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Xxxxxxxx Xxxxxx 2000/32/XX

xx xxx 19. xxxxxx 2000,

xxxxxx xx xx xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxx Xxxx 67/548/XXX x xxxxxxxxxx xxxxxxxx x xxxxxxxxx předpisů týkajících xx klasifikace, xxxxxx x označování xxxxxxxxxxxx xxxxx [1]

(Text x xxxxxxxx xxx EHP)

KOMISE XXXXXXXXXX SPOLEČENSTVÍ,

s xxxxxxx xx Xxxxxxx o xxxxxxxx Evropského společenství,

s xxxxxxx xx xxxxxxxx Xxxx 67/548/EHS xx xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx x správních xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení a xxxxxxxxxx xxxxxxxxxxxx látek [2], xxxxxxxxx xxxxxxxxxx xxxxxxxx Xxxxxxxxxx parlamentu x Xxxx 1999/33/XX [3], x xxxxxxx xx článek 28 xxxxxxx xxxxxxxx,

xxxxxxxx k xxxxx xxxxxxx:

(1) Xxxxxxx X směrnice 67/548/XXX xxxxxxxx seznam xxxxxxxxxxxx xxxxx společně x xxxxxxxxxx údaji x xxxxxxxxxxx a xxxxxxxxxx xxxxx xxxxx. Současné xxxxxxx a technické xxxxxxxx ukazují, xx xx měl být xxxxxx xxxxxxxxxxxx xxxxx x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx jazykové xxxxx směrnice vyžadují xxxxxx xxxxxxxx oddílů xxxxxxxxx x tabulky X v xxxxxxx X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/XXX obsahuje xxxxxx xxx udávajících xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx s nebezpečnými xxxxxxx x přípravky. Xxxxxxx IV směrnice 67/548/XXX xxxxxxxx seznam xxx x xxxxxxxxxxxxxx xxxxxx týkajícími xx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/EHS obsahuje xxxxx xx xxxxxxxxxxx x x označování xxxxxxxxxxxx látek x xxxxxxxxx. Některé xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx určitých oddílů xxxxxx III, IV x XX.

(3) X xxxxxxx V xxxxxxxx 67/548/XXX xx xxxxxxx xxxxxx xxx stanovení xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, toxicity x xxxxxxxxxxx látek x přípravků. Xx xxxxxxxx xxxxxxxxxxx tuto xxxxxxx xxxxxxxxxxx pokroku.

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX obsahuje xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx. Xxxx xxxxxxxx xx xxxx xxx xxxxxxxxxxxx a aktualizovány. Xx nezbytné xxxxxxxx xxxxxx, xxx xx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx používají.

(5) Xxxxxxxx xxxx směrnice xxxx x souladu xx xxxxxxxxxxx Xxxxxx xxx přizpůsobení xxxxxxxxxxx xxxxxxx xxxxxxx xxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxx na xxxxx xxxxxxxxxxxx látek x xxxxxxxxx,

XXXXXXX XXXX XXXXXXXX:

Xxxxxx 1

Xxxxxxxx 67/548/XXX xx xxxx xxxxx:

1. Xxxxxxx I se xxxx takto:

a) xxxxxxxxxxxx xxxxxxxx x xxxxxxxxx xx nahrazuje poznámkou X v xxxxxxx 1X této směrnice;

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

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

x) xxxxxxxx xx xxxxxxx x xxxxxxx 1X xxxx xxxxxxxx.

2. Xxxxxxxxxxxx xxxx x xxxxxxx XXX xx xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxx specifickou xxxxxxxxxx x xxxxxxx 2 xxxx xxxxxxxx.

3. Xxxxxxx XX xx xxxx takto:

a) xxxxxxxxxxxx xxxxxx x příloze XX xx xxxxxxxxx xxxxxxxxxxxx pokyny xxx xxxxxxxx xxxxxxxxx v xxxxxxx 3X xxxx xxxxxxxx;

x) xxxxxxxxxxxx xxxxxx x příloze IV xx xxxxxxxxx kombinovanými xxxxxxxxxxxx pokyny xxx xxxxxxxx xxxxxxxxx v xxxxxxx 3X xxxx xxxxxxxx.

4. Xxxx B xxxxxxx V se xxxx xxxxx:

x) xxxxxxxx X.10 xx xxxxxxxxx xxxxxx x příloze 4X xxxx xxxxxxxx;

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

x) xxxxxxxx X.12 xx xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx xxxxxxxx;

x) kapitoly X.13 x B.14 xx xxxxxxxxx xxxxxx x příloze 4X xxxx xxxxxxxx;

x) kapitola X.17 xx nahrazuje xxxxxx v xxxxxxx 4X xxxx xxxxxxxx;

x) xxxxxxxx X.23 xx xxxxxxxxx textem x xxxxxxx 4F xxxx xxxxxxxx. Xxxxx kapitoly X.23 xx xxxxxxxxxxx xx xxxx xxxxxxxxxxxxx xxxxxxxx;

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

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

6. Odpovídající xxxxx v příloze XX xx nahrazují xxxxx x xxxxxxx 5 této xxxxxxxx.

7. Xxxxxxx IX xx xxxx způsobem xxxxxxxx x příloze 6 xxxx xxxxxxxx.

Xxxxxx 2

1. Xxxxxxx xxxxx xxxxxx v xxxxxxxx právní a xxxxxxx předpisy xxxxxxxx xxx xxxxxxxx souladu x xxxxx směrnicí xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x nich xxxxxxx Xxxxxx.

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

2. Xxxxxxx xxxxx xxxxx Xxxxxx znění xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx xxxxxxx x xxxxxxx působnosti xxxx směrnice, x xxxxxxxxxx xxxxxxx xxxx xxxxxxxx a xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.

Xxxxxx 3

Xxxx xxxxxxxx xxxxxxxx v xxxxxxxx xxxxxx xxxx xx xxxxxxxxx x Xxxxxxx xxxxxxxx Evropských xxxxxxxxxxxx.

Článek 4

Tato xxxxxxxx xx určena xxxxxxxx xxxxxx.

V Xxxxxxx dne 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Xxxxxx

[1] Xxxxxxx xx xxxxxxxxxxxx xx dvacáté xxxxx.

[2] Úř. xxxx. 196, 16.8.1967, s. 1.

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

XXXXXXX 1A

PŘEDMLUVA K XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx xx identifikace, xxxxxxxxxxx a xxxxxxxxxx xxxxx

(Xxxxxx xx xxxxxxx xxxxx)

PŘÍLOHA 1X

"XXXXXXX A

Z

Symbol

ES

DA

DE

EL

EN

FI

FR

IT

NL

PT

SV

18

Ar

Argón

Argon

Argon

Αργό

Argon

Argon

Argon

Argon

Argon

Árgon

Argon

64

Gd

Gadolinio

Gadolinium

Gadolinium

Γαδολίνιο

Gadolinium

Gadolinium

Gadolinium

Gadolinio

Gadolinium

Gadolínio

Gadolinium"

XXXXXXX 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x látkám

Číslo XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx limity

Poznámky x xxxxxxxxxx

006–011–00–7

xxxxxxxx (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

Xxxx. xxx. 3; X40 Xx; R22 X; X50

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx

205–293–0

137–42–8

Xx; X22 X31 C; X34 X43 X; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

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

Xx; X 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 X; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

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

204–123–2

116–06–3

X+; X26/28 X; X24 X; X50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; X24/25 N; X50–53

X; X X: 24/25–50/53 S: (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 Xn; X22 X; X50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xx; X22 X43 X; R50–53

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

006–023–00–2

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

217–991–2

2032–65–7

X; X25 N; X50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; X22 Xx; X38 X; X51–53

Xx; X R: 22–38–51/53 X: (2-)13-61

006–026–00–9

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

216–353–0

1563–66–2

X+; X26/28 X; X50–53

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

006–028–00-X

xxxxxxxxx (XXX) 2-(1-xxxxxxxxxxxx)-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx 2-xxx-xxxxx-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx

213–546–1

973–21–7

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

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

230–253–4

6988–21–2

X; X25 X; X51–53

X; N R: 25–51/53 S: (1/2-)37–45–61

006–033–00–7

metoxuron (XXX) 3-(3-xxxxx-4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx

243–433–2

19937–59–8

X; X50–53

X X: 5 0/ 5 3 S: 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 X: 22–51/53 X: (2-)23-61

006–035–00–8

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

245–430–1

23103–98–2

T; X25 X; X50–53

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

006–037–00–9

xxxxxxxxx (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–113–0

2631–37–0

X; R25 X; X50–53

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

006–038–00–4

xxxxxxxxx (XXX) 2-xxxxxxxxxx-X,X-xxxxxxxxxxxxxxxxxxxxxx

X

202–388–9

95–06–7

Xxxx. kat. 2; R45 Xx; X22 N; X50–53

X; 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; X22–48/22 R43 X; R50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; R40 Xx; R22 N; X50–53

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

006–043–00–1

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

—

140–41–0

Xx; R36/38 Xxxx. xxx. 3; X40 X; X50–53

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

006–045–00–2

xxxxxxxx (XXX) methyl-N-[(N-methylkarbamoyl)oxy]thioacetimidát

240–815–0

16752–77–5

T+; X28 X; R50–53

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

006–046–00–8

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

245–216–8

22781–23–3

X; X23/25 Xx; X21 N; X50–53

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

006–047–00–3

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

—

8065–36–9

X; X24/25 X; X50–53

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

006–048–00–9

xxxxxxxxxxxx (XXX) 2-[(xxxxxxxxxxxxx)xxxxxx]xxxxx-X-xxxxxxxxxxxxxx

249–981–9

29973–13–5

Xx; X22 X; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

006–050–00–X

xxxxxxx-XXX 3-fenyl-1,1-dimethyluronium-trichloracetát

—

4482–55–7

Xi; R38 X; X50–53

Xx; N X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-isopropylfenyl-N-methylkarbamát

220–114–6

2631–40–5

Xn; X22 X; X50–53

Xx; X R: 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+; X28 Xn; X21 X; X50–53

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

006–057–00–8

xxxxxxxxxx (ISO) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; X R: 22–51/53 S: (2-)24-61

006–060–00–4

xxxxxxxxxxx (XXX) 2-xxxxxx-4,4-xxxxx-5,6-xxxxxxx-4λ4-1,4-xxxxxxxx-3-xxxxxxxxxxxx

226–066–2

5259–88–1

Xx; X22 X52–53

Xx R:22–52/53 X: (2-)61

006–069–00–3

xxxxxxxxx-xxxxxx (XXX) 1,2-di[3-(methoxykarbonyl)thioureido]benzen

245–740–7

23564–05–8

Muta. xxx. 3; X40 X; R50–53

Xn; X X: 40–50/53 X: (2-)36/37–60–61

006–070–00–9

xxxxxxxxxxx X-xxxxxxxxxx-X-xxxxxxx-2,5-xxxxxxxx-3-xxxxxxx

262–302–0

60568–05–0

Xxxx. kat. 3; X40 X; X50–53

Xx; X R: 40–50/53 S: (2-)36/37–60–61

006–088–00–7

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

—

82560–54–1

T; X23/25 X; R50–53

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

007–012–00–5

N,N-dimethylhydrazin 1,1-xxxxxxxxxxxxxxxx

X

200–316–0

57–14–7

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

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

007–013–00–0

X,X-xxxxxxxxxxxxxxxx 1,2-dimethylhydrazin

E

—

540–73–8

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

X; N X: 45–23/24/25–51/53 X: 53–45–61

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

009–003–00–1

kyselina xxxxxxxxxxxxxx … %

B

231–634–8

7664–39–3

T+; X26/27/28 X; X35

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

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

015–039–00–9

xxxxxxx-xxxxxx (XXX) O,O-dimethyl-S -[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx

201–676–1

86–50–0

X+; R26/28 X; X24 X43 X; R50–53

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

015–048–00–8

xxxxxxxx (ISO) O,O-dimethyl-O-[3-methyl-4-(methylsulfanyl)fenyl]-fosforothioát

200–231–9

55–38–9

Muta. xxx. 3; X40 X; X23–48/25 Xx; X21/22 N; X50–53

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

015–056–00–1

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

220–147–6

2642–71–9

T+; X28 X; X24 N; X50–53

X+; X X: 24–28–50/53 X: (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 Xx; 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 sirnatý

234–129–0

10545–99–0

R14 X; X34 N; X50

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

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

016–014–00–5

chlorid siřičitý

—

13451–08–6

R14 X; X34 X; X50

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

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

016–023–00–4

xxxxxxxx-xxxxxx

X

201–058–1

77–78–1

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

X+ R: 45–25–26–34–43 X: 53-4 5

X ≥ 25 %: X+; X45–25–26–34–43 10 % ≤ X &xx; 25 %: X+; R45–22–26–34–43 7 % ≤ X &xx; 10 %: X+; X45–22–26–36/ 37/38–43 5 % ≤ X &xx; 7 %: T; X45–22–23–36/37/38–43 3 % ≤ X < 5 %: X; X45–22–23–43 1 % ≤ X < 3 %: T; X45–23–43 0,1 % ≤ X &xx; 1 %: T; 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; X22 N; X50–53

Xx; N R: 22–50/53 S: (2-)60-61

016–071–00–6

3-amino-6,13-dichlor-10-[(3-{[4-chlor-6-(2-sulfonatoanilino)- 1,3,5-xxxxxxx-2-xx]xxxxx}xxxxxx)xxxxx][1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx trisodný

410–130–3

136248–03–8

R43

Xi X: 43 X: (2-)22–24–37

022–001–00–5

xxxxxxx xxxxxxxxxx

231–441–9

7550–45–0

X14 C; R34

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

X ≥ 10 %: X; X34 5 % ≤ X < 10 %: Xx; X36/37/38

030–004–00–8

xxxxxxxxxxxxx [1] diethylzinek [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

X14 X; X17 X; X34 N; X50–53

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

050–002–00–0

cyhexatin (XXX) xxxxxxxxxxxxx(xxxxxxx)xxxxxxx tricyklohexylstannium-hydroxid

236–049–1

13121–70–5

Xn; X20/21/22 X; X50–53

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

050–012–00–5

xxxxxxxxxxxxxxxxxxxxxx [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] butyl(tricyklohexyl)stannan [3]

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

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

Xx; X20/21/22 X; R50–53

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

X ≥ 1 %: Xn; X20/21/22

1

050–017–00–2

xxxxxxxxxxxxxx (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 R: 26–36/38–50/53 X: (1/2-)28–36/37–45–60–61

082–009–00–X

xxxx (xxxxxxxxxxxx xxxxxxxx) XX Xxxxxxx Xxxxxx 34 (XX 77603) CI xxxxxxxxxx xxxx 34 (XX 77603)

215–693–7

1344–37–2

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

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

1

082–010–00–5

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

235–759–9

12656–85–8

Xxxx. xxx. 3; X40 Xxxx. xxx. 1; R61 Xxxx. xxx. 3; X62 R33 N; X50–53

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

1

601–024–00-X

xxxxx [1] propylbenzen [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

R10 Xx; X65 Xx; X37 X; X51–53

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

4

601–032–00–3

benzo[a]pyren xxxxx[xxx]xxxxxxx

200–028–5

50–32–8

Xxxx. xxx.2; R45 Xxxx. xxx. 2; R46 Xxxx. xxx. 2; X60–61 X; X50–53

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

601–034–00–4

xxxxx[x]xxxxxxxxxxxxxxx

205–911–9

205–99–2

Xxxx. xxx.2; X45 X; R50–53

T; X R: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-xxxxxxxxxxxxx x-xxxxxxxxxxxxx

203–400–5

106–46–7

Xx; X36 X; X50–53

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

602–054–00–6

3-xxxxxxx-1-xx xxxxxxxxxx

209–130–4

556–56–9

X10 X; R34

C R: 10-34 X: (1/2-)7–26–45

603–076–00–9

xxx-2-xx-1,4-xxxx

203–788–6

110–65–6

X; X23/25 Xx; X21–48/22 X; X34

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

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

603–091–00–0

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

402–470–6

87172–89–2

O; R8 Xx; X22 Xi; X36

X; Xx X: 8–22–36 X: (2-)26

603–093–00–1

xxx-(±)-4-xxxxxxxxx-1-xxxxxx-2-[(2-xxxxxxxxxxxx)xxx]-7-xxxxxxxxxx[2.2.1]xxxxxx

402–410–9

87818–31–3

Xx; X20 X; R51–53

Xn; X R: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; X36 X52–53

Xx X:36–52/53 X: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx isopropanol

200–661–7

67–63–0

F; X11 Xx; R36 R67

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

604–020–00–6

bifenyl-2-ol 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 xxx xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx sodný xxxxxxx-xxxxxxx-2-xxxx

205–055–6

132–27–4

Xx; R22 Xx; X37/38–41 N; R50

Xn; 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 N; X50–53

X; X R: 60–36–50/53 S: 53–45–60–61

604–041–00–0

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

256–634–5 [1] 263–560–7 [2]

50594–66–6 [1] 62476–59–9 [2]

Xn; R22 Xx; X38–41 X; X50–53

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

604–043–00–1

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

203–083–3

103–16–2

Xi; X36 R43

Xi R: 36-43 X: (2-)24/25–26–37

604–044–00–7

mechinol 4-xxxxxxxxxxxx hydrochinonmonomethylether

205–769–8

150–76–5

Xn; X22 Xx; X36 X43

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

605–016–00–7

xxxxxxx… % xxxxxxxxx… %

X

203–474–9

107–22–2

Xxxx. xxx. 3; X40 Xx; R20 Xx; X36/38 X43

Xx X: 20–36/38–40–43 X: (2-)36/37

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

606–016–00-X

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

201–462–8

83–26–1

X; X25–48/25 X; X50–53

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

606–018–00–0

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

204–210–5

117–80–6

Xx; X22 Xx; R36/38 X; X50–53

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

606–019–00–6

xxxxxxxxxx (XXX) perchlorpentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-on 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 T; X24/25 N; X50–53

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

606–034–00–8

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

244–209–7

21087–64–9

Xn; X22 X; X50–53

Xx; X R: 22–50/53 X: (2-)60-61

606–035–00–3

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

216–920–2

1698–60–8

R43 X; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

606–036–00–9

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

219–455–3

2439–01–2

Repr. xxx. 3; X62 Xx; X20/21/22–48/22 Xx; X36 X43 X; X50–53

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

606–037–00–4

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

256–103–8

43121–43–3

Xx; X22 N; 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; X36 X; X50–53

Xx; X X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; X22 Xx; X41 X52–53

Xx; X X: 22–41–52/53 X: (2-)26-61

607–057–00–6

xxxxxxxxx (XXX) 3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X-xxxxxxx-2-xx

201–378–1

81–82–3

Xx; X48/22 R52–53

Xn X:48/22–52/53 X: (2-)37-61

607–058–00–1

kumafuryl (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -xxxxxxx-2-xx 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; X25–48/25 X52–53

X X:25–48/25–52/53 S: (1/2-)37–45–61

607–079–00–6

kelevan (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx xxxxx-5-(1,2,3,5,6,7,8,9,10,10-xxxxxxxxx-4-xxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx)-4-xxxxxxxxxxxx xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx

—

4234–79–1

X; X24 Xx; X22 N; X51–53

X; X X: 22–24–51/53 X: (1/2-)36/37–45–61

607–097–00–4

benzen-1,2,4-trikarbox-1,2-anhydrid 1,2-anhydrid xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx trimellitanhydrid

209–008–0

552–30–7

Xi; 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 X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

2,3,6-XXX (ISO) 2,3,6-xxxxxxxxxxxxxxxx xxxxxxxx

200–026–4

50–31–7

Xx; X22 X; X51–53

Xx; X X: 22–51/53 S: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; X36/38 R52–53

Xi X:36/38–52/53 X: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xx; X22 Xx; X38 N; X50–53

Xx; X X: 22–38–50/53 X: (2-)37–60–61

607–158–00–5

xxxxx xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx sodný

223–498–3

3926–62–3

T; X25 Xx; X38 X; X50

X; N X: 25–38–50 X: (1/2-)22–37–45–61

607–159–00–0

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

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

400–830–7

—

X43 X; R51–53

Xi; N X: 43–51/53 X: (2-)36/37–61

607–188–00–9

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

402–970–4

—

X43 X; X51–53

Xx; 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 N; R50–53

Xn; X R: 22–43–50/ 53 S: (2-)36/37–60–61

607–213–00–3

xxxxx-3,3-xxx(xxxx-xxxxxxxxxxxx)xxxxxxxx

403–320–2

67567–23–1

X; X2 X; X7 X10 N; X51–53

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

607–217–00–5

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

403–960–2

—

X43 X53

Xx X: 43-53 X: (2-)24–37–61

607–243–00–7

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

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

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

X52–53

X: 52/53 X: 61

607–248–00–4

Xxxxxxxx-xxxxxxx Xxxxxxx-X-(1-xxxxxx)xxxxxxxx

205–073–4

132–67–2

Xx; R22

Xn X: 22 S: (2)

607–249–00-X

(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx xxxxxxxxxxxxxxxxx-xxxxxxxxx XXXXX

