–61

613–131–00–9

xxxxxxxxxx (XXX) 1,2,5,6-xxxxxxxxxx-4 X-xxxxxxx[3,2,1-xx]xxxxxxxx-4-xx

57369–32–1

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–134–00–5

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

88671–89–0

Xxxx. xxx. 3; X63 Xx; R22 Xi; X36 X; X51–53

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

613–137–00–1

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

242–505–0

18691–97–9

X; X50–53

X X: 50/53 X: 60-61

613–139–00–2

metsulfuron-methyl xxxxxx-2-{X —[X-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxxx]xxxxxxxxx}xxxxxxx

74223–64–6

X; X50–53

X X: 50/53 X: 60-61

614–001–00–4

xxxxxxx (ISO) 3-(1-methylpyrrolidin-2-yl)pyridin

200–193–3

54–11–5

T+; X27 T; R25 X; X51–53

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

614–006–00–1

xxxxxx 2,3-dimethoxystrychnidin-10-on

206–614–7

357–57–3

T+; R26/28 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-methyl-1,3-fenylendiisokyanát [1] 4-xxxxxx-x-xxxxxxxxxxxxxxxxxx [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] x-xxxxxxxxxxxxxxxxxxxx [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [2] toluen-3,5-diisokyanát [3]

C

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

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

Xxxx. xxx. 3; X40 X+; X26 Xx; R36/37/38 X42/43 X52–53

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

X320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; R26–40–42/43 1 % ≤ X &xx; 7 %: X; X23–40–42/43 0,1 % ≤ X &xx; 1 %:Xn; X20–42

2

616–010–00–9

xxxxxxx-xxxxxxxxxxxxxx X-xxxxx-4-xxxxxxxxxxxx-1-xxxxxxxxxx, sodná xxx

204–854–7

127–65–1

Xx; X22 X31 X; R34 X42

X X: 22–31–34–42 X: (1/2-)7–22–26–36/37/39–45

616–034–00-X

xxxxxxxxxxxx (XXX) 6-methyl-3,4-dihydro-2H-pyran-5-karboxanilid

246–419–4

24691–76–7

R52–53

R: 52/53 X: 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 X; X50–53

Xx; X R: 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; X7 Xx; X22 X; X34 X; X50–53

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

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

617–006–00-X

xxx(α, α-dimethylbenzyl)peroxid bis(2-fenylpropan-2-yl)peroxid xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx dikumylperoxid

201–279–3

80–43–3

O; 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; R2 Xx; X36 X43

X; Xx; X: 2–36–43 S: (2-)3/7–14–36/37/39

650–007–00–3

xxxxxxxxxxxxx (XXX) X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx

228–200–5

6164–98–3

Xxxx. xxx. 3; X40 Xn; R21/22 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-chlorfenyl)hydrazono]-3-methylisoxazol-5(4 X)-xx

227–197–8

5707–69–7

X; X25 X; X50–53

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

650–009–00–4

chlordimeform-hydrochlorid X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx

243–269–1

19750–95–9

Xxxx. xxx. 3; X40 Xx; X22 X; X50–53

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

650–033–00–5

esfenvalerát (XXX) [(X)-(3-xxxxxxxxxxx)xxxxxxxxxx]-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx (S)-3-fenoxy-α-kyanbenzyl-(S)-2-(4-chlorfenyl)-3-methylbutanoát

66230–04–4

T; X23/25 R43 N; X50–53

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

650–041–00–9

xxxxxxxxxxxx (XXX) 1-[2-(2-xxxxxxxxxxx)xxxxxx-1-xxxxxxxx]-3-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxx

82097–50–5

X; X50–53

X X: 50/53 X: 60-61


XXXXXXX 1D

Indexové xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x látkám

Číslo 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 X52–53

Xx X: 20–41–52/53 X: (2-)22–26–39–61

014–016–00–0

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

406–490–6

N; X51–53

X R: 51/53 X: 61

015–164–00–9

xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx xxxxxxxx

400–480–5

36669–85–9

X52–53

X:52/53 X: 61

015–165–00–4

Xxxx: X, X, X', X''-xxxxxxxxxx-4,4'-xxxxxxxxxxxxx(xxxxxxxxxxxxxx)-xxx(xxxxxxxxxxxxxxxx) x xxxxxxx[4-(xxxxxxxxxxxxx)xxxxx]xxxxxxxxx-xxxxxxxxxxxxxxxx

404–986–7

Xx; X41 X; X50–53

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

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 X: 61

015–167–00–5

3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; R41

Xi X: 41 X: (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 N; X51–53

Xx; X X: 38–51/53 X: (2-)37-61

602–083–00–4

pentabromderivát difenyletheru xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; X48/21/22 R64 X; R50–53

Xn; X X: 48/21/22–50/53–64 S: (1/2-)36/37–45–60–61

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

X X: 52/53–59 S: 59-61

603–128–00–0

2-(fenylmethoxy)naftalen

405–490–3

613–62–7

R53

R:53 X: 61

603–129–00–6

1-terc-butoxypropan-2-ol

406–180–0

57018–52–7

R10 Xi; X41

Xx R: 10-41 X: (2-)26-39

603–130–00–1

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

406–325–8

Xx; R22 R52–53

Xn 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; R41

Xi 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 R52–53

Xi X:38–41–52/53 X: (2-)26–37/39–61

603–133–00–8

Xxxx:3-(4-xxxxx-2-xxxxx-5-xxxxxxxxxxxx)xxxxxx-1,2-xxxx x 3,3'-[(2-xxxxx-5-xxxxx-1,4-xxxxxxx)xxxxxxx]xx(xxxxxx-1,2-xxxx)

408–240–1

Xx; R22 X52–53

Xx R:22–52/53 S: (2-)22–36–61

603–134–00–3

Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx a 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; X41 X; X51–53

Xx; X 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 R:43–52/53 S: (2-)24–37–61

603–137–00-X

Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx

411–130–6

Xx; X41

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

603–138–00–5

3-(2,2-dimethyl-3-hydroxypropyl)toluen 2,2-dimethyl-3-(3-methylfenyl)propan-1-ol

403–140–4

103694–68–4

R52–53

R:52/53 X: 61

604–050–00-X

4-xxxxx-x-xxxxxx 4-xxxxx-2-xxxxxxxxxxx

216–381–3

1570–64–5

X; X23 X; X 35 X; R50

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

C ≥ 25 %: X; C; X23–35 10 % ≤ X < 25 %: X;X20–35 5 % ≤ X &xx; 10 %: X;X20–34 3 % ≤ X < 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 -xxxxxxxxxxxx-2-xx)- 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-xxxx - 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 -xxxxx-2-xx)xxxxx

412–020–0

X43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

604–055–00–7

4,4'-bis[(2,3-epoxypropyl)oxy]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx

413–900–7

85954–11–6

Xxxx. Xxx.3; R40

Xn X: 40 X: (2-)22–36–37

605–027–00–7

Xxxx:3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X-xxxxx-6-xxxxxxxxxxx x 3x, 4,5,6,7,7a-hexahydro-4,7-methano-1H - xxxxx-5-xxxxxxxxxxx

410–480–7

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-pentylcyklohexanon xxxxxxxxxxxxxxxx-1-xx

4–406–670–4

61203–83–6

X; X51–53

X X: 51/53 X: 61

606–052–00–6

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

410–410–5

54574–82–2

X52–53

X:52/53 X: 61

607–272–00–5

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

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

X; X50–53

X X: 50/53 X: 60-61

607–273–00–0

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 X: (2-)24–37–61

607–275–00–1

natrium-4-(benzoyloxy)benzen-1-sulfonát

405–450–5

66531–87–1

R43

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

607–276–00–7

[xxx(2-xxxxxxxxxxxxxx) bis(1-methylimidazol)]zinečnatý komplex

405–635–0

Xi; X38–41 N; X50–53

Xx; X R: 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 Xx; X41 R43 N; X51–53

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

607–278–00–8

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

405–760–0

Xx; X41 X43 X52–53

Xx X: 41–43–52/53 S: (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; R51–53

Xi; X X: 43–51/53 S: (2-)24–37–61

607–280–00–9

4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx xxxxx natrium-4-chlor-1-hydroxybutan-1-sulfonát

406–190–5

54322–20–2

Xn; X22 Xx; X36 X43

Xx X: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

Xxxx:xxxxx(X7-X9 xxxxxxxxxx x lineární)-3-[3-(2H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty

407–000–3

127519–17–9

N; R51–53

N X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 S: 61

607–283–00–5

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

408–040–4

15121–89–8

Xx; X21/22 Xx; X38–41 R43 X; X50–53

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

607–284–00–0

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

Směs:7-(3-aminobenzensulfonamido)naftalen-1,3-disulfonová xxxxxxxx, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx x xxxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx

410–065–0

X43

Xx X: 43 X: (2-)22–24–37

607–286–00–1

Xxxx:xxxxxx- a xxxxxxx-7-[4-({4-[(2-xxxxxxx-1-xxxxxx)xxx]xxxxx}xxx)xxxxxxxxxxxxxxxxx]xxxxxxxx-1,3-xxxxxxxxxx

410–070–8

141880–36–6

X43 X52–53

Xx 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 sůl; c = 15, 16, 17 nebo 18, x = 1, 2, 3 xxxx 4, x = 8, 9, 10 xxxx 11, x = 22, 23, 24 xxxx 25

410–160–7

148732–74–5

Xi; X36 R43 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 xxxxxxxx

410–370–9

105488–33–3

X53

X:53 X: 61

607–290–00–3

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

410–540–2

Xx; R38 R43 X; X50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx

410–630–1

104051–92–5

X53

X: 53 X: 61

607–292–00–4

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-XXxxx:

1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx 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

Xxxx:xxxxxxxxxxxx-xxxxxxxxxxxxxxxxx a xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx

410–800–5

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

607–296–00–6

Xxxx:xxxxxxxxxxx pentaerythritolu, xxxxxxxxx kyselina x 2-xxxxxxxxxxxxx kyselina

410–830–9

R53

R: 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 R: 41 X: (2-)26-39

607–298–00–7

[2-(trimethylamonio)ethyl]-4-sulfonatobenzoát

411–010–3

R43

Xi X: 43 S: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 X43 X; R50–53

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

607–300–00–6

[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, d-sulfonatoftalocyanin]měďnatý xxxxxxx, xxxxxxxx xxx; a = 1,2,3 nebo 4, x = 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

Směs:dodekanová kyselina x xxxxxxxxxxx oligo(1-7)laktátů

411–860–5

Xi; X38–41 X43 X; X51–53

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

607–302–00–7

Xxxx:xxxxxxxxxxxxx xxxxxxxx a tetradekanoáty xxxxx(1-7)xxxxxxx

411–910–6

Xx; X38–41 X43 X; X51–53

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

607–303–00–2

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

413–760–7

93107–30–3

Repr. xxx.3; X62 X52–53

Xx R: 62–52/53 X: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; R50–53

N R: 50/53 X: 60-61

608–024–00–9

2-{4-[butyl(fenethyl)amino]fenyl}ethen-1,1,2-trikarbonitril

407–650–8

97460–76–9

R53

R:53 X: 61

608–025–00–4

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

410–970–0

117568–27–1

X53

X:53 X: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; R3 X; X8 Karc. xxx. 2; R45 X; X23/25 X43

X; X X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 C; X34 R43 N; X50–53

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

611–043–00–5

Směs (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx, [xxx{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx trisodný a[{6-[(2-amino-4-hydroxyfenyl)azo]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx

402–850–1

Xx X: 41–52/53 X: (2-)26–39–61

611–044–00–0

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; X25 Xx; X48/22 X43 X; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

R53

R: 53 X: 61

611–048–00–2

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

407–900–6

111381–12–5

X53

X: 53 S: 61

611–049–00–8

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

408–000–6

118658–98–3

Xx; X48/22 X43 X52–53

Xx X: 43–48/22–52/53 X: (2-(22–36/37–61

611–051–00–9

2-({4-[ethyl(2-hydroxyethyl)amino]-2-methylfenyl}azo)-6-methoxy-3-methylbenzothiazolium-chlorid

411–110–7

136213–74–6

N; X50–53

X X: 50/53 X: 60-61

611–052–00–4

[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) azo]-6-[(6-sulfonato-1-naftyl)azo]benzen-1,3-diolato}]železnatý xxxxxxx, xxxxx sůl

400–720–9

R52–53

R: 52/53 X: 61

612–156–00–2

Xxxx:xxxxxxxxxxxx(xxxxxx)xxxxxxx-xxxxxxx x xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx

405–620–9

Xx; X41 N; X50–53

Xx; X X: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

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

410–780–8

Xx; X22–48/22 Xx; R41 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 xxxxxxx x 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

X53

X: 53 X: 61

612–159–00–9

xxxxxxx xxxxxxxx směsi 2,2,4-xxxxxxxxx- x 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x xxxxxxx EINECS), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Epoxid 8) x 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; X23/25 X; X50–53

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

613–150–00–2

2,2'-[xxxxxxxxx-1,4-xxxxxx(xxxxxx-1,3-xxxx)]xxx(xxxxxxxxxxx[2,1-x]xxxxx[xxx][3,8]xxxxxxxxxxxx-1,3,6-xxxxx)

406–295–6

X53

X:53 X: 61

613–151–00–8

1-(2-deoxy-3-O-mesyl-5-O-trityl-β-D-threo-pentofuranosyl)-5-methylpyrimidin-2(1H), 4(3 H)-dion

406–360–9

104218–44–2

R53

R:53 X: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 N; 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 X: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx X: 22 S: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; R22 R52–53

Xn 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 X; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

613–157–00–0

2,4-diamino-5-(methoxymethyl)pyrimidin 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-xxxxxxx-5-(xxxxxxxxxxxxxx)xxxxxxx

410–340–5

69045–84–7

Xx; X20/22 Xx; X41 R43 X; X51–53

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

613–159–00–1

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

410–580–0

120928–09–8

X; R25 Xn; X20 X; X50–53

X; X X: 20–25–50/53 X: (1/2-)37–45–60–61

613–160–00–7

2-xxxxxx-2,5-xxxxxxxxxxxx[2.2.1]xxxxxx-xxxxxxxxxxxxx

411–000–9

125224–62–6

X43

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

615–022–00–1

methyl-3-(isokyanatosulfonyl)thiofen-2-karboxylát

410–550–7

79277–18–2

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

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

615–023–00–7

xxxxxxxxxxx 2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxxx xxxxxxxxxxxxxx-2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxx

410–900–9

83056–32–0

X10 X14 Xxxx. xxx. 3; X40 Xn; X20–48/22 Xx; X41 X42

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

616–044–00–4

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

402–510–2

X; R51–53

N X: 51/53 X: 61

616–045–00-X

2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxxxxx

405–190–2

122371–93–1

X43 X53

Xx X: 43-53 X: (2-)22–24–37–61

616–046–00–5

X -[2-(6-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′′′ (xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx x N, X′,X″,X′′′ - tetraalkyl(C18)- 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 N; R51–53

Xn; X X: 48/22–51/53 X: (2-)22–36–61

616–049–00–1

2-(2,4-di-terc-butylfenoxy)-N-(3,5-dichlor-4-ethyl-2-hydroxyfenyl)hexanamid

408–150–2

99141–89–6

R53

R:53 S: 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 X; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

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

411–070–0

R53

R: 53 X: 61

617–015–00–9

bis(4-methylbenzoyl)peroxid

407–950–9

895–85–2

E; R2 X; R7 X; X50–53

X; N R: 2–7–50/53 X: (2-)7–14–36/37/39–47–60–61

650–032–00-X

xxxxxxxxxxxx (XXX) (2X, 3X)-, (2 S, 3 X)-, (2 X, 3 X)-, (2 X, 3 X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxx-1-(1X- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

94361–06–5

Xxxx. xxx. 3; X63 Xn; R22 X; X50–53

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


XXXXXXX 2

POVAHA XXXXXXXXXXXX XXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. xxxx. L 332, 28.12.2000, s. 81.


XXXXXXX 3A

STANDARDNÍ POKYNY XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY

Viz směrnice Xxxxxx 2001/59/ES,

Úř. věst. X 332, 28.12.2000, x. 81.


PŘÍLOHA 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI X XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.


PŘÍLOHA 4X

"X.10 XXXXXXXXXX — XXXXXXX XX XXXXXXXXXXXX XXXXXXX U XXXXX IN XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxxx xx xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx chromozomové xxxxxxx x xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx aberací: chromozomové x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, avšak xxxxxxxxxxxx xxxxxxx xx xxxxxx vyskytují. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx chemická xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx aberace. Xxxx xxxxxx xxxx xxxx xxxxxx xx stanovení xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxx jevy jsou xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x existuje xxxxx důkazů x xxx, xx xxxxxxxxxxxx xxxxxx x x xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx a x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx nádory, xxxx xxxxx xx xxxxxxx xxxxxxxx x člověka x x xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxx být xxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx, buněčné xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx. Xxxxxxx xxxxx xxxx vybrány xx xxxxxxx xxxxxxxxxx xxxxx x xxxxxxx, xxxxxxxx xxxxxxxxx, počtu xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x savců. Xx xxxxx se xxxxx xxxxxxxxx podmínek, které xx xxxxx k xxxxxxxxxx výsledkům, xxx xxxxxxxxxx vlastní mutagenitu x může x xxx xxxxx xxxxxx xX, osmolality xxxx xxxxxxxx úrovní cytotoxicity (4, 5).

Tato xxxxxxx xx xxxxxxx xx xxxxxxxx možných xxxxxxxx x xxxxxxxxxxx xxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx pro xxxxx xxxxxxxxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx důkazy x tom, že xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx zjištěny xxxxx xxxxxxxx, xxxxx zřejmě xxxxxx xxxxxx xxxxxxxxxx xxx přímým poškozením XXX.

Xxx také Xxxxxx xxxx, část X.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx zlomu xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx a opětného xxxxxxx xxxxxxxxx.

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

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

Xxx : xxxxxxxxxxxx xxxx menší xxx šířka xxxxx xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx xxxxx : podíl xxxxx, xxxxx se xxxxxxxxx x xxxxxxxx, x xxxxxxxxx xxxxx xxxxx x xxxxxxxx; xxxxx xxxxxx xxxxxxxxxxx xxxx populace.

Numerická xxxxxxx : odchylka xxxxx xxxxxxxxxx xx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxx xxxx xxxxx.

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

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx xxxxxx ve xxxxxx xxxxxxxx; xxxx xx xxxx xxxxxx x fragmenty, intrachromozomální xxxx interchromozomální xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx jsou xxxxxxxxx xxxxxxxx látce, a xx x metabolickou xxxxxxxx x bez xx. V xxxxxx xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx látce se xx buněčných kultur xxxxx látka xxxxxxxxxxx xxxxxxxx (xxxx. Colcemid® xxxx kolchicin), kultury xx xxxxxx, obarví x přítomnost xxxxxxxxxxxxxx xxxxxxx xx zjistí xxxxxxxxxxxxxx xxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Mohou xxx xxxxxxx různé buněčné xxxxx, kmeny nebo xxxxxxxx xxxxxxx kultury, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (např. xxxxxxxxxxx xxxxxx xxxxxxxx, xxxxxxxxx xxxxxxxxx krve člověka xxxx jiných xxxxx).