256–032–2

42978–66–5

Xx; X36/37/38 R43 N; X51–53

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

C ≥ 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 S)-cis-3-((Z)-2-chlor-3,3,3-trifluorprop-1-en-1-yl)-2,2-dimethylcyklopropan-1-karboxylát

415–130–7

91465–08–6

T+; X26 X; R25 Xx; X21 X; R50–53

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

607–255–00–2

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

—

69377–81–7

X52–53

X: 52/53 X: 61

608–003–00–4

xxxxxxxxxxxx

X X

203–466–5

107–13–1

X; Xxx Xxxx. xxx. 2; X45 X; X23/24/25 Xi; R37/38–41 X43 N; R51–53

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

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

43

608–016–00–5

2,3,5,6-tetrachlor-1,4-dikyanbenzen xxxxxxxxxxxxxxxxxxxxxxxxx

401–550–8

1897–41–2

X43 X; R50–53

Xi; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. kat. 2; X61 X+; X28 X; X24 R44 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. xxx. 2; X61 Xn; X22 X; X50–53

X; 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 R43 N; X50–53

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

611–008–00–4

4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. kat. 2; X45 N; R50–53

T; X R: 45–50/53 X: 53–45–60–61

611–013–00–1

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

403–650–7

117409–78–6

E; 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 Red 9 XX basická xxxxxx 9

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-methoxyanilin x-xxxxxxxx

X

201–963–1

90–04–0

Xxxx. xxx. 2; X45 Xxxx. kat. 3; X40 X; R23/24/25

T X: 45–23/24/25 X: 53-45

612–042–00–2

xxxxxxxx bifenyl-4,4'-diamin 4,4'-xxxxxxxxxxxxxx xxxxxxx-4,4'-xxxxxxxxxx

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xn; X22 X; X50–53

X; X X: 45–22–50/53 X: 53–45–60–61

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

612–051–00–1

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

E

202–974–4

101–77–9

Karc. xxx. 2; R45 Xxxx. xxx. 3; X40 X; X39/23/24/25Xx; X48/20/21/22 X43 X; R51–53

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

612–081–00–5

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

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; R45 Xx; X22 X; X51–53

X; N X: 45–22–51/53 X: 53–45–61

612–099–00–3

4-xxxxxx-x-xxxxxxxxxxxxx4-xxxxxx-1,3-xxxxxxxxxxxxx4-xxxxxxxxxxxx-1,3-xxxxxx 2,4-xxxxxxxxxxxx

X

202–453–1

95–80–7

Xxxx. xxx. 2; X45 T; X25 Xx; R21 Xi; X36 X43 X; X51–53

X; N 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; R21/22 X43 X; R51–53

Xn; X R: 21/22–40–43–51/53 X: (2-)24–36/37–61

612–125–00–3

2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,4-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,4-xxxxxx 2,5-xxxxxxxxxxxx

202–442–1

95–70–5

X; X25 Xx; X20/21 X43 X; R51–53

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

612–144–00–7

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

—

62924–70–3

Xx; X36/38 R4 3 N; R50–53

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

612–151–00–5

xxxxxxxxxxxxx toluendiamin xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. xxx. 2; R45 T; X25 Xx; X20/21 Xx; X36 X43 X; R51–53

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

613–018–00–4

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

—

7411–47–4

Xx; X22 Xx; X36/37/38 X52–53

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

613–031–00–5

xxxxxxxxx xxxxxxxxxxxxxxxxxxxx xxxxxxxx xxxxxxxx-1,3,5-xxxxxxxxxxxx 1,3,5-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5X)-xxxxx

201–782–8

87–90–1

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

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

202–095–6

91–76–9

Xn; X22 R52–53

Xn 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 N; X41 X; X50–53

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

613–043–00–0

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

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; R22 N; X50–53

Xx; X X: 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'-bis[(3,5-dimethylmorfolin-4-karbonyl)methyl]-4,4'-bipyridin-1,1'-dium-disulfát [2]

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xn; X22 Xx; X36/37/38 X52–53

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

613–098–00–0

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

403–700–8

2687–94–7

X; X34 X; X51–53

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

613–130–00–3

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

—

79983–71–4

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

613–131–00–9

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

—

57369–32–1

Xx; X22 R52–53

Xn X:22–52/53 S: (2-)61

613–134–00–5

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

—

88671–89–0

Repr. xxx. 3; X63 Xx; X22 Xx; X36 N; X51–53

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

613–137–00–1

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

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

—

74223–64–6

X; R50–53

N X: 50/53 S: 60-61

614–001–00–4

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

200–193–3

54–11–5

X+; X27 X; X25 X; X51–53

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

614–006–00–1

xxxxxx 2,3-dimethoxystrychnidin-10-on

206–614–7

357–57–3

T+; X26/28 X52–53

X+ R:26/28–52/53 X: (1/2-)13–45–61

614–007–00–7

xxxxxx-xxxxxx [1] xxxxxx-xxxxxx [2] brucin-(R)-(1-methylheptyl)-hydrogen-ftalát [3] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [4]

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

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

X+; R26/28 X52–53

X+ X: 26/28–52/53 S: (1/2-)13–45–61

615–006–00–4

2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-methyl-1,3-fenylendiisokyanát [1] 4-methyl-m-fenylendiisokyanát [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] m-tolylidendiisokyanát [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [2] xxxxxx-3,5-xxxxxxxxxxx [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. kat. 3; X40 T+; X26 Xx; X36/37/38 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+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; R23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42

2

616–010–00–9

xxxxxxx-xxxxxxxxxxxxxx N-chlor-4-methylbenzen-1-sulfonamid, xxxxx xxx

204–854–7

127–65–1

Xx; X22 X31 X; X34 X42

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

616–034–00-X

xxxxxxxxxxxx (XXX) 6-xxxxxx-3,4-xxxxxxx-2X-xxxxx-5-xxxxxxxxxxxx

246–419–4

24691–76–7

X52–53

X: 52/53 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; N X: 22–43–50/53 X: (2-)36/37–60–61

617–004–00–9

(1,2,3,4-tetrahydro-1-naftyl)hydroperoxid xxxxxxxxxxxxxxxxxxxx

212–230–0

771–29–9

X; X7 Xx; X22 X; X34 X; 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 %: C; X22–34 10 % ≤ C &xx; 25 %: C; X34 5 % ≤ X < 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 xxxxxxxxxxxxxx

201–279–3

80–43–3

X; X7 Xx; X36/38 X; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xi; X36 X43

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

650–007–00–3

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

228–200–5

6164–98–3

Xxxx. kat. 3; X40 Xx; 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-xxxxxxxxxx)xxxxxxxxx]-3-xxxxxxxxxxxxxx-5(4 X)-xx

227–197–8

5707–69–7

X; X25 X; X50–53

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

650–009–00–4

chlordimeform-hydrochlorid X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx N2-(4-chlor-o-tolyl)-N1,N1-dimethylformamidin-hydrochlorid

243–269–1

19750–95–9

Karc. xxx. 3; X40 Xx; R22 N; X50–53

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

650–033–00–5

xxxxxxxxxxxx (XXX) [(S)-(3-fenoxyfenyl)kyanmethyl]-(S)-2-(4-chlorfenyl)-3-methylbutanoát (S)-3-fenoxy-α-kyanbenzyl-(S)-2-(4-chlorfenyl)-3-methylbutanoát

—

66230–04–4

T; X23/25 X43 X; X50–53

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

650–041–00–9

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

—

82097–50–5

X; X50–53

X X: 50/53 X: 60-61

PŘÍLOHA 1D

Indexové číslo

Chemický xxxxx

Xxxxxxxx k látkám

Číslo XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x přípravkům

006–090–00–8

2-[(3-jodprop-2-yn-1-yl)oxy]ethyl-N-fenylkarbamát

408–010–0

88558–41–2

Xn; X20 Xx; R41 X52–53

Xx X: 20–41–52/53 S: (2-)22–26–39–61

014–016–00–0

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

406–490–6

—

X; X51–53

X X: 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

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

404–986–7

—

Xi; X41 X; X50–53

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

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 X: 61

015–167–00–5

3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; X41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; X50

X X: 50 S: 61

601–051–00–7

4-xxxxxxxx-1-xx

405–980–7

768–56–9

Xx; X38 X; X51–53

Xx; X X: 38–51/53 X: (2-)37-61

602–083–00–4

xxxxxxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; X48/21/22 X64 X; R50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

X R: 52/53–59 X: 59-61

603–128–00–0

2-(fenylmethoxy)naftalen

405–490–3

613–62–7

R53

R:53 X: 61

603–129–00–6

1-xxxx-xxxxxxxxxxxx-2-xx

406–180–0

57018–52–7

X10 Xx; X41

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

603–130–00–1

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

406–325–8

—

Xx; X22 X52–53

Xx X:22–52/53 S: (2-)39-61

603–131–00–7

Xxxx (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxxx)xxxxx]-X-xxxxxxxx

407–290–1

—

Xx; X41

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

603–132–00–2

2-(xxxxxxxxxxxxx)-6-xxxxxxxxx-9-xxxxxx-1,4-xxxxxxxxxx[4.5]xxxxx

408–200–3

63187–91–7

Xx; X38–41 X52–53

Xx X:38–41–52/53 X: (2-)26–37/39–61

603–133–00–8

Směs:3-(4-amino-2-chlor-5-nitroanilino)propan-1,2-diol x 3,3'-[(2-xxxxx-5-xxxxx-1,4-xxxxxxx)xxxxxxx]xx(xxxxxx-1,2-xxxx)

408–240–1

—

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)22–36–61

603–134–00–3

Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx x xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (dodecyl a xxxxxxxxxx nerozvětvené)

410–450–3

—

R53

R: 53 X: 61

603–135–00–9

bis[2-(2-methoxyethoxy)ethanolato]bis(2,2', 2-nitrilotriethan-1-olato-N,O)titaničitý xxxxxxx

410–500–4

—

Xx; R41 X; X51–53

Xx; X X: 41–51/53 X: (2-)26–39–61

603–136–00–4

3-{4-[xxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxxx}xxxxxx-1-xx

410–910–3

104226–19–9

X43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

603–137–00-X

Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 1-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-xxxxxxxx-3-(3-xxxxxxxxxxx)xxxxxx-1-xx

403–140–4

103694–68–4

X52–53

X:52/53 X: 61

604–050–00-X

4-chlor-o-kresol 4-xxxxx-2-xxxxxxxxxxx

216–381–3

1570–64–5

X; X23 C; X 35 N; R50

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

X ≥ 25 %: X; X; X23–35 10 % ≤ X &xx; 25 %: C;R20–35 5 % ≤ X &xx; 10 %: X;X20–34 3 % ≤ C &xx; 5 %: Xn;R20–36/37/38 1 % ≤ X < 3 %:Xx;X36/37/38

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 X: 61

604–052–00–0

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

403–800–1

103597–45–1

X53

X:53 S: 61

604–053–00–6

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

410–760–9

157661–93–3

Xx; R38 X43 N; R50–53

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

604–054–00–1

Xxxx:2-xxxxxxx-4-(4-xxxxxxxxxxxxxxxxxxxxxxxxx-2-xx)xxxxx a 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -pyran-2-yl)fenol

412–020–0

—

R43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

604–055–00–7

4,4'-xxx[(2,3-xxxxxxxxxxx)xxx]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx

413–900–7

85954–11–6

Xxxx. Xxx.3; X40

Xx X: 40 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, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X - xxxxx-5-xxxxxxxxxxx

410–480–7

—

X43 N; X51–53

Xx; 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 R: 51/53 X: 61

606–052–00–6

4-(X, N-dibutylamino)-2-hydroxy-2'-karboxybenzofenon 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx xxxxxxxx

410–410–5

54574–82–2

X52–53

X:52/53 X: 61

607–272–00–5

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

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

X; X50–53

X R: 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-[benzyl(methyl)amino]ethyl}-3-aminobut-2-enoát

405–350–1

54527–73–0

R43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–275–00–1

xxxxxxx-4-(xxxxxxxxxx)xxxxxx-1-xxxxxxxx

405–450–5

66531–87–1

X43

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

607–276–00–7

[xxx(2-xxxxxxxxxxxxxx) xxx(1-xxxxxxxxxxxxxx)]xxxxxxxxx komplex

405–635–0

—

Xi; X38–41 X; X50–53

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

607–277–00–2

Směs:2-(hexylsulfanyl)ethylamin-hydrochlorid x xxxxxxx-xxxxxxxxx

405–720–2

—

Xx; R22 Xx; X41 X43 X; X51–53

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

607–278–00–8

Směs:alkyl(C7-C9 xxxxxxxxxx a xxxxxxxxxxxx)-3-[3-(2 X - benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty

405–760–0

—

Xi; X41 X43 X52–53

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

607–279–00–3

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

405–960–8

—

R43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

607–280–00–9

4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx sodný xxxxxxx-4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx

406–190–5

54322–20–2

Xx; X22 Xx; R36 X43

Xx X: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

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

407–000–3

127519–17–9

X; X51–53

X X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 X: 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 X43 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 R: 51/53 X: 61

607–285–00–6

Xxxx:7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxxx kyselina, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx x xxxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx

410–065–0

—

X43

Xx X: 43 X: (2-)22–24–37

607–286–00–1

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

410–070–8

141880–36–6

X43 X52–53

Xx R:43–52/53 X: (2-)22–24–37–61

607–287–00–7

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

410–140–8

—

X52–53

X:52/53 S: 61

607–288–00–2

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

410–160–7

148732–74–5

Xx; X36 R43 R52–53

Xi X: 36–43–52/53 S: (2-)22–26–36/37–61

607–288–00–8

3-[(3-{X —[4-(2,4-di-terc-pentylfenoxy)butyl]karbamoyl}-4-hydroxy-1-naftyl)sulfanyl]propanová xxxxxxxx

410–370–9

105488–33–3

X53

X:53 X: 61

607–290–00–3

Směs (o xxxxxxxx poměru):amonium-1-alkyl(C14-C18)-4-[3-(allyloxy)-2-hydroxypropyl]-2-sulfonatobutandioát x xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx

410–540–2

—

Xx; R38 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

Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(alkyl(C14)oxy)-1-(methoxymethyl)]octová kyselina

410–640–6

—

Xi; X38–41 X; 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 x 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx

410–650–0

—

Xx; X41 X43 X; X51–53

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

607–294–00–5

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

410–680–4

—

X43

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

607–295–00–0

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

410–800–5

—

X43 X; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

607–296–00–6

Směs:tetraestery 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 kyselina)2,2'-dioxo-3,3'-(1,4-fenylendimethyliden)bis(1,7,7-trimethylbicyklo[2.2.1]heptan-1-methansulfonová xxxxxxxx)

410–960–6

92761–26–7

Xx; X41

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

607–298–00–7

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

411–010–3

—

R43

Xi X: 43 X: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 R43 X; X50–53

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

607–300–00–6

[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, x-xxxxxxxxxxxxxxxxxxxx]xxxxxxx xxxxxxx, xxxxxxxx xxx; x = 1,2,3 xxxx 4, x = 8, 9, 10 xxxx 11, x = 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 xxxxxxxx x xxxxxxxxxxx xxxxx(1-7)xxxxxxx

411–860–5

—

Xx; X38–41 X43 N; X51–53

Xx; X 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; R51–53

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

607–303–00–2

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

413–760–7

93107–30–3

Xxxx. xxx.3; X62 X52–53

Xx X: 62–52/53 X: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; X50–53

X X: 50/53 X: 60-61

608–024–00–9

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

407–650–8

97460–76–9

X53

X:53 X: 61

608–025–00–4

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

410–970–0

117568–27–1

X53

X:53 X: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

—

X; X3 X; X8 Xxxx. 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 X; X34 X43 N; X50–53

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

611–043–00–5

Xxxx (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx trisodný, [bis{6-[(2-amino-4-hydroxyfenyl)azo]- xxxx 6-[(2-amino-6-hydroxyfenyl)azo]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx xxxxxxxx a[{6-[(2-amino-4-hydroxyfenyl)azo]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}(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 S: (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, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx a[(4(5)-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato) (3-xxxxx-5-xxxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx

403–720–7

117527–94–3

X; R51–53

Xi; R41 X52–53

611–045–00–6

2-({4-[(4-xxxxxxxxxxxx)xxxxxxxxxx]-2-xxxxxxxxxxx}xxx)-3-xxxxxx-5-xxxxxxxxxxxx

404–830–8

—

X53

X:53 X: 61

N X: 51/53 S: 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 N; X50–53

X; X R: 25–43–48/22–50/53 S: (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 x 2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx

407–890–3

111381–11–4

X53

X: 53 X: 61

611–048–00–2

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 X: 61

611–049–00–8

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

408–000–6

118658–98–3

Xx; X48/22 R43 X52–53

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

611–051–00–9

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

411–110–7

136213–74–6

N; X50–53

X X: 50/53 S: 60-61

611–052–00–4

[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) xxx]-6-[(6-xxxxxxxxx-1-xxxxxx)xxx]xxxxxx-1,3-xxxxxxx}]xxxxxxxxx xxxxxxx, xxxxx sůl

400–720–9

—

R52–53

R: 52/53 X: 61

612–156–00–2

Směs:trihexadecyl(methyl)amonium-chlorid x xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx

405–620–9

—

Xx; R41 N; X50–53

Xx; X R: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

(Z)-1-(1-benzothiofen-2-yl)ethan-1-on-oxim-hydrochlorid

410–780–8

—

Xn; X22–48/22 Xi; 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 C12))-2-hydroxybenzaldoximato)]měďnatý xxxxxxx x 4-dodecyl-2-hydroxybenzaldoxim[bis(5-alkyl(rozvětvený X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx a 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

—

X53

X: 53 X: 61

612–159–00–9

xxxxxxx xxxxxxxx xxxxx 2,2,4-xxxxxxxxx- x 2,4,4-trimethylhexan-1,6-diaminu (x xxxxxxx XXXXXX), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Epoxid 8) a 4-xxxxxxxxxxxx-1-xxxxxxxxx xxxxxxxx

410–880–1

—

Xx; X22 X; X34 X; X50–53

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

613–149–00–7

2-xxxx-xxxxx-5-[(4-xxxx-xxxxxxxxxxx)xxxxxxxx]-4-xxxxxxxxxxxxxx-3(2X)-xx

405–700–3

96489–71–3

X; R23/25 X; X50–53

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

613–150–00–2

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

406–295–6

—

X53

X:53 S: 61

613–151–00–8

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

406–360–9

104218–44–2

X53

X:53 X: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 X; R51–53

Xi; 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 X: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; R22 X52–53

Xx X: 10–22–52/53 X: (2-)23–36–61

613–156–00–5

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

410–260–0

83857–96–9

X43 X; X51–53

Xx; N X: 43–51/53 X: (2-)24–37–61

613–157–00–0

2,4-xxxxxxx-5-(xxxxxxxxxxxxx)xxxxxxxxx 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx

410–330–0

54236–98–5

Xx; X22–48/22 Xi; X36

Xx X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

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

410–340–5

69045–84–7

Xn; X20/22 Xx; X41 X43 X; R51–53

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

613–159–00–1

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

410–580–0

120928–09–8

X; X25 Xx; X20 N; R50–53

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

613–160–00–7

2-methyl-2,5-diazabicyklo[2.2.1]heptan-dihydrobromid

411–000–9

125224–62–6

R43

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

615–023–00–7

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

410–900–9

83056–32–0

R10 X14 Xxxx. xxx. 3; R40 Xx; X20–48/22 Xi; X41 X42

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

616–044–00–4

N-(3,5-dichlor-4-ethyl-2-hydroxyfenyl)-2-(3-pentadecylfenoxy)butanamid

402–510–2

—

N; X51–53

X X: 51/53 S: 61

616–045–00-X

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

405–190–2

122371–93–1

X43 R53

Xi X: 43-53 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 S: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx x X, X′,X″,X′′′ - tetraalkyl(C18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx

406–640–0

—

X43

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

616–048–00–6

3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx

406–740–4

1939–27–1

Xx; X48/22 N; R51–53

Xn; X R: 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 N; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

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

411–070–0

—

X53

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

650–032–00-X

xxxxxxxxxxxx (XXX) (2X, 3R)-, (2 S, 3 X)-, (2 X, 3 X)-, (2 X, 3 R)-2-(4-chlorfenyl)-3-cyklopropyl-1-(1H- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

—

94361–06–5

Xxxx. kat. 3; X63 Xn; R22 X; R50–53

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

XXXXXXX 2

XXXXXX XXXXXXXXXXXX XXXXX SPOJENÝCH S XXXXXXXXXXXX LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Komise 2001/59/XX,

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

XXXXXXX 3A

STANDARDNÍ XXXXXX XXX BEZPEČNÉ XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.

XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX BEZPEČNÉ XXXXXXXXX X NEBEZPEČNÝMI LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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

PŘÍLOHA 4X

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

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx metody OECD XX 473 — Xxxxxxx xx chromozomové xxxxxxx x xxxxx xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx u savců xx xxxxx má xxxxxxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx savců (1, 2, 3). Rozlišují xx dva xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx chemických xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Nárůst xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx indukovat xxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxx xxxx xxxxxx xx stanovení xxxxxxxxxxx aberací a xxxx x xxxxxx xxxxx rutinně používána. Xxxxxxxxxxxx mutace x xxxxxxx jevy xxxx xxxxxxxx mnoha geneticky xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx důkazů o xxx, xx chromozomové xxxxxx x s xxxx xxxxxxxxxxx jevy xxxxxxxxxxx xxxxx v xxxxxxxxxx x v xxxxxx somatických buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx indukci xxxxxxxx u xxxxxxx x u pokusných xxxxxx.

Xx zkoušce xx xxxxxxxxxxxx aberace xx xxxxx mohou xxx xxxxxxx stabilizované xxxxxxx xxxxx, buněčné kmeny xxxx xxxxxxxx xxxxxxx xxxxxxx. Xxxxxxx xxxxx xxxx xxxxxxx na xxxxxxx xxxxxxxxxx xxxxx x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx chromozomů x xxxxxxxxx xxxxxxxx chromozomových xxxxxxx.

Xxxxxxx xxxxxxxxx in xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx zdroje xxxxxxxxxxx xxxxxxxx. Tento xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx zcela napodobit xxxxxxxx xx xxxx x xxxxx. Je xxxxx se zcela xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx vlastní xxxxxxxxxx x může k xxx xxxxx změnou xX, osmolality xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Tato zkouška xx xxxxxxx ke xxxxxxxx xxxxxxx xxxxxxxx x karcinogenů pro xxxxx. Mnoho xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx xxx xxxxx xxxxxxxxxxx; xxxx xxxxx xxxxxxxx x karcinogenitou xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx závisí xx chemické xxxxx x xxxxxxxxx xxxxxx x tom, xx xxxxxxxx xxxxxxxxxxx, které xxxxxx xxxxxxxx touto xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx mechanismy xxx přímým poškozením XXX.

Xxx také Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu x podobě xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x opětného xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x podobě xxxxx nebo xxxxx x xxxxxxx obou xxxxxxxxx x xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : proces, xxx xxxxxx x xxxxx po S-fázi xxxxxxxxx XXX xxxxxxx x xxxxxx, xxxxx xxxxxxxxx xxxxx S-fáze. Xxxxxxxxx jsou xxxxxxxxxx xx 4, 8, 16… chromatidami.

Gap : xxxxxxxxxxxx xxxx menší xxx šířka jedné xxxxxxxxxx a x xxxxxxxxx xxxxxxxxx chromatid.

Mitotický xxxxx : xxxxx xxxxx, které xx xxxxxxxxx x metafázi, x celkového xxxxx xxxxx x xxxxxxxx; xxxxx stupeň xxxxxxxxxxx xxxx xxxxxxxx.

Xxxxxxxxx aberace : xxxxxxxx xxxxx xxxxxxxxxx xx xxxxxxxxxx xxxxx obvyklého u xxxxxxxxx typu xxxxx.

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

Xxxxxxxxxx aberace : xxxxxxxxxxxxx pozorovatelné změny xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx; jeví xx jako delece x xxxxxxxxx, intrachromozomální xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ METODY

Buněčné xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, a xx s metabolickou xxxxxxxx x bez xx. X xxxxxx xxxxxxxxxxx intervalech po xxxxxxxx xxxxx xx xx xxxxxxxxx kultur xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx), xxxxxxx xx sklidí, xxxxxx x přítomnost xxxxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx různé xxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (xxxx. fibroblasty xxxxxx xxxxxxxx, lymfocyty xxxxxxxxx xxxx člověka xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx x kultivační xxxxxxxx

Xxx xxxxxxxxx kultur xx xxxx být xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx nádoby, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). U xxxxxxxxxxxxxxx buněčných xxxxx x xxxxx xx xxxx xxx rutinně xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx počtu xxxxxxxxxx x mělo by xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x xxxxxxx kontaminace xx neměly být xxxxxxx. Xxx použité xxxxx a xxxxxxxxx xxxxxxxx by xxxx xxx xxxxx normální xxxxx xxxxxxxxx xxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx a xxxxx: xxxxx xx pomnoží x xxxxxxxxx kultur, xxxxxx se xx xxxxxxxxxxxx xxxxx x xxxxxx hustotě, aby xxxxxxxxx konfluence před xxxxxxxxx, a xxxxxxxx xx při 37 °X.

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

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, a xx x xxxxxxx xxxxxxxxxxxx xxxxxxxx x xxx xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx x xxxxx hlodavců xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (6, 7, 8 x 9), xxxx směs xxxxxxxxxxxxx x β-naftoflavonu (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx v xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx metabolického xxxxxxxxxxx xxxxxxx může xxxxxxx xx xxxxx xxxxxxxx xxxxx, která xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx může být xxxxxx použít více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce.

Řada xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx enzymy, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx linií xx xxxx xxx vědecky xxxxxxxxxx (xxxx. důležitostí xxxxxxxxx cytochromu P450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Xxxxxxxx látka/příprava

Pevné xxxxxxxx látky xx xxxx xxx před xxxxxxxx na xxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx přidány xxxxx x testovacím xxxxxxxx x/xxxx mohou xxx xxxx aplikací xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxx, xxxxx xxxxx x stálosti xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx buněk x x xxxxxxxxx X9. Xxxx-xx použita xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx nestálých xx xxxx xx xxxx xxx použita xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx. Vodu xxx xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Cytotoxicita xx xxxx být stanovena x metabolickou xxxxxxxx x bez ní x xxxxxxx experimentu xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x růstu, xxxx xxxx xxxxxx xxxxxxxxxx, xxxxx životaschopných xxxxx xxxx xxxxxxxxx xxxxx. Xxxx xxx xxxxxxx xxxxxxxx cytotoxicitu a xxxxxxxxxxx x předběžném xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx by xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, xxx obvykle xxxxxxx, xx by xx xxxxxxxxxxx xxxxxx xxxxx více nežli xxxxxxxx 2 až Ö10. X xxxxxxxx xxxxxxx xx xxxx xxxxxxxx xxxxxxxxxxx vykazovat xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, počtu xxxxx xxxx mitotického xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx je xxxxx nepřímým měřítkem xxxxxxxxxxxxx xxxx cytostatických xxxxxx x závisí xx době, xxxxx xxxxxxxx od xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx xxxxxxxxxx x xxxxxxxxxxx xxxxxx, u xxxxx xxxxx být xxxx metody xxxxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx buněčného xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (XXX), xxxxx xxx xxxxxxx xxxx xxxxxxxxx xxxxxxxxx. V xxxxxxx XXX xxxx xxx x celkovou xxxxxxxxx xxxxxxx, z xxx xxxxx usoudit xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, a i xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx může xxx za xxxxxxxx xxxxx xxxxxxxxx oddálení xxxxxxxx xxxxxxxxxxx výtěžku xxxxxxx.

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx by xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, která x xxxx xx xxxxxxxx.

X xxxxxxx relativně xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx xxxxxxx xxx xxxxxxxxxxxxx xxxxxxx, než xx xxxxxx xxxxxxxxxxx, xx měla xxx xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxx, xxx xx nad mezí xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx médiu xx xxxxx xxxx xxxxxxxx. X xxxxxxxx xxxxxxxxx (xxxx. projeví-li xx xxxxxxxx pouze xxx xxxxxxx xxxxxxxxxxxxx, xxx xx rozpustnost) se xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, při xxxxx xxxxxxx xx xxxxxxx. Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx x na xxxxx xxxxxxxx, neboť xxxxxxxxxxx x testovacím xxxxxxx se může x xxxxxxx expozice xxxxx v xxxxxxxx xxxxxxxxxxx xxxxx, xxxx X9 xxx. Nerozpustnost xxx xxxxxxx vizuálně. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxx rozpouštědla xxxx xxxxxxxx). Xxx xxxxxxx metabolické xxxxxxxx xx měla xxx xxx pozitivní xxxxxxxx xxxxxxx chemická xxxxx, xxxxx k xxxxxxxxx xxxxxx xxxxxxxx aktivaci.

K xxxxxxxxx kontrole by xxx xxx xxxxxx xxxxx elastogen x xxxxxxxxxxx xxxxxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x detekovatelný nárůst xxx xxxxxx, čímž xx xxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx by měly xxx xxxxxxx tak, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xxxxxxxx xxxxxxxxxxx x negativních xxxxxxx:

Xxxx xxxxxxxxxxx aktivace

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

Xxx xxxxxx xxxxxxxxxxx xxxxxxxx

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X xxxxxx 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 xxxxx být xxxxxxx i xxxx xxxxxx xxxxx. Xxx xxxxxxxxx kontrolu xx xxxx xxx xxxxx xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx třídy.

V xxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula x xxxxxxxxxxx médiu x xxxxxxxxxx stejným způsobem xxxx xxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také tehdy, xxxxxxxxxx-xx dosud xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx se xxxxxxx xxxxxxxx xxxxx xxx xx přítomnosti xxxxxxxxxxxxx aktivačního xxxxxxx, xxx xxx xxxx. Xxxxxxxx xxxxxxxxx by xxxx být zahájena xxx 48 hodin xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx xxxxxx xxxxxxxxxxx xx měly být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, x totéž xx xxxxxxx doporučuje x xxxxxx xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxx. Jestliže xxx xx základě xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx duplicitními xxxxxxxxx xx minimální rozdíl, xxxx být xxxxxxxxx xxxxxxx xxxxxx xxxxxxx.

Xxxxxx xxxx xxxxxx látky xx měly xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. v těsně xxxxxxxxxx kultivačních xxxxxxxx (15, 16).

1.4.3.3 Xxxx xxxxxxx xxxxxx

X prvním xxxxxxxxxxx by měly xxx xxxxx vystaveny xxxxxxxx xxxxx, xxx x xxxxxxxxxxxx aktivací, xxx xxx ní, xx dobu 3 — 6 hodin, x měly xx xxx odebrány xx xxxxxx xxxx xx xxxxxxxx aplikace, která xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného cyklu (12). Xxxxxxxx xxxxx xxxxxx xxxx negativní xxxxxxxx xxx s xxxxxxxx, xxx bez xxxxxxxx, xxx xx xxx xxxxxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx x nepřetržitou xxxxxxxx xx xx xxxxxx x xxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx chemické xxxxx xxx snáze detekovat xxx dobách xxxxxxxx xxxx xxxxxx delších xxx 1,5xxxxxxx délky xxxxx. Xxxxxxxxx xxxxxxxx xxx xxxxxxxxxxx aktivaci xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. X xxxxxxxxx, xxx xx nepovažuje potvrzení xxxxxxxxxxx výsledků za xxxxxxxx, xx xxxx xxx podáno zdůvodnění.

1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů

Do xxxxxxx xxxxxxx xx obvykle 1-3 xxxxxx xxxx xxxxxxxxx xxxxx Colcemid® xxxx xxxxxxxxx. Xxx xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx se xxxxx buněčná xxxxxxx xxxxxx a xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx analýzu xxxxxxxxxx xxxxxxxx hypotonizaci xxxxx, xxxxxx x obarvení xxxxx.

1.4.3.5 Analýza

Všechny xxxxxxxxx, xxxxxx preparátů xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx analýzou xxx xxxxxxxxxxx nezávisle kódovány. Xxxxxxxx xxx fixaci xxxxx xxxxxxx ke xxxxx xxxxx xxxxx x metafázi x xx ztrátě chromozomů, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxx xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx buněk. Xx xxxxxx xxxxxxxxxxx a xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxxx 200 xxxxx rozprostřených xxxxxxxx, případně xxxxxxxxxx xxxxxxxxxxx xxxx duplicitní xxxxxxx. Xxxxx xxxxx xxx xxxxxx, je-li xxxxxxxxx velký xxxxx xxxxxxx.

Xxxxxx xx xxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx, je xxxxxxxx xxxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxxxxxx, xxxx-xx xxxxxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxxxx jednotkou xx xxxxx a xxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx buněk xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (aberacemi) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx a xxxxxxxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx s xxxxxx xxxxxx x xxxxxxxx. Xxxx xx zaznamenávají xxxxxxxx a xxxxxxx xx, xxx xxxxxxxxxx xx xx xxxxxxx xxxxxxxx xxxxxxx.

Xxxx xx xxx xxxx xxxxxxxxxxx xxxxxxxx, xxxxx xxxx xxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxx. Dále xx měly být xxxxxxx xxxxx xxxxxxx xx formě xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxx negativní xxxxxxxx xxxx xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx posuzovaných xxxxxxxx xx měla xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, např. xxxxxx počtu xxxxx x chromozomovými xxxxxxxxx x xxxxxxxxxx na xxxxxxxxxxx, nebo reprodukovatelný xxxxxx xxxxxx xxxxx. Xxxxxxxx by měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Statistická významnost xx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx.

Xxxxxx xxxxx polyploidie xxxxx xxxx znamenat, xx xxxxxxxx látka má xxxxxxxxx potlačit xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxx počtu xxxxx x endoreduplikovanými xxxxxxxxxx xxxx xxxxxxxx, že xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxx progresi xxxxxxxxx cyklu (17, 18).

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

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok o xxxxxxxx xxxxxxxx látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxxxxx na xxxxxxxxxxxx aberace in xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx neindukuje x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx aberace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Buňky:

- typ x xxxxx buněk,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx typu xxxxx,

- popřípadě nepřítomnost xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxx krve, xxx xxxx xxxxxxx xxxx xxxx nebo xxxxxxxxxx lymfocyty, použitý xxxxxxx,

- případně xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x počtu kultur, xxxxxx např. údajů x xxxxxxxxxxxx a xxxxxx xxxxxxxxxxxx, xxxx-xx x xxxxxxxxx,

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- případně xxxxxxx xxxxx xxx nasazení,

- xxx x xxxxxxx xxxxxxxxx metabolického aktivačního xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,

- xxxxxxxxx a xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx metafází,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity, xxxx. stupeň konfluence, xxxxx x xxxxxxxx xxxxx, počty xxxxx, xxxxxxxxx xxxxx,

- známky xxxxxxx,

- údaje x xX x xxxxxxxxxx xxxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxx,

- xxxxxxxx xxxxxxx, xxxxxx xxxx,

- xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx a xxxx aberací xxxxxx xxx xxxxxx exponovanou x xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

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

2) Xxxxxxxx, X. Xx., Xxxxxx, X. (1985), Xxx Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Xxxxx Xxxxxxx Xxxxxxx Xxxx (CHL) Xxxxxxxxxx Xxxxx in Xxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxx Research, Xxx. 5, Xxxxx, X. xx xx., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Amsterdam-New York-Oxford, 427-432.

3) Xxxxxxxx, X. X., Xxxxxxxxx, X. X., Reuben, C., Xxxxxx, S., Brown, X., Xxxxxx, X., Xxxxx, X. D., Xxxxxxxx, X., Xxxxx, X., Xxx, X., Xxxxx, J., Xxxxxxxx, X. H., Xxxxxxx, X. X., Xxxxxxxx, X., Zeiger X. (1978), Xxxxxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx cells: Xxxxxxxxxx xx 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Xxxxx, X., Galloway, X. X., Marshall, X. X., Xxxxxxxx, M. Xx., Brusick, X., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. A xxxxxx xxxx XXXXXX Xxxx Group 9, Xxxxxxxxxx Xxx., 257, 147-204.

5) Morita, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxx, X., (1992), Clastogenicity of xxx xX xx Xxxxxxx Xxxxxxxx Mammalian Xxxxx, Xxxxxxxxxx Xxx., 268, 297-305.

6) Ames, X. X., XxXxxx, X., Xxxxxxxx, E. (1975), Methods xxx Xxxxxxxxx Carcinogens and Xxxxxxxx with xxx Xxxxxxxxxx/Xxxxxxxxx Microsome Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 31, 347-364.

7) Maron, X. X., Xxxx, X. X. (1983), Xxxxxxx Xxxxxxx xxx xxx Xxxxxxxxxx Mutagenicity Xxxx, Mutatation Xxx., 113, 173-215.

8) Xxxxxxxxx, X. X., Xxxxx, X. X., xxx Xxxx, X. P. X., Xxxxxxx, X., xx Vogel, X. (1976), Xxxxxxxxxxx Effects xx Xxxxxxx/Xxxxxxxxxxx xxxxx Xxxxxxxxxx xx x Xxxxxxxxxxx Xxxxxx Xx xxxxx, I. Xxxxxxxxx xx Xxxxxxxxxx Aberrations xxx Sister Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Xxxxxxxxxxxxxxxxxxx (XXX) xx XXX Xxxxx xx the Xxxxxxxx xx Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

9) Matsuoka, X., Xxxxxxx, X., Xxxxxxxx, X. Jr. (1979), Xxxxxxxxxxx Xxxxxxxxxx Xxxxx on 29 Xxxxxxxxx Xxxxxxxx with X9 Mix In xxxxx, Mutation Xxx., 66, 277-290.

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

11) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X. Xxxx Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, xx: xx Xxxxxx, F. X., Fouts, X. X. Bend, J. X., Philpot, X. X. (xxx), In xxxxx Xxxxxxxxx Activation xx Mutagenesis Testing, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

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

13) Xxxxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X. X., Xxxxxxxx, X., Chanter, X. X., Xxxxxxxx, X. (1989), Xxxxxxxx xx Data from Xx xxxxx Xxxxxxxxxxx Xxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Xxxxxxxx, X. X., (xx) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 141-154.

14) Xxxxx, X. X., Xxxxxxxx, X. X. (1994), Xxxxxxxxx Xxxxxx are xxx Xxxxxxxxx xxx Xx vitro Xxxxxxxxxx Xxxxxxxxxx Xxxxxx xx XXX Xxxxx, Mutatation Xxx., 312, 139-149.

15) Xxxxx, X. F., Xxxxxx, X. X., XxXxxxx, X. T. (1982), CHO/HGPRT Mutation Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Xxxx, X. R., Costa, X. X., Schaich, X. M. (xxx), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, X. X., Xxxxxx, X. X., Xx, X. P., Xxxxxx, X. L. (1983), Xxxxxxxxxx of xx Xxxxxxxx System Xxxxx Cells Grown xx Xxxxxxxx Gels xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxx., 5, 795-801.

17) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx xx Chinese hamster xxxxx xxxxxx xxxxx-xxxxxxxxx xxxxxxx G2 xxxxxx, Xxxxxxxxxx Res., 119, 403-413.

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

XXXXXXX 4B

"B.11 XXXXXXXXXX–XXXXXXX XX XXXXXXXXXXXX XXXXXXX X BUŇKÁCH XXXXXX XXXXX SAVCŮ IN XXXX

1. XXXXXX

Xxxx xxxxxx xx replikou metody XXXX XX 475 — Zkouška xx xxxxxxxxxxxx xxxxxxx x xxxxxxx kostní dřeně xxxxx (1997).

1.1 ÚVOD

Zkouška xx xxxxxxxxxxxx aberace x savců in xxxx xx xxxxxxxxx xxx xxxxxxx strukturních xxxxxxxxxxxxxx aberací indukovaných xxxxxxxxx xxxxxx v xxxxxxx kostní dřeně xxxxx, obvykle xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx se xxx typy strukturních xxxxxxx — xxxxxxxxxxxx x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx rovněž xxxxxxxxx. Xxxxxxxxxxxx mutace x xxxxxxxxxxx xxxx jsou xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx a xxxxxxxx xxxxx důkazů x xxx, xx xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x onkogenech a x xxxxxx somatických xxxxx xxxxxxxxx nádory, xxxx podíl na xxxxxxx rakoviny u xxxxxxx x x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx jsou rutinně xxxxxxxxx xxxxxxxx. Cílovou xxxxx xx x xxxx xxxxxxx xxxxxx xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx x rychlým xxxxxx, xxxxx xx xxxxxx xxxxxxx x xxxxxxxxxxxx. Xxxx xxxxx x cílové xxxxx xxxxxx předmětem této xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxx xxxxxx k xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a xxxxxxx reparace DNA, xxxxxxx xx mohou x xxxxxxx xxxxx x xxxxx měnit. Xxxxxxx in xxxx xx rovněž xxxxxxxx xxx xxxxx výzkum xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx xx xxxxx.

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

Viz xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : strukturní xxxxxxxxx xxxxxxxxxx v podobě xxxxx xxxxxxxxxxxx chromatid xxxx xxxxx x xxxxxxxx spojení xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu x xxxxxx zlomu xxxx xxxxx x spojení xxxx chromatid x xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : xxxxxx, při xxxxxx x xxxxx po X-xxxx replikace XXX xxxxxxx x xxxxxx, xxxxx xxxxxxxxx xxxxx X-xxxx. Výsledkem jsou xxxxxxxxxx xx 4, 8, 16,… chromatidami.

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

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

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx struktury chromozomů xxx xxxxxxxx dělení xx xxxxxx xxxxxxxx; xxxx se xxxx xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx jsou xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xx xxxxxxx okamžiku xx xxxxxxxx xx usmrtí. Xxxx xxxxxxxxx xx xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Colcemid®). X xxxxx xxxxxx xxxxx se xxxx xxxxxxxx xxxxxxxxx chromozomů, xxxxxx xx x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx v xxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxx x xxxxxx xxxxxx, xxxxxx xxx použít xxxxxxxx xxxxxx xxxxx xxxx. Měly by xxx použity běžně xxxxxxx laboratorní xxxxx xxxxxxx zdravých pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx xx měla xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx x xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

Xxxxx xxxxxx podmínky xxxxx obecného úvodu x části B, xxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx xxxxxxx xx xxxxxxxx výběrem rozdělí xx xxxxxxxxx xxxxxxx x xxxxxxx, xxxxx xx xxxxxxx zkoušené xxxxx. Xxxxx by xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx jejich polohy xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx alespoň pět xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx zvířatům xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx vehikulech a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky mohou xxx podávány xxxxx xxxx mohou být xxxx xxxxxxx xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by nemělo xxx xxx použitých xxxxxxxx xxxxx xxxxxxx xxxxxx x mělo xx xxx xxxxxxxxx xxxxxxxxx, že reaguje xx xxxxxxxxx látkou. Xxxx-xx xxxxxxx jiná xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx xxx pohlaví. X xxxxxxxx aplikace xxxxxxxx xxxxx by xxxx zvířata xxxxxxxxx xxxxxxx podstoupit identický xxxxxx jako zvířata xx xxxxxxxxx, x xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx vivo xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, xx poskytnou xxxxxxxxxxxxx nárůst nad xxxxxx. Xxxxx pozitivní xxxxxxxx xx měly xxx zvoleny xxx, xxx xxx účinek xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx najevo kódovaná xxxxxxxxxxxx preparátu. Je xxxxxxxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx xxxxx a xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxxx být xxxxxxx xxxxxxxx xxxxx ze xxxxxx chemické xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X okamžiku xxxxxxx xxxxxx xx xxx xxx proveden xxxxx u negativních xxxxxxx, xxxx xx xxxxxxxxxx pouze rozpouštědlo xxxx xxxxxxxxx x xxx jinak podstupují xxxxxx proces xxxx xxxxxxxxxx xxxxxxx, pokud xxxxxx z xxxxxxxxxxx xxxxxxxxxxx údajů x xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx zvířat x xxxxxxxx xxxxx x chromozomovými aberacemi. Xxxxxxx-xx xx xxx xxxxxxxxx kontrolu xxxxx xxxxx, xx nejvhodnějším xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx měly být xxxxxxxxxxxx kontroly použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, že zvolené xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx žádné xxxxxxx nebo mutagenní xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx se xxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx pohlaví. Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx ze xxxxxx xx xxxxxxx xxxxxx x za použití xxxxxxxx xxxxxxx expozice, xxx xxxxxxxxx, že xxxxxxxxxx mezi xxxxxxxxx xxxxxx v xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx pohlaví. Je-li xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx xx zvířaty xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky by xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx látky xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, xxx. xxx xxxxx x xxx den x rozmezí ne xxxx než xxxxxxxx xxxxx, xxx bylo xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx materiálu. Jiné xxxxxx podávání xx xxxx být xxxxxxx xxxxxxxxxx.

Xxxxxx by xxxx xxx xxxxxxxx xx xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxx podané x xxxxxx dni. X hlodavců se xxxxx xxxxxxx po xxxxxx xxxx xx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx normální xxxxx xxxxxxxxx xxxxx (jenž xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx a xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxx xxxxxx na kinetiku xxxxxxxxx cyklu xxxx xxx vliv xx xxxxxxxxx okamžik pro xxxxxxxxx chromozomových xxxxxxx, xxxxxxxxxx se xxxxxxx xxxxx xxxxx xx 24 h od xxxxxxx xxxxxx. Je-li xxxxxxxx xxxxxxxxx xx xxxx xxx jednoho xxx, xxx xx xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx aplikace, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® nebo kolchicin). Xxxx xx xx xxxxxx době xxxxxxx x xxxxxx xxxxx. X xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 x; x xxxxxx xxxxxxxx xx tato xxxx xxxxxxxxx 4 — 5 h. X xxxxxx dřeně xx odeberou buňky x xxxxxxxxx xx xx chromozomové xxxxxxx.

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, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx studii (5). X případě xxxxxxxx xx xxx první xxxxx xxxxxxx xxx xxxxxx dávky. Xxxx xxxxxx xxxxx by xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx vyšší xxxxx xx xxxxx xxx stejném xxxxxx xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Látky xx specifickou xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx by xxx xxxxxxxxx případ od xxxxxxx. Xxxxxxxx xxxxx xxxx xxx také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx v xxxxxx xxxxx některé xxxxxx xxxxxxxx (např. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx x xxxxxx dni nevykazuje xxxxx xxxxxxxxxxxxx toxické xxxxxx x není-li xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X déle xxxxxxxxxx xxxxxx je limitní xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx xxx 14xxxxx aplikaci je xxxxxxx xxxxxx 1000 xx/xx xxxxxxx hmotnosti/den. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx vhodnou xxxxxxxxx kanylou, nebo xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx xxxxxxxx xxxx x odůvodněných xxxxxxxxx xxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx může xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx xxxx injekčně, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Objem xx xxxxx překročit 2 xx/100 g xxxxxxx hmotnosti. Použití xxxxxxx objemů, než xx xxxxxxx objem, xxxx být zdůvodněno. Xx na xxxxxxxx x žíravé látky, xxxxx obvykle při xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx

Xxxxx po xxxxxxxx xx odebere xxxxxx xxxx, xxxxxxxxxxxx xx a fixuje. Xxxxx se xxxxxxx xx podložní sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx měřítko xxxxxxxxxxxx xx měl xxx x všech exponovaných xxxxxx (xxxxxx pozitivních xxxxxxx) a u xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx, x xx xxxxxxx u 1000 buněk xx xxxxx xxxxx.

X každého xxxxxxx xx mělo xxx analyzováno alespoň 100 xxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx velký xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx kontrol xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx xxxxxxx xx chromozomálním xxxxxx xxxx xx ztrátě xxxxxxxxxx u xxxxx xxxxx v metafázi, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx xxxxxxxxxx zvířata xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Pro xxxxx xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx, počet aberací xx buňku x xxxxx buněk x xxxxxxxxxxxxx aberací (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx exponované x xxxxxxxxx skupiny xx xxxx xxx xxxxxxx různé typy xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx počtem x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx xxxxxx xx xxxxxxxxxx do celkové xxxxxxxx xxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x odpovědi mezi xxxxxxxxx, xxxxx být xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx zkombinovány.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx kritérií, xxxx. nárůst relativního xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx na dávce xxxx jasný xxxxxx xxxxx xxxxx s xxxxxxxxx pro xxxxxxx x xxxxxxx dávkou x x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx zkoušky mohou xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Statistická xxxxxxxxxx xx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx pro pozitivní xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravami xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Nárůst xxxxx buněk s xxxxxxxxxxxxxxxxxxx chromozomy může xxxxxxxx, xx zkoušená xxxxx má xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (7, 8).

Zkoušená xxxxx, xxxxx xxxxxxxx xxxxxxxxx výše uvedená xxxxxxxx, se xxxxxxxx x tomto xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, v ojedinělých xxxxxxxxx neumožní xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx xxxxxx xx xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx chromozomové xxxxxxx xx xxxx znamenají, xx xxxxxxxx xxxxx xxxxxxxx x kostní xxxxx testovacího druhu xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxx dřeni xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx do xxxxxxxx xxxxx, xxxx xxxxxxxxxx xx xxxxxx xxxxx (např. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

- xxxxxxxxxxx a xxxxxxx zkoušené xxxxx x rozpouštědle/vehikulu, je-li xxxxx.

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- xxxxx, xxxxx x pohlaví xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- individuální xxxxxxxx zvířat xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx hmotnosti, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- xxxxx xx xxxxxx pro xxxxxxxx rozsahu, pokud xxxx xxxxxxxxx,

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, zda xx xxxxxxxx látka xxxxxxx xx xxxxxxxx oběhu xxxx xx xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx a xxxx,

- podrobný xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx xxxxx xxxxxxxxxxx metafázi, její xxxxxxxxxxx a xxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx analyzovaných xxxxx na xxxxx xxxxx,

- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- mitotický xxxxx,

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx každé xxxxx,

- celkový počet xxxxxxx xx xxxxxxx xx xxxxxxxxx hodnotami x xxxxxxxxxxxx odchylkami,

- xxxxx xxxxx x xxxxxxxxx ve skupině xx xxxxxxxxx hodnotami x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- údaje x xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxx údaje x xxxxxxxxx xxxxxxxx x xxxxxxxxx, středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Adler, X. X. (1984), Xxxxxxxxxxx Xxxxx xx Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: a Xxxxxxxxx Xxxxxxxx, X. Xxxxxx, X. X. Xxxxx (xxx), XXX Xxxxx, Xxxxxx, Washington X. X., 275-306.

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

3) Xxxxxxx, X., Chandley, X., Xxxxx, J., Gatehouse, X. G., Xxxxxxx, X., Xxxxxxxxx, L. (1990), Xx vivo Xxxxxxxxxxx Xxxxxx, xx: X. J. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Recommended Xxxxxxxxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx I revised, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Chester, Melbourne, Xxxxxx, 115-141.

4) Tice, X. X., Hayashi, X., XxxXxxxxxx, X. X., Xxxxxxxx, X., Xxxxxx, D. X., Xxxxxx, X. X., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X. J., Romagna, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Report xxxx xxx Working Xxxxx xx the xx vivo Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, R. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, P. A., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. G., Hodson-Walker, X., Xxxxxx, X. X., Kirkland, D. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Society/UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, D., Xxxxxxxx, X., Amphlett, G. X., Xxxxx, G., Xxxxxxxx, R., Xxxxxxx, X., Papworth, D. X., Savage, X. X. K. (1989), Xxxxxxxxxxx Analysis xx Xx xxxx Cytogenetic Xxxxxx, xx: UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxxxx Xxxx III. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Xxxx Xxxx, X. J. Xxxxxxxx (xx.) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 184-232.

7) Xxxxx-Xxxxx, C. (1983), Xxxxxxxxxxxxxxxxx xx Chinese xxxxxxx xxxxx during xxxxx-xxxxxxxxx-xxxxxxx G2 xxxxxx, Xxxxxxxxxx Xxx., 119, 403-413.

8) Huang, Y., Xxxxxx, C., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx endoreduplication xx Xxxxxxx hamster xxxxx, Xxxxxx Xxx., 43, 1362-1364."

XXXXXXX 4X

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

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX TG 474 — Xxxx xxxxxxx erytrocytárních mikrojader xx vivo (1997).

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxxx pro xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx mitotického xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx, x xx xxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxx x kostní xxxxx x/xxxx xxxxx periferní xxxx, xxxxxxx hlodavců.

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

Xxxx xx erytroblast xxxxxx dřeně xxxx xx xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxx jádro xx xxxxxxxx x xxxxxxxxxx, xxxxx xxx xxx xxxxx xxxxxxxxx, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx mikrojader xx x xxxxxx xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx xxxxxx xxxxx. Xxxxxx výskytu xxxxxxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xx xxxxxxx indukovaného xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx je rutinně xxxxxxxxx kostní dřeň xxxxxxxx, poněvadž xxxx xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Stanovení xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx x xxxxxxxxx xxxx xx xxxxxxxxxx xxxxxxxxxx x xxxxxxxxxxx xxxxx, u něhož xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx odstraňovat xxxxxxxxxx x xxxxxxxxxx, xxxx xxxxxxxxxx citlivost detekovat xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxxxxxxxx xxx xxxxxxxx xxxxx xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx přítomnosti xxxx xxxxxxxxxxxxx xxxxxxxxxxx (kinetochorní) XXX x xxxxxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx v xxxxxxxxx xxxx, xxxxx obsahují xxxxxxxxxx, xxxxxxxxxxx xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx lze rovněž xxxxxx xxxx konečný xxxxxxxx zkoušky, xxxxxxxx xxxx zvířata xxxxxxxxxx xxxxx xxxxx nebo xxxx.

Xxxxx test xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx zvláště xxxxxx x posouzení xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx in vivo, xxxxxxxxxxxxxxx x procesy xxxxxxxx XXX, třebaže xx xxxxx xxxxx x xxxxxxx xxxxx x tkání, xxxxx x z genetického xxxxxxxx. Zkouška xx xxxx je xxxxxx xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx v xxxxxxxxx xx xxxxx.

Xxxxxxxx existuje xxxxx x xxx, xx xx xxxxxxxx xxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (oblasti) chromozomu, x xxx (x xxxx) se xxxxx xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx k pólům xxxxxxxxx xxxxx.

Xxxxxxxxxx : xxxx xxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx x vedle xxxx, xxxxxxxxx xxxxx xxxxxxxx mitosy (xxxxxx) xxxxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxx chromozomy.

Normochromatický xxxxxxxxx : zralý xxxxxxxxx xxxxxxxxxxxx xxxxxxxx, xxxxx xxx rozlišit xx xxxxxxxxx xxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

Xxxxxxxxxxxxxxx erytrocyt : xxxxxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx obsahuje ribozomy, x může xxx xxxx rozlišen xx xxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx selektivním xxx xxxxxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx dřeně xx xxxxxxx xx xxxxxxx xxxxxxxx xx expozici xxxxxx, xxxxxxx se xxxxxx xxxx, xxxxxxxx xx xxxxxxxxx x xxxxxx se (1, 2, 3, 4, 5, 6, 7). Xxx použití periferní xxxx se krev xx xxxxxxx xxxxxxxx xx xxxxxxxx odebere, xxxxxxxxxx se xxxxxxxx xxxxxxxx a obarví xx (4, 8, 9, 10). Při xxxxxxxx x periferní xxxx xx xxxx xxxx poslední xxxxxxxx x sklizením xxxxx xxxxxxxx xx xxxxxxxxx xxxx. Preparáty xxxx xxxxxxxxxxx xx xxxxxxxxxx xxxxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx xxxxxxx xxxxxx dřeně xx xxxx xxxxxxxxx zvíře xxxxxxxxxx xxx nebo xxxxxx, xxxxxx lze xxxxxx jakýkoli xxxxxx xxxxx druh. Xxx xxxxxxx periferní xxxx xx xxxxxxxxxx myš. Xxx však použít xxxxxxxx xxxxxx xxxx xxxxx xx xxxxxxxxxxx, xx jde o xxxx, x xxxxx xxxxxxx neodstraňuje xxxxxxxxxx x xxxxxxxxxx, nebo xxxx xxxxxxxxxx dostatečnou xxxxxxxxx xxxxxxxxx činitele, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx xx xxxx být xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx u xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx xxxxxxx xx xxxxxxxx výběrem rozdělí xx xxxxxxxxx skupinu x xxxxxxx, x xxx xx xxxxxxx xxxxxxxx. Xxxxxxx se xxxxxxxxxxx xxxxxxxxxxxx. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx alespoň pět xxx xxxxxxxxxxxxx. Xxxxx xx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx rozpuštěny nebo xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx před podáním xxxxxxx. Měly xx xxx xxxxxxx čerstvě xxxxxxxxxx zkoušené xxxxxxxx xxxxx, xxxxx xxxxx x jejich stálosti xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxxxx mít xxx použitých úrovních xxxxx xxxxxxx xxxxxx x mělo xx xxx xxxxxxxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx. Jsou-li xxxxxxx xxxx xxx xxxxx rozpouštědla/vehikula, mělo xx xxx jejich xxxxxxxx podloženo údaji x xxxxxx kompatibilitě. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. S xxxxxxxx aplikace xxxxxxxx xxxxx xx měla xxxxxxx kontrolní xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx in xxxx xxx expozičních xxxxxxxx, u nichž xx očekává, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx pozadí. Xxxxx xxxxxxxxx xxxxxxxx by xxxx být zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx při odečtu xxxxxxx ihned xxxxxx xxxxxxxx identifikace xxxxxxxxx. Xx xxxxxxxxxx, aby xxxxxxxxx kontrola xxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx xxx xxxxx x tomto xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx navíc může xxx xxxxx x xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou-li x dispozici. Příklady xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx 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 okamžiku xxxxxx xx měl xxx xxxxxxxx xxxxx u xxxxxxx xxxxxxxxx kontroly, xxxxx je aplikováno xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x dosavadních xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx údaje x xxxxxxxxxxx zvířat a xxxxxxxx xxxxx x xxxxxxxxxx. Provádí-li xx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx okamžikem xxxx xxxxxxx odběru. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx rozpouštědlo/vehikulum xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx xxxx xxxx xxx xxxx xxxxxxxxx xxxxxxxx přijatelný také xxxxxx xxxx odebraný xxxx xxxxxxxx, xxxxx xxxx u xxxxxxxx xxxxxx x xxxxxxxxx xxxx (např. 1 — 3 xxxxxxxx) xx předpokladu, xx xxxxxxxx xxxxx xxxxx x rozpětí, xxxxx xx na xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx musí xxxxxxx x alespoň pěti xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx pohlaví (11). Xxxxxxxx jsou v xxxx studie x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, jež xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx rozdíl x xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx expozice člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx xxxxxxxxx xxxxx standardní xxxx (xx. jednu, dvě xxxx tři xxxxxxxx x intervalu 24 xxxxx). Xxxxxx xx xxxxxx s xxxxxxxxxxxx xxxxxxx podávání xxxx xxxxxxxxxx, pokud xx x xxxxxx xxxxxx xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –x xxxxxxx xxxxxxxxxxx studií — xxxxx byla xxxxxxxxx xxxxxxxx xxxx byla xxxxxxxxx limitní xxxxx x xxxxxxxx pokračuje xx xx xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx být podávány xxxx xx xxxx xxxxxxx, xxx. dvě xxxxx x xxx xxx v xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx xxx proveden xxxxx xxxxxxx:

x) xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx xxxxxx. Vzorky xxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx provede nejdříve 24 hodin xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 hodin xx xxxxxxxx x x xxxxxxxxxx odstupem xxxx odběry. Xxxxx xxxxx xxx 24 xxxxx po xxxxxxxx xxxx být xxxxxxxxx. Xxxxxx periferní xxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 36 hodin xx xxxxxxxx a xxxxxxxx xxxxxxxxxx 72 xxxxx xx xxxxxxxx x po xxxxxxxxxxxx xx xxxxxx odpovídající xxxxxx. Xx-xx po xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx xxxxx xxxxx;

x) xxxx-xx podávány xxx xxxx více dávek xxxxx (např. xxx xxxx více dávek x intervalu 24 xxxxx), xxxx by xxx xxxxxx xxx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx po 18 xx 24 xxxxxxxx po xxxxxxxx xxxxxxxx a při xxxxxxx xxxxxxxxx krve xxxxxx po 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).