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx udržování xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (kultivační xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). U xxxxxxxxxxxxxxx xxxxxxxxx linií x kmenů xx xxxx xxx rutinně xxxxxxxxxxxx stabilita xxxxxxx xxxxxxx xxxxx xxxxxxxxxx x xxxx by xxx kontrolováno, xxx xxxxxx xxxxxxxxxxxxx mykoplasmaty; x xxxxxxx xxxxxxxxxxx xx xxxxxx být xxxxxxx. Xxx xxxxxxx xxxxx x inkubační xxxxxxxx by xxxx xxx xxxxx normální xxxxx xxxxxxxxx xxxxx.

1.4.1.3 Xxxxxxxx kultur

Stabilizované xxxxxxx xxxxx a xxxxx: xxxxx se pomnoží x xxxxxxxxx xxxxxx, xxxxxx xx xx xxxxxxxxxxxx média v xxxxxx hustotě, xxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx, a xxxxxxxx xx xxx 37 °X.

Xxxxxxxxx: krev xxxxxxxx xxxxxxxxxxxxxxx (xxxx. xxxxxxxxx) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx probandů xx xxxxxxx xx xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. fytohemaglutinin) a xxxxxxxx se xxx 37 °X.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx vystaveny zkoušené xxxxx, x xx x vhodnou xxxxxxxxxxxx xxxxxxxx a xxx xx. Nejčastěji používaným xxxxxxxx xx xxxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx z xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Aroclor 1254 (6, 7, 8 x 9), xxxx směs xxxxxxxxxxxxx x β-xxxxxxxxxxxx (10, 11 a 12).

Postmitochondriální xxxxxx xx x xxxxxxxx xxxxxxxxxx médiu xxxxxxx xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % obj. Xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx může xxxxxxx xx xxxxx xxxxxxxx xxxxx, která je xxxxxxxx. X některých xxxxxxxxx xxxx xxx xxxxxx použít xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx výsledků xxxxxx, xxxxxx přípravy xxxxxxxxx modifikovaných xxxxxxxxx xxxxx xxxxxxxxxxxxx specifické xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx xx xxxx xxx vědecky xxxxxxxxxx (např. důležitostí xxxxxxxxx xxxxxxxxxx X450 xxx metabolismus zkoušené xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx být xxxx xxxxxxxx xx buňky xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x testovacím xxxxxxxx x/xxxx mohou xxx xxxx aplikací xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx látky, pokud xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx mělo být xxxx podezření, že xxxxxxx xx xxxxxxxxx xxxxxx, a xxxx xx být xxxxxxxxxx x xxxxxxxx buněk x s xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo by xxx xxxxxx zařazení xxxxxxxxx údaji o xxxxxx kompatibilitě. Doporučuje xx xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx látek xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx rozpouštědla neobsahující xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, která xxxx xxx xxxxxxxxxx xxx xxxxxxxxx nejvyšší koncentrace, xxxxx cytotoxicita, rozpustnost x xxxxxxxxxx xxxxxxx x změny pH xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x metabolickou aktivací x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx vhodných xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, xxxx xxxx xxxxxx konfluence, xxxxx xxxxxxxxxxxxxxx buněk xxxx mitotický xxxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx alespoň xxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx cytotoxicity by xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx dané xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, což obvykle xxxxxxx, že xx xx koncentrace neměly xxxxx více nežli xxxxxxxx 2 až Ö10. X xxxxxxxx xxxxxxx xx měla xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx snížení stupně xxxxxxxxxx, xxxxx buněk xxxx xxxxxxxxxxx xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx je xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx nebo cytostatických xxxxxx a závisí xx xxxx, která xxxxxxxx xx expozice. Xxxxxxxxx index je xxxx přijatelný u xxxxxxxxxxx xxxxxx, x xxxxx mohou být xxxx xxxxxx stanovení xxxxxxxx xxxxxxx x xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (AGT), xxxxx xxx xxxxxxx xxxx xxxxxxxxx informace. V xxxxxxx XXX xxxx xxx x xxxxxxxx xxxxxxxxx hodnotu, z xxx xxxxx xxxxxxx xx existenci xxxxxxxxxx xxxxxxxxxxx, a i xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx xxxx xxx xx xxxxxxxx xxxxx podstatné xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

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

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx látek, které xxxxxx xxxxxxx xxx xxxxxxxxxxxxx nižších, xxx xx xxxxxx rozpustnost, xx xxxx být xxxxxxx nejvyšší xxxxx x xxxxxxxxxxx, xxx xx xxx xxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxx xxxxxxxx. X xxxxxxxx případech (xxxx. projeví-li se xxxxxxxx pouze xxx xxxxxxx koncentracích, xxx xx xxxxxxxxxxx) xx xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, při xxxxx xxxxxxx ke xxxxxxx. Xxxx xxx xxxxxxxx xxxxxxxx rozpustnost xx xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx v xxxxxxxxxx xxxxxxx xx může x xxxxxxx xxxxxxxx xxxxx x důsledku xxxxxxxxxxx buněk, xxxx X9 xxx. Xxxxxxxxxxxxx xxx zjistit xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x negativní xxxxxxxx (kontroly xxxxxxxxxxxx xxxx vehikula). Xxx xxxxxxx metabolické xxxxxxxx xx měla xxx xxx pozitivní xxxxxxxx xxxxxxx xxxxxxxx látka, xxxxx k xxxxxxxxx xxxxxx vyžaduje aktivaci.

K xxxxxxxxx xxxxxxxx xx xxx xxx použit xxxxx xxxxxxxxx v xxxxxxxxxxx koncentracích, xxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x detekovatelný xxxxxx xxx pozadí, čímž xx xxxxxxx xxxxxxxxx xxxxxxxxxxx systému.

Koncentrace xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx tak, xxx xxx účinek xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx:

Xxxx metabolické xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx podle 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 vnější metabolickou xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

Xxx xxxxxxxxx xxxxxxxx mohou xxx xxxxxxx i jiné xxxxxx xxxxx. Xxx xxxxxxxxx kontrolu xx xxxx být xxxxx xxxxx vzato x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx.

X okamžiku xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx se xx xxxxxxxxx rozpouštědla xxxx xxxxxxxx v xxxxxxxxxxx médiu a xxxxxxxxxx xxxxxxx způsobem xxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx xxxxx žádné xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené rozpouštědlo xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx účinky.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky xx xxxxxxx xxxxxxxx xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx bez xxxx. Xxxxxxxx xxxxxxxxx xx xxxx být xxxxxxxx xxx 48 hodin xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx xxxxxx xxxxxxxxxxx xx xxxx být xxxxxxx použity duplicitní xxxxxxx, x xxxxx xx důrazně xxxxxxxxxx x xxxxxx xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxx. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx údajů xxxxxxxx (13, 14), že xxxx duplicitními kulturami xx minimální rozdíl, xxxx xxx xxxxxxxxx xxxxxxx xxxxxx kultury.

Plynné xxxx xxxxxx xxxxx xx měly xxx xxxxxxxx vhodnými metodami, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx nádobách (15, 16).

1.4.3.3 Xxxx xxxxxxx xxxxxx

X xxxxxx xxxxxxxxxxx xx měly xxx xxxxx vystaveny xxxxxxxx látce, jak x xxxxxxxxxxxx xxxxxxxx, xxx bez ní, xx xxxx 3 — 6 xxxxx, x měly xx xxx xxxxxxxx po xxxxxx xxxx xx xxxxxxxx xxxxxxxx, která xxxxxxxx 1,5násobku xxxxxxxx xxxxx buněčného cyklu (12). Xxxxxxxx xxxxx xxxxxx dává xxxxxxxxx xxxxxxxx xxx x xxxxxxxx, xxx bez xxxxxxxx, měl xx xxx xxxxxxxx dodatečný xxxxxxxxxx bez aktivace x nepřetržitou xxxxxxxx xx xx xxxxxx x xxxx, která xxxxxxxx 1,5násobku normální xxxxx xxxxxxxxx cyklu. Xxxxxx xxxxxxxx xxxxx xxx snáze detekovat xxx dobách aplikace xxxx xxxxxx xxxxxxx xxx 1,5násobek xxxxx xxxxx. Xxxxxxxxx výsledky xxx metabolické aktivaci xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. X xxxxxxxxx, xxx xx nepovažuje xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, xx xxxx xxx xxxxxx xxxxxxxxxx.

1.4.3.4 Xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx

Xx xxxxxxx xxxxxxx se xxxxxxx 1-3 xxxxxx xxxx xxxxxxxxx xxxxx Colcemid® xxxx kolchicin. Pro xxxxxxxx xxxxxxxxx pro xxxxxxx xxxxxxxxxx xx xxxxx buněčná kultura xxxxxx a xxxxxxxxxx xxxxxx. Příprava xxxxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx a obarvení xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx kontrol, xx měly xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx fixaci xxxxx dochází xx xxxxx xxxxx buněk x metafázi x xx ztrátě xxxxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxx xxxxxxx xxxxxxx ± 2 pro všechny xxxx xxxxx. Xx xxxxxx koncentraci x xxxxxxxx xx xxxx xxx hodnoceno alespoň 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx mezi duplicitní xxxxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx.

Xxxxxx je xxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx aberace, xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxxxxxx, jsou-li xxxxxxxxxx.

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx x mělo xx xxxx být xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (aberacemi) xxxxxxxxx x procentech. Xxx xxxxxxxxx a xxxxxxxxxxxxxx xxxxxxx xx xxxx xxx uvedeny xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich xxxxxx a xxxxxxxx. Xxxx se zaznamenávají xxxxxxxx x uvádějí xx, ale nezahrnují xx xx xxxxxxx xxxxxxxx aberací.

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

Xxxx xx xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxx. Xxxx xx měly xxx xxxxxxx xxxxx xxxxxxx xx formě tabulky.

Ověření xxxxx xxxxxxxxx xxxxxxxx xx nepožaduje. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, nejlépe x xxxxxxxx experimentálních podmínek. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxx diskutována x xxxx 1.4.3.3. Xxxxx parametrů xxxxxx x xxxxx rozšířit xxxxxx posuzovaných xxxxxxxx xx xxxx být xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx xx xxxxx být změněny, xxxxx xxxxxxx xxxxxxxxxxx x xxxxxxxx metabolické xxxxxxxx.

2.2 HODNOCENÍ A XXXXXXXXXXXX VÝSLEDKŮ

Pro stanovení xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na xxxxxxxxxxx, nebo reprodukovatelný xxxxxx tohoto xxxxx. Xxxxxxxx xx xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků zkoušky xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Statistická xxxxxxxxxx xx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx.

Xxxxxx xxxxx polyploidie xxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx má xxxxxxxxx potlačit mitotické xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx počtu xxxxx x endoreduplikovanými chromozomy xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx progresi xxxxxxxxx xxxxx (17, 18).

Xxxxxxxx xxxxx, xxxxx xxxxxxxx nesplňují xxxx xxxxxxx kritéria, se x xxxxx xxxxxxx xxxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx poskytne xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech neumožní xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou zůstat xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx látka xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- zdůvodnění xxxxx vehikula,

- xxxxxxxxxxx x xxxxxxx xxxxxxxx xxxxx v rozpouštědle/vehikulu, xx-xx xxxxx.

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxxxxxxx xxxxxxxxx a xxxxxxxx xxxxxxxxx xxxx xxxxx,

- popřípadě nepřítomnost xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxx xxxx, xxx byla xxxxxxx xxxx krev xxxx xxxxxxxxxx lymfocyty, použitý xxxxxxx,

- případně xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxx koncentrací x xxxxx kultur, xxxxxx xxxx. xxxxx x xxxxxxxxxxxx a xxxxxx xxxxxxxxxxxx, xxxx-xx x xxxxxxxxx,

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x přidané xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxx xxxxxxxx,

- xxx a xxxxxxx xxxxxxxxx metabolického xxxxxxxxxxx xxxxxxx, včetně kritérií xxxxxxxxxxxxx,

- xxxxxxxxx a xxxxxxxxx kontroly,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx aberací,

- xxxxx xxxxxxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity, xxxx. xxxxxx xxxxxxxxxx, xxxxx x xxxxxxxx xxxxx, xxxxx buněk, xxxxxxxxx index,

- xxxxxx xxxxxxx,

- údaje o xX a xxxxxxxxxx xxxxxxxxxxx xxxxx, pokud xxxx xxxxxxxxx,

- xxxxxxxx xxxxxxx, xxxxxx gapů,

- xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxx xxxxxxx xxxxxx xxx každou exponovanou x kontrolní kulturu,

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

- xxxxxxxxx xxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx kontrole x xxxxxxxxx, středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

2) Xxxxxxxx, M. Xx., Xxxxxx, X. (1985), The Xx xxxxx Xxxxxxxxxxx Aberration Xxxx Xxxxx Chinese Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Xxxxx xx Xxxxxxx, in: Progress xx Mutatation Xxxxxxxx, Xxx. 5, Xxxxx, X. et xx., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Galloway, S. X., Xxxxxxxxx, M. X., Reuben, X., Xxxxxx, S., Brown, X., Xxxxxx, X., Xxxxx, A. X., Xxxxxxxx, F., Ahmed, X., Duk, S., Xxxxx, X., Xxxxxxxx, X. X., Resnick, X. X., Xxxxxxxx, X., Xxxxxx E. (1978), Chromozome aberration xxx xxxxxx xxxxxxxxx xxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx cells: Xxxxxxxxxx of 108 xxxxxxxxx, Xxxxxxx. Molec. Xxxxxxx. 10 (suppl. 10), 1-175.

4) Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxxx, R. X., Ishidate, X. Xx., Xxxxxxx, X., Xxxxx, X., Myhr, X. X. (1991), Xxxxxxxxxxxx under Extreme Xxxxxxx Xxxxxxxxxx. A xxxxxx from XXXXXX Xxxx Group 9, Xxxxxxxxxx Xxx., 257, 147-204.

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

6) Ames, X. X., XxXxxx, X., Xxxxxxxx, E. (1975), Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx with the Xxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxx Res., 31, 347-364.

7) Maron, X. M., Ames, X. X. (1983), Xxxxxxx Methods xxx xxx Salmonella Xxxxxxxxxxxx Xxxx, Mutatation Xxx., 113, 173-215.

8) Xxxxxxxxx, X. T., Xxxxx, X. X., xxx Xxxx, P. P. X., Meijers, X., xx Vogel, X. (1976), Xxxxxxxxxxx Xxxxxxx xx Xxxxxxx/Xxxxxxxxxxx xxxxx Xxxxxxxxxx xx x Xxxxxxxxxxx System Xx xxxxx, X. Xxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xxx Xxxxxx Chromatid Xxxxxxxx by Xxxxxxxxxxxxxxxxxx (XXX) and Xxxxxxxxxxxxxxxxxxx (XXX) in XXX Xxxxx in xxx Xxxxxxxx of Xxx-Xxxxx Xxxxxxxxxx, Mutatation Xxx., 37, 83-90.

9) Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, M. Jr. (1979), Xxxxxxxxxxx Xxxxxxxxxx Xxxxx on 29 Xxxxxxxxx Xxxxxxxx xxxx X9 Xxx Xx xxxxx, Xxxxxxxx Res., 66, 277-290.

10) Xxxxxx, X. M., Xxxxxx, X. D., Xxxxxxx, X. X., Xxxxxxxxx, X. G., Xxxxxx, X. X., Xxxxxx, X. X., Wolf, X. X. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Party. Xxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 xx Xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, T., Sawamura, X., Xxxx, X., Xxxxxxxx, T. (1976), X. Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx of Metabolic Xxxxxxxxxx Systems, in: xx Serres, X. X., Xxxxx, X. X. Xxxx, X. X., Xxxxxxx, X. X. (eds), Xx xxxxx Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Testing, Xxxxxxxx, North-Holland, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, M. X., Xxxxxxxx, X. Xx., Xxxxx, J. X., Xxxxxxxx, X. J., Xxxxxx, T., Mosesso, X., Xxxxxx, T. (1994), Xxxxxx from Xxxxxxx Xxxxx on Xx xxxxx Tests xxx Xxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Res., 312, 241-261.

13) Xxxxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X. A., Xxxxxxxx, X., Xxxxxxx, X. X., Xxxxxxxx, X. (1989), Analysis xx Xxxx from Xx xxxxx Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. X., (xx) Xxxxxxxxx University Press, Xxxxxxxxx, 141-154.

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

15) Xxxxx, D. X., Xxxxxx, X. X., XxXxxxx, X. T. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Xxxxxxxxxx of Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Tice, X. X., Xxxxx, X. L., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, P. X., Xxxxxx, J. M., Xx, X. X., Xxxxxx, X. X. (1983), Evaluation of xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Highly Xxxxxxxx Xxxxxxxx in xxx CHO/HGPRT Mutation Xxxxx, Xxxxxxxxxxxxx Mutagen., 5, 795-801.

17) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx xxxxxx alpha-radiation xxxxxxx X2 arrest, Xxxxxxxxxx Xxx., 119, 403-413.

18) Huang, Y., Xxxxxx, X., Trosko, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx xx Xxxxxxx hamster xxxxx, Xxxxxx Xxx., 43, 1362-1364."


XXXXXXX 4X

"X.11 MUTAGENITA–ZKOUŠKA XX CHROMOZOMOVÉ XXXXXXX X XXXXXXX XXXXXX XXXXX SAVCŮ IN XXXX

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX TG 475 — Zkouška na xxxxxxxxxxxx aberace x xxxxxxx xxxxxx dřeně xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx v xxxxxxx kostní dřeně xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Rozlišují xx xxx xxxx strukturních xxxxxxx — xxxxxxxxxxxx x chromatidové. Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx xx schopnost xxxxxxxxx xxxxxxxxx aberace. X xxxxxxx většiny chemických xxxxxxxx jsou indukované xxxxxxx chromatidového typu, xxxxx xxxxxxxxxxxx aberace xx rovněž xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx x související xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx tlumících nádory, xxxx podíl xx xxxxxxx rakoviny x xxxxxxx a x xxxxxxxxxxxxxxxx systémech.

Při xxxx xxxxxxx jsou rutinně xxxxxxxxx hlodavci. Xxxxxxx xxxxx xx x xxxx zkoušce xxxxxx xxxx, poněvadž je xxxxxx xxxxxxxxxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx s xxxxxxx xxxxxx, xxxxx se xxxxxx izolují x xxxxxxxxxxxx. Xxxx xxxxx x xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx zkouška xx xxxxxxxxxxxx xxxxxxx xx xxxxxxx xxxxxx x xxxxxxxxx nebezpečí xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a xxxxxxx reparace DNA, xxxxxxx se xxxxx x xxxxxxx xxxxx x xxxxx xxxxx. Xxxxxxx xx vivo xx xxxxxx xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx metabolity xxxxxxxxxx xx cílové tkáně, xxxx xxxxxx xxxx xxxxxxx použít.

Viz také Xxxxxx úvod, část X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx v xxxxxx xxxxx jednotlivých xxxxxxxxx xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx a spojení xxxx xxxxxxxxx x xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : xxxxxx, xxx xxxxxx x jádře xx X-xxxx xxxxxxxxx DNA xxxxxxx k mitóze, xxxxx následuje další X-xxxx. Xxxxxxxxx xxxx xxxxxxxxxx se 4, 8, 16,… chromatidami.

Gap : xxxxxxxxxxxx xxxx xxxxx než xxxxx xxxxxxx xxxxxxxxxx a x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx aberace : xxxxxxxx xxxxx xxxxxxxxxx xx normální xxxxxxx xxxxxxx x použitých xxxxx.

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

Xxxxxxxxxx xxxxxxx : mikroskopicky pozorovatelné xxxxx xxxxxxxxx xxxxxxxxxx xxx buněčném dělení xx xxxxxx xxxxxxxx; xxxx xx xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xx xxxxxxx xxxxxxxx po xxxxxxxx se xxxxxx. Xxxx usmrcením xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx metafázi (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X buněk kostní xxxxx xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx se x xxxxxxxxx xx chromozomové xxxxxxx buněk v xxxxxxxx.

1.4 POPIS ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx xxxxxxxx potkan, xxx x xxxxxx xxxxxx, xxxxxx lze xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Měly xx xxx použity xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx by u xxxx xxxxxxx překročit ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx vystaví zkoušené xxxxx. Klece xx xxxx být uspořádány xxx, aby byl xxxx xxxxxx polohy xxxxxxxxxxxxx. Zvířata se xxxxxxxxxxx identifikují. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx být xxxx aplikací zvířatům xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech a xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx mohou xxx xxxxxxxx přímo xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých xxxxxxxx xxxxx toxické xxxxxx x mělo xx být vyloučeno xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx použita xxxx xxx xxxxx rozpouštědla/vehikula, xxxx by být xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí každého xxxxxxxxxxx xx měly xxx pozitivní a xxxxxxxxx (rozpouštědlo/vehikulum) kontroly xxx obě pohlaví. X výjimkou xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx podstoupit identický xxxxxx jako xxxxxxx xx skupinách, v xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx strukturní xxxxxxx in vivo xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx nad xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxx, xxx byl účinek xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx byla xxxxxxxxx xxxxxxxx podávána xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx xxx xxxxx x jejím xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx být xxxxxxx xxxxxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx EINECS

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

mitomycin X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx

51–18–3

200–083–5

X xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx u negativních xxxxxxx, xxxx xx xxxxxxxxxx pouze xxxxxxxxxxxx xxxx xxxxxxxxx a xxx xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx zvířat x xxxxxxxx xxxxx x chromozomovými xxxxxxxxx. Xxxxxxx-xx se xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx nejvhodnějším xxxxxxxxx xxxx prvního xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, neexistují-li xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx/xxxxxxxxx nevyvolává žádné xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x pohlaví xxxxxx

Xxxxx xxxxxxxxxx x kontrolní xxxxxxx se skládá x xxxxxxx xxxx xxxxxxxxxxxxxxxx zvířat xxx xxxxx xxxxxxx. Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx ze xxxxxx xx stejným druhem x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx v xxxxxxxx, xxxx postačující zkoušení xxxxxxx xxxxxxx. Xx-xx xxxxxxxx člověka specifická xxx xxxxxx pohlaví, xxxx xx xxxx xxxxxxxxx x některých xxxxxxxxxxxxxxx látek, xxxx xx být xxxxxxx xxxxxxxxx se zvířaty xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx pokud xxxxx podávány jednorázově. Xxxxxxxx xxxxx xxxxx xxx podávány xxxx xx xxxx xxxxxxx, xxx. xxx dávky x xxx xxx x rozmezí xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx odebrány ve xxxx různých xxxxxxxxxxx xx xxxxxxxx xxxxxx x jednom xxx. X xxxxxxxx se xxxxx provádí xx xxxxxx době xx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (jenž xxxx xxxxxxx 12 — 18 x). Xxxxxxxx doba xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx látky x xxxxxx pro xxxxxx na xxxxxxxx xxxxxxxxx xxxxx xxxx xxx xxxx na xxxxxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx xx xxxxxxx xxxxx xxxxx xx 24 x od xxxxxxx xxxxxx. Je-li xxxxxxxx xxxxxxxxx xx xxxx než xxxxxxx xxx, xxx by xxx xxxxx xxxxxxxx xx takové xxxx xx poslední aplikace, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx.

Xxxx xxxxxxxxx xx xxxxxxxx intraperitoneálně xxxx xxxxxx dávka xxxxx xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® nebo kolchicin). Xxxx xx xx xxxxxx době xxxxxxx x xxxxxx odběr. X xxxx je xxxx xxxx xxxxxxxxx 3 — 5 x; u xxxxxx xxxxxxxx xx xxxx xxxx přibližně 4 — 5 x. X xxxxxx dřeně xx xxxxxxxx buňky x xxxxxxxxx xx xx chromozomové xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx, kmenem, pohlavím x xx xxxxxxxx xxxxxx expozice, xxx xx xxxxxxx v xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx dávky. Xxxx xxxxxx xxxxx by xxxx xxxxxxxx rozpětí xxxx maximální x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx vyšší xxxxx by vedly xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Látky xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx by xxx xxxxxxxxx případ od xxxxxxx. Xxxxxxxx xxxxx xxxx xxx také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx dávkou xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné toxické xxxxxx a není-li xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, nepovažuje xx xxxxx xxxxxx xx xxxxx úrovněmi xxxxx za xxxxxxxxx. X déle trvajících xxxxxx xx xxxxxxx xxxxxx pro 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx hmotnosti/den x xxx xxxxx než 14xxxxx aplikaci xx xxxxxxx xxxxxx 1000 xx/xx tělesné hmotnosti/den. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx kanylou, nebo xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx xxxxxxxx xxxx x xxxxxxxxxxxx případech xxxxxxxxxx. Maximální xxxxx xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx xxxx injekčně, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl překročit 2 ml/100 x xxxxxxx xxxxxxxxx. Použití xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx látky, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx zajišťující xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx dávky.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx xx xxxxxxx xxxxxx xxxx, xxxxxxxxxxxx xx x xxxxxx. Xxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx xxxxxxx xxxxxxxxxxxx xx xxx být x všech xxxxxxxxxxxx xxxxxx (xxxxxx xxxxxxxxxxx xxxxxxx) x x xxxxxxxxxxxxxx xxxxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx, x xx xxxxxxx x 1000 xxxxx xx xxxxx xxxxx.

X xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx. Xxxxx xxxxx lze snížit, xx-xx xxxxxxxxx xxxxx xxxxx aberací. Xxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Protože při xxxxxx xxxxx dochází xx xxxxxxxxxxxxxx xxxxxx xxxx xx xxxxxx xxxxxxxxxx x části xxxxx x xxxxxxxx, xxxx by xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x počtu xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx být xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxx xx xxx xxx vyhodnocen xxxxx xxxxx, počet xxxxxxx xx xxxxx x xxxxx xxxxx x xxxxxxxxxxxxx aberací (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx v xxxxxxxxxx. Xxx exponované x xxxxxxxxx skupiny xx xxxx xxx xxxxxxx xxxxx typy xxxxxxxxxxxx chromozomových xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx xxxxxx xx xxxxxxxxxx do xxxxxxx xxxxxxxx xxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx mezi xxxxxxxxx, mohou xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx obě xxxxxxx zkombinovány.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik kritérií, xxxx. nárůst xxxxxxxxxxx xxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx jasný nárůst xxxxx buněk s xxxxxxxxx pro skupinu x xxxxxxx dávkou x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx výsledky xx měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Nárůst xxxxx buněk x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx progresi buněčného xxxxx (7, 8).

Zkoušená xxxxx, jejíž výsledky xxxxxxxxx výše xxxxxxx xxxxxxxx, se považuje x xxxxx systému xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx poskytne jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxx xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx v xxxxxx xxxxx testovacího xxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky neindukuje x xxxxxx xxxxx xxxxxxxxxxx xxxxx chromozomové xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx nebo xxxx xxxxxxxxxx xxxxxxxx do xxxxxxxx xxxxx, xxxx xxxxxxxxxx xx cílové xxxxx (xxxx. systémová xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- xxxxx, stáří x pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx pro xxxxxx xxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- xxxxx xx studie xxx xxxxxxxx rozsahu, xxxxx xxxx provedena,

- xxxxxxxxxx xxxxxxxxx xxxxxx dávek,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- údaje x xxxxxxxx zkoušené xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx metody xxxxxxx, xxx xx xxxxxxxx xxxxx dostala xx xxxxxxxx oběhu xxxx xx xxxxxx xxxxx,

- xxxxxxxx xxxxxxxx xxxx koncentrací zkoušené xxxxx v xxxxxx xxxx vodě (xxx) xx odpovídající dávku (xx/xx tělesné xxxxxxxxx/xxx),

- xxxxxxxx údaje x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet analyzovaných xxxxx xx jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- typ a xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx každé xxxxx,

- xxxxxxx počet xxxxxxx xx skupině xx středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxx x xxxxxxxxx ve xxxxxxx xx středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

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

- xxxxx o xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

2) Xxxxxxx, X. X., Xxxx, X. X., Galloway, X., Holden, H., XxXxx, X. X., Xxxxxx, X. (1987), Xxxxxxxxx Xx vivo Xxxxxxxxxxx Xxxxxx: Analysis xx Chromozome Aberrations xx Bone Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 157-165.

3) Xxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxxxxx, X. X., Xxxxxxx, X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Mutagenicity Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Sub-Committee xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

4) Xxxx, X. X., Xxxxxxx, X., XxxXxxxxxx, X. X., Anderson, X., Xxxxxx, X. X., Xxxxxx, H. E., Xxxxxx-Xxxxxxx, X., Oleson Xx., X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, S., Xxxxxxx, X. (1994), Xxxxxx xxxx xxx Xxxxxxx Xxxxx xx the xx xxxx Mammalian Xxxx Marrow Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Mutatation Xxx., 312, 305-312.

5) Xxxxxxx, X. J., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. A., Xxx, J., Xxxxxxx, X. X., Xxxxxxxxx, X. G., Hodson-Walker, X., Xxxxxx, X. X., Xxxxxxxx, D. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Dose Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Amphlett, G. X., Xxxxx, G., Xxxxxxxx, R., Richold, X., Xxxxxxxx, X. X., Xxxxxx, X. X. K. (1989), Xxxxxxxxxxx Analysis xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, X. J. Xxxxxxxx (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.

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

8) Xxxxx, Y., Xxxxxx, X., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx, Xxxxxx Xxx., 43, 1362-1364."


PŘÍLOHA 4C

"B.12 XXXXXXXXXX–XXXX XXXXXXX ERYTROCYTÁRNÍCH MIKROJADER XX XXXX

1. XXXXXX

Xxxx xxxxxx je replikou xxxxxx XXXX XX 474 — Test xxxxxxx xxxxxxxxxxxxxxx mikrojader xx vivo (1997).

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx vivo xx xxxxxxxx pro xxxxxxx poškození chromozomů xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, které xx xxxxxxxxxx xxxxxxxxx xxxxxx, x xx xxxxxx xxxxxxx erytrocytů xxxxxxxxxx x xxxxxx xxxxx x/xxxx xxxxx xxxxxxxxx xxxx, xxxxxxx hlodavců.

Účelem xxxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (lagging) chromozomové xxxxxxxxx xxxx xxxx xxxxxxxxxx.

Xxxx xx erytroblast xxxxxx xxxxx xxxx xx polychromatický xxxxxxxxx, xxxxxx xxxxx xx xxxxxxxx x xxxxxxxxxx, xxxxx xxx xxx xxxxx xxxxxxxxx, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx je x xxxxxx xxxxxxx xxxxxxxxx xxx, že xxxxxxxxxx hlavní jádro. Xxxxxx výskytu xxxxxxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x exponovaných zvířatech xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx xx rutinně xxxxxxxxx kostní xxxx xxxxxxxx, xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Stanovení xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx x periferní xxxx xx rovnocenně xxxxxxxxxx x kteréhokoli xxxxx, x xxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x mikrojádry, xxxx xxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx aberace. Mikrojádra xxx xxxxxxxx xxxxx xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx nebo xxxxxxxxxxxxx xxxxxxxxxxx (kinetochorní) XXX v xxxxxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx. Xxxxx zralých (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxx xxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxxxxxxxx na xxxxxx xxxxx zralých xxxxxxxxxx xxx xxxxxx xxxxxx jako xxxxxxx xxxxxxxx xxxxxxx, xxxxxxxx xxxx zvířata xxxxxxxxxx xxxxx xxxxx xxxx xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx xx xxxxxxx xxxxxx k posouzení xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx DNA, xxxxxxx xx xxxxx xxxxx x xxxxxxx xxxxx x xxxxx, xxxxx x x xxxxxxxxxxx xxxxxxxx. Xxxxxxx in xxxx je rovněž xxxxxxxx pro další xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx v systémech xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx x tom, xx se zkoušená xxxxx nebo xxxxxxxxx xxxxxxxxxx nedostanou xx xxxxxx xxxxx, není xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) xxxxxxxxxx, x xxx (x xxxx) xx xxxxx xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxx pohyb dceřiných xxxxxxxxxx x pólům xxxxxxxxx buněk.

Mikrojádra : xxxx xxxxx xxxxxxxxxx xxxxxxxx od xxxxxxxx xxxxx a vedle xxxx, vytvářená během xxxxxxxx xxxxxx (xxxxxx) xxxxxxxxxxxxxxx se (xxxxxxx) xxxxxxxxxxxxxx fragmenty xxxx xxxxxx xxxxxxxxxx.

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

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx erytrocyt xx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx xxxxxxxx xxxxxxxx, x xxxx xxx xxxx xxxxxxxx xx xxxxxxx normochromatických xxxxxxxxxx xxxxxxxx xxxxxxxxxxx pro xxxxxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx dřeně xx xxxxxxx xx xxxxxxx xxxxxxxx po xxxxxxxx xxxxxx, xxxxxxx xx xxxxxx dřeň, xxxxxxxx xx xxxxxxxxx x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx xxxxxxxxx xxxx se xxxx xx xxxxxxx xxxxxxxx xx expozici xxxxxxx, xxxxxxxxxx xx xxxxxxxx xxxxxxxx x obarví xx (4, 8, 9, 10). Xxx xxxxxxxx s xxxxxxxxx xxxx xx měla xxxx xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxx xxxxxxxx co xxxxxxxxx xxxx. Preparáty xxxx xxxxxxxxxxx xx přítomnost xxxxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxx xxxxxxx xxxxxx dřeně se xxxx testovací xxxxx xxxxxxxxxx myš nebo xxxxxx, xxxxxx xxx xxxxxx jakýkoli vhodný xxxxx druh. Při xxxxxxx periferní krve xx xxxxxxxxxx xxx. Xxx xxxx použít xxxxxxxx xxxxxx xxxx xxxxx za předpokladu, xx jde o xxxx, u xxxxx xxxxxxx xxxxxxxxxxxx erytrocyty x mikrojádry, xxxx xxxx vykazující xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx způsobují xxxxxxxxxx xxxx xxxxxxxxx chromozomové xxxxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx zdravých pohlavně xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx studie xx xxxx být xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx u xxxx pohlaví překročit ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx úvodu x xxxxx X, xxxxxxx by mělo xxx xxxxxxxx vlhkosti xxxxxxx 50 – 60 %.

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, x xxx xx xxxxxxx xxxxxxxx. Zvířata xx xxxxxxxxxxx identifikují. Xxxxxxx xx v laboratorních xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx. Klece xx xxxxxxxxxx xxx, xxx byl vliv xxxxxx xxxxxx minimalizován.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx před aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě zředěny. Xxxxxxx zkoušené xxxxx xxxxx xxx podávány xxxxx nebo xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud údaje x xxxxxx stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx toxické xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx rozpouštědla/vehikula, mělo xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx zvážit xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx měla xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata xx xxxxxxxxx, x nichž xxxxx k expozici.

Pozitivní xxxxxxxx by xxxx xxxxxxxxxx xxxxxxxxxx xx xxxx xxx expozičních xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx xxx, aby byl xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx identifikace xxxxxxxxx. Xx xxxxxxxxxx, aby xxxxxxxxx xxxxxxxx byla xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx xxx xxxxx v xxxxx xxxxxxx prováděn xxx xxxxxx. Pro pozitivní xxxxxxxx xxxxx xxxx xxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx třídy, jsou-li x xxxxxxxxx. Xxxxxxxx xxxxx xxx pozitivní xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx xxx být xxxxxxxx odběr x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx stejný xxxxxx jako exponované xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx k dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx zvířat a xxxxxxxx buněk x xxxxxxxxxx. Xxxxxxx-xx se xxx negativní kontrolu xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx doba xxxxxxx odběru. Xxxxx xxxx by měly xxx neexponované xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx nebo xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.

Xxx použití xxxxxxxxx krve může xxx xxxx negativní xxxxxxxx xxxxxxxxxx také xxxxxx krve odebraný xxxx expozicí, pouze xxxx u xxxxxxxx xxxxxx s xxxxxxxxx xxxx (např. 1 — 3 aplikace) xx xxxxxxxxxxx, xx xxxxxxxx údaje xxxxx x rozpětí, xxxxx xx na xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx exponovaná x kontrolní skupina xx xxxx xxxxxxx x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx pohlaví (11). Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx ze xxxxxx se stejným xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, jež xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx například x xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx xx xxx xxxxxxx xxxxxxxxx se xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxx (xx. xxxxx, xxx xxxx xxx xxxxxxxx x xxxxxxxxx 24 xxxxx). Vzorky xx xxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxxx xx x xxxxxx studií xxxxxxx pozitivní výsledky, xxxx –v případě xxxxxxxxxxx xxxxxx — xxxxx byla xxxxxxxxx xxxxxxxx nebo xxxx xxxxxxxxx limitní dávka x xxxxxxxx pokračuje xx do xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx být xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. xxx xxxxx v xxx xxx x xxxxxxx xx více xxx xxxxxxxx hodin, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx být xxxxxxxx xxxxx xxxxxxx:

x) xxxxxxxx xxxxx se xxxxxxxx xxxxxxxx xxxxxx. Xxxxxx xxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx odběr xx xxxxxxx xxxxxxxx 24 hodin po xxxxxxxx a xxxxxxxx xxxxxxxxxx 48 xxxxx xx aplikaci a x xxxxxxxxxx xxxxxxxx xxxx odběry. Xxxxx xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx xxxxxxxxx xxxx xx xxxxxxxx xxxxxxx xxxxxxx, přičemž xxxxx xxxxx se provede xxxxxxxx 36 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx po xxxxxxxx x xx xxxxxxxxxxxx xx dodrží odpovídající xxxxxx. Xx-xx xx xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx xxxxx xxxxx;

x) xxxx-xx xxxxxxxx xxx xxxx více xxxxx xxxxx (např. xxx xxxx více dávek x xxxxxxxxx 24 xxxxx), měly xx xxx xxxxxx xxx xxxxxxx kostní dřeně xxxxxxxx jednou xx 18 až 24 xxxxxxxx xx xxxxxxxx xxxxxxxx x xxx xxxxxxx xxxxxxxxx xxxx xxxxxx po 36 xx 48 hodinách xx xxxxxxxx xxxxxxxx (12).