Xxxxx potřeby xxxxx xxx navíc použity xxxx doby xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se kvůli xxxxxxxxxxx xxxxxxxx dostupných xxxxx xxxxxx xxx xxxxxxxx xxxxxxx dávek, xxxx by xxx xxxxxxxxx xx stejné xxxxxxxxxx, se xxxxxxx xxxxxx, xxxxxx, pohlavím x za stejného xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx studii (13). X xxxxxxx toxicity xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx xxxxxxxx rozpětí xxxx maximální xx xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako dávka xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že vyšší xxxxx by xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx vyhovovat x xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší xxxxx xxxx xxx také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x xxxxxx xxxxx některé xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx v xxxxxxxxx xxxx).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx o xxxxxxx 2000 xx/xx xxxxxxx hmotnosti podanou xxxxxxxxxxx nebo xx xxxx xxxxxxx v xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx základě xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx úplná xxxxxx xx xxxxx xxxxxxxx xxxxx za xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx je limitní xxxxxx xxx 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx x xxx xxxxx než 14xxxxx aplikaci xx xxxxxxx xxxxxx 1000 xx/xx xxxxxxx hmotnosti/den. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx znamenat potřebu xxxxxx x limitní xxxxxxx vyšší úroveň xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx nebo vhodnou xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx injekcí. Jiné xxxxxxx podávání jsou xxxxxxxxxx x odůvodnitelných xxxxxxxxx. Maximální objem xxxxxxxx, xxxxx může xxx xxxxxxxx xxxxx xxxxxxxxx sondou nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Až na xxxxxxxx x xxxxxx xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx zesílené xxxxxx, xx měla xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx xxxxxxxxx x xxxxxx xxxx xxxxx xxxxx po xxxxxxxx. Xxxxx se odeberou x xxxxxx nebo xxxxx x xxxxxxxxxx xxxxxxxx xx xxxxxxxxx x xxxxxx. Xxxxxxxxx xxxx xx xxxxxxx x xxxxxx xxxx xxxx xxxx xxxxxx xxxxxx xxxx. Krevní xxxxx xx xxxxx xxxxxxxxxxxx obarví (8, 9, 10), xxxx xx xxxxxxxx xxxxxxxxx xxxxxxxx x poté xx xxxxxx. Xxxxxxxx xxxxxxx xxxxxxxxxxxx pro XXX (xxxx. akridinová xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx vyhnout xxxxxxxx xxxxxxxxxx xxxxxxxx s xxxxxxxx barviva xxxxxxxxxxxxxx xxx XXX. Xxxx xxxxxx nebrání použití xxxxxxxxxxx barviv (např. Xxxxxx). Přídavné systémy (xxxx. xxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx použít xx xxxxxxxxxxx, xx xx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx xxx xxxxxxxxx mikrojader x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx xx stanoví xxxxx nezralých xxxxxxxxxx x xxxxxxxxx (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx se x xxxxxxx xxxxxx xxxxx použije xxxxxxx xxxxxxx 200 erytrocytů x x případě xxxxxxxxx xxxx xxxxxxx 1000 erytrocytů (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx kontrol, by xxxx xxx xxxx xxxxxxxx xxx mikroskopem xxxxxxxxx xxxxxxxx. X xxxxxxx zvířete xx xxxxxxx alespoň 2000 xxxxxxxxx erytrocytů na xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxx erytrocytů xx xxxxxx xxxxxxxxxx. Xxx mikroskopické analýze xx xxxxx xxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx než 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx nepřetržitě xxxxx xxxxx xxxx xxxx, xxx také xxxxxxxx na výskyt xxxxxxxxxx alespoň 2000 xxxxxxx xxxxxxxxxx xx xxxxx xxxxx. Systémy xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx x xxxxxxxxx cytometrická xxxxxxx xxxxxxx xxxxxxxx) jsou xx odpovídajícím xxxxxxxxxx x xxxxxxxx přijatelnými xxxxxxxxxxxxx manuálního hodnocení.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx jednotlivá xxxxxxx xx xxxx být xxxxxxxxxx xx formě xxxxxxx. Experimentální xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxxxxxxxx xxxxx xx měl xxx xxxxxx počet xxxxxxxxxxx xxxxxxxxx erytrocytů, xxxxx xxxxxxxxx erytrocytů s xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx jsou zvířata xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx déle, xxxx xx být xxxx xxxxxxx údaje x xxxxxxx erytrocytech, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx xxxxx xx xxxxx xxxxx xxxxxxxxx xxxxxxxxxx z celkového xxxxxxxx xxxxxxxxxx a xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x procentech. Neexistuje-li xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, mohou být xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx několik kritérií, xxxx. xxxxxx xxxxx xxxxx s mikrojádry x závislosti na xxxxx nebo jasný xxxxxx xxxxx xxxxx x mikrojádry pro xxxxxxx s xxxxxxx xxxxxx a x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Při xxxxxxxxx výsledků zkoušky xxxxx být xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (18, 19). Statistická xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím faktorem xxx pozitivní odpověď. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x úpravou experimentálních xxxxxxxx.

Xxxxxxxx látka, xxxxx xxxxxxxx nesplňují xxxx xxxxxxx kritéria, xx xxxxxxxx x tomto xxxxxxx xx nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx poskytne xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx mikrojádra, xxx xxxx xxxxxxxxx xxxxxxxxxxxxxx poškození xxxx xxxxxxxxx mitotického aparátu xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx látka xx xxxxxxxx xxxxxxx xxxxxxxxxxx mikrojádra x xxxxxxxxx xxxxxxxxxxxx testovacího xxxxx.

Xxxx by xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx se xxxxxxxx xxxxx nebo xxxx xxxxxxxxxx dostanou do xxxxxxxx oběhu, xxxx xxxxxxxxxx xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x pohlaví zvířat,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx na xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx hmotnosti, xxxxxxx hodnota a xxxxxxxxxx odchylka pro xxxxxx skupinu.

Zkušební xxxxxxxx:

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

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- údaje x přípravě xxxxxxxx xxxxx,

- údaje x xxxxxxxx zkoušené xxxxx,

- xxxxxxxxxx způsobu podávání,

- xxxxxxxxx xxxxxx xxxxxxx, xxx xx xxxxxxxx xxxxx dostala xx xxxxxxxx xxxxx nebo xx cílové xxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxxx xxxx (ppm) na xxxxxxxxxxxx dávku (mg/kg xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx o xxxxxxx xxxxxx x xxxx,

- xxxxxxxx popis rozvrhu xxxxxxxx a xxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxx mikrojader x xxxxxxxxx erytrocytech,

- xxxxx xxxxxxxxxxxxx buněk xx jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx studie xx pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx xxxxxxx xxxxxxxxxx xxx každé xxxxx,

- xxxxxxx xxxxxxx ± xxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx erytrocytů s xxxxxxxxxx xx xxxxxxx,

- xxxxx možnosti závislost xxxxxxxx na dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x metody,

- xxxxx x xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxxx, X. X. (1973), X Xxxxx Xx xxxx Xxxx for Chromozomal Xxxxxx, Mutatation Res., 18, 187-190.

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

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

4) Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, M. X., Xxxxxxxx, X. F., Xxxxxx, J. X. (1990), Xxx Xx xxxx Xxxxxxxxxxxx Assay xx Xxxxxxxxx Xxxx Xxxxxx and Xxxxxxxxxx Xxxxx. X xxxxxx xx xxx X. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) XxxXxxxxx, X. X., Schlegel, X., Xxxx, X. X., Xxxx, X. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Erythrocytes: A Xxxxx Xxxxxx xxx Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Xxxxxxxx Xxxxxxx xx Mice, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx xx Xxxxxxxxxx, ed. X. X. Xxxxx, X. X. Xxxxxxx, T. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) MacGregor, X. X., Heddle, X. A. Xxxx, X., Margolin, X. X., Xxxxx, X., Xxxxxxxx, X. X., Xxxx, X. R., Xxxx, X. (1987), Xxxxxxxxxx for xxx Xxxxxxx xx Micronucleus Xxxxxx xx Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) XxxXxxxxx, X. X., Xxxx, C. X., Xxxxxx, X. X., Xxxxxx, X. X. (1990), The xx xxxx Erythrocyte Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Steady State Xxxxxxxxx Assay Xxxxxxxxxx xxx Permits Integration xxxx Toxicity Xxxxxxx, Xxxxxx. Xxxx. Xxxxxxx. 14, 513-522.

8) Xxxxxxx, X., Morita, X., Xxxxxx, X., Sofumi, X., Xxxxxxxx, X. Xx. (1990), The Xxxxxxxxxxxx Xxxxx xxxx Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxxx Xxxxx Xxxxxxxx Xxxxxx-Xxxxxx Slides, Xxxxxxxxxx Xxx., 245, 245-249.

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

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx for the Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: Xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxx Group xx xxx Xxxxxxxxxxxxx Xxxxxxx Society xx Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx xxx xxx xxxxx-xxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, M., Xxxx, X. X., XxxXxxxxx, X. X., Xxxxxxxx, X., Blackey, D. X., Xxxxxx-Xxxxxxx, M., Xxxxxx, Xx. X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxxxx Xxxxx, Xxxxx. Res., 312, 293-304.

12) Higashikuni, N., Xxxxx, X. (1995), Xx xxxxxxx, xxxxxxxxxxx xxxxxxxx xxxx xx 30 ± 6 x after double xxxxxx xx xxx xxxxx peripheral xxxxxxxxxxxx xxxx, Mutagenesis, 10, 313-319.

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

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

15) XxxXxxxxx, X. T., Xxxx, X. M., Xxxxxxxx, R. G. (1983), A Xxxxxx Xxxxxxxxxxx Staining Procedure xxx Xxxxxxxxxxx and XXX xx Xxxxxxxxxxxx Xxxxx Xxxxxxx 33258 xxx Pyromin X, Xxxxxxxx Xxx., 120, 269-275.

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

17) Gollapudi, X., XxXxxxxx, X. X. (1995), Xxxxxx Xxxx xxx xxx Xxxxxxxxxx xx Polychromatic xx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxx xx xxx Xxxx Marrow Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 347, 97-99.

18) Xxxxxxx, X., Ashby, X., Xxxxxxx, J., Xxxxxxxx, X., Xxxxxxxxx, X. X., Henderson, L. (1990), Xx xxxx Xxxxxxxxxxxx Xxxxx, xx: X. X. Kirkland (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Guidelines for Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, revised, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Anderson, X., Xxxxxxxx, X., Xxxxxxxx, G. X., Xxxxx, G., Ferguson X., Xxxxxxx, X., Xxxxxxxx, X. G., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Cytogenetic Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Xxxxxxx. Xxxxxx, Part XXX, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."

PŘÍLOHA 4X

"X.13/14 MUTAGENITA — ZKOUŠKA XX XXXXXXXX MUTACE S XXXXXXXXXX

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX TG 471 — Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx xx reverzní xxxxxx x bakteriemi xx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Escherichia coli, x detekci bodových xxxxxx, xxxxx zahrnují xxxxxxxxxx, adici x xxxxxx xxxxxxx xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Podstata této xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xxxxxxx x xxxxxxx xxxxxx, xxxxx xxxxxxxxx xxxxxx xxxxxxxx v xxxxxxxxxxx xxxxxxx a xxxxxxxx tak funkční xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx aminokyseliny. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx xxxx xxx xxxxxxxxxx růst x xxxxxxxxxxxxx aminokyselin, xxxxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx kmenem.

Bodové mutace x xxxxxxx xxxx xxxx příčinou mnoha xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx xxxxx xxxxxx x tom, xx xxxxxx xxxxxx v xxxxxxxxxx x v xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx mají xxxxx xx xxxxxx xxxxxxxx u xxxxxxx x u pokusných xxxxxx. Zkouška na xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxx, xxxxxxxxxx a xxxxxxxxx xxxxxx. Mnoho testovacích xxxxx má xxxx xxxxxxxxxx, xxxx nimž xxxx citlivější xx xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx xxxxxxxx DNA xx reverzních místech, xxxxxxx permeability buněk xxx velké molekuly x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxx xxxxxxxx reparačních xxxxxxx XXX náchylných k xxxxxx. Xxxxxxxxxxxx testovacích xxxxx může xxxxxxxxxx xxxxxxx užitečné informace x typech mutací, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx činiteli. Xxx xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx x dispozici xxxxx xxxxxxxx databáze xxxxxxxx pro širokou xxxxx xxxxxxxx a xxxx byly vyvinuty xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx xxxxxxxx sloučenin, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx také xxxxxx xxxx, část B.

1.2 XXXXXXXX

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx x xxxxx vyžadujícím xxxxxxxxxxxxx (xxxxxxxx xxxx. xxxxxxxxx), xxxxxxx vzniká xxxx xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx xxxx činitele, xxx xxxxxxxxx změny x xxxxxx XXX. Xxx xxxxxxx xxxxxxxxxx mutací xx xxxxx tyto xxxxx xxxxxxxxxx xx xxxxx xxxxxxx mutace xxxx xxxxx místě xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx xxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx xxxx xxxxxx jednoho nebo xxxx párů xxxx XXX x xxxxxxxx xxx čtecí rámec XXX.

1.3 XXXXXXX ÚVAHY

Při xxxxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx se xxxx xx xxxxx xxxxx faktory, jako xxxx xxxxxx, metabolismus, xxxxxxxxxxxx struktura x xxxxxxxxx xxxxxxx DNA. Xxxxxxx xxxxxxxxx xx xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx nemohou xxxxx xxxxxxxxx xxxxxxxx xx xxxx x savců. Xxxxxxx tedy neposkytuje xxxxxx xxxxxxxxx x xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx látky xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx s bakteriemi xx xxxxxxxxx využívána xxx počáteční vyšetření xxxxxxxxxxx xxxxxxxx, x xxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxxx, xx xxxxx xxxxxxxxxx xxxxx, xxxxx jsou x xxxx zkoušce xxxxxxxxx, vykazuje mutagenní xxxxxxxx x x xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx činitelů, xxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx. Příčiny xxxxxx xxxxxxxxxxx lze xxxxxxxxx xx xxxxxxxxxx xxxxxx detekovanéhokonečného jevu, x xxxxxxxxx x xxxxxxxxxxx aktivaci nebo x xxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx na xxxxxxxxxx, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xxxxxx xxx xxxxxx xxx xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx xxxxxxxxxxx) x xxx xxxxxxxx xxxxx, x xxxxx xx xxxxxxxxxxx (xxxx x xxxxx xx ví), xx xxxxxxxxxx xxxxxxxx xx replikačního xxxxxxx xxxxx savců (xxxx. xxxxxxx xxxxxxxxxx topoisomerasy x xxxxxxx analogy xxxxxxxxxx). X xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx xxxxx xxxxxxxxx, pro něž xx tato xxxxxxx xxxxxxxxx, xx xxxxxxxxxxxx xxx xxxxx, xxxx xxxxxxxx xxxxxxxxx. Xxxxxx xx xxxxxxxx třídě x xxxxxxxx xxxxx xxxxxxxxxxx, jež xxxxxx xxxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx mechanismy, xxxx xxxxxxxxxx, které v xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4 XXXXXXXX ZKUŠEBNÍ METODY

Suspenze xxxxxxxxxxxxx xxxxx jsou xxxxxxxxx zkoušené xxxxx, x to xx xxxxxxxxxxx vnějšího xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx x xxx xxxx. Xx xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx x vrchním xxxxxx x xxxxx se xxxxxxx xx xxxxxxxxx xxxx. X xxxxxxxxxxxx xxxxxx se zkoušená xxxx xxxxxxxx a xxxx se před xxxxxxxxx na xxxxxxxxx xxxx smíchá x xxxxxxx agarem. Xxx xxxx technikách xx xx xxxx nebo xxxxx dnech inkubace xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxx xx xxxxxxxx s xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

Xx popsáno xxxxxxx xxxxxxx provedení xxxxxxx xx reverzní xxxxxx s bakteriemi. Xxxx běžně používané xxxxx xxxxxxxxxx xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx test (9, 10) x xxxxxxxxx xxxxxx (11). Xxxxxx pro xxxxxxxx xxxxx a par xxxx popsány (12).

Zde xxxxxxx xxxxxxx xx xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Každá x nich xx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx ní. Xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxx xxxxx xxxxx xx xxxxxxxxxx tříd, do xxxxx xxxxx mezi xxxxx xxxxxx alifatické xxxxxxxxxxx, dvojvazné xxxx, xxxxxxxx, xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, allylové xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx připouští, xx xxxxxx xxxxx xxxxxxxx nelze xxxx xxxxxxxxx xxxxxxxxxxxx postupy, xxxx xx standardní xxxxxxx xxxx xxxx xxxxxxxxxxxx metoda. Měly xx xxx xxxxxxxxxx xx "xxxxxxxx případy" x x xxxxxx xxxxxxx xx xxxxxxx xxxxxxxxxx použít xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (xxxxxxxx s xxxxxxxx postupů xxxxxx xxxxxxx): azobarviva x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx a xxxxxx xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx xx xxxxxxxxxxxx postupu musí xxx xxxxxxx zdůvodněna.

1.5 XXXXX XXXXXXXX METODY

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx kultury xxxxxxxx xx xxxx xxx xxxxxxxxxxx xx xxxxxx xxxxxxxxxxxxx fáze xxxx xx xxxxx xxxxxxxxxxx xxxx xxxxx (xxxxxxxxx 109 xxxxx xx xx). Buňky x xxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx použity. Xx xxxxxxxx, xxx měly xxxxxxx bakterie xxxxxx xxxx xxxxxxxxxxxxxxx bakterií. Xxxx může xxx xxxxxxxx buď xx xxxxxxx dosavadních kontrolních xxxxx x xxxxxxx xxxxxx, nebo xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx xxxxx xx xxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxx je 37 °X.

Xxxx by xxx xxxxxxx alespoň xxx xxxxx xxxxxxxx. Mezi xxxx xx měly xxx xxxxx xxxxx X. xxxxxxxxxxx (XX1535; XX1537 xxxx XX97x xxxx XX97; TA98 x TA100), xxxxxxx xxxxxxx xx xxxxxxx x xxxxxxx laboratořích xxxx spolehlivá x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx S. typhimurium xxxx pár xxxx XX xx xxxxxxxxx xxxxxxxxx xxxxx a xx známo, xx xxxxxx prostřednictvím nelze xxxxxxxxx určité xxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Xxxx xxxxx mohou být xxxxxxxxxx xxxxx E. xxxx XX2 xxxx X. xxxxxxxxxxx TA102 (19), xxxxx mají xx primárním xxxxxxxxx xxxxx xxx xxxx XX. Xxxxxxxxxx xxxxxxxxx xxxxx je xxxx xxxx:

- S. xxxxxxxxxxx XX1535 a

- X. xxxxxxxxxxx TA1537 xxxx XX97x a

- S. xxxxxxxxxxx XX98 a

- X. typhimurium XX100 x

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

Pro xxxxxxx xxxxxxxx způsobujících xxxxxxxxxx vláken XXX xxxx xxx xxxxxxxxx xxxxxxx XX102 nebo xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx reparace XXX, (xxxx. X. xxxx XX2 (pKM101)).

Měly by xxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxxxxx xxxxxxx x xxxxxxxxxx. Potřeba xxxxxxxxxxxxx xxx xxxx xx xxxx xxx xxxxxxxxx pro každou xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx xxx xxxxx X. xxxxxxxxxxx a xxxxxxxxx pro X. xxxx). Podobně by xxxx xxx xxxxxxxxxxxx xxxx fenotypové xxxxxxxxxxxxxxx, xxxxxxxxx xxxxx xxxxxxx xxxxxxxxxx nebo nepřítomnost X-xxxxxxx plasmidů (xx. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, TA100 x XX97x xxxx XX97, WP2 xxxX x XX2 xxxX (xXX101) x xxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxx x xxxxx TA102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx mutací (xx. xxx xxxxxx x X. typhimurium xxxxxxxxxx na xxxxxxxxxxx xxxxxx x uvrA xxxxxx x X. xxxx nebo uvrB xxxxxx u X. xxxxxxxxxxx citlivostí xx xxxxxxxxxxxx xxxxxx) (2, 3). Xxxxx xx xxxx xxxxxx dávat xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx na misce x xxxxxxx četností xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxxxxx xxxxxxx x xxxxxxx x rozmezí xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Médium

Použije xx xxxxxx xxxxxxxxx xxxx (např. xxxxxxxxxx xxxxxxxxx půdu X (Xxxxx-Xxxxxx) x xxxxxxx) x xxxxxx xxxx xxxxxxxxxx xxxxxxxx x xxxxxx xxxx tryptofan xxxxxxxxxx xxxxxxx buněčných xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx měly xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx a xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx hlodavců xxxxxxxxxx xxxxxxxxxxx indukujícím xxxxxx, xxxx je Aroclor 1254 (1, 2) xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (18, 20, 21). Postmitochondriální xxxxxx xx obvykle xxxxxxxxx x xxxxxxxxxxxxx x xxxxxxx 5 xx 30 % xxx. xx xxxxx X9. Xxxxx x podmínky xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx na xxxxx xxxxxxxx xxxxxxxx xxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx použít xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. U xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxx může xxx xxxxxxxxx xxxxxxx redukčního xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).

1.5.1.4 Zkoušená xxxxx nebo xxxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx být xxxx xxxxxxxx xx xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxx xxxxx x testovacím xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje o xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx podezření, xx xxxxxxx se xxxxxxxxx xxxxxx, x xxxx by xxx xxxxxxxxxx x přežitím xxxxxxxx x s xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx podloženo xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při zkoušení xxxxx xxxxxxxxx xx xxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Zkušební xxxxx (viz 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx mají být xxxxxxxxxx při xxxxxxxxx xxxxxxxxxx xxxxxxxx zkoušené xxxxx xxxxx xxxxxxxxxxxx x rozpustnost v xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx toxicitu a xxxxxxxxxxxxx x předběžných xxxxxxxxxxxxx. Cytotoxicita může xxx xxxxxxxxxx snížením xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx zeslabením xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx se xxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx by xxxx xxx xxxxxxxxx xx xxxxxxx viditelného srážení x xxxxxxx xxxxx xx skutečných zkušebních xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxxx xxxxx xx 5 xx/xxxxx nebo 5 μx/xxxxx. X xxxxxxxxxxxxxxx látek xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx nebo 5 μx/xxxxx xx měla xxx xxxxx nebo xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, xxx xxxxx xxxx x xxxxxxx xxxxx pro aplikaci xxxxxxxxxxx. Zkoušené látky, xxxxx xxxx cytotoxické xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, by měly xxx xxxxxxxx až xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

Mělo xx xxx použito xxxxxxx pět různých xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, přičemž při xxxxxx xxxxxxxxxxx by xxxx xxx intervaly xxxx zkušebními xxxx xxxxx xxxxxxxxx polovině xxxxx logaritmické xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx jsou vhodné x případě, kdy xx xxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxx. Zkoušení xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx může být xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx významné xxxxxxxx potenciálně xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Negativní x xxxxxxxxx kontroly

Součástí každého xxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx. Pro xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx koncentrace xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X případě zkoušek x použitím xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxx (xxxxx) pro pozitivní xxxxxxxx xxxxxxx (xxxxxxx) xx xxxxxxx typu xxxxxxxxx kmene bakterií.

Příkladem xxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx x xxxxxxxxxxxx aktivací xxxx xxxx látky:

Látka

Číslo XXX

Xxxxx xxxxx EINECS

9,10-dimethylanthracen

781–43–1

212–308–4

7,12-dimethylbenzo[a]anthracen

57–97–6

200–359–5

benzo[a]pyren

50–32–8

200–028–5

2-aminoanthracen

613–13–8

210–330–9

Cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

Xxxx xxxxx je vhodnou xxxxxxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx metabolické xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx podle XXXXXX

XX Xxxxxx Red 28

573–58–0

209–358–4

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

Xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxx kontroly x xxxxxxx bez xxxxxx xxxxxxxxxxx xxxxxxxx xxxx xxxx xxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxxx

xxxx sodný

26628–22–8

247–852–1

TA1535 x TA100

2-nitrofluoren

607–57–8

210–138–5

TA98

9-aminoakridin

90–45–9

201–995–6

TA1537, XX97 x TA97a

ICR 191

17070–45–0

241–129–4

TA1537, XX97 x TA97a

Kumenhydroperoxid

80–15–9

201–254–7

TA102

mitomycin X

50–07–7

200–008–6

XX2xxxX x TA102

1-methyl-3-nitro-1-nitrosoguanidin

70–25–7

200–730–1

WP2, XX2 uvrA x XX2 uvrA (pKM101)

4-nitrochinolin-1-oxid

56–57–5

200–281–1

WP2, XX2 xxxX a XX2 uvrA (xXX101)

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

3688–53–7

xxxxx xxxxxxxxxx xxxxxxxx

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

Xxxx xx xxx xxxxxxx negativní xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, zpracované xxxxx stejným xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx být neexponované xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.5.3 Xxxxxx

X standardní xxxxxxx xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx aktivace xx xxxxxxx smíchá 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx xxxxxxxxxx pufru x 2,0 ml xxxxxxxx agaru. V xxxxxxx zkoušky x xxxxxxxxxxxx aktivací se xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx obsahující xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x xxxxxxx 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx xxxxx) x xxxxxxx xxxxxx (2,0 xx) x zároveň x bakteriemi x xxxxxxxxx xxxxxx nebo xxxxxxxxx xxxxxxxx. Xxxxx xxxxx zkumavky se xxxxxxxx x xxxxxxx xxxx povrch xxxxxxxxxxx xxxxx xx xxxxx. Xxxx xxxxxxxx se xxxxx xxxxxx xxxx xxxxxxxx.

X xxxxxxxxxxxx metody (2, 3, 5, 6) xx zkoušená xxxxx nebo xxxxxxxx xxxxxx xxxx xxxxxxxxx x xxxxxxx xxxxxx x přelitím přes xxxxxx minimálního xxxxx xx xxxxx xxxxxxx 20 xxxxx xxxx xxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxx (obsahujícím xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x xxxxxxxxx xxxxxx nebo xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx se smíchá 0,05 nebo 0,1 xx zkoušené xxxxx xxxx zkušebního xxxxxxx, 0,1 xx bakterií x 0,5 xx xxxxx S9 nebo xxxxxxxxxx xxxxx x 2,0 xx xxxxxxxx xxxxx. Zkumavky xx xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx xxxxxxxx xx měly xxx při xxxxx xxxxxx xxxxx xxxxxxx 3 xxxxx. Použití xxxx xxxxx je xxxxxxxxxx po xxxxxxxx xxxxxxxxxx. Případná ztráta xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxx.

Xxxxxx xxxx xxxxxx látky by xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, např. x těsně xxxxxxxxxx xxxxxxxxxxxx nádobách (12, 14, 15, 16).

1.5.4 Xxxxxxxx

Xxxxxxx xxxxx v xxxx xxxxxxx by xxxx xxx xxxxxxxxxx xxx 37 °X xx 48 –72 xxxxxxxx. Po xxxxxxxx xxxxxxxxx xxxx xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx misku.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxx xxxxx by měly xxx počty xxxxxxx xxxxxxxxxx připadající xx xxxxx. Měl xx xxx xxxxxx xxxxxx xxxxx kolonií xxxxxxxxxx xxx xx xxxxxxx x negativní xxxxxxxxx (xxxxxxxx xxxxxxxxxxxx a xxxxxxxx neexponovaná xxxxxxxx), xxx xx xxxxxxx x xxxxxxxxx kontrolou. Xxxxx na xxxxxxxxxxxx xxxxxxx, střední xxxxxxx xxxxx kolonií revertantů xx xxxxx x xxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxxx xxx xxxxxxxxx látku x xxxxxxxxx a xxxxxxxxx xxxxxxxx (neexponovanou xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx jasně xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx experimentálních xxxxxxxx. Xxxxxxxxx výsledky xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xx potvrzení xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx zvážena x xxxxxxxxxx experimentech. K xxxxxxxxxx studie, xxxxx xx xxxxx být xxxxxxx, patří xxxxxxx xxxxxxxxxxx, metoda xxxxxxxxxx (xxxxxxxxxx xxxxxxx xxxxxx xxxx xxxxxxxxxxx v xxxxxxxx médiu) a xxxxxxxx metabolické xxxxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx stanovení pozitivního xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. nárůst xxxxx kolonií revertantů xx xxxxx xxx xxxxxxxxx rozsah x xxxxxxx jednoho kmene x metabolickým xxxxxxxxxx xxxxxxxx xxxx xxx xxxx, x xx x xxxxxxxxxx na xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx tohoto xxxxx xxx xxxxx xxxx xxxx koncentrací (23). Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx výsledků. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx významnost xx xxxxxx být jediným xxxxxxxxx xxxxxxxx pro xxxxxxxxx odpověď.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx bez xxxxxx xx to, kolikrát xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx x xxxxxx xxxxx Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx coli bodové xxxxxx xxxxxxxxxx bází xxxx posunem čtecího xxxxx. Negativní xxxxxxxx xxxxxxxxx, xx zkoušená xxxxx není xx xxxxxxxx xxxxxxx xxx xxxxxxxxx druhy mutagenní.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx x xxxxxxx,

- xxxxxxxxxxxxxxx kmene.

Zkušební xxxxxxxx:

- xxxxxxxx xxxxxxxx xxxxx xx misku (xx/xxxxx xxxx μl/misku) x xxxxxxxxxxx xxxxxx xxxxx x počtu misek xx xxxxxxxxxxx,

- použitá xxxxx,

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

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

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

- xxxxx xxxxxxxx závislost xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx analýzy,

- xxxxx o souběžné xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) a xxxxxxxxx xxxxxxxx s xxxxxxxxx, středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) x xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx odchylkami.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxx, X. X., McCann, X., Xxxxxxxx X. (1975), Xxxxxxx of Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Mutagenicity Test, Xxxxxxxxxx Xxx., 31, 347-364.

2) Maron, X. X., Xxxx, B. X. (1983), Xxxxxxx Xxxxxxx xxx the Xxxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Res., 113, 173-215.

3) Xxxxxxxxx, X., Xxxxxxx, S., Xxxxxx, X., Xxxxx, X., Xxxx, X., Xxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxx, X., Zeiger, E. (1994), Xxxxxxxxxxxxxxx for xxx Performance of Xxxxxxxxx Mutation Xxxxxx, Xxxxxxxxxx Res., 312, 217-233.

4) Xxxx, L. X., Xxxxxxx X. X., Xxxxxxx, X. X., Xxx Xxxxx, X. S., Xxxxx, X. X., Xxxxxx, X. F., Xxxxxx, X., XxXxxx, X., Xxxxxxxxxx, K., Xxxxxx, X., Xxx, X. X., Xxx X. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Report of xxx U. S. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

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

6) Xxxxxxxxxx, X., Xxxxxxxx, T., Xxxxx, X., Yahagi, X., Xxxxxx, X., Xxxxxxxx, X. (1980), Factors Xxxxxxxxxx Mutagenicity Xxxxxxxxx Xxxxx, xx: Xxxxx-xxxx Xxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx X. X., Xxxxxx, X. X., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

7) Gatehouse, D. X., Xxxxxxx, X. X., Wilcox, P., Xxxxxxxxx, X. X., Xxxxxx, R. (1980), Xxxxxxxxx Mutation Xxxxxx, xx: Xxxxx Xxxxxxxxxxxx Xxxxx: XXXXX Xxxx 1 Xxxxxxx, xx. X. X. Xxxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, 13-61.

8) Xxxxxxxxxx, X. X., Xxxxxx, X., Xxxxxxx, X. (1987), Xxxxxx Preincubation Xxxxxxxxxxxx Xxxx for Xxxxx, X. Xxxx Xxxxxx., 8, 167-177.

9) Xxxxx, X. X. L., Xxxxxx, W. J., Xxxxxxx, B. A. (1976), Use xx x xxxxxxxxxx fluctuation xxxx xx xxxxxx xxx xxxxxx xx xxxxxxxx, Mutatation Xxx., 38, 33-42.

10) Hubbard, X. X., Xxxxx, X. X. X., Xxxxxxxxx, D., Xxxxxxx, X. X. (1984), Xxx Fluctuation Test xx Xxxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures, 2. xxx., Xxxxxx, B. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (xxx.), Xxxxxxxx, Xxxxxxxxx-Xxx York-Oxford, 141-161.

11) Xxxxxxxx, X. X., Xxxxxxx, P. X. (1981), Xx Examination xx the Xxxxxxxxxxxx Xxxxxxxxxx Assay xxx Xxxxxxxxxxx xxxx Strains xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Araki, A., Xxxxxxx, X., Xxxx, X., Matsushima, T. (1994), Xxxxxxxx Xxxxxx xxx Xxxxxxxxxxxx Testing xx Xxxxxxx Xxxxxxxxx xx Xxxxx x Xxx Xxxxxxxx Xxx, Xxxxxxxxxx Res., 307, 335-344.

13) Xxxxxx, X. X., Xxxx, S. X., Xxxxxxxx, X. X., Reipert, X. X., Vaughan, X. X. (1984), Xxxxxxxxxxxx xx Xxxxxxxxx and Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Dyes xx a Modified Xxxxxxxxxx Assay, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, X., Anderson, X. X., Xxxxxxx, X., Lawlor, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx xxxx xxx Xxxxxxx xx 311 Xxxxxxxxx, Xxxxxxx. Xxx. Mutagen., 19, 2-141.

15) Xxxxxx, X., Xxxxxxxx, X., Xxxxxxx, X. X. (1977), Xxxxxxxxx Activity xx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxx Xxxxx, xx Xxxxxxxx xx Genetic Xxxxxxxxxx, X. Scott, X. Xxxxxxx, X. Xxxxxx (eds.) Elsevier, Xxxxxxxxx, 249-258.

16) Xxxxxx, X. X., Simmons, X. X., Monteith, X. X., Xxxxxxx, X. D. (1987), Xxxxxxxxxxxx Technique xx Xxxxxxx Xxxxxxxxx Activity xx Xxxxxxxx Xxxxxxx Xxxxxxxxx xx xxx Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, X., Xxxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx xxx Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Cycasin xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxxxx Conjugates in Xxxxxxxxxx xxxxxxxxxxx, Cancer Xxx., 39, 3780-3782.

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

19) Wilcox, X., Naidoo, X., Xxxx, X. X., Xxxxxxxxx, D. X. (1990), Comparison xx Xxxxxxxxxx xxxxxxxxxxx XX 102 xxxx Xxxxxxxxxxx xxxx XX2 Tester 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 Activation Systems, xx: Xx xxxxx Xxxxxxxxx Activation in Xxxxxxxxxxx Xxxxxxx, xxx. X. X. xx Xxxxxx xx al. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.

21) Elliot, X. X., Xxxxxx, X. X., Elcombe, C. X., Xxxxxxxxx, X. X., Xxxxxx, G. X., Mackay, J. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-induced X9 xx xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, X., Katzenellenbogen, X., Xxxx, X. X. (1981), Xxxxxxxxxxxxx xx Xxxxxxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 88, 343-350.

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

24) Xxxxx, X. X. X., Green, M. X. X., Middleton, X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, D. X. (1989), Xxxxxxxx xx Xxxx xxxx Xxxxxxxxx Xxxxxx Xxxxxx, in: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Xxxx XX. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Xxxx Data, xx. Xxxxxxxx, X. X., Cambridge Xxxxxxxxxx Xxxxx, 28-65."

PŘÍLOHA 4X

"X.17 XXXXXXXXXX — XXXXXXX NA XXXXXX XXXXXX X XXXXXXX XXXXX XX XXXXX

1. XXXXXX

Xxxx xxxxxx xx replikou xxxxxx XXXX XX 476 — Xxxxxxx xx xxxxxx xxxxxx v xxxxxxx savců xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx genové mutace x xxxxxxx savců xx vitro xxx xxxxxx xxx xxxxxxx xxxxxxxx mutací xxxxxxxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xxxxxx buněčné linie xxxxx buňky xxxxxxx X5178X myší, xxxxxxx xxxxx CHO, XXX-XX52 x V79 xxxxxx xxxxxxxx x xxxxxxxxxxxxxxx xxxxx XX6 xxxxxxx (1). U xxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx xxxxxx xxxx xxx xxxxxxxxxxxxxx (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x xxxxxxxx xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx na xxxxxx TK, XXXX x XPRT xxxxxxxx xxxxx spektrum xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX x XXXX xxxx umožnit detekci xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx delece), xxxxx xxxxx detekovat x XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx xx xxxxx xxx xxxxxx xxxxxxx xxxxxxxxxx linií xxxxx xxxx xxxxxxx xxxxx. Buňky xx xxxxxxxx xxxxx xxxxxxxxxx xxxxx x xxxxxxx x stálosti xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx vitro obecně xxxxxxxx použití xxxxxxxx xxxxxx metabolické xxxxxxxx. Xxxxx metabolický xxxxxxxxx xxxxxx nemůže xxxxx xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx by vedly x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. K xxxxxxxxxx xxxxxxxxx, xxx neodrážejí xxxxxxx xxxxxxxxxx, může xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Tato xxxxxxx xx xxxxxxx xx zjištění xxxxxxx xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx xxxxxxxxxxx savců; xxxx touto xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx absolutní korelace. Xxxxxxxx závisí xx xxxxxxxx xxxxx a xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx nejsou xxxxxxxx xxxxx zkouškou, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx mechanismy, xxxx mechanismy, xxxxx x bakteriálních xxxxxxx xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxx mutace : xxxxxx mutace xxxxxxxxx xxxx xxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxxxxxx aktivity xxxxxxxxxx xxxxxxxx.

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

Xxxxxxxx xxxxxxxx : xxxxx, xxxxx způsobují xxxxx xxxx xxxxxx xxxxxxx xxxx xxxx xxxx xxxx x xxxxxxxx DNA.

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

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

Xxxxxxxxx xxxxxxx xxxx : xxxxxx xxxxx xxxxx x xxxx ve xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx xx xxxx součin xxxxxx xxxxxxxxx růstu v xxxxxxxx x x xxxxxxxxx xxxxxxxx x xxxxxxxxx účinnosti klonování xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxx v xxxxxxxx : nárůst xxxxx buněk x xxxxxxx exprese xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxxxxxxxx : xxxxxxxx xxxxxxxxx xxxxx v xxxxxxxx xxxxxxxx xx xxxxx xx xxxxxxxxxxxx xxxxxxxx xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx na xxxxx xx konci xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx vyjádřeno x xxxxxx k xxxxxxx xxxxxxxxx xxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxx, xxxxx v xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) xxxx xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx analogu xxxxxxxxxx xxxxxxxxxxxxxxxxx (XXX). Xxxxx xxxxxxxxxxx thymidinkinasu jsou xxxxxxx xx XXX, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxx xxxxx buněčné xxxxxx. Xxxxxxxx xxxxx xxxx tedy xxxxxxx xxxxxxxxxxx za xxxxxxxxxxx XXX, zatímco xxxxxxxx xxxxx, xxxxx obsahují xxxxxxxxxxxxxx tuto schopnost xxxxxx. Xxxxxxx xxx x xxxxx s xxxxxxxxxxxx HPRT xxxx XXXX provést xxxxxxx xxxxxxxxxxxxxxx rezistence x 6-xxxxxxxxxxx (XX) nebo 8-xxxxxxxxxx (XX). Vlastnosti xxxxxxxx xxxxx by xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx xx xx zkoušce xx xxxxxx mutace v xxxxxxx xxxxx zkoušen xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx na xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxx xxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, musí xxxx xxx xxxxxxxxx xxxxxxxx systému xxxx xxxxxxx xxx selekci (8).

Xxxxx x xxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxx xxxx vhodnou dobu xxxxxxxxx zkoušené látce xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, x xxxxxxxxxxxxxx xx účelem xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx xxxxxxx fenotypu xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx obvykle xxxxxx xxxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (přežití) xxxx xxxxxxxxxx xxxxxxxxxxx celkového xxxxx xxxxxx xx xxxxxxxx xxxx expozice. Xxxxxxxxxx xxxxxxx xx xxxxxxx v růstovém xxxxx po xxxxxxx xxxx xxxxxxxxxxxxxxxxx xxx xxxxx xxxxxxx xxxxx x typ xxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx exprese xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx se xxxxxxx xxx, xx xx xxxxxx xxxxx xxxxx xxxxx xx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxx a do xxxxx xxx xxxxxxxxxx xxxxxxx, xxx byla xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx xx xxxxxxxxx xxxxxxx. Četnost xxxxxxx xx vypočte x xxxxx xxxxxxxxxx xxxxxxx v selekčním xxxxx x počtu xxxxxxx v xxxxx xxx xxxxxxxxxx činidla.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx xxxxxxx x této xxxxxxx xxxx k dispozici xxxxx typy xxxxx, xxxxxx xxxxxxxx buněk X5171X, CHO, CHO-AS52, X79 xxxx XX6. Xxxx xxxxx x xxxx xxxxxxx xx xxxx vykazovat xxxxxxxxx x chemickým mutagenům, xxxxxxx xxxxxxxxx schopnost x stabilní xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx být xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, x x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx.

Xxxxxxx by xxxx xxx xxxxxxxx xxx, xxx xxxx xxxxxx xxxxxxxxxx citlivost x xxxx. Xxxxx xxxxxxxxx xxxxx, kultur x xxxxxxxxxxx xxxxxxxx xxxxx xx měl tyto xxxxxxxxxx parametry xxxxxxx (14). Xxxxxxxxx xxxxx xxxxx, které xxxxxxx xxxxxxxx a které xxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx, xx měl xxx xxxxxxx xx četnosti xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx xx, xxx xxx xxxxxx počet xxxxx, který je xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx však xxxxxxxxxx, xxx xxxx xxxxxxx xxxxxxx 106 xxxxx. Xxxx xx xxx x xxxxxxxxx dostatečné xxxxxxxxx xxxxx o xxxxxxxx buněčném xxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx podmínky

Pro xxxxxxxxx xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx podmínky (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x vlhkost). Xxxxx xx xxxx xxx zvolena xxxxx xxxxxxxxxx xxxxxxx x xxxx xxxxx použitých xxx xxxxxxx. Xx xxxxxxx xxxxxxxx, xxx xxxxxxxxxx xxxxxxxx byly xxxxxxx tak, aby xxxx xxxxxxxxx optimální xxxx xxxxx během xxxxxx xxxxxxx a xxxxxxxxx jak mutovaných, xxx nemutovaných xxxxx xxxxxx kolonie.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx xx xxxx xxx získávány x xxxxxxxxx kultur, nasazeny xx xxxxxxxxxxxx xxxxx x xxxxxxxxxx xxx 37 °C. Xxxx xxxxxxxx x xxxx xxxxxxx může být xxxxxxxx xxxxxxxxx x xxxxxxx xxx xxxxxxxx xxxxxxxx xxxxx.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx vystaveny xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx indukujícím xxxxxx, jako xx Xxxxxxx 1254 (15, 16, 17 x 18), xxxx xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (19, 20).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % obj. Xxxxx x xxxx metabolického xxxxxxxxxxx xxxxxxx xxxx xxxxxxx na třídě xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. V xxxxxxxxx xxxxxxxxx může xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx exprimujících xxxxxxxxxx aktivační xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx buněčných linií xx xxxx xxx xxxxxxx xxxxxxxxxx (např. xxxxxxxxxxx isoenzymu cytochromu X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Příprava xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx před aplikací xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx xxx xxxxxxx přímo x xxxxxxxxxx xxxxxxxx a/nebo xxxxx být xxxx xxxxxxxx zředěny. Xxxx xx být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx látky, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx být xxxx podezření, xx xxxxxxx se xxxxxxxxx xxxxxx, x mělo xx xxx slučitelné x xxxxxxxx buněk x s aktivitou X9. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul. Při xxxxxxxx látek nestálých xx xxxx by xxxx být xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx při xxxxxxxxx xxxxxxxx koncentrace, xxxxx xxxxxxxxxxxx, rozpustnost x testovacím systému x xxxxx pH xxxx osmolality.