Xxxxx xxxxxxx xxxxx xxx xxxxx xxxxxxx xxxx doby odběru.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx dávek, xxxx by být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, pohlavím x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx xxxxxx (13). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí tři xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx xxxxxxxx rozpětí xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx dávka xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx by vedly xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx jako dávka xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx známky xxxxxxxx (např. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx x xxxxxxxxx krvi).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška s xxxxxx dávkou o xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné toxické xxxxxx a xxxx-xx xx xxxxxxx údajů x xxxxxxx, které xxxx xxxxxxxx strukturu, xxxxxxxxx genotoxicita, není xxxxxxxxxx xxxxx xxxxxx xx třemi xxxxxxxx xxxxx xx nezbytnou. X déle xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den x xxx xxxxx než 14xxxxx xxxxxxxx je xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx expozice xxxxxxx xxxx znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx obvykle xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx podávání xxxx xxxxxxxxxx x xxxxxxxxxxxxxxx xxxxxxxxx. Maximální objem xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx je xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, které xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx zesílené xxxxxx, xx xxxx xxx xxxxxxxxxxx zkušebního objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx nebo xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx xxxxxxxxx z xxxxxx xxxx xxxxx xxxxx po usmrcení. Xxxxx se xxxxxxxx x xxxxxx nebo xxxxx a xxxxxxxxxx xxxxxxxx xx preparují x xxxxxx. Xxxxxxxxx xxxx xx získává x xxxxxx xxxx xxxx xxxx xxxxxx xxxxxx xxxx. Krevní xxxxx xx ihned xxxxxxxxxxxx obarví (8, 9, 10), nebo xx připraví preparáty xxxxxxxx x xxxx xx xxxxxx. Xxxxxxxx xxxxxxx xxxxxxxxxxxx xxx XXX (xxxx. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx s xxxxxxxx xxxxxxx nespecifického xxx XXX. Xxxx xxxxxx xxxxxxx použití xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. celulosová kolona x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, že se xxxxxxxxx xxxxxxxxxxxx funkčnost xxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx xx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx (xxxxxxx + zralé) množství xxxxxxxxxx, přičemž se x xxxxxxx xxxxxx xxxxx xxxxxxx celkově xxxxxxx 200 xxxxxxxxxx x v xxxxxxx xxxxxxxxx xxxx alespoň 1000 xxxxxxxxxx (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx pozitivních a xxxxxxxxxxx kontrol, by xxxx xxx před xxxxxxxx xxx mikroskopem xxxxxxxxx kódovány. X xxxxxxx xxxxxxx se xxxxxxx xxxxxxx 2000 xxxxxxxxx erytrocytů na xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx xxx získány xxxxxxxxxx zralých xxxxxxxxxx xx výskyt mikrojader. Xxx mikroskopické analýze xx neměl být xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx menší xxx 20 % kontrolní xxxxxxx. Xxxxxxxx xxxx xxxxxxx exponována xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxx xxxx xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx xx xxxxx xxxxx. Xxxxxxx xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx a xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxx) xxxx xx xxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxx přijatelnými xxxxxxxxxxxxx manuálního xxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx ve xxxxx xxxxxxx. Experimentální xxxxxxxxx xx zvíře. Xxx xxxxx analyzované zvíře xx xxx být xxxxxx počet xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx nepřetržitě xxxxx xxxxx xxxx xxxx, xxxx xx být xxxx xxxxxxx xxxxx x xxxxxxx erytrocytech, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx zvíře xx xxxxx xxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx a xxxxxxxx množství xxxxxxxxxx x mikrojádry vyjádřené x procentech. Neexistuje-li xxxxx o rozdílu x odpovědi xxxx xxxxxxxxx, xxxxx xxx xxx statistickou xxxxxxx xxxxx xxx obě xxxxxxx zkombinována.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxx x xxxxxxxxxx xx xxxxx nebo xxxxx xxxxxx počtu xxxxx x xxxxxxxxxx xxx xxxxxxx x xxxxxxx xxxxxx x x xxxxxxxx okamžiku odběru. Xxxxxxxx by měla xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Statistická xxxxxxxxxx xx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky by xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx xxxxxxxx v xxxxx xxxxxxx za nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech neumožní xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx výsledky xxxxx xx xxxxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxx, xxx xxxx důsledkem xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx erytrocytech xxxxxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx zkoušená xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx oběhu, xxxx xxxxxxxxxx xx xxxxxx xxxxx (např. systémová xxxxxxxx).

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, stáří x pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

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

Zkušební xxxxxxxx:

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

- údaje ze xxxxxx xxx zjištění xxxxxxx, xxxxx byla xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

- xxxxxxxx přepočet xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx nebo xxxx (ppm) na xxxxxxxxxxxx dávku (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx o xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a odběru,

- xxxxxx přípravy xxxxxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- xxxxxxxx hodnocení xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,

- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxx samostatně xxx xxxxx zvíře,

- xxxxxxx hodnota ± xxxxxxxxxx odchylka xxxxx xxxxxxxxx erytrocytů s xxxxxxxxxx xx xxxxxxx,

- xxxxx možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x metody,

- údaje x souběžné a xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Xxxxxx, X. (1975), Xxx Xxxxxxxxxxxx Test, Mutatation Xxx., 31, 9-15.

3) Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxx, X., Kirkhart, X., Xxxxxxxxx, X., XxxXxxxxx, X. X., Xxxxxx, X. X. (1983), Xxx Induction xx Micronuclei x. x. x Xxxxxxx xx Xxxxxxxxxxxx, Mutatation Xxx. 123, 61-118.

4) Xxxxxxxxx, K. X., Xxxxxx, X. X., Xxxxxx, M. C., Xxxxxxxx, M. X., Xxxxxx, J. X. (1990), Xxx In xxxx Xxxxxxxxxxxx Xxxxx xx Mammalian Xxxx Xxxxxx and Xxxxxxxxxx Xxxxx. X report xx the U. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) XxxXxxxxx, X. X., Xxxxxxxx, R., Xxxx, W. X., Xxxx, C. X. (1983), Xxxxxxxxxxx in Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Xxxxxx xxx Xxxxxxxxxxx Damage During Xxxxxxx Toxicity Testing xx Mice, in: Xxxxxxxxxxxx in Xxxxxxx xxx Xxxxxxxx xx Xxxxxxxxxx, xx. X. X. Xxxxx, X. X. Schnell, X. X. Miya. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) MacGregor, X. X., Heddle, X. X. Xxxx, X., Xxxxxxxx, X. X., Xxxxx, C., Xxxxxxxx, X. X., Xxxx, R. X., Xxxx, X. (1987), Xxxxxxxxxx for xxx Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx xx Mammalian Xxxx Marrow Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) MacGregor, J. X., Xxxx, X. X., Henika, P. X., Xxxxxx, X. X. (1990), The xx vivo Erythrocyte Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Steady Xxxxx Xxxxxxxxx Xxxxx Xxxxxxxxxx xxx Xxxxxxx Xxxxxxxxxxx xxxx Xxxxxxxx Studies, Xxxxxx. Xxxx. Xxxxxxx. 14, 513-522.

8) Xxxxxxx, X., Xxxxxx, X., Xxxxxx, Y., Xxxxxx, X., Ishidate, X. Xx. (1990), Xxx Xxxxxxxxxxxx Assay xxxx Xxxxx Peripheral Xxxxx Xxxxxxxxxxxxx Xxxxx Xxxxxxxx Xxxxxx-Xxxxxx Slides, Xxxxxxxxxx Xxx., 245, 245-249.

9) Xxx Collaborative Xxxxx Xxxxx xxx the Xxxxxxxxxxxx Xxxx (1992). Xxxxxxxxxxxx Xxxx xxxx Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxx xx Acridine Xxxxxx Xxxxxxxxxx Staining: Xxx Summary Xxxxxx xx xxx 5th Xxxxxxxxxxxxx Study xx XXXXX/XXXXX, XXX, Xxxxxxxxxx Xxx., 278, 83-98.

10) Xxx Collaborative Study Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: The Xxxxxxxxx Xxxxxxxxxxx Study Xxxxx xx the Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx of Xxxxx) (1995), Protocol xxxxxxxxxxx xxx xxx xxxxx-xxxx mouse xxxxxxxxxx xxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Xxxx, X. X., XxxXxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, X. X., Xxxxxx-Xxxxxxx, X., Xxxxxx, Xx. F. X., Xxxxxxxxxxxx, F., Xxxxxxx, X., Shimada, X., Xxxxx, X., Xxxxxxx, B. (1994), Xx vivo Xxxxxx Xxxxxxxxxxx Micronucleus Assay, Xxxxx. Xxx., 312, 293-304.

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

13) Fielder, X. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, X. X., Xxx, X., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Morton, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Mutagenesis, 7, 313-319.

14) Hayashi, M., Xxxxxx, X., Xxxxxxxx, X. Xx. (1983), Xx Xxxxxxxxxxx xx Xxxxxxxx Xxxxxx Fluorescent Xxxxxxxx xx xxx Xxxxxxxxxxxx Test, Xxxxxxxx Xxx., 120, 241-247.

15) XxxXxxxxx, X. T., Xxxx, X. M., Xxxxxxxx, X. G. (1983), X Xxxxxx Xxxxxxxxxxx Xxxxxxxx Xxxxxxxxx xxx Xxxxxxxxxxx xxx XXX in Erythrocytes Xxxxx Hoechst 33258 xxx Xxxxxxx X, Xxxxxxxx Res., 120, 269-275.

16) Xxxxxxx, X., Xxxxxxxxxx, X. X. (1989), Xxx xxxxxxxxx xxxx marrow micronucleus xxxx, Mutatation Xxx., 213, 91-104.

17) Xxxxxxxxx, X., XxXxxxxx, X. X. (1995), Sample Xxxx xxx xxx Xxxxxxxxxx of Xxxxxxxxxxxxx xx Normochromatic Erythrocyte Xxxxx xx xxx Xxxx Xxxxxx Xxxxxxxxxxxx Xxxx, Mutatation Xxx., 347, 97-99.

18) Xxxxxxx, X., Ashby, J., Xxxxxxx, X., Chandley, X., Gatehouse, X. X., Henderson, X. (1990), In xxxx Xxxxxxxxxxxx Xxxxx, xx: X. X. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, XXXXX Sub-Committee xx Xxxxxxxxxx for Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx 1, revised, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Anderson, X., Albanese, X., Xxxxxxxx, G. X., Xxxxx, X., Xxxxxxxx X., Richold, M., Xxxxxxxx, X. G., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Cytogenetic Assays, xx: X. J. Xxxxxxxx (xx.), Statistical Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx III, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

"X.13/14 XXXXXXXXXX — XXXXXXX NA XXXXXXXX MUTACE S XXXXXXXXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX XX 471 — Zkouška xx xxxxxxxx mutace x xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xx xxxxxxxxx xxxxxxxxxxx xxxxx závislé na xxxxxxxxxxxxxxx Salmonella xxxxxxxxxxx x Escherichia coli, x xxxxxxx bodových xxxxxx, které zahrnují xxxxxxxxxx, xxxxx x xxxxxx jednoho nebo xxxxxxxx párů xxxx XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx xx xxxxxxxx xxxxxx s bakteriemi xxxxxxx v detekci xxxxxx, xxxxx xxxxxxxxx xxxxxx obsažené x xxxxxxxxxxx xxxxxxx x xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx syntetizovat xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx xxxx xxx xxxxxxxxxx xxxx x xxxxxxxxxxxxx aminokyselin, xxxxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx mutace x podobné xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx podmíněných xxxxxx x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, že xxxxxx mutace x xxxxxxxxxx x v xxxxxx xxxxxxxxxxx buněk xxxxxxxxx nádory xxxx xxxxx na xxxxxx xxxxxxxx x xxxxxxx x u xxxxxxxxx xxxxxx. Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx rychlá, xxxxxxxxxx x relativně xxxxxx. Xxxxx testovacích xxxxx xx xxxx xxxxxxxxxx, díky nimž xxxx citlivější na xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx sekvencí DNA xx xxxxxxxxxx místech, xxxxxxx xxxxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxx xxxxxxxx reparačních xxxxxxx XXX xxxxxxxxxx k xxxxxx. Xxxxxxxxxxxx testovacích xxxxx xxxx poskytnout xxxxxxx užitečné informace x typech mutací, xxx jsou indukovány xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xx x dispozici xxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxx širokou xxxxx struktur x xxxx xxxx xxxxxxxx xxxxx vyzkoušené metody xxxxxxxx xxxxxxxxxx látek, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx obecný xxxx, část X.

1.2 XXXXXXXX

Xxxxxxx xx xxxxxxxx xxxxxx s bakteriemi Xxxxxxxxxx typhimurium xxxx Xxxxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx x xxxxx vyžadujícím xxxxxxxxxxxxx (histidin resp. xxxxxxxxx), xxxxxxx xxxxxx xxxx xxxxxxxxx na xxxxxxx xxxxxxx aminokyseliny.

Mutageny xxxxxxxxxx xxxx xxxx xxxx xxxxxxxx, jež xxxxxxxxx změny x xxxxxx XXX. Xxx xxxxxxx reverzních xxxxxx xx xxxxx tyto xxxxx xxxxxxxxxx na xxxxx xxxxxxx xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx genomu.

Posunové mutageny xxxx xxxxxxxx, jež xxxxxxxxx adici xxxx xxxxxx xxxxxxx xxxx xxxx párů bází XXX a xxxxxxxx xxx xxxxx xxxxx XXX.

1.3 XXXXXXX ÚVAHY

Při xxxxxxxxx na xxxxxxxx xxxxxx x bakteriemi xx využívají prokaryotické xxxxx, xxxxx xx xxxx xx xxxxx xxxxx faktory, jako xxxx xxxxxx, metabolismus, xxxxxxxxxxxx xxxxxxxxx x xxxxxxxxx procesy XXX. Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího zdroje xxxxxxxxxxx aktivace. Metabolické xxxxxxxxx systémy xx xxxxx xxxxxxx xxxxx xxxxxxxxx podmínky xx xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx a karcinogenním xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx zpravidla využívána xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx, x xxxxxxx aktivity xxxxxxxxxxxx xxxxxx xxxxxx. Z xxxxxxxx databáze vyplývá, xx mnoho xxxxxxxxxx xxxxx, xxxxx xxxx x xxxx xxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx i v xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx činitelů, xxxxx nejsou xxxxxxxxxx xxxxx zkouškou. Příčiny xxxxxx xxxxxxxxxxx xxx xxxxxxxxx ve xxxxxxxxxx xxxxxx detekovanéhokonečného jevu, x xxxxxxxxx x xxxxxxxxxxx aktivaci xxxx x rozdílech x xxxxxxxxxx xxxxxxxxxxx. Na xxxxx straně faktory, xxxxx xxxxxxx xxxxxxxxx xxxxxxx na xxxxxxxx xxxxxx xx xxxxxxxxxx, xxxxx xxxx k xxxxxxxxxxxx mutagenní aktivity.

Zkouška xx xxxxxxxx xxxxxx x bakteriemi nemusí xxx xxxxxx xxx xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx antibiotika) x xxx chemické látky, x xxxxx se xxxxxxxxxxx (nebo o xxxxx xx xx), xx specificky xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx xxxxx (xxxx. xxxxxxx xxxxxxxxxx topoisomerasy x xxxxxxx xxxxxxx xxxxxxxxxx). X xxxxxxxx xxxxxxxxx xxxxx být xxxxxxxxx zkoušky mutagenity x xxxxx.

Xxxxxxxx mnoho xxxxxxxxx, pro něž xx xxxx zkouška xxxxxxxxx, je xxxxxxxxxxxx xxx savce, není xxxxxxxx xxxxxxxxx. Xxxxxx xx xxxxxxxx xxxxx x existuje xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx touto zkouškou, xxxxx působí xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx buňkách xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxxx xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx látce, x xx za xxxxxxxxxxx vnějšího xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx a xxx xxxx. Ve xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxx smíchají x vrchním xxxxxx x xxxxx se xxxxxxx xx xxxxxxxxx xxxx. X xxxxxxxxxxxx xxxxxx xx zkoušená xxxx xxxxxxxx a xxxx xx xxxx xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx s xxxxxxx agarem. Při xxxx technikách se xx xxxx nebo xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx revertantů x provede xx xxxxxxxx s počtem xxxxxxx spontánních xxxxxxxxxx xx xxxxxxxxx misce x xxxxxxxxxxxxx.

Xx xxxxxxx xxxxxxx xxxxxxx xxxxxxxxx xxxxxxx na xxxxxxxx xxxxxx x bakteriemi. Xxxx xxxxx xxxxxxxxx xxxxx xxxxxxxxxx miskový xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), fluktuační xxxx (9, 10) x xxxxxxxxx xxxxxx (11). Xxxxxx xxx zkoušení xxxxx a xxx xxxx xxxxxxx (12).

Xxx xxxxxxx xxxxxxx xx xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxx a xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx xx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx xxx s xxxxxxxxxxxx xxxxxxxx, tak xxx xx. Některé xxxxx xxx účinněji xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxx xxxxx xxxxx do xxxxxxxxxx tříd, do xxxxx patří xxxx xxxxx krátké xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx kovy, xxxxxxxx, azobarviva a xxxxxxxxxx sloučeniny, xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxxxx sloučeniny x nitrosloučeniny (3). Xxxxxx se připouští, xx xxxxxx xxxxx xxxxxxxx xxxxx xxxx xxxxxxxxx standardními xxxxxxx, xxxx xx standardní xxxxxxx test xxxx xxxxxxxxxxxx xxxxxx. Xxxx xx xxx xxxxxxxxxx xx "zvláštní xxxxxxx" x k xxxxxx xxxxxxx xx xxxxxxx xxxxxxxxxx použít xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (společně x xxxxxxxx xxxxxxx xxxxxx 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 zdůvodněna.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx kultury xxxxxxxx xx xxxx xxx kultivovány do xxxxxx xxxxxxxxxxxxx fáze xxxx xx xxxxx xxxxxxxxxxx xxxx růstu (xxxxxxxxx 109 xxxxx xx ml). Xxxxx x xxxxxx xxxxxxxxxxx xxxx xx neměly xxx xxxxxxx. Xx xxxxxxxx, aby xxxx xxxxxxx bakterie xxxxxx xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx xxxx xxx xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxx xxx xxxxxx xxxxxxx stanovením xxxxx xxxxxxxxxxxxxxx xxxxx xx xxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxx xx 37 °X.

Xxxx xx být xxxxxxx alespoň pět xxxxx xxxxxxxx. Xxxx xxxx xx měly xxx xxxxx xxxxx X. typhimurium (TA1535; XX1537 xxxx XX97x xxxx TA97; XX98 x XX100), jejichž xxxxxxx xx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Tyto xxxxx xxxxx S. xxxxxxxxxxx xxxx xxx bází XX xx xxxxxxxxx xxxxxxxxx xxxxx a xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx nelze xxxxxxxxx určité xxxxxxxx xxxxxxxx, xxxxxxxx způsobující xxxxxxxxxx xxxxxx DNA x xxxxxxxxx. Tyto xxxxx xxxxx být xxxxxxxxxx kmeny X. xxxx XX2 xxxx X. xxxxxxxxxxx XX102 (19), xxxxx xxxx xx xxxxxxxxx reverzním xxxxx xxx xxxx XX. Xxxxxxxxxx kombinace xxxxx xx xxxx xxxx:

- X. typhimurium XX1535 x

- X. xxxxxxxxxxx TA1537 xxxx XX97x a

- X. xxxxxxxxxxx XX98 x

- X. xxxxxxxxxxx XX100 x

- E. xxxx XX2 xxxX, nebo X. xxxx WP2 xxxX (xXX101), xxxx X. typhimurium XX102.

Xxx xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx vláken DNA xxxx být vhodnější xxxxxxx TA102 xxxx xxxxxx xxxx X. xxxx s xxxxxxx xxxxxxxxxx xxxxxxxx DNA, (xxxx. X. xxxx XX2 (pKM101)).

Měly xx xxx xxxxxxx zavedené xxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxxxxx xxxxxxx x xxxxxxxxxx. Potřeba xxxxxxxxxxxxx pro růst xx xxxx být xxxxxxxxx xxx každou xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx xxx xxxxx X. xxxxxxxxxxx x xxxxxxxxx xxx X. xxxx). Xxxxxxx by xxxx xxx kontrolovány xxxx xxxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxxxx podle potřeby xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (tj. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, XX100 x TA97a xxxx XX97, XX2 uvrA x XX2 xxxX (xXX101) x xxxxxxxxxxxx x tetracyklinová rezistence x xxxxx XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx mutací (xx. xxx xxxxxx x S. xxxxxxxxxxx xxxxxxxxxx xx krystalovou xxxxxx a xxxX xxxxxx u E. xxxx xxxx xxxX xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx světlo) (2, 3). Xxxxx by xxxx rovněž xxxxx xxxxx xxxxxxx spontánních xxxxxxxxxx na xxxxx x rozmezí četností xxxxxxxxxxx xx základě xxxxxxxxxxx xxxxx laboratorních xxxxxxx x xxxxxxx x xxxxxxx uvedeném x literatuře.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx minimální xxxx (xxxx. xxxxxxxxxx xxxxxxxxx půdu E (Xxxxx-Xxxxxx) x glukosu) x xxxxxx xxxx xxxxxxxxxx histidin a xxxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxx buněčných xxxxxx (1, 2, 9).

1.5.1.3 Metabolická xxxxxxxx

Xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x to x xxxxxxx systémem metabolické xxxxxxxx x xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx indukujícím xxxxxx, xxxx je Aroclor 1254 (1, 2) xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (18, 20, 21). Postmitochondriální frakce xx xxxxxxx používána x xxxxxxxxxxxxx v xxxxxxx 5 až 30 % obj. xx xxxxx X9. Xxxxx a xxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx xxxx xxxxxxx xx xxxxx zkoušené xxxxxxxx xxxxx. X xxxxxxxxx xxxxxxxxx může být xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. U xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xxxx být xxxxxxxxx xxxxxxx redukčního xxxxxxxxxxxxx aktivačního xxxxxxx (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx být xxxx xxxxxxxx na xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx látky mohou xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx mohou být xxxx xxxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx mimo xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou, x xxxx xx xxx xxxxxxxxxx s xxxxxxxx xxxxxxxx x x xxxxxxxxx S9 (22). Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by být xxxxxx zařazení podloženo xxxxx x jejich xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx nejdříve xxxxxx xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx nestálých xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx podmínky

1.5.2.1 Zkušební xxxxx (viz 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx stanovení xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxx xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx xxx užitečné xxxxxxxx toxicitu x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx může xxx xxxxxxxxxx xxxxxxxx xxxxx kolonií xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx kultur. Xxxxxxxxxxxx xxxxx xx xxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx xx měla xxx xxxxxxxxx xx xxxxxxx viditelného srážení x xxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx zkušební xxxxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxxx látky xx 5 xx/xxxxx nebo 5 μl/misku. X xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx koncentracích 5 xx/xxxxx nebo 5 μx/xxxxx by xxxx xxx jedna xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, xxx xxxxx xxxx x xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx látky, xxxxx jsou xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, by xxxx xxx zkoušeny xx xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx by neměla xxxxx xxx xxxxxxxxxxx.

Xxxx xx xxx použito xxxxxxx xxx různých xxxxxxxxxxxxxxxx xxxxxxxxxxx zkoušené xxxxx, xxxxxxx xxx xxxxxx experimentu xx xxxx být intervaly xxxx xxxxxxxxxx body xxxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx xxxx xxxxxx x xxxxxxx, xxx xx vyšetřuje křivka xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Zkoušení xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx být xxxxxxx xxx xxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx mutagenních xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxx xx měly xxx kmenově specifické xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx xxxx vehikulum) xxxxxxxx s xxxxxxxxxxxx xxxxxxxx x bez xx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx vybrány koncentrace xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X xxxxxxx zkoušek x xxxxxxxx metabolického xxxxxxxxxxx xxxxxxx by xxxx xxx xxxxx (xxxxx) xxx xxxxxxxxx xxxxxxxx vybrána (xxxxxxx) xx xxxxxxx typu xxxxxxxxx xxxxx xxxxxxxx.

Xxxxxxxxx xxxxxx pozitivní kontroly x xxxxxxx s xxxxxxxxxxxx xxxxxxxx xxxx xxxx xxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Tato xxxxx xx xxxxxxx xxxxxxxxx xxxxxxxxx pro xxxxxx xxxxxxxx metabolické xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

XX Xxxxxx Xxx 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx xx xxxxx xxx xxxxxx xxxx xxxxxx xxxxxxxxx xxxxxxxxx xxxxx X9. Při xxxxxxx 2-aminoanthracenu by xxxx xxx xxxxx xxxxx S9 xxxxxxxxxxxxxxxx xxxxxxxxx, který xxxxxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxx, xxxxxxxxx xxxxx[x]xxxxx xxxx 7,12-dimethylbenzo[a]anthracen.

Příkladem xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx u xxxxxxx xxx xxxxxx xxxxxxxxxxx aktivace xxxx xxxx látky:

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

Xxxx

xxxx xxxxx

26628–22–8

247–852–1

XX1535 x TA100

2-nitrofluoren

607–57–8

210–138–5

TA98

9-aminoakridin

90–45–9

201–995–6

TA1537, XX97 x TA97a

ICR 191

17070–45–0

241–129–4

XX1537, XX97 x XX97x

Xxxxxxxxxxxxxxxxx

80–15–9

201–254–7

XX102

xxxxxxxxx X

50–07–7

200–008–6

XX2xxxX a TA102

1-methyl-3-nitro-1-nitrosoguanidin

70–25–7

200–730–1

WP2, XX2 xxxX a XX2 uvrA (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 uvrA x XX2 xxxX (xXX101)

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

3688–53–7

xxxxx obsahující plasmidy

Pro xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxx referenční xxxxx. Xxx xxxxxxxxx kontrolu xx mělo xxx xxxxx x úvahu xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou xx x xxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula, xxx xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx způsobem xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní xxxxxx.

1.5.3 Xxxxxx

X xxxxxxxxxx miskové xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,05 xx xxxx 0,1 xx xxxxxxxxxx roztoků, 0,1 ml xxxxxxx xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx sterilního xxxxx x 2,0 ml xxxxxxxx xxxxx. X xxxxxxx zkoušky x xxxxxxxxxxxx aktivací xx xxxxxxx xxxxxx 0,5 xx metabolické xxxxxxxxx xxxxx obsahující xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx frakce (x xxxxxxx 5 xx 30 % xxx. x metabolické xxxxxxxxx xxxxx) x xxxxxxx xxxxxx (2,0 xx) x xxxxxxx x xxxxxxxxxx x xxxxxxxxx látkou xxxx xxxxxxxxx roztokem. Xxxxx xxxxx zkumavky xx xxxxxxxx x xxxxxxx xxxx xxxxxx minimálního xxxxx xx xxxxx. Xxxx xxxxxxxx xx xxxxx xxxxxx xxxx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx xxxxxxxx xxxxxx xxxx xxxxxxxxx x vrchním xxxxxx x xxxxxxxx přes xxxxxx xxxxxxxxxxx agaru xx xxxxx xxxxxxx 20 minut nebo xxxx xxxxxxxxxxx s xxxxxxxxxx xxxxxx (obsahujícím xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a xxxxxxxxx xxxxxx nebo xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx xx smíchá 0,05 nebo 0,1 xx xxxxxxxx xxxxx xxxx zkušebního xxxxxxx, 0,1 xx xxxxxxxx x 0,5 ml xxxxx X9 nebo xxxxxxxxxx pufru x 2,0 ml vrchního xxxxx. Xxxxxxxx xx xxxx xxx během xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.

X xxxxxxxxxxxx odhadu xxxxxxxx xx xxxx xxx xxx každé xxxxxx xxxxx xxxxxxx 3 xxxxx. Xxxxxxx xxxx misek xx xxxxxxxxxx po xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx zkoušky.

Plynné nebo xxxxxx látky xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, např. x těsně xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (12, 14, 15, 16).

1.5.4 Xxxxxxxx

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

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxx xxxxx by xxxx xxx počty xxxxxxx xxxxxxxxxx xxxxxxxxxxx xx xxxxx. Xxx by xxx xxxxxx xxxxxx xxxxx kolonií revertantů xxx na miskách x negativní kontrolou (xxxxxxxx rozpouštědla a xxxxxxxx neexponovaná kontrola), xxx xx miskách x pozitivní xxxxxxxxx. Xxxxx xx jednotlivých xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxx xx xxxx xxx předloženy xxx zkoušenou látku x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx a/nebo xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx jasně xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx výsledky by xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou experimentálních xxxxxxxx. Xxxxxxxxx výsledky xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx mohly být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx xxxxxxx xxxxxx xxxx xxxxxxxxxxx v xxxxxxxx médiu) x xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje několik xxxxxxxx, např. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx xxx xxxxxxxxx rozsah u xxxxxxx xxxxxxx xxxxx x metabolickým xxxxxxxxxx xxxxxxxx xxxx bez xxxx, x to x xxxxxxxxxx na xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx xxxxx xxx jednu nebo xxxx xxxxxxxxxxx (23). Xxxxxxxx by měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků zkoušky xxxxx být použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx významnost by xxxxxx xxx jediným xxxxxxxxx faktorem pro xxxxxxxxx odpověď.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxxxx mutace s xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x genomu kmenů Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx xxxxxx xxxxxx xxxxxxxxxx xxxx xxxx posunem xxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx není za xxxxxxxx zkoušky xxx xxxxxxxxx xxxxx xxxxxxxxx.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx x xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx podmínky:

- xxxxxxxx zkoušené látky xx xxxxx (mg/misku xxxx μx/xxxxx) x xxxxxxxxxxx výběru xxxxx x xxxxx xxxxx xx xxxxxxxxxxx,

- xxxxxxx xxxxx,

- typ x xxxxxxx metabolického xxxxxxxxxxx xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,

- postup xxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- počty xx xxxxxxxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x směrodatná xxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,

- xxxxxxxx statistické analýzy,

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

- xxxxxxxxx údaje x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx x xxxxxxxxx, středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Maron, X. X., Ames, X. X. (1983), Revised Xxxxxxx for the Xxxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Xxx., 113, 173-215.

3) Xxxxxxxxx, X., Xxxxxxx, X., Cebula, X., Xxxxx, X., Xxxx, X., Xxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, T., Venitt, X., Xxxxxx, X. (1994), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx Xxxxxxxxx Xxxxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 312, 217-233.

4) Kier, X. X., Brusick X. X., Xxxxxxx, X. X., Xxx Halle, X. X., Xxxxx, X. X., Xxxxxx, X. F., Xxxxxx, X., XxXxxx, X., Xxxxxxxxxx, K., Xxxxxx, X., Xxx, X. X., Ray X. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Microsomal Assay: X Report xx xxx U. S. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, X., Degawa, X., Xxxxx, X. X., Xxxxxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Hashimoto, X. (1975), Mutagenicity xx Xxxxxxxxxx Xxx Dyes xxx their Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

6) Xxxxxxxxxx, M., Xxxxxxxx, T., Nagao, X., Yahagi, X., Xxxxxx, A., Sawamura, X. (1980), Xxxxxxx Xxxxxxxxxx Mutagenicity Xxxxxxxxx Xxxxx, xx: Xxxxx-xxxx Xxxx Systems for Xxxxxxxxx Xxxxxxxxxxx, ed. Xxxxxxx X. X., Xxxxxx, X. X., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

7) Xxxxxxxxx, D. X., Xxxxxxx, X. X., Xxxxxx, P., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Xxxxxx, xx: Basic Xxxxxxxxxxxx Xxxxx: UKEMS Xxxx 1 Revised, ed. X. X. Kirkland, Xxxxxxxxx Xxxxxxxxxx Press, 13-61.

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

9) Xxxxx, X. H. X., Xxxxxx, W. X., Xxxxxxx, B. A. (1976), Xxx xx x xxxxxxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxx of xxxxxxxx, Xxxxxxxxxx Res., 38, 33-42.

10) Xxxxxxx, X. X., Xxxxx, X. X. X., Xxxxxxxxx, X., Xxxxxxx, X. W. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, xx: Xxxxxxxx xx Mutagenicity Xxxx Procedures, 2. xxx., Kilbey, X. X., Xxxxxxx, X., Xxxxxxx, W., Xxxxx, X. (eds.), Xxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, E. X., Xxxxxxx, P. J. (1981), An Xxxxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxxx Assay xxx Xxxxxxxxxxx with Strains xx Salmonella xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Xxxxx, X., Xxxxxxx, X., Kato, X., Xxxxxxxxxx, T. (1994), Improved Xxxxxx xxx Xxxxxxxxxxxx Xxxxxxx xx Xxxxxxx Compounds xx Xxxxx x Xxx Xxxxxxxx Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

13) Prival, X. X., Xxxx, X. X., Xxxxxxxx, X. X., Reipert, M. X., Xxxxxxx, V. X. (1984), Xxxxxxxxxxxx xx Benzidine and Xxxxxxxxx-Xxxxxxxx Dyes xxx Xxxxxxxx Monoazo Xxxx xx x Xxxxxxxx Xxxxxxxxxx Xxxxx, Mutatation Xxx., 136, 33-47.

14) Xxxxxx, X., Xxxxxxxx, X. E., Xxxxxxx, X., Lawlor, T., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx from xxx Xxxxxxx xx 311 Xxxxxxxxx, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

15) Simmon, V., Xxxxxxxx, X., Xxxxxxx, X. X. (1977), Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxx Identified xx Xxxxxxxx Xxxxx, xx Xxxxxxxx xx Xxxxxxx Xxxxxxxxxx, X. Scott, X. Xxxxxxx, X. Xxxxxx (xxx.) Xxxxxxxx, Xxxxxxxxx, 249-258.

16) Xxxxxx, X. J., Xxxxxxx, X. M., Xxxxxxxx, X. X., Xxxxxxx, X. D. (1987), Xxxxxxxxxxxx Xxxxxxxxx xx Xxxxxxx Xxxxxxxxx Activity xx Xxxxxxxx Xxxxxxx Xxxxxxxxx xx xxx Xxxx/Xxxxxxxxxx Assay, Environmental Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, T., Xxxxxxxxx, X., Shirai, X., Xxxxxxxx, X., Sugimura, X. (1979), Mutagenicity xx xxx Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Methylazoxy Xxxxxxx Conjugates xx Xxxxxxxxxx typhimurium, Xxxxxx Xxx., 39, 3780-3782.

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

19) Xxxxxx, X., Naidoo, X., Xxxx, D. J., Xxxxxxxxx, D. X. (1990), Xxxxxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx XX 102 xxxx Escherichia xxxx WP2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: In vitro Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, eds. X. X. de Xxxxxx xx xx. Xxxxxxxx, North Xxxxxxx, 85-88.

21) Xxxxxx, X. X., Combes, X. X., Xxxxxxx, C. X., Xxxxxxxxx, X. X., Gibson, G. X., Xxxxxx, X. X., Wolf, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 xx xx xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, X., Xxxxxxxxxxxxxxxx, X., Xxxx, X. X. (1981), Xxxxxxxxxxxxx xx Organic Xxxxxxxx xxxx the Xxxxxxxxxx/Xxxxxxxxx Xxxx, Mutatation Xxx., 88, 343-350.

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

24) Xxxxx, X. X. X., Green, M. X. L., Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. D., Xxxxxx, X. X. (1989), Analysis xx Xxxx xxxx Microbial Xxxxxx Xxxxxx, xx: XXXXX Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxx XX. Xxxxxxxxxxx Evaluation of Xxxxxxxxxxxx Xxxx Xxxx, xx. Kirkland, X. X., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 28-65."


XXXXXXX 4X

"X.17 XXXXXXXXXX — XXXXXXX XX XXXXXX XXXXXX V XXXXXXX SAVCŮ IN XXXXX

1. XXXXXX

Xxxx metoda xx xxxxxxxx xxxxxx XXXX XX 476 — Zkouška na xxxxxx mutace v xxxxxxx xxxxx in xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx vitro xxx xxxxxx pro xxxxxxx xxxxxxxx mutací xxxxxxxxxxxx xxxxxxxxxx látkami. Mezi xxxxxx xxxxxxx linie xxxxx xxxxx lymfomu X5178X xxxx, xxxxxxx xxxxx XXX, XXX-XX52 x X79 xxxxxx xxxxxxxx x lymfoblastoidní xxxxx XX6 člověka (1). X xxxxxx xxxxxxxxx linií xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx xxxxxx xxxx xxx thymidinkinasu (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (HPRT) x xxxxxxxx xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx na xxxxxx XX, XXXX x XXXX xxxxxxxx xxxxx spektrum genetických xxxxxxxx. Autosomální xxxxxx XX x XPRT xxxx umožnit xxxxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx xxxxxx), které xxxxx detekovat x XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx xxxxxx v xxxxxxx xxxxx xx xxxxx xxx použít xxxxxxx xxxxxxxxxx linií xxxxx nebo xxxxxxx xxxxx. Xxxxx se xxxxxxxx xxxxx xxxxxxxxxx xxxxx v xxxxxxx x xxxxxxxx četnosti xxxxxxxxxxx xxxxxx.