Cytotoxicita xx xxxx být xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x bez xx x xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, xxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x předběžném xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx xxxxxxxxxxx. V xxxxxxx toxicity xx xxxx tyto xxxxxxxxxxx xxxxxxxx rozmezí dané xxxxxxxxx x xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx, což bude xxxxxxx xxxxxxxx, xx xx xx xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. Xx-xx xxxxxxxxx koncentrace xxxxxxxx xx xxxxxxxxxxxx, xxxx by xxx xxxxxxxxx přibližně 10 — 20 % (xxx nejméně 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx celkový růst. X případě xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx být xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 M, xxxxx xxxx, která x xxxx xx xxxxxxxx.

Xxxxxxxxx nerozpustné xxxxx xx měly xxx xxxxxxxx xx x xxxx rozpustnosti za xxxxxxxxxxxx xxxxxxxx, xxxx xx xx tuto xxx. Měla xx xxx stanovena xxxxxxxx xxxxxxxxxxxxx v xxxxxxxx xxxxx, ve kterému xxxx buňky xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx a xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx xx může x průběhu xxxxxxxx x xxxxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx buněk, X9 xxxx, atd. Nerozpustnost xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx xxxx vehikulum) xxxxxxxx xxx x xxxxxxxxxxxx aktivací, xxx xxx xx. Při xxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, která k xxxxxxxxx odpovědi vyžaduje xxxxxxxx.

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx být xxxx xxxxx:

Xxxx metabolické xxxxxxxx

Xxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

Xxx xxxxxx metabolické xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx 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 x 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 použity xxxx xxxx referenční xxxxx xxx pozitivní xxxxxxxx, xxxx. má-li xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxx x 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, EINECS 200–415–9), xxxx být xxxx referenční látka xxxxxx použita. Pro xxxxxxxxx kontrolu xx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx pokud xxxxx xx xxxxxx xxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxx negativní xxxxxxxx tvořené xxxxxx xxxxxxxxxxx xxxxxxx rozpouštědlo xxxx vehikulum x xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx jako xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx kontroly použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Postup

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx xxx za přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx xx xxxx xxxxx vhodnou xxxx (xxxxxxx xx účinná xxxx 3 xx 6 hodin). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx xx xxxxx xxxx xxxx xxxxxxxxx xxxxx.

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

Xxxxxx nebo xxxxxx látky xx xxxx být xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x těsně xxxxxxxxxx xxxxxxxxxxxx nádobách (21, 22).

1.4.3.2 Stanovení přežití, xxxxxxxxxxxxxxxx a xxxxxxxx xxxxxx

Xx xxxxx xxxxxxxxx xxxx se xxxxx xxxxxxx a kultivují xx xxxxxx xxxxxxxxx xxxxxxx x xx xxxxxx umožnění xxxxxxx xxxxxxxx mutantu. Xx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx relativní účinnosti xxxxxxxxx (přežití) xxxx xxxxxxxxxxx xxxxxxxxx růstu xxxxxx xx započne xxxxxxx xx expoziční xxxx.

Xxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (HPRT a XXXX xxxxxxxx alespoň 6 xx 8 xxx, TK alespoň xxx xxx). Xxxxx xxxx kultivovány v xxxxx xx xxxxxxxxx xxxxxxxx (selekčními činidly) x bez něho (xxx nich) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx. Se stanovením xxxxxxxxxxxxxxxx (xxxxxxx pro xxxxxxx četnosti mutantů) xx xxxxxxx xx xxxxx xxxx exprese xxxxxxxxx xx xxxxx xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx xxxxx xxxxxxxxx xx zkoušce X5178X XX+/-, xxxx xx xxx xxxxxxxxx xxxxxxx xx xxxxx xx xxxxxxxxxx kultur (x xxxxxxxx xxxxxxxxx koncentrací) x na negativních x xxxxxxxxxxx kontrolách xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií. Je-li xxxxxxxx xxxxx ve xxxxxxx X5178X TK+/- xxxxxxxxx, xxxx by xxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií xxxxxxxxx xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx za xxxxxxx XX6 TK+/- xxxx xxx xxxx xxxxxxxxx rozdělení kultury xxxxx xxxxxxxxx xxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xx xxxx zahrnovat xxxxxxxxx cytotoxicity x xxxxxxxxxxxxxxxx, počtu kolonií x xxxxxxxx xxxxxxx xxx exponované x xxxxxxxxx xxxxxxx. V xxxxxxx pozitivní xxxxxxxx xx xxxxxxx L5178Y XX+/- se xxxxxxx xxxxxxxxx xxxxxxx x xxxxx xxxxxxxxxxx xxxxxxxx xxxxx (nejvyšší xxxxxxxxx xxxxxxxxxxx) x x xxxxxxxxx a xxxxxxxxx xxxxxxxx za xxxxxxx xxxxxxxx xxxx xxxxxxx — xxxxx xxxxxxx. Xxxxxxxxxxx x cytogenetická xxxxxx xxx xxxxxxx xxxxxxxxx xxxxx kolonie, xxx xxxxxxx tvořících xxxx kolonie byla xxxxxxxx zkoumána (23, 24). Ve zkoušce XX+/- xxxx xxxxxxx xxxxxxxxxxx za použití xxxxxxxx kolonie x xxxxxxxxx xxxxxx (velká) x kolonie x xxxxxxx xxxxxx (xxxx) (25). X mutantních xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx xxxx xxxxxxxx, x xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx má xxxxxxx xxxxxx xx xxxxx xxxxxx xxxx xx xx xxxxxxxxxxxx viditelné xxxxxxxxxxxx aberace. Xxxxxxx xxxxxxx xxxxxxxxx malé xxxxxxx xx xxxxxxx x xxxxxxxxxx xxxxxxx, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx aberace (26). Xxxx xxxxxxx xxxxxxxxx xxxxx xxxxxxx rostou xxxxxxxx tempem jako xxxxxxxx xxxxx x xxxxx xxxxx kolonie.

Mělo xx být xxxxx xxxxxxx (relativní xxxxxxxx xxxxxxxxx) xxxx relativní xxxxxxx xxxx. Xxxxxxx xxxxxxx xx xxxx xxx vyjádřena xxxx xxxxx xxxxxxx k xxxxx xxxxxxxxxx buněk.

Měly xx xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxx. Xxxx by xxxx být všechny xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx odpovědi xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx musí xxx xxxxxxxxx případ od xxxxxxx. Xxx, xxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx považováno xx xxxxx, xx xxxxx xxxxx zdůvodnění. Změna xxxxxxxxx xxxxxx s xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx by xxxx být xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx xxx pro xxxxxxxxxx xxxxxxxx, xxx pro xxxxxxxxx výsledky. X xxxxxxxxxx studie, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x podmínky xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxxxxx xxxxxxx v xxxxxxxxxx xx koncentraci, xxxx xxxxxxxxxxxxxxxx xxxxxx této xxxxxxxx. Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx jako pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx výrok x aktivitě zkoušené xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx xx xxxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x použitých xxxxxxxxxxxxx xxxxxxx xxxxx genové xxxxxx. Reprodukovatelná pozitivní xxxxxxxxx odpovědi xx xxxxxxxxxxx je xxxxx xxxxxxxx. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx neindukuje x xxxxxxxxx xxxxxxxxxxxxx buňkách xxxxx genové xxxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Buňky:

- xxx x zdroj xxxxx,

- počet xxxxxxxxx xxxxxx,

- případně xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- složení xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- koncentrace xxxxxxxx xxxxx,

- xxxxx vehikula x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- případně xxxxxxx xxxxx xxxxx expozice,

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

- xxxxxxxxx a xxxxxxxxx xxxxxxxx,

- xxxxx xxxx xxxxxxx (xxxxxxxx xxxxxx počtu xxxxxxxxxx xxxxx, xxxxxxxxx a xxxxxx xxxxx),

- selekční xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx buněk,

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

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxx xxxxxxx,

- údaje x pH x xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxx xxxxxxxxx,

- velikost xxxxxxx, xxxx-xx xxxxxxxxxxx, xxxxxxx pro negativní x xxxxxxxxx kontroly,

- xxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx mutanty xxxxxxx xxxx xxxxxxx xxxxxxxx X5178X XX+/-,

- xxxxx xxxxxxxx závislost xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

- xxxxxxxxx xxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx kontrole x rozmezími, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- četnost xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Moore, X. X., XxXxxxxx, X. M., DeSerres, X. X., Xxxxxx, X. R. (xxx.) (1987), Xxxxxxx Xxxxxx 28; Mammalian Cell Xxxxxxxxxxx, Xxxx Spring Xxxxxx Laboratory, Xxx Xxxx.

2) Xxx, E. X. X., Xxxxxxx X. X. (1968), Xxxxxxxxx Xxxx Genetics. XX. Chemical Induction xx Specific Xxxxx Xxxxxxxxx in Chinese Xxxxxxx Xxxxx Xx xxxxx, Xxxx. Xxxx. Xxxx. Xxx. U. X. A, 61, 1306-1312.

3) Xxxxx, X. X., Xxxxxx, W. X. (1982), Xxxxxxxx Xxxxx at xxx Xxxxxxxxx Xxxxxx Xxxxx xx Xxxxxxx Xxxxx Xxxxxxxxxxxx, Mutation Xxx. 94, 467-485.

4) Xxxxx, X. X., Xxxxxxxxx-Xxxxx, X., Xxxxx, X. X., Dearfield, X. X. (1989), Xxxxxxxxxxxx Xxxxxx Quantitation at xxx Mouse Lymphoma XX xxx XXX XXXXX Loci, Xxxxxxxxxxx, 4, 394-403.

5) Aaron, X. X., Xxxxxxxxxx, Xx. X. X., (1989), Xxxxxxxxxx of xxx XX52/XXXX xxx xxx XXX/XXXX Assays: Xxxxxxxxxx xx Xxx Xxxx Candidates, Xxxxxxxxxx Xxx. 223, 121-128.

6) Xxxxx, X. X., Xxxxxxxxxx, G., Glatt, X. X., Xxxxx, X., Xxxxx, X., Xxxxxxxxxx, Xx. X. X., Xxxxxx, J., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Xxxx Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Report. Xxxxxx xx the International Xxxxxxxx on Xxxxxxxxxxxxxxx xx Genotoxicity Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Scott, X., Galloway, X. X., Xxxxxxxx, R. X., Xxxxxxxx, M., Xxxxxxx, X., Ashby, X., Xxxx, B. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

8) Xxxxx, X., McCuen, X., Xxxxxxx, J. X. X., Xxxxx, X., Xxxxxxxxx, X. X. (1983), Xxxxxxxx Xxxx Xxxxxxxxx in X5178X Cells xx Xxxxxxx. A Report xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 115, 225-251.

9) Xx, X. X., Gupta, X. X., Xxxxxxx, X. X., Wasson, J. X. (1988), X Xxxxxx xxx Xxxxxxxx xx the Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Transferase Xxxxxx xx Xxxxxxxxx xxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx: A Xxxxxx xx Xxxxx XXX xx the U. X. Environmental Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Res., 196, 17-36.

10) Xx, X. X., Carver, J. X., Xxxx, X. X., Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. X., X'Νxxxx, X. X., Xxxxxx, J. X., Xxxxxxxxxx, X. X. Jr., Xxxx, X. X. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx of xxx Xxxxxxx Hamster Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Mutatation Xxx., 189, 135-141.

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

17) Xxxxx, D., Johnson, X. X., Spector, X. X. S., Xxxxxx A. X., Xxxxx M. X. X. (1979), Xxxxxxxxxx xxx Characterisation xx xxx X5178X/XX+/--Xxxxx Lymphoma Xxxxxxx Xxxxx System, Xxxxx. Res. 59, 61-108.

18) Maron, X. X., Ames, X. X. (1983), Xxxxxxx Xxxxxxx xxx xxx Xxxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Xxx. 113, 173-215.

19) Xxxxxxx, X. X., Combes, R. X., Xxxxxxx, C. X., Xxxxxxxxx, D. X., Xxxxxx, G. X., Xxxxxx, X. X., Xxxx, R. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-Induced X9 xx: Xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, T., Sawamura, X., Xxxx, K., Xxxxxxxx, T. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, X: Xx vitro Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xx Xxxxxx, X. X., Xxxxx, X. X., Xxxx, X. X., Philpot, X. X. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

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

22) Xxxxxx, X. X., Xxxxxx, X. X., Xx, X. P., Xxxxxx, X. L. (1983), Xxxxxxxxxx xx xx Exposure System Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Highly Xxxxxxxx Mutagens xx xxx CHO/HGPRT Xxxxxxxx Xxxxx, Xxxxxxx. Xxxxxxxxxxx, 5, 795-801.

23) Applegate, X. L., Xxxxx, X. X., Broder, X. X., Burrell, X., Hozier, X. X. (1990), Xxxxxxxxx Xxxxxxxxxx xx Mutations xx xxx Heterozygous Xxxxxxxxx Xxxxxx Xxxxx xx Mouse Lymphoma Xxxxx, Proc. Xxxx. Xxxx. Xxx. X. X. X, 87, 51-55.

24) Xxxxx, M. X., Clive, D., Xxxxxx, J. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. T., Xxxxxx, X. (1985), Xxxxxxxx of Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (XXX+) Xxxxxxx xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx. 151, 161-174.

25) Yandell, X. W., Dryja, X. X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxx Analysis xx Recessive Mutations xx x Heterozygous Xxxxxxxxx Xxxxx xx Xxxxx Xxxxx, Mutatation Xxx. 229, 89-102.

26) Xxxxx, X. X., Xxxxx, C. X. (1990), Comparison xx Xxxxxxxxxx Xxxxxxxxxx Frequency xxx Small Xxxxxx XX-Xxxxxxxxx Xxxxxx Frequency xx L5178Y/TK+/- 3.7.2C Xxxxx Lymphoma Xxxxx, Xxxxxxxxxxx, 5, 609-614."

XXXXXXX 4X

"X.23 XXXXXXX XX XXXXXXXXXXXX XXXXXXX XX XXXXXXXXXXXXXXX SAVCŮ

1. XXXXXX

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

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx in vivo xx identifikovat xxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx spermatogoniích xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx xxxxxxxxxx mutagenů xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace se xxxxxx vyskytují. Xxxx xxxxxx xxxx určena xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx x xxxxxx účelu xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x podobné xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx podmíněných xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx ve xxxxxxxxxxxxxxx a xxxxxxxxxxx xx xxxx, že xxxx xxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx x xxxxxxxxxxxx xxxxxxx.

X xxxx zkoušce xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Touto xxxxxxxxxxxxxx xxxxxxxx in xxxx xx detekují chromozomové xxxxxxx při xxxxxx xxxxxxxxxxxxx. Jiné xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx chromatidového xxxx xx xxxxxxxxxxxxxxx xx xxxx xxx — xxxxx než dojde xx ztrátě léze — xxxxxxxxx první xxxxxxxxx buněčné xxxxxx, xxxxx xxxxxxxxx xx xxxxxxxx. Xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxx chromozomového xxxx v xxxxxxxxx-xxxxxxxx X, kdy xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxxxx, xxx xxxx mutageny somatických xxxxx aktivní také x xxxxxxxxxxxx xxxxxxx. Xxxxx xx xxxx xxxxxxx se xxxxxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx zohlednit faktory xxxxxxxxxxx xx vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx DNA.

Ve xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx spermatogonií x xxxxxx citlivostí xx xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxxxx aberace xxxx xxxxxxxxxxx xxxxxxxxx odpověď xxxxxxxxxx populace spermatogonií x xxxxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. V závislosti xx své poloze xx xxxxxxxxx, xxxxx xxxx nemusí xxx xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx celkovému krevnímu xxxxx x xxxxxxxx xxxxxxxxx x fyziologické xxxxxxx Xxxxxxxxx buněk x bariéry xxxx xxxxxxx xxxxxx x xxxxxxx.

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

Viz xxxx xxxxxx úvod, xxxx B.

1.2 DEFINICE

Chromatidová xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx zlomu xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.

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

Xxx : xxxxxxxxxxxx léze xxxxx xxx xxxxx xxxxx xxxxxxxxxx x x minimální xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx xxxxxxx : xxxxxxxx počtu chromozomů xx xxxxxxxx hodnoty x použitých xxxxx.

Xxxxxxxxxxx : xxxxxxx haploidního xxxxx chromozomových xxx (x), xxxx xxx xxxxxxxxx (tj. 3 x, 4 n xxx.).

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx změny xxxxxxxxx chromozomů při xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx xxx xxxxxxxxxxx, xxxx se xxxx xxxxxx x xxxxxxxxx, intrachromozomální xxxx xxxxxxxxxxxxxxxxxx změny.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxx xxxxxxxx exponována xxxxxxxx látce x xx vhodné xxxx xx xxxxxxxx xxxxxxxx. Xxxx xxxxxxxxx se xxxxxxxx xxxx látka xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx nebo Xxxxxxxx®). X xxxxxxxxxxxx buněk xx xxxx xxxxxxxx xxxxxxxxx chromozomů, xxxxxx xx x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 POPIS XXXXXXXX METODY

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx x xxxx; xxx však xxxxxx samce jakéhokoli xxxxxx xxxxxxxx druhu xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx a xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladí pohlavně xxxxxxx xxxxx xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, xxxxx xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx tak, xxx xxx xxxx xxxxxx xxxxxx minimalizován. Zvířata xx xxxxxxxxxxx identifikují. Xxxx xxxxxxxxx xxxxxx xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx před xxxxxxxx xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx být xxxxxxxx xxxxx xxxx xxxxx xxx před xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx při xxxxxxxxx xxxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx podezření, že xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx xxxx než známá xxxxxxxxxxxx/xxxxxxxx, mělo by xxx xxxxxx xxxxxxxx xxxxxxxxx údaji o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by xxxx být souběžné xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) kontroly. S xxxxxxxx aplikace xxxxxxxx xxxxx by měla xxxxxxx kontrolní xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata ve xxxxxxxxx, v nichž xxxxx k expozici.

Pozitivní xxxxxxxx xx měly xxxxxxxxxx strukturní xxxxxxx xx xxxxxxxxxxxxxxx in xxxx při expozičních xxxxxxxx, x xxxxx xx předpokládá, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx.

Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx zvoleny xxx, xxx xxx účinek xxxxxxxx, xxx aby xxx odečtu nevyšla xxxxx xxxxxx kódovaná xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx byla xxxxxxxxx kontrola xxxxxxxx xxxxx způsobem než xxxxxxxx látka x xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx kontrolu xxxx xxx navíc xxxxx x xxxxx xxxxxxx xxxxxxxxxx látek xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Příklady xxxxx xxx pozitivní xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx 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 odběru xx xxx být xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x která xxxxx podstupuje xxxxxx xxxxxx jako exponované xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx xxxxx o xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Kromě xxxx by xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx kontrolní xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xxxx xxxxxxxxx alespoň xxx xxxxxxxxxxxxxxxx xxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xx xxxx xxx xxxxx možno xxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxx (xx. při xxxxx xxxxxxxx xxxx xxxx xxxxxxxxxx). Zkoušené xxxxx xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, tzn. xxx xxxxx x xxx xxx x rozmezí xx xxxx než xxxxxxxx hodin, xxx xxxx usnadněno xxxxxxxx xxxxxxx objemů xxxxxxxxx. Xxxx režimy xxxxxxxx xx měly xxx xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x xxxxxxxx dávkou xx měly xxx xx expozici provedeny xxx xxxxxx. Xxxxxxxx xxxxxxxx buněčného xxxxx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, provede xx xxxxx časný xxxxx a xxxxx xxxxxxxx xxxxx xxxxxxxxx 24 x 48 xxxxx xx xxxxxxxx. X případě xxxx xxx xxxxxxxx xxxxx xx xxx xxx xxxxx xxxxxxxx xx 24 hodin xxxx xx takové xxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxx buněčného xxxxx, pokud xxxx xxxxx xxxx vhodnější xxxx pro xxxxxxx xxxxxx (6).

Xxxxx mohou xxx odběry provedeny xxxx x xxxx xxxx. Xxxxxxxxx x xxxxxxx xxxxxxxxxx látek, xxxxx mohou indukovat xxxxxxxx xxxxxxxxx (xxxxxxx) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx být xxxxxxxxx xxxxxxxx xxxxx (1).

Xxxxxxxx xxxxx opakované xxxxxxxx xxxx být xxxxxx xxxxxx od případu. X xxxxxxx plánu x xxxxxxxxxx expozicí xx xxxx xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx xxxxx xxxxx) xx poslední xxxxxxxx. Xxxxx xxxxxxx xxxxx xxx prováděny xxxxx xxxxxx x xxxx xxxx.

Xxxx xxxxxxxxx xx zvířatům intraperitoneálně xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Poté xx xx xxxxxx době xxxxxxx x zvířat xxxxx. X xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 xxxxx; x xxxxxx xxxxxxxx xx xxxx xxxx přibližně 4 — 5 xxxxx.