Xxxxxxx prováděné xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx metabolické aktivace. Xxxxx xxxxxxxxxxx aktivační xxxxxx nemůže zcela xxxxxxxxx podmínky xx xxxx x xxxxx. Xx xxxxx se xxxxx vyvarovat xxxxxxxx, xxxxx by xxxxx x xxxxxxxxxx výsledkům, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. K xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx, xxxx xxxxx xxxxxx xX, xxxxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx a xxxxxxxxxxx xxxxx. Xxxxx sloučenin, xxx něž xx xxxx xxxxxxx xxxxxxxxx, xxxx karcinogeny savců; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx xxxxxx na xxxxxxxx třídě x xxxxxxxxx xxxxxx o xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx nejsou xxxxxxxx touto xxxxxxxx, xxxxx zřejmě xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, které x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxx xxxxxx : xxxxxx xxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxx, která způsobuje xxxxx nebo ztrátu xxxxxxxxxxx aktivity kódovaných xxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx : látky, xxxxx způsobují xxxxxxxxxx xxxxxxx xxxx xxxx xxxx xxxx x XXX.

Xxxxxxxx xxxxxxxx : xxxxx, které xxxxxxxxx xxxxx nebo deleci xxxxxxx xxxx xxxx xxxx xxxx x xxxxxxxx DNA.

Doba xxxxxxx xxxxxxxx : doba, xxxxx xxx vymizí x xxxx mutovaných xxxxx xxxxxxxxx xxxxxx xxxxxxxx.

Xxxxxxx xxxxxxx : xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxxxxx xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxx xxxxxxx xxxx : xxxxxx xxxxx buněk x xxxx ve xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx xx xxxx součin xxxxxx xxxxxxxxx xxxxx x xxxxxxxx a x xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxx růst x xxxxxxxx : xxxxxx xxxxx xxxxx v xxxxxxx xxxxxxx xxxxxxxx x negativní xxxxxxxx.

Xxxxxxxxxxxxxxx : xxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xx misku xx xxxxxxxxxxxx xxxxxxxx xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx nasazení na xxxxx xx konci xxxxxx expozice; xxxxxxx xx obvykle xxxxxxxxx x poměru x xxxxxxx xxxxxxxxx xxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx TK+/-® XX— /- neobsahují xxxxxxxxxxxxxx (XX) jsou xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx analogu xxxxxxxxxx xxxxxxxxxxxxxxxxx (XXX). Buňky xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx xx TFT, xxx xxxxxxxxx inhibici xxxxxxxxx metabolismu x xxxxxxxxx další buněčné xxxxxx. Xxxxxxxx xxxxx xxxx xxxx xxxxxxx xxxxxxxxxxx za xxxxxxxxxxx XXX, xxxxxxx xxxxxxxx xxxxx, které xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Xxxxxxx xxx x xxxxx s xxxxxxxxxxxx XXXX xxxx XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx rezistence k 6-xxxxxxxxxxx (TG) xxxx 8-xxxxxxxxxx (AG). Xxxxxxxxxx xxxxxxxx látky xx xxxx xxx xxxxxxx xxxxxxx, jestliže je xx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx zkoušen xxxxxx xxxx xxxx xxxxxxxxxx podobná xxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxxxx vyšetřeno xxxxxxxx xxxxxxxxx na xxxxxxxxxx toxicitu xxxxxxxx xxxxx xxx xxxxxxxx xxxx xxxxxxxxxx buňky. Xxx xxxxxxxx chemických xxxxx, které xxxx xxxxxxxx xxxxxxxxx jako xxxxxxxx xxxxxxx, musí xxxx xxx xxxxxxxxx xxxxxxxx systému nebo xxxxxxx xxx xxxxxxx (8).

Xxxxx v suspenzní xxxx xxxxxxxxxxxxx xxxxxxx xxxx xxxxxxx dobu xxxxxxxxx xxxxxxxx xxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, a xxxxxxxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx xxxxxxx fenotypu xxxx selekcí xxxxxxx (9, 10, 11, 12, 13). Cytotoxicita xx xxxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxxx relativního celkového xxxxx kultur po xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx x xxxxxxxx xxxxx xx xxxxxxx xxxx xxxxxxxxxxxxxxxxx pro xxxxx xxxxxxx xxxxx x xxx buněk, xxx xxxxxxx přibližně xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx se stanoví xxx, že xx xxxxxx xxxxx xxxxx xxxxx do xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx xxxxxxx mutantních xxxxx x xx xxxxx bez selekčního xxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx se xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx xx xxxxxxx x počtu mutantních xxxxxxx v xxxxxxxxx xxxxx a počtu xxxxxxx x xxxxx xxx xxxxxxxxxx činidla.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx xxxxxxx x xxxx xxxxxxx xxxx x xxxxxxxxx xxxxx xxxx xxxxx, xxxxxx xxxxxxxx xxxxx X5171X, XXX, XXX-XX52, X79 xxxx XX6. Xxxx buněk x xxxx xxxxxxx by xxxx xxxxxxxxx xxxxxxxxx x chemickým xxxxxxxxx, xxxxxxx xxxxxxxxx schopnost x xxxxxxxx frekvenci xxxxxxxxxxx xxxxxx. Xxxxx xx měly xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, a x případě kontaminace xx neměly být xxxxxxx.

Xxxxxxx xx xxxx xxx xxxxxxxx tak, xxx měly xxxxxx xxxxxxxxxx xxxxxxxxx x xxxx. Počet xxxxxxxxx xxxxx, xxxxxx a xxxxxxxxxxx xxxxxxxx látky xx xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxx (14). Xxxxxxxxx xxxxx xxxxx, které přežijí xxxxxxxx x které xxxxx xxxxxxx v xxxxxx xxxxxx xxxxxxx, xx xxx být xxxxxxx xx xxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx xx, aby xxx xxxxxx xxxxx xxxxx, který je xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx však xxxxxxxxxx, xxx xxxx použito xxxxxxx 106 xxxxx. Xxxx xx být x dispozici xxxxxxxxxx xxxxxxxxx xxxxx o xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx doložena xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx podmínky

Pro xxxxxxxxx xxxxxx by měla xxx xxxxxxx xxxxxx xxxxxxxxxx média x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, koncentrace XX2, xxxxxxx a vlhkost). Xxxxx xx xxxx xxx zvolena xxxxx xxxxxxxxxx systémů a xxxx buněk použitých xxx xxxxxxx. Je xxxxxxx důležité, xxx xxxxxxxxxx podmínky byly xxxxxxx xxx, xxx xxxx xxxxxxxxx optimální xxxx xxxxx během xxxxxx exprese x xxxxxxxxx xxx xxxxxxxxxx, xxx xxxxxxxxxxxx xxxxx xxxxxx xxxxxxx.

1.4.1.3 Příprava xxxxxx

Xxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxx, xxxxxxxx xx xxxxxxxxxxxx xxxxx x xxxxxxxxxx xxx 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx může xxx xxxxxxxx odstranit x xxxxxxx xxx xxxxxxxx xxxxxxxx xxxxx.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx aktivace x xxx něho. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx x jater hlodavců xxxxxxxxxx činidlem xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (15, 16, 17 x 18), nebo směs xxxxxxxxxxxxx x β-naftoflavonu (19, 20).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx v xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxxx x stav xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx zkoušena. V xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx použít xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce.

Řada xxxxxxxx xxxxxx, včetně xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx enzymy, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx xxxxx xx xxxx být xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx isoenzymu xxxxxxxxxx X450 xxx xxxxxxxxxxxx xxxxxxxx látky).

1.4.1.5 Příprava xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx xxxx aplikací xx xxxxx rozpuštěny xxxx xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx být xxxxxxx přímo x xxxxxxxxxx xxxxxxxx a/nebo xxxxx být před xxxxxxxx xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx látky, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx být xxxx xxxxxxxxx, xx xxxxxxx se zkoušenou xxxxxx, x mělo xx xxx slučitelné x xxxxxxxx buněk x x aktivitou X9. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx nestálých xx vodě by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx mají xxx zohledněna xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x změny xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx aktivací x xxx xx x xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, jako xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxx celkový růst. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x předběžném xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx alespoň xxxxx xxxxxxxxxxxxxx koncentrace. V xxxxxxx xxxxxxxx xx xxxx xxxx koncentrace xxxxxxxx rozmezí dané xxxxxxxxx a xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx, xxx bude xxxxxxx xxxxxxxx, že xx xx xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. Xx-xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx cytotoxicity, xxxx xx xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) přežití (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx celkový xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx by xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx toho, která x nich xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx látky xx měly xxx xxxxxxxx až x xxxx rozpustnosti xx xxxxxxxxxxxx podmínek, nebo xx za xxxx xxx. Xxxx xx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x konečném xxxxx, xx xxxxxxx xxxx xxxxx xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx rozpustnost na xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx se xxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx systému xxxxx x důsledku xxxxxxxxxxx xxxxx, X9 xxxx, atd. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly xxx xxxxxxxxx a negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx xxx x xxxxxxxxxxxx aktivací, xxx xxx ní. Při xxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx pozitivní kontroly xxxxx xxx tyto xxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

Xxx xxxxxx xxxxxxxxxxx xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx a 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 xxxxxx xxxxxxxxxxxx xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (xxxx a xxxxx kolonie)

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

xxxxx[x]xxxxx

50–32–8

200–028–5

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–5

XXXX

X-xxxxxxxxxxxxxxxxxxx (xxx xxxxxx úrovně X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx xxx xxxxxxx xxxx jiné referenční xxxxx xxx pozitivní xxxxxxxx, např. xx-xx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxx x 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, XXXXXX 200–415–9), xxxx xxx xxxx xxxxxxxxxx látka xxxxxx xxxxxxx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx x úvahu použití xxxxxxxxxx xxxxx xxxxx xxxxx xx stejné xxxxxxxx xxxxx.

Xxxx xx xxx použity xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx samotné rozpouštědlo xxxx xxxxxxxxx x xxxxxxxxxx jinak stejným xxxxxxxx jako xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Expozice xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému, xxx xxx něho. Xxxxxxxx xx xxxx xxxxx xxxxxxx xxxx (xxxxxxx xx xxxxxx xxxx 3 xx 6 hodin). Expoziční xxxx xxxx být xxxxxxxxxxx na xxxxx xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx zkušební xxxxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx xxxxxxxxxx xxxxxxx. Xx-xx použita xxxxx kultura, xxx xx být xxxxx xxxxxxxxxxx xxxxxx tak, xxx byl xxxxxxxx xxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxx (xxxx. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx by xxx použity xxxxxxxxxx xxxxxxxxx xxxxxxxxx kultury (xxxxxxxx xxxxxxxxxxxx).

Xxxxxx xxxx xxxxxx xxxxx xx xxxx být xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x xxxxx uzavřených xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Xxxxxxxxx přežití, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx konci xxxxxxxxx xxxx xx xxxxx xxxxxxx a kultivují xx xxxxxx xxxxxxxxx xxxxxxx x za xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Xx xxxxxxxxxx cytotoxicity prostřednictvím xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (přežití) nebo xxxxxxxxxxx celkového xxxxx xxxxxx xx započne xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx xxxxx xx xxxxxxxxxx minimální časové xxxxxx, aby xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (XXXX x XXXX xxxxxxxx xxxxxxx 6 xx 8 xxx, XX xxxxxxx xxx dny). Buňky xxxx xxxxxxxxxxx x xxxxx se selekčním xxxxxxxx (selekčními činidly) x xxx něho (xxx xxxx) xx xxxxxx stanovení xxxxx xxxxxxx a xxxxxxxxx xxxxxxxxx. Xx stanovením xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx xxxxxxxx mutantů) xx xxxxxxx xx xxxxx xxxx exprese xxxxxxxxx na misku xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx látka xxxxxxxxx xx xxxxxxx X5178X XX+/-, xxxx xx xxx xxxxxxxxx xxxxxxx xx xxxxx ze xxxxxxxxxx xxxxxx (x xxxxxxxx pozitivní xxxxxxxxxxx) x xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx podle xxxxxxxxx kolonií. Xx-xx xxxxxxxx xxxxx ve xxxxxxx X5178X TK+/- xxxxxxxxx, xxxx by xxx xxxxxxxxx xxxxxxx xxxxx velikosti xxxxxxx xxxxxxxxx na xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx XX6 XX+/- xxxx být také xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx velikosti xxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xx xxxx zahrnovat xxxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x četnosti xxxxxxx xxx exponované x xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxx X5178X XX+/- xx xxxxxxx xxxxxxxxx xxxxxxx u xxxxx koncentrace xxxxxxxx xxxxx (xxxxxxxx pozitivní xxxxxxxxxxx) x x xxxxxxxxx x xxxxxxxxx xxxxxxxx za použití xxxxxxxx xxxx xxxxxxx — xxxxx xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx velké xxxxxxx, xxx mutantů xxxxxxxxx xxxx xxxxxxx byla xxxxxxxx zkoumána (23, 24). Xx xxxxxxx XX+/- xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx kolonie x xxxxxxxxx xxxxxx (velká) x xxxxxxx x xxxxxxx xxxxxx (malá) (25). X mutantních xxxxx, xxxxx utrpěly xxxxxxxxxxxxxx genetické poškození, xx prodloužily doby xxxxxxxx, a xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx xx obvykle xxxxxx od ztrát xxxxxx xxxx xx xx xxxxxxxxxxxx viditelné xxxxxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx xxxxxxxxx xxxx xxxxxxx se xxxxxxx x chemickými xxxxxxx, xxxxx indukují silné xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx xxxxxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxx buňky a xxxxx xxxxx kolonie.

Mělo xx xxx xxxxx xxxxxxx (relativní účinnost xxxxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. Xxxxxxx xxxxxxx xx měla xxx xxxxxxxxx jako xxxxx mutantů x xxxxx xxxxxxxxxx buněk.

Měly xx xxx uvedeny xxxxx xxx xxxxxxxxxx xxxxxxx. Dále by xxxx být všechny xxxxx xxxxxxx ve xxxxx tabulky.

Ověření jasně xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Dvojznačné výsledky xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx případ xx xxxxxxx. Xxx, xxx xxxx xxxxxxxxx negativních xxxxxxxx xxxxxxxxxx xx xxxxx, xx třeba xxxxx xxxxxxxxxx. Změna xxxxxxxxx studie x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, tak xxx xxxxxxxxx xxxxxxxx. X xxxxxxxxxx studie, xxxxx xx xxxxx xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx a xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxx xxxxxxx v xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Xxxxxxxx xx xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxxxx xxxxx, xxxxx výsledky xxxxxxxxx xxxx uvedená kritéria, xx x xxxxx xxxxxxx xxxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých případech xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx xx to, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx savců in xxxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx kultivovaných xxxxxxx xxxxx xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx odpovědi xx xxxxxxxxxxx xx xxxxx xxxxxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx zkoušená xxxxx za podmínek xxxxxxx neindukuje x xxxxxxxxx xxxxxxxxxxxxx buňkách xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x zkoušce xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxx a xxxxx xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- případně xxxxxx xxxxxxxxx buněčné kultury,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x počtu kultur, xxxxxx xxxx. údajů x xxxxxxxxxxxx x xxxxxx xxxxxxxxxxxx, jsou-li x xxxxxxxxx,

- xxxxxxx xxxxx, xxxxxxxx koncentrace XX2,

- koncentrace zkoušené xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxxxx expozice,

- xxx a složení xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxxxxx kritérií xxxxxxxxxxxxx,

- pozitivní a xxxxxxxxx xxxxxxxx,

- délka xxxx xxxxxxx (xxxxxxxx xxxxxx xxxxx nasazených xxxxx, xxxxxxxxx a xxxxxx xxxxx),

- xxxxxxxx xxxxxxx,

- xxxxxxxx klasifikace xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx xxxxx,

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

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

- xxxxx x pH a xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxx,

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

- xxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxxxxxx systémem X5178X TK+/-,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

- xxxxxxxxx údaje x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx kontrole x rozmezími, xxxxxxxxx xxxxxxxxx a směrodatnými xxxxxxxxxx,

- xxxxxxx xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., XxXxxxxx, X. X., XxXxxxxx, X. X., Xxxxxx, X. X. (xxx.) (1987), Xxxxxxx Xxxxxx 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Xxxx Xxxxxx Xxxxxx Xxxxxxxxxx, Xxx Xxxx.

2) Chu, X. X. X., Malling X. X. (1968), Xxxxxxxxx Cell Genetics. XX. Xxxxxxxx Xxxxxxxxx xx Specific Xxxxx Xxxxxxxxx xx Chinese Xxxxxxx Xxxxx Xx xxxxx, Proc. Natl. Xxxx. Xxx. X. X. X, 61, 1306-1312.

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

4) Xxxxx, X. X., Harington-Brock, X., Xxxxx, X. X., Xxxxxxxxx, K. X. (1989), Xxxxxxxxxxxx Xxxxxx Quantitation at xxx Xxxxx Lymphoma XX xxx CHO XXXXX Xxxx, Mutagenesis, 4, 394-403.

5) Xxxxx, X. X., Xxxxxxxxxx, Xx. L. F., (1989), Comparison xx xxx AS52/XPRT xxx xxx XXX/XXXX Xxxxxx: Xxxxxxxxxx xx Xxx Xxxx Xxxxxxxxxx, Mutatation Xxx. 223, 121-128.

6) Xxxxx, X. X., Xxxxxxxxxx, X., Glatt, X. R., Moore, X., Xxxxx, Y., Xxxxxxxxxx, Xx. X. X., Theiss, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Xxxx Gene Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Xxxxxx. Xxxxxx xx xxx International Xxxxxxxx on Xxxxxxxxxxxxxxx xx Genotoxicity Test Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, X. X., Marshall, X. X., Xxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Myhr, B. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Culture Xxxxxxxxxx. X report xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

8) Xxxxx, X., XxXxxx, X., Xxxxxxx, X. X. X., Xxxxx, X., Mavournin, X. X. (1983), Specific Xxxx Xxxxxxxxx xx X5178X Cells xx Xxxxxxx. A Report xx xxx X. X. Environmental Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 115, 225-251.

9) Xx, X. X., Xxxxx, X. X., Xxxxxxx, X. X., Xxxxxx, J. X. (1988), X Xxxxxx and Xxxxxxxx xx the Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Guanine Xxxxxxxxxxxxxx Transferase Xxxxxx xx Determine xxx Xxxxxxxxxxxx of Xxxxxxxx Xxxxxx: X Xxxxxx xx Phase XXX xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, X. X., Xxxxxx, X. X., Xxxx, W. X., Hsie, A. X., Xxxxx, X. X., Xxxxxxx, X. X., O'Νeill, X. X., Xxxxxx, J. X., Xxxxxxxxxx, X. X. Xx., Xxxx, X. X. (1987), X Xxxxx for xxx Xxxxxxxxxxx xx xxx Chinese Hamster Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Gene Mutation Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

11) Xxxxx, X. X., Xxxxxxx, X. X., Xxxxxx, X. X. (1989), X Comparison xx Xxxxxxxx Xxxxxxxxx at xxx TK xxx XXXX Xxxx xx Xxxxx Lymphoblastoid Xxxxx: Xxxxxxxxxxxx Differences are Xxx xx an Xxxxxxxxxx Xxxxx xx Xxxxxxxxx xx the Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Res., 216, 9-17.

12) Xxxxxxxxxx, X. X. Xx., Xxxxxx, X. R., Xxxx, X. X. (1986), Xxxxxxxxxxxx xxx Xxxxxxxxx Xxxxxxxx of Xxxxx Xxxxxxxxxxxxxxxxx xxx ICR 191-Xxxxxxx Molecular Xxxxxxxx xx Xxxxx Xxxxxxxxxxxxxxxxx xxx XXX 191 Xxxxxxx Xxxxxxxx xx XX52 Xxxxx, Xxxxxxxxxx Xxx., 160, 133-147.

13) Xxxxxx, X. X., Xxxxxx, X. X., Xxxxx, X. (1984), Xxxxxxxxx xxx the X5178X/XX+/--XX+/- Xxxxx Lymphoma Xxxx Mutagenicity Assay, xx: Kilbey, X. X. xx xx (xxx.) Xxxxxxxx xx Xxxxxxxxxxxx Test Xxxxxxxxxx, Xxxxxxxx Xxxxxxx Publishers, Xxx York, 239-268.

14) Xxxxxx, X. F., Xxxxx, X. X., Xxxxxx, X. M., Xxxxx, M. X. X., Xxxx, X., XxXxxxxx, X. X., Xxxxxxx S. C. (1989), Xxxxxxxxx Cell Xxxx Mutation Xxxxxx Xxxxx xxxx Xxxxxx Xxxxxxxxx, in: Statistical Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. X., ed., Xxxxxxxxx University Xxxxx, 66-101.

15) Xxxxxxxxxxxx, A., Xxxxxxx, X., Xxxxx, X., Fiorio, R., Xxxxxxxx, X., Xxxxxxxxxx, X. (1977), Xxxxxxxxx xx 6-Xxxxxxxxxxx-Xxxxxxxxx Mutants xx V79 Xxxxxxx Xxxxxxx Xxxxx xx Xxxxx-Xxxxx Microsome-Activated Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Xxx. 46, 365-373.

16) Ames, B. X., McCann, X., Xxxxxxxx, X. (1975), Xxxxxxx for Detecting Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx. 31, 347-364.

17) Xxxxx, D., Xxxxxxx, X. X., Spector, X. X. S., Xxxxxx A. G., Xxxxx M. X. X. (1979), Xxxxxxxxxx xxx Xxxxxxxxxxxxxxxx of xxx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxxxx Xxxxx System, Xxxxx. Xxx. 59, 61-108.

18) Xxxxx, D. X., Ames, X. X. (1983), Xxxxxxx Xxxxxxx for xxx Xxxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Res. 113, 173-215.

19) Xxxxxxx, X. X., Combes, R. X., Xxxxxxx, X. X., Gatehouse, X. X., Gibson, G. X., Xxxxxx, J. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-Induced X9 xx: Xx xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Sawamura, X., Xxxx, K., Xxxxxxxx, X. (1976), X Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, V: Xx xxxxx Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xx Xxxxxx, X. X., Fouts, X. X., Xxxx, X. X., Philpot, X. X. (eds), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. F., Xxxxxx, F. C., XxXxxxx, K. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Evaluation of Xxxxx and Volatile Xxxxxxx, xx: Xxxx, X. X., Xxxxx, X. X., Schaich, X. M. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Agents, Xxx Xxxx, Xxxxxx, 91-103.

22) Xxxxxx, X. O., Xxxxxx, J. M., Xx, X. P., Xxxxxx, X. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx System Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Detecting Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Environ. Xxxxxxxxxxx, 5, 795-801.

23) Xxxxxxxxx, X. X., Moore, X. X., Xxxxxx, X. X., Xxxxxxx, X., Hozier, J. X. (1990), Molecular Xxxxxxxxxx xx Xxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Xxxxx xx Mouse Xxxxxxxx Xxxxx, Xxxx. Xxxx. Xxxx. Sci. U. X. X, 87, 51-55.

24) Moore, X. X., Xxxxx, X., Xxxxxx, X. X., Xxxxxx, B. X., Xxxxxx, A. G., Xxxxxx, X. X., Xxxxxx, X. (1985), Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (XXX+) Xxxxxxx xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx. 151, 161-174.

25) Yandell, X. X., Xxxxx, X. X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxx Xxxxxxxx xx Recessive Mutations xx a Xxxxxxxxxxxx Xxxxxxxxx Xxxxx xx Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.

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


PŘÍLOHA 4F

"B.23 XXXXXXX XX XXXXXXXXXXXX XXXXXXX XX XXXXXXXXXXXXXXX XXXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx OECD XX 483 — Xxxxxxx xx chromozomové xxxxxxx xx spermatogoniích xxxxx (1997).

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx xx vivo xx xxxxxxxxxxxxx takové xxxxx, které způsobují xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: chromozomové x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxx xxxxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x není x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxx xxxx xxxx příčinou xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx xx xxxxxxxxxxxxxxx a předpokládá xx tedy, xx xxxx xxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx dědičných xxxxxx v xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx rutinně používáni xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx xx xxxx xx xxxxxxxx xxxxxxxxxxxx xxxxxxx při xxxxxx xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxxx.

Xxx detekci xxxxxxx chromatidového xxxx xx spermatogoniích by xxxx xxx — xxxxx než xxxxx xx xxxxxx xxxx — vyšetřeno xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx následuje po xxxxxxxx. Xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx x diakinese-metafázi X, xxx xx xxxxxxxxxx buňky xxxxxxx xxxxxxxxxxxx.

Xxxx zkouška xx xxxx xx xxxxxxxx xxx vyšetření, zda xxxx mutageny xxxxxxxxxxx xxxxx xxxxxxx xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx je tato xxxxxxx se xxxxxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx DNA.

Ve varlatech xx xxxxxxxx řada xxxxxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxxxx xx xxxxxxxx chemické xxxxx. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx souhrnnou xxxxxxx xxxxxxxxxx populace xxxxxxxxxxxxx x převládajícími xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X xxxxxxxxxx xx xxx xxxxxx xx xxxxxxxxx, xxxxx xxxx xxxxxx být xxxxx xxxxxxxx spermatogonií xxxxxxxxxx xxxxxxxxx krevnímu xxxxx x xxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxx Xxxxxxxxx xxxxx x xxxxxxx xxxx xxxxxxx oběhem x xxxxxxx.

Xxxxxxxx existuje xxxxx x xxx, že xx xxxxxxxx látka xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, není xxxxxx xxxx xxxxxxx použít.

Viz xxxx obecný xxxx, xxxx B.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx aberace : xxxxxxxxxx poškození xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx x xxxxxxx obou xxxxxxxxx x tomtéž místě.

Gap : achromatická léze xxxxx xxx xxxxx xxxxx chromatidy x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

Xxxxxxxxxxx : xxxxxxx xxxxxxxxxxx xxxxx chromozomových xxx (x), xxxx než xxxxxxxxx (xx. 3 x, 4 x xxx.).

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx xxxxxx xx xxxxxx metafáze xxx xxxxxxxxxxx, xxxx xx xxxx xxxxxx a xxxxxxxxx, intrachromozomální xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxx způsobem exponována xxxxxxxx xxxxx a xx vhodné xxxx xx xxxxxxxx xxxxxxxx. Xxxx xxxxxxxxx se xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X germinálních buněk xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx a xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xxxx používáni xxxxx xxxxxx xxxxxxxx x xxxx; xxx xxxx xxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxx xxxxx. Xxxx by xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx zvířat. V xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx x hmotnosti xxxxxx minimální a xxxxxx xx překročit ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladí xxxxxxxx xxxxxxx xxxxx se xxxxxxxx xxxxxxx xxxxxxx xx kontrolní skupinu x skupinu, která xx exponuje. Xxxxx xx měly xxx xxxxxxxxxx tak, aby xxx vliv xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx xxxxxxxxx xxxxxx xx nechají x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xxxxxxxx rozpuštěny nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx být xxxxxxxx xxxxx xxxx xxxxx xxx xxxx podáním xxxxxxx. Měly by xxx použity čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, pokud údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx mít xxx xxxxxxxxx xxxxxxxxx dávek xxxxxxx xxxxxx x xxxx by xxx xxxxxxxxx podezření, že xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Doporučuje xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx xx xxxx xxx souběžné xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx měla xxxxxxx kontrolní skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx ve xxxxxxxxx, x xxxxx xxxxx k expozici.

Pozitivní xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xx xxxx xxx expozičních xxxxxxxx, x xxxxx xx předpokládá, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx pozitivní xxxxxxxx xx měly xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby xxxx xxxxxxxxx kontrola podávána xxxxx xxxxxxxx než xxxxxxxx xxxxx a xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxx xxx navíc xxxxx x xxxxx xxxxxxx xxxxxxxxxx látek xx xxxxxx chemické xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx kontrolu:

Látka

Číslo XXX

Xxxxx xxxxx Xxxxxx

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxx (xxxxxxx)

79–06–1

201–173–7

2,4,6-xxxx(xxxxxxxx-1-xx)-1,3,5-xxxxxxx

51–18–3

200–083–5

X xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx odběr x xxxxxxx negativní xxxxxxxx, xxxxx xx aplikováno xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x xxxxx xxxxx podstupuje stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, pokud xxxxxx x xxxxxxxxxxx kontrolních xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx o xxxxxxxxxxx xxxxxx a xxxxxxxx buněk s xxxxxxxxxxxxxx aberacemi. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx dosud xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xxxx zahrnovat xxxxxxx xxx analyzovatelných xxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xx xxxx být xxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxx nadvakrát (xx. xxx xxxxx xxxxxxxx nebo xxxx xxxxxxxxxx). Xxxxxxxx xxxxx xxxxx xxx podávány xxxx xx dvou xxxxxxx, xxx. dvě xxxxx x xxx xxx v rozmezí xx více xxx xxxxxxxx hodin, xxx xxxx xxxxxxxxx podávání xxxxxxx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xx skupině x xxxxxxxx xxxxxx xx xxxx xxx xx expozici xxxxxxxxx xxx odběry. Poněvadž xxxxxxxx xxxxxxxxx cyklu xxxx xxx zkoušenou xxxxxx xxxxxxxxx, xxxxxxx xx xxxxx xxxxx xxxxx x xxxxx xxxxxxxx odběr přibližně 24 x 48 xxxxx xx xxxxxxxx. X xxxxxxx xxxx xxx xxxxxxxx dávky xx xxx xxx xxxxx xxxxxxxx xx 24 xxxxx xxxx xx xxxxxx xxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx xxxx xxxxx xxxx vhodnější xxxx xxx xxxxxxx xxxxxx (6).

Xxxxx xxxxx xxx xxxxxx provedeny xxxx v xxxx xxxx. Xxxxxxxxx x xxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxxx xxxxxxxxx xxxxxxxx replikace (xxxxxxx) xxxxxxxxxx xxxx mohou xxxxxxxxxx X-xxxxxxxxx účinky, xxxx být xxxxxxxxx xxxxxxxx xxxxx (1).

Xxxxxxxx xxxxx xxxxxxxxx expozice xxxx xxx určena xxxxxx od případu. X xxxxxxx xxxxx x xxxxxxxxxx expozicí xx měla být xxxxxxx usmrcena 24 xxxxx (1,5xxxxxxx xxxxx xxxxx) po poslední xxxxxxxx. Xxxxx xxxxxxx xxxxx být prováděny xxxxx odběry v xxxx xxxx.

Xxxx usmrcením xx xxxxxxxx intraperitoneálně xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx metafázi (xxxx. Colcemid® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx době xxxxxxx x xxxxxx xxxxx. X xxxx xx xxxx doba xxxxxxxxx 3 — 5 xxxxx; x xxxxxx čínského xx xxxx doba přibližně 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx zjištění xxxxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx x xxxxxx x za xxxxxxxx xxxxxx xxxxxxxx, který xx xxxxxxx x xxxxxx xxxxxx (7). X případě toxicity xx xxx první xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx toxicitou, případně xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx nejvyšší xxxxx. Xxxxxxxx xxxxx je xxxxxxxxxx jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx by xxxxx dávky xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) nemusí xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x měly xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx dávka xxxx xxx xxxx definována xxxx xxxxx xxxxxxxxxxxx xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx počtu xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx meiotické xxxxxxxx; xxxx xxxxxxx xx xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x jednou xxxxxx alespoň 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx dvou xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx základě xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, očekávána xxxxxxxxxxxx, xxxxxxxxxx se úplná xxxxxx xx xxxxx xxxxxxxx xxxxx za xxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx znamenat xxxxxxx použít x xxxxxxx xxxxxxx xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx podává nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Maximální xxxxx xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx testovacího xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx být xxxxxxxxxx. Až na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx xxx xxxxxxxxxxx zkoušeného objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní objem xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxx

Xxxxx xx usmrcení se x jednoho xxxx xxxx xxxxxx xxxxx xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx x xxxxxx. Xxxx xx xxxxxx xx podložní xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx zvířete xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx v dobře xxxxxxxxxxxx metafázi (tj. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Xxxxx xxxxx xxx snížit, xx-xx xxxxxxxxx velký xxxxx aberací. Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x negativních xxxxxxx, xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx při fixaci xxxxx xxxxxxx xx xxxxxxxxxxxxxx zlomům nebo xxxxxx xxxxxxxxxx u xxxxx metafází, měly xx vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx v xxxxx odpovídajícímu xxxxx 2 x ± 2.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxxxxx ve xxxxx tabulky. Experimentální xxxxxxxxx je zvíře. Xxx každé xxxxx xx měl xxx xxxxxxxxxx xxxxx xxxxx xx strukturními xxxxxxxxxxxxxx xxxxxxxxx x počet xxxxxxxxxxxxxx xxxxxxx na xxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx měly být xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx odděleně x xxxxxxx se, xxx obecně xx xxxxxxxxxx xx xxxxxxx xxxxxxxx aberací.

Je-li pozorována xxxxxx x také xxxxxx, měl xx xxx xxx xxxxxxxxx xxxxxxx cytotoxických xxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxxxx x všech xxxxxxxxxxxx xxxxxx a xxxxxx xxxxxxxxxx jako xxxxxxxxx xxxxxxxx poměr xxxxxxxxxxxxx v mitose xxxxxxxx x první x druhé meiotické xxxxxxxx, a to x xxxxxxxx xxxxxx 100 dělících xx xxxxx na xxxxx xxxxx. Pokud je xxxxxxxxx xxxxx xxxxxx, xxxxxxx x 1000 xxxxxxx na xxxxx xx měl být xxxxxxxx xxxxxxxxx xxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx existuje několik xxxxxxxx, xxxx. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx na dávce xxxx xxxxx nárůst xxxxx buněk s xxxxxxxxx xxx skupinu x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravami xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx výsledky xxxxxxxxx xxxx uvedená xxxxxxxx, xx v tomto xxxxxxx xxxxxxxx za xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx negativní xxxxxxxx, x ojedinělých případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx aberace ve xxxxxxxxxxxxxxx savců xx xxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx strukturní xxxxxxxxxxxx aberace. Negativní xxxxxxxx znamenají, xx xxxxxxxx xxxxx za xxxxxxxx zkoušky neindukuje x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx pravděpodobnost, x xxxxx se xxxxxxxx xxxxx xxxx její xxxxxxxxxx xxxxxxxx xx xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol o xxxxxxx musí obsahovat xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx x xxxxx zvířat,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx na xxxxxxx zkoušky, včetně xxxxxxx xxxxxxx hmotnosti, xxxxxxx hodnoty x xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- údaje o xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x podávání xxxxxxxx xxxxx,

- zdůvodnění xxx xxxxxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx v xxxxxx xxxx xxxx (xxx) xx xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx údaje x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- xxxxxxxxxxxx xxxxx zastavující metafázi, xxxx koncentrace x xxxxx xxxxxxxx,

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx buněk xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky toxicity,

- xxxxxxxxx xxxxx,

- xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x druhé xxxxxxxx xxxxxx,

- typ x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx xx xxxxxxx,

- xxxxx xxxxx x xxxxxxxxx xx xxxxxxx,

- xxxxx možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx statistické analýzy,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. D., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Xxxxxxxxxxxxx of Xxxxxxxx Mutagens Xxxxxxx xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, in: Genetic Xxxxxxxxxx xx Environmental Xxxxxxxxx, Part X: Xxxxxxx Xxxxxxx and Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Xxxxxxx, X., Xxxxxxxxx, X. (eds) Xxxx, Xxx Xxxx, 477-484.

2) Xxxxx, X. X., (1984), Cytogenetic xxxxx xx Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Practical Xxxxxxxx, (xx.) X. Xxxxxx, X. M. Parry, XXX Press, Xxxxxx, Xxxxxxxxxx XX, 275-306.

3) Xxxxx, X. P., Xxxxxxx, X., Xxxx, X. X. (1964), Xx Air-drying Method xxx Xxxxxxx Xxxxxxxxxxxx xxxx Xxxxxxxxx Xxxxxx, Xxxxxxxxxxxx Xxxx Xxxxxxxx, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, J., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Xxxxx Xxxxxxxxxxxx Tests, UKEMS Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx X xxxxxxx, Cambridge University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Chester, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, X. D., Xxxxxx M. X., Xxxxxxx, J., Favor, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Shibuya, X., Tanaka X. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxx Xxxxxx of xxx Xxxxxxx Xxxxx xx Mammalian Germ Xxxx Xxxxx, Mutatation Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, X. X., Xxx, J., Esdaile, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. (1992), Xxxxxx of Xxxxxxx Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. X., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, G. X., Xxxxx, X., Xxxxxxxx, X., Richold, X., Xxxxxxxx, X. X., Savage X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Cytogenetic Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data. XXXXX Subcommittee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Sydney, 184-232."


PŘÍLOHA 4X

"X.39 XXXXXXX XX NEPLÁNOVANOU XXXXXXX XXX (UDS) X XXXXXXXXX BUŇKÁCH SAVCŮ XX XXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX TG 486 — Zkouška xx xxxxxxxxxxxx xxxxxxx XXX (UDS) v xxxxxxxxx xxxxxxx xxxxx xx xxxx (1997).

1.1 XXXX

Xxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx DNA (XXX) x jaterních xxxxxxx savců xx xxxx xx identifikovat xxxxxxxx látky, xxxxx xxxxxxxx xxxxxxxx XXX x xxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).

Xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxx chemických xxxxx x xxxxxxx. Xxxxxxxxxxx xxx xx xxxxxxxxxx xxxxxxxxx DNA x xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx místem, kde xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Xxxx tedy xxxxxxx xxxxxx pro xxxxxxxxx xxxx xxxxxxxxx XXX in vivo.

Jestliže xxxxxxxx důkaz x xxx, xx xx xxxxxxxx xxxxx xxxxxxxxx xx xxxxxx xxxxx, xxxx vhodné xxxx xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx XXX (UDS) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx nukleosidů xx xxxxx, xxxxx xxxxxxxx plánovanou xxxxxxxx XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx je autoradiografické xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx xxxxxxx xx XXX in xxxx xx přednostně používají xxxxx potkana. Xxxx xxxxx xxx xxxxx xxxxx xxx xxxxxx xxxxxxx, nejsou xxxx xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx XXX závisí xx xxxxx xxxx XXX xxxxxxxxxxx a xxxxxxxxxxx v místě xxxxxxxxx. Xxxxxxx na XXX xx xxxx xxxxxx zvláště pro xxxxxxx dlouhých xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 xxxx) xxxxxxxxxxxx látkou. Xxxxxx xxxxxx ("short-patch xxxxxx") (xxxxx xx xxx xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx s xxxxxx menší citlivostí. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx reparace, xxxxxx xxxxxxxx xxxx chybné xxxxxxxxx xxxx DNA xxxxx x mutagenním xxxxxxxxx. Xxxxxx odpovědi XXX xxxxxxxxxxx žádnou xxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx možné, xx xxxxxxx reaguje s XXX, xxx poškození XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Nedostatek xxxxxxxxxxxx xxxxxxxxx, xxxxx xxxx zkouška xxxxxxxxx x xxxxxxxxx aktivitě, xx vyvážen potenciální xxxxxxxxxx xxxxxx xxxx, xxxxx je vyšetřován x xxxxx xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : čistý xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX), xxxxx xxx předvolená xxxxxxx xxxxxxxxx laboratoří xxxxxxxxxxx xxxxxxx.

Xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx xxxx UDS xxxxxxxx xxxxx x xxxxxxxxxxxxxxxxx zkoušce na XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxx zrn x cytoplasmatických oblastech (XX) xxxxxxxxxxxxxx xxxxxx xx xxxxx zrn xxxxxxxxxxxxxx buněčným jádrům (XX): XXX = XX — XX. Xxxxxxx XXX se xxxxxxx xxx jednotlivé xxxxx, xxxx společně xxx xxxxx x xxxxxxx, x xxxxxxxxxxx xxxxxxxxx atd.

Neplánovaná xxxxxxx XXX (XXX) : Xxxxxxx reparací XXX xx vyštěpení a xxxxxxxxxx xxxxx DNA xxxxxxxxxxxx xxxxxx x xxxxxxxxxx indukovaným chemickými xxxxxxx xxxx fyzikálními xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx XXX x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxxxxxx XXX xx vyštěpení x xxxxxxxxxx xxxxx XXX obsahujícího region x xxxxxxxxxx indukovaným xxxxxxxxxx látkami xxxx xxxxxxxxxxx činiteli. Xxxxxxx xx xxxxxxx založena xx xxxxxxxxxxx 3X-XxX xx XXX xxxxxxxxx xxxxx, xxx xx xxxx xxxxxxx buněk x X-xxxx xxxxxxxxx xxxxx. Xxxxxxxxxxx 3H-TdR xx obvykle xxxxxxxxx xxxxxxxxxxxxxxx, jelikož xxxx xxxxxxxx xxxx tak xxxxxxx xx vliv X-xxxx buněk xxxx xxxx. xxxxxxx scintilační xxxxxxxxxxxxx.

1.4 POPIS METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx používán xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Xxxx xx být xxxxxxx xxxxx xxxxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx dospělých xxxxxx. X xxxxxxxx zahájení xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx minimální x xxxxxx xx xxxxxxxxx ± 20 % střední xxxxxxx xxxxxxxxx pro xxx xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x strava

Platí xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx X, xxxxxxx by xxxx být xxxxxxxx xxxxxxxx vzduchu 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x skupinu, xxxxx xx xxxxxxxx. Klece xx xxxx xxx xxxxxxxxxx tak, xxx xxx vliv xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx x před započetím xxxxxx se xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx zkoušené xxxxx

Xxxxx zkoušené látky xx xxxx být xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx být xxxx xxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx použitých xxxxxxxx dávek toxické xxxxxx x xxxx xx být xxxxxxxxx xxxxxxxxx, že reaguje xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx zařazení podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx xx měly xxx souběžné xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx látky xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxx ve skupinách, x xxxxx xxxxx x expozici.

Pozitivními xxxxxxxxxx xx xxxx xxx xxxxx, x xxxxx xx xxxxx, xx xxxxxx podávání x xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx nad xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx metabolickou xxxxxxxx xx xxxx xxx xxxxxxx v dávkách xxxxxxxxxxxx mírnou xxxxxxx (4). Dávky mohou xxx zvoleny xxx, xxx byl účinek xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx CAS

Číslo xxxxx Xxxxxx

Xxxxx doby xxxxxx (2 xx 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx xxxx xxxxxx (12 až 16 x)

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

53–96–3

200–188–6

Xxxxx xxx xxxxxxx xxxx xxxx látky pro xxxxxxxxx kontrolu. Xx xxxxxxxxx, aby byla xxxxxxxxx kontrolní xxxxx xxxxxxxx jiným xxxxxxxx, xxx xxxxxxxx látka.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx xxxxxx

Xxx xx xxx xxxxxx xxxxxxxxxx xxxxx xxxxxx, xxx xxxx zohledněno xxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xx zkoušku. Každá xxxxxxx xx se xxxx xxxxxxx alespoň xx tří xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxxxx dosavadní xxxxx, je xxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxx xxxxx jedno až xxx xxxxxxx.

Xxxxxxxx xxxx x xxxx studie x dispozici údaje xx studií se xxxxxxx xxxxxx a xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, jež xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx zkoušení xxxxxxx xxxxxxx, nejlépe xxxxx. Xx-xx xxxxxxxx člověka xxxxxxxxxx pro xxxxxx xxxxxxx, xxxx je xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by xxx xxxxxxx xxxxxxxxx se xxxxxxxx odpovídajícího pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx.

1.5.3 Dávkování

Za normálních xxxxxxxx xx xxxxxxxxx xxxxxxx dvě xxxxxx xxxxx. Nejvyšší xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že xxxxx xxxxx xx xxxxx xxxxx očekávání xxx xxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx dávka by xxxx xxx xxxxxxxxx 50 % xx 25 % vyšší xxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. hormony x xxxxxxxx) nemusí xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x měly xx xxx xxxxxxxxx případ xx xxxxxxx. Provádí-li xx xxxxx neexistenci xxxxxxxx xxxxxxxxxx údajů xxxxxx pro xxxxxxxx xxxxxxx, měla xx xxx xxxxxxxxx xx xxxxxx laboratoři, xx xxxxxxx druhem, xxxxxx, xxxxxxxx a xx xxxxxxxx režimu expozice, xxx xx použijí x xxxxxx xxxxxx.

Xxxxxxxx xxxxx xxxx být xxxxxxxxxx xxxx jako xxxxx vyvolávající xxxxxx xxxxxxxx x játrech (xxxx. xxxxxxxxxx jádra).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx tělesné hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, očekávána genotoxicita, xxxxxx xxx úplná xxxxxx nezbytná. Očekávaná xxxxxxxx xxxxxxx xxxx xxxxxxxx potřebu xxxxxx x xxxxxxx zkoušce xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou xxxxx, xxx-xx xx zdůvodnit. Xxxxxxxx intraperitoneálně se xxxx xxxxxxxxxxxx, neboť xx játra mohla xxx exponována xxxxxxxx xxxxx přímo a xxxxxx prostřednictvím oběhového xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx může xxx xxxxxxxx podán xxxxxxxxx sondou xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx testovacího xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx zesílené účinky, xx měla být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxxxx

Xxxxxxx buňky se xxxxxxxxxx x exponovaných xxxxxx zpravidla 12 xx 16 xxxxx xx podání dávky. Xxxxxxxxxx dřívější xxxxxxxx xxxxxx (obecně dvě xx čtyři hodiny xx expozici) xx xxxxxxxx, není-li po 12 xx 16 xxxxxxxx xxxxx pozitivní xxxxxxx. Xxxxx však xxx xxxxxxx jiné xxxx xxxxxx, xxxx-xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxxxxxxxx údajů.

Krátkodobé xxxxxxx xxxxxxxxx xxxxx savců xx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxxx xx situ a xxxxxx se, xxx xx čerstvě xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx buňky x xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxx se obvykle xxxxxxx xxxx, xxxx. xxx xx xxx xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3X-XxX. Xx xxxxx xxxxxxxxx xxxx xx xxxx xxx médium x xxxxx xxxxxxxxxx a xxxxx xxxx xxxxx xxx inkubovány s xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("cold chase"). Xxxxx xx xxxx xxxxxxx, xxxxxx x xxxxxx. Při xxxxx xxxxxxxxx době xxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Preparáty xx xxxxxx xx autoradiografické xxxxxx, xxxxxxxx xx x temnu (xxxx. x chladu 7 xx 14 xxx), xxxxxxxx xx, obarví x xxxxxxxxx xx xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx zvířete xx xxxxxxxx xxx xx xxx preparáty.

1.5.8 Xxxxxxx

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

Před počítáním xxx xx xxxx xxx preparáty xxxxxxxx. Xxxxxxxxx se xxxxxxxxx 100 xxxxx xx xxxxx xxxxx xxxxxxx xx xxxx xxxxxxxxx; xxxxxxxxx méně xxx 100 buněk/zvíře xx xxxx xxx xxxxxxxxxx. Xxx xxxxxxxx xxx xx jádra x X-xxxx xxxxxxxxxxx, ale xxxxx buněk x X-xxxx xxxx být xxxxxxxxxx.

Xxxxxxxx 3H-TdR xxxxxxxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxx stříbra by xxxx xxx stanoveno xxxxxxx xxxxxxx.

Xxxxx buněk xx xxxxxxx x xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx jádrŭm (xx) x x xxŭxxxxxxx xxxxx xxx v xxxxxxxxxxxxxxxxx xxxxxxxxx (cg) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx xx se xxxxxxx buď xxxxx xxxxx xxx nejsilněji xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx xxŭxxxxx hodnota xxxx až xxx xxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxx. xx xxxxxxxxxxxxx zdŮvodnění xxxxx xxx xxxxxxx i xxxx postupy xxxxxxxxx xxxxx buněk (např. xxxxxxxx celých xxxxx) (6).

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxx xx xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx x xxxxxxx. Xxxxx by xxxx xxx dále xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx hodnoty XX xx hodnoty XX xx měl xxx xxxxxxxx pro xxxxxx xxxxx, xxx xxxxx xxxxx a xxx xxxxxx xxxxx x čas čistý xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX). Xxxxxxxx jsou xxxxxxxx "xxxxxxxxxx" buňky, měla xx být xxxxxxxx xxx definování "opravovaných" xxxxx odůvodněna x xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx údajích x xxxxxxxxxxx kontrolách. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx být xxxxxxx, xxxx by xxx statistické xxxxx xxxxxxx x xxxxxxxxxx xxxx provedením xxxxxx.

2.2 XXXXXXXXX A INTERPRETACE XXXXXXXX

Xxxx xxxxxxxx kritérií xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx

x)

xxxxxxx XXX xxxx nad xxxxxxxx xxxxxx, xxxxx xx xxxxxxxxxx xx xxxxxxx dosavadních xxxxx xxxxxxxxxx;

xxxx

xx)

xxxxxxx XXX je xxxxxxxx vyšší xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx XXX xxxx xx xxxxxxxxx xxxxxxx xxxxxxx xxxx pod xx;

xxxx

xx)

xxxxxxx NNG není xxxxxxxx vyšší xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx.

Xxxx xx xxx xxxxxxxxx xxxxxxxxxx relevance xxxxx, xx. měly xx xxx xxxxx x xxxxx parametry, xxxx xxxx xxxxxxxxxxx xxxxxx, xxxxx xxxxx x xxxxxxxx a xxxxxxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx mohou xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Statistická významnost xx xxxx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x ojedinělých případech xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky na XXX x jaterních xxxxxxx xxxxx in xxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxx xxxxx xx vivo xxxxxxxxx DNA, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx DNA xx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že zkoušená xxxxx xx xxxxxxxx xxxxxxx neindukuje poškození XXX, xxxxx lze xxxxxxxxx xxxxx xxxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x jakou xx xxxxxxxx látka xxxxxxx xx krevního xxxxx xxxx. xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- xxxxxxxxxxx x stálost zkoušené xxxxx v xxxxxxxxxxxx/xxxxxxxx, xx-xx známa.

Testovací zvířata:

- xxxxxxx druh/kmen,

- xxxxx, xxxxx a xxxxxxx xxxxxx,

- zdroj, podmínky xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx zvířat xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx hodnoty x xxxxxxxxxx odchylky xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- pozitivní x xxxxxxxxx (vehikulum/rozpouštědlo) xxxxxxxx,

- xxxxx ze xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx byla provedena,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

- popřípadě xxxxxx ověření, zda xx zkoušená xxxxx xxxxxxx do xxxxxxxx xxxxx xxxx xx xxxxxx tkáně,

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

- podrobné údaje x xxxxxxx xxxxxx x vody,

- xxxxxxxx xxxxx xxxxxxx expozice x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx x xxxxxxxxx xxxxxxxxx buněk,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,

- kritéria xxxxxxxxx,

- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxxx xxxxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx x počtu xxx odpovídajících cytoplasmě, x xxxxx počet xxx, jednotlivě xxx xxxxxxxxx, xxxxxxx x xxxxxxx,

- xxxxx možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxx,

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

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

- počet xxxxx "xxxxxxxxxxxx" buněk, xx-xx stanoven,

- xxxxx xxxxx x X-xxxx, xx-xx stanoven,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, X. Xxxxxxx, X. X., Xxxxxxxxx, X., Penman, M. X. (1985), An Xxxxxxxxxx of xxx Xx xxxx Rat. Xxxxxxxxxx DNA Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.

2) Xxxxxxxxxxx, X. X., Ashby, X., Xxxxxxxx, X., Xxxxxxxx, D., Xxxxxxxx, X., Probst, X., Xxxxxxxx, X. (1987), X Xxxxxxxx and Xxxxx xxx xxx Xx xxxx Xxx Xxxxxxxxxx XXX Xxxxxx Xxxxx, Mutatation Xxx., 189, 123-133.

3) Kennelly, X. C., Waters, X., Xxxxx, J., Xxxxxxx, X. A., Xxxxxxxxx, X., Xxxxxxx, X. X., Xxxx, X. X., Mitchell, X. de X. (1993), Xx xxxx Xxx Xxxxx XXX Xxxxx, xx: Kirkland X. J., Xxx X., (eds), Supplementary Xxxxxxxxxxxx Xxxxx: UKEM Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Testing. Xxxxxx. Xxxx XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Sydney, 52-77.

4) Xxxxx, X., Xxxx, X. W., Xxxxxx, X., Xxxxxxxxx. X., Xxxxxxxxx, X., Xxxxxxxxx, X. X., Furihata, X., Xxxxxxx, X., XxXxxxx, X. X., Xxxx, H. (1993), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx of XXX Xxxxx Xx xxxxx xxx Xx xxxx, Xxxxx. Xxx., 312, 263-285.

5) Fautz, R., Xxxxxxx, X., Efstathiou, X., Hechenberger-Freudl, X. (1993), Xxxxxxxxxx xx xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxx xxx xxx Xxxxxxxxxx xx Xxxxxxx Xxxxxxxx Xxx Hepatocytes Xxxx xxx xxx Xx xxxx/Xx vitro XXX Xxxxxx Xxxxx (XXX), Xxxxxxxxxx Xxx., 291, 21-27.

6) Mirsalis, X. X., Xxxxx, C. X., Xxxxxxxxxxx, B. X. (1982), Xxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xx xxx Xx xxxx/Xx xxxxx Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxx.Xxxxxxx. 4, 553-562."


PŘÍLOHA 5

XXXXXX XXXXXXXXX XX KLASIFIKACI X XXXXXXXXXX XXXXXXXXXXXX XXXXX X XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/XX, Xx. xxxx. X 332, 28. 12. 2000, x. 81.


PŘÍLOHA 6

"

XXXXXXX XX

XXXX X

xxxxxxxx týkající xx xxxxxxx odolných xxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 xxxx. 1 xxxx. e) xxxx xxxxxxxx, musí xxx xxxxx x xxxxxxxxx objemu obsahující xxxxx, x xxxxx xx spojeno xxxxxx xxx xxxxxxxxxx (Xx; X 65) x xxxxx jsou xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 přílohy XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx xx xxx xx xxxxx xxxxxxxx xxxx v xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx, xxxxxxxx uzávěry xxxxxxxx xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx uzavíratelných xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx XXX 8317 (xxxxxx xx xxx 1. července 1989) "Xxxxx xxxxxx xxxxx — Xxxxxxxxx na xxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxx xxxxxxxx" xxxxxxxx Xxxxxxxxxxx xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Opakovaně xxxxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx dětmi použité xx opakovaně neuzavíratelných xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx CEN XX 862 (vydání x xxxxxx 1997) "Xxxxx — Xxxxx xxxxxx dětem — Xxxxxxxxx a xxxxxxxx xxxxxxx xxx opakovaně xxxxxxxxxxxxxx xxxxx jiných xxx farmaceutických xxxxxxx" xxxxxxxx Evropským xxxxxxx xxx xxxxxxxxxxx (CEN).

3. Xxxxxxxx

1. Xxxxxxxxx xxxxx x xxxx xxxxxxxxx xxxxxxx mohou xxxxxxxxxx xxxxx xxxxxxxxxx, xxxxx xxxxxxx xxxxxxxx normy xxxx XX 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx xxxxxx, xx obal xx xxxxxxxxxx xxxxxxxx xxx xxxx, xxxxx xx xxxxxxx xxxxxx x xxxxxx xxx pomoci xxxxxxxx, xxxxxx být xxxxxxx xxxxxxxxx.

Xx všech xxxxxxxxx případech x xxxxx xxxxxxxx oprávněné xxxxxx x xxxxxxxx x xxxxxxxxxxx xxxxxxx xxx xxxx, xxxx xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx xxxxx xxxxxxxxx xx xxxxxxx výrobku xx trh xxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx buď

- xxx xxxxxxx xx takový, xx jej není xxxxxxxx zkoušet podle xxxx xxxxxxxxx norem XXX x XXX,

xxxx

- xx xxxxxx xxx xxxxxxx x xxx xxxxxxx vyhovujícím xxxxx xxxx xxxxxxxxx xxxxx.

XXXX X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx

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

"