1.5.3 Dávkování

Provádí-li se xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx údajů xxxxxx xxx xxxxxxxx rozsahu, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx x xxxxxx x xx xxxxxxxx xxxxxx expozice, xxxxx xx použije x xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx tři xxxxxx dávky. Xxxx xxxxxx dávky xx xxxx xxxxxxxx rozmezí xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx stačí, xxxx bude xxxxxxx xxxxx nejvyšší xxxxx. Xxxxxxxx dávka je xxxxxxxxxx jako dávka xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx xx xxxxx xxxxx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx podle očekávání x xxxxxxxx.

Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. hormony x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx xxxxx xxxx xxx také definována xxxx xxxxx vyvolávající xx spermatogoniích xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxx xxxxxxxxxxxxx x mitose vzhledem x xxxxx x xxxxx meiotické xxxxxxxx; xxxx xxxxxxx xx xxxxxx překročit 50 %).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx x jednou xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx dvou dávkách x xxxxxx xxx xxxxxxxxxx žádné pozorovatelné xxxxxxx účinky x xxxx-xx xx základě xxxxx x látkách, xxxxx mají xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx se úplná xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. Očekávaná xxxxxxxx xxxxxxx může xxxxxxxx xxxxxxx použít x xxxxxxx xxxxxxx xxxxx xxxxxx dávky.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx sondou xxxx xxxxxxx intubační xxxxxxx, xxxx intraperitoneální xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx neměl xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx xx xxxxxxx xxxxx, musí xxx xxxxxxxxxx. Xx xx xxxxxxxx a xxxxxx xxxxx, které xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx zkoušeného xxxxxx xxxxxxxxxxxxxx nastavením koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx se x xxxxxxx xxxx xxxx xxxxxx xxxxx xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx a xxxxxx. Xxxx xx xxxxxx xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx x dobře xxxxxxxxxxxx metafázi (xx. xxxxxxxxx 500 xxxxxxxx xx skupinu). Xxxxx xxxxx lze snížit, xx-xx xxxxxxxxx velký xxxxx xxxxxxx. Všechny xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x negativních xxxxxxx, xx xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx dochází ke xxxxxxxxxxxxxx xxxxxx nebo xxxxxx xxxxxxxxxx u xxxxx xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx odpovídajícímu xxxxx 2 n ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx každé xxxxx xx měl xxx xxxxxxxxxx počet xxxxx xx xxxxxxxxxxxx chromozomovými xxxxxxxxx x počet xxxxxxxxxxxxxx xxxxxxx na xxxxx. Pro xxxxxxxxxx x xxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxxxx typy xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx xxxxxx se xxxxxxxxxx do celkové xxxxxxxx xxxxxxx.

Xx-xx pozorována xxxxxx a také xxxxxx, xxx xx xxx xxx stanovení xxxxxxx xxxxxxxxxxxxx účinků xxxx xxxx xxxxxxxxxxxx xxxxxxxx u xxxxx xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxxx xxxxxxxx, x to x xxxxxxxx xxxxxx 100 xxxxxxxx xx xxxxx xx xxxxx xxxxx. Pokud xx xxxxxxxxx pouze xxxxxx, xxxxxxx v 1000 xxxxxxx xx zvíře xx měl xxx xxxxxxxx mitotický xxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx stanovení pozitivního xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx dávce xxxx xxxxx xxxxxx xxxxx xxxxx s xxxxxxxxx pro xxxxxxx x určitou dávkou x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx měly být xxxxxxxxx xxxxxx zkoušením, xxxxxxx x úpravami xxxxxxxxxxxxxxxx podmínek.

Zkoušená xxxxx, xxxxx xxxxxxxx nesplňují xxxx xxxxxxx xxxxxxxx, xx x xxxxx xxxxxxx xxxxxxxx za xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx negativní výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xxxxx in xxxx znamenají, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx strukturní xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx látka za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx vehikula,

- rozpustnost x xxxxxxx xxxxxxxx xxxxx x rozpouštědle/vehikulu, xx-xx xxxxx.

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet x stáří xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx na xxxxxxx zkoušky, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx hodnoty a xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební podmínky:

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxx x podávání xxxxxxxx látky,

- zdůvodnění xxx xxxxxxxx,

- xxxxxxxx xxxxxxxx xxxx koncentrací xxxxxxxx xxxxx x xxxxxx nebo vodě (xxx) na xxxxxxxxxxxx xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),

- podrobné údaje x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x odběru,

- metody xxxxxxxxx toxicity,

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

- metody xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx buněk xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx index,

- poměr xxxxxxxxxxxxx x mitose xxxxxxxx k xxxxx x druhé xxxxxxxx xxxxxx,

- xxx a xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx počet xxxxxxx xx xxxxxxx,

- xxxxx xxxxx x xxxxxxxxx ve xxxxxxx,

- xxxxx možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx statistické xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

- xxxxx ploidie, xxxxx xxxx pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Adler, X. D., (1986), Xxxxxxxxxxx Potential xx Xxxxx Xxxxxxxxxxxxx xx Xxxxxxxx Xxxxxxxx Related xx xxxxx Cell-Cycle Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxxx Xxxxxxxxx, Xxxx X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Lambert, X., Xxxxxxxxx, J. (eds) Xxxx, New Xxxx, 477-484.

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

3) Xxxxx, X. X., Xxxxxxx, X., Xxxx, X. X. (1964), Xx Xxx-xxxxxx Method xxx Xxxxxxx Xxxxxxxxxxxx xxxx Xxxxxxxxx Testes, Xxxxxxxxxxxx Xxxx Xxxxxxxx, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. G., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: D. J. Xxxxxxxx (ed.), Xxxxx Xxxxxxxxxxxx Tests, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx on Guidelines xxx Xxxxxxxxxxxx Testing. Xxxxxx. Part I xxxxxxx, Cambridge University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Sydney, 115-141.

5) Xxxxxxxx, X., Xxxxxxx, X. (1978), X Xxx Xxxxxx for Xxxxxxxxxxx of Xxxxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx, Mutatation Xxx., 52, 207-209.

6) Xxxxx, X. X., Xxxxxx X. D., Xxxxxxx, X., Favor, X., Xxxxxxxx, W., Xxxxxxxxxxxx, F., Xxxxxxx, X., Tanaka N. (1994), Xxxxxxxxxxxxx Workshop xx Standardisation of Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Xxxxxx xx xxx Xxxxxxx Group xx Xxxxxxxxx Xxxx Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, X. X., Xxx, J., Xxxxxxx, X. X., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Morton, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. (1992), Report of Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. X., Xxxxxxxx, X., Albanese, X., Xxxxxxxx, G. X., Xxxxx, X., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx X. X. X. (1989), Xxxxxxxxxxx Analysis of Xx xxxx Xxxxxxxxxxx Xxxxxx, in: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Subcommittee on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Report, Xxxx XXX. Cambridge University Xxxxx, Cambridge, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."

XXXXXXX 4G

"B.39 XXXXXXX XX XXXXXXXXXXXX XXXXXXX XXX (XXX) X XXXXXXXXX BUŇKÁCH XXXXX XX XXXX

1. METODA

Tato xxxxxx xx replikou xxxxxx OECD XX 486 — Xxxxxxx xx neplánovanou xxxxxxx XXX (UDS) x xxxxxxxxx buňkách savců xx xxxx (1997).

1.1 XXXX

Xxxxxx zkoušky na xxxxxxxxxxxx xxxxxxx XXX (XXX) x xxxxxxxxx xxxxxxx savců xx xxxx xx xxxxxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxx XXX x xxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).

Tato xxxxxxx xx xxxx xxxxxxxxx metodu xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxx. Xxxxxxxxxxx jev xx xxxxxxxxxx xxxxxxxxx DNA x následné reparace x xxxxxxxxx xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx xxxxxx, xxx xxxx absorbované xxxxxxxxxx xxxxxxxxxxxxxx. Jsou xxxx xxxxxxx xxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx XXX in xxxx.

Xxxxxxxx xxxxxxxx důkaz o xxx, že xx xxxxxxxx xxxxx nedostane xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx použít.

Rozsah xxxxxxxxxxx xxxxxxx XXX (XXX) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx syntézou XXX (S-fází). Nejrozšířenější xxxxxxxxx xx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx thymidinu xxxxxxxxx tritiem (3X-XxX). Xxx zkoušky na XXX in vivo xx xxxxxxxxxx xxxxxxxxx xxxxx xxxxxxx. Jiné xxxxx xxx xxxxx xxxxx xxx rovněž xxxxxxx, xxxxxx však xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx UDS xxxxxx xx počtu xxxx XXX vyštěpených x xxxxxxxxxxx v xxxxx xxxxxxxxx. Zkouška xx XXX xx tedy xxxxxx xxxxxxx xxx xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx repair") (20 xx 30 bází) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("xxxxx-xxxxx xxxxxx") (xxxxx až xxx xxxx) xxxx naproti xxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxx. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx chybné xxxxxxxxx lézí DNA xxxxx k xxxxxxxxxx xxxxxxxxx. Xxxxxx xxxxxxxx XXX neposkytuje xxxxxx xxxxxxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx. Navíc xx xxxxx, xx xxxxxxx xxxxxxx s XXX, ale xxxxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx informací, které xxxx zkouška xxxxxxxxx x xxxxxxxxx aktivitě, xx vyvážen xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxx, xxxxx je xxxxxxxxxx x xxxxx genomu.

Viz xxxx obecný xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (NNG), xxxxx xxx xxxxxxxxxx xxxxxxx xxxxxxxxx laboratoří xxxxxxxxxxx xxxxxxx.

Xxxxx počet xxx xxxxxxxxxxxxxx buněčným xxxxxx (XXX) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx buněk x xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxx xxx x cytoplasmatických xxxxxxxxx (XX) xxxxxxxxxxxxxx xxxxxx xx xxxxx zrn xxxxxxxxxxxxxx buněčným xxxxxx (XX): XXX = XX — CG. Xxxxxxx XXX xx xxxxxxx xxx jednotlivé xxxxx, xxxx xxxxxxxx xxx buňky x xxxxxxx, x xxxxxxxxxxx xxxxxxxxx atd.

Neplánovaná xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx xxxxxxxxx a xxxxxxxxxx úseku XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xx XXX x xxxxxxxxx buňkách xxxxx xx xxxx xxxxxxxx xxxxxxx reparací XXX xx xxxxxxxxx x odstranění úseku XXX obsahujícího xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx. Zkouška xx obvykle xxxxxxxx xx xxxxxxxxxxx 3H-TdR xx DNA jaterních xxxxx, kde xx xxxx četnost buněk x S-fázi buněčného xxxxx. Xxxxxxxxxxx 3X-XxX xx xxxxxxx stanoveno xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx xxxx xxx xxxxxxx xx xxxx X-xxxx buněk jako xxxx. xxxxxxx scintilační xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxx savce. Měly xx xxx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx dospělých zvířat. X okamžiku xxxxxxxx xxxxxx by měla xxx xxxxxxxx x xxxxxxxxx zvířat minimální x neměla xx xxxxxxxxx ± 20 % střední xxxxxxx xxxxxxxxx pro obě xxxxxxx.

1.4.1.2 Podmínky xxxxx x strava

Platí obecné xxxxxxxx podle obecného xxxxx x xxxxx X, xxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxx 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx pohlavně xxxxxxx zvířata xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x skupinu, která xx xxxxxxxx. Klece xx xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují x xxxx xxxxxxxxx xxxxxx se xxxxxxx x xxxxxxxxxxxxx podmínkách xxxxxxx pět dní xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxxxxx xxxxx

Xxxxx zkoušené látky xx měly být xxxx aplikací zvířatům xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx mohou xxx podávány xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by být xxxxxxx xxxxxxx připravené xxxxxxxx chemické xxxxx, xxxxx xxxxx 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 xxxx xx být xxxxxxxxx xxxxxxxxx, xx reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx zvážit použití xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx prováděné části xxxxxxxxxxx xx xxxx xxx souběžné pozitivní x negativní (rozpouštědlo/vehikulum) xxxxxxxx. S xxxxxxxx xxxxxxxx zkoušené xxxxx xx měla xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxx ve xxxxxxxxx, x xxxxx xxxxx x expozici.

Pozitivními xxxxxxxxxx xx xxxx xxx xxxxx, x xxxxx xx xxxxx, že xxxxxx xxxxxxxx v xxxxxxxxxxx expozičních xxxxxxxxxxxxx xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Pozitivní xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx aktivaci xx xxxx xxx xxxxxxx x dávkách xxxxxxxxxxxx mírnou xxxxxxx (4). Xxxxx xxxxx xxx xxxxxxx tak, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

Xxxxx xxxx xxxxxx (2 xx 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx xxxx xxxxxx (12 xx 16 h)

N-(fluoren-2-yl)acetamid (2-AAF)

53–96–3

200–188–6

Mohou xxx použity xxxx xxxx látky xxx xxxxxxxxx kontrolu. Je xxxxxxxxx, xxx xxxx xxxxxxxxx kontrolní xxxxx xxxxxxxx xxxxx xxxxxxxx, xxx zkoušená xxxxx.

1.5 XXXXXX

1.5.1 Počet a xxxxxxx xxxxxx

Xxx xx xxx xxxxxx xxxxxxxxxx xxxxx xxxxxx, xxx xxxx zohledněno xxxxxxxxx xxxxxxxxxx xxxxxxxx odpovědi xx zkoušku. Xxxxx xxxxxxx xx xx xxxx xxxxxxx alespoň xx xxx xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx dostatečné dosavadní xxxxx, xx pro xxxxxxxxx x pozitivní xxxxxxxxx xxxxxxx nezbytné xxxxx xxxxx xx xxx xxxxxxx.

Xxxxxxxx jsou x xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx druhem a xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx pohlavími rozdíl x toxicitě, xxxx xxxxxxxxxxx xxxxxxxx jednoho xxxxxxx, nejlépe samců. Xx-xx expozice xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, jako je xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx provedena se xxxxxxxx odpovídajícího pohlaví.

1.5.2 Xxxx expozice

Zkoušené látky xxxx xxxxxxxxx podávány xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx xxxxxxxxxx xxxxxxxx se xxxxxxxxx xxxxxxx dvě úrovně xxxxx. Nejvyšší xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxxxx xxxxxxxxx xxx xxxxxxx režimu xxxxxxxxx x xxxxxxxx. Xxxxx dávka xx xxxx xxx xxxxxxxxx 50 % až 25 % vyšší xxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) nemusí kritériím xxxxxxxxx xxxxx xxxxxxxxx x měly by xxx xxxxxxxxx xxxxxx xx xxxxxxx. Provádí-li xx kvůli xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx xxxxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx laboratoři, se xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx xxxxxx.

Xxxxxxxx xxxxx xxxx xxx xxxxxxxxxx také xxxx xxxxx xxxxxxxxxxxx známky xxxxxxxx x játrech (xxxx. xxxxxxxxxx xxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx xxxxxx x alespoň 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx žádné pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx xxx xxxxx xxxxxx nezbytná. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x limitní zkoušce xxxxx úroveň dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx sondou xxxx vhodnou xxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou xxxxx, xxx-xx xx zdůvodnit. Xxxxxxxx xxxxxxxxxxxxxxxxx xx xxxx nedoporučuje, xxxxx xx játra xxxxx xxx xxxxxxxxxx zkoušené xxxxx xxxxx a xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx měla xxx xxxxxxxxxxx zkušebního xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx konstantní objem xxx všech úrovních xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx x xxxxxxxxxxxx xxxxxx zpravidla 12 xx 16 xxxxx xx podání xxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (xxxxxx xxx xx čtyři xxxxxx xx expozici) xx xxxxxxxx, není-li po 12 až 16 xxxxxxxx jasná xxxxxxxxx xxxxxxx. Xxxxx však xxx xxxxxxx xxxx xxxx xxxxxx, xxxx-xx xxxxxxxxxx xx základě xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxx savců xx zpravidla xxxxxxxxx xxxxxxx jater xxxxxxxxxxx xx xxxx x xxxxxx xx, xxx xx čerstvě disociované xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx povrchu. Xxxxxxx buňky z xxxxxxxxx kontroly xx xxxx vykazovat životaschopnost (5) alespoň 50 %.

1.5.7 Stanovení XXX

Xxxxxxx xxxxxxxxx jaterní buňky xxxxx se xxxxxxx xxxxxxx dobu, např. xxx až xxx xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3H-TdR. Xx xxxxx inkubační xxxx xx xxxx xxx xxxxxx x xxxxx xxxxxxxxxx x xxxxx xxxx xxxxx xxx inkubovány s xxxxxx obsahujícím přebytek xxxxxxxxxxx xxxxxxxxx, xxx xxxx snížena xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx chase"). Xxxxx xx xxxx xxxxxxx, xxxxxx x xxxxxx. Při xxxxx xxxxxxxxx xxxx xxxxxx xxx snížení radioaktivity xxxxxxxx. Xxxxxxxxx se xxxxxx do xxxxxxxxxxxxxxxxx xxxxxx, xxxxxxxx xx x xxxxx (např. x xxxxxx 7 xx 14 dnů), xxxxxxxx xx, xxxxxx x xxxxxxxxx se xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxxx xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx xx měly xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx, xxx xxxx xxxxxxxxx XXX xxxxxxxxx hodnotu. Xxxxxxxxx xx xxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxx zjevné cytotoxicity (xxxx. na xxxxxxx, xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx).

Xxxx xxxxxxxxx xxx by xxxx xxx xxxxxxxxx xxxxxxxx. Xxxxxxxxx xx vyšetřuje 100 xxxxx xx xxxxx xxxxx xxxxxxx xx dvou xxxxxxxxx; xxxxxxxxx méně xxx 100 buněk/zvíře xx xxxx xxx xxxxxxxxxx. Xxx xxxxxxxx xxx xx xxxxx v X-xxxx nevyšetřují, xxx xxxxx xxxxx x X-xxxx xxxx být xxxxxxxxxx.

Xxxxxxxx 3H-TdR inkorporovaného xx xxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxx stříbra xx xxxx být xxxxxxxxx xxxxxxx xxxxxxx.

Xxxxx buněk xx stanoví x xxxxx xxx odpovídajících xxxxxxxx jádrŭm (xx) x x xxŭxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (cg) xxxxxxxxxxxxxx jádrŭm. xxxx xxxxxxx xx xx xxxxxxx buď počet xxxxx xxx xxxxxxxxxx xxxxxxxxx xxxxxx cytoplasmy, xxxx xxŭxxxxx xxxxxxx xxxx xx xxx xxxxxxx vybraných xxxxxxx x xxxxxxxxx dotyčných xxxxxxxxx xxxxx. xx xxxxxxxxxxxxx zdŮvodnění xxxxx xxx xxxxxxx i xxxx xxxxxxx stanovení xxxxx buněk (xxxx. xxxxxxxx xxxxxx buněk) (6).

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx xx být xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx a xxxxxxx. Xxxxx xx xxxx být dále xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX xx xxxxxxx XX xx xxx xxx vypočten pro xxxxxx buňku, pro xxxxx xxxxx x xxx xxxxxx dávku x xxx xxxxx xxxxx zrn odpovídajících xxxxxxxx xxxxxx (XXX). Xxxxxxxx jsou počítány "xxxxxxxxxx" buňky, měla xx být xxxxxxxx xxx definování "opravovaných" xxxxx xxxxxxxxxx x xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx výsledky xxxxx xxx zhodnoceny xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx xxx xxxxxxx, xxxx xx xxx xxxxxxxxxxx xxxxx xxxxxxx x xxxxxxxxxx xxxx provedením studie.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx

x)

xxxxxxx XXX leží xxx xxxxxxxx xxxxxx, xxxxx xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxx;

xxxx

xx)

xxxxxxx XXX xx xxxxxxxx xxxxx než xxxxxxx xxx xxxxxxxxx xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx NNG xxxx xx xxxxxxxxx xxxxxxx xxxxxxx xxxx pod xx;

xxxx

xx)

xxxxxxx XXX není xxxxxxxx xxxxx než xxxxxxx xxx xxxxxxxxx xxxxxxxx.

Xxxx by xxx xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx. xxxx xx být vzaty x xxxxx xxxxxxxxx, xxxx xxxx variabilita xxxxxx, vztah xxxxx x xxxxxxxx x xxxxxxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost xx xxxx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx negativní výsledky, x ojedinělých xxxxxxxxx xxxxxxxx soubor údajů xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx XXX x jaterních xxxxxxx xxxxx xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxxx XXX, xxxxx xxx opravit neplánovanou xxxxxxxx XXX xx xxxxx. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxxxx touto xxxxxxxx.

Xxxx xx xxx diskutována xxxxxxxxxxxxxxx, x xxxxx xx xxxxxxxx látka xxxxxxx xx xxxxxxxx xxxxx popř. xx xxxxxx tkáně (např. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol o xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx a pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx hodnoty x směrodatné xxxxxxxx xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- pozitivní x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

- xxxxx xx studie xxx zjištění rozsahu, xxxxx xxxx xxxxxxxxx,

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- údaje o xxxxxxxx xxxxxxxx látky,

- xxxxx x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

- případně xxxxxxxx xxxx koncentrací xxxxxxxx xxxxx x xxxxxx xxxx vodě (xxx) xx xxxxxxxxxxxx xxxxx (mg/kg tělesné xxxxxxxxx/xxx),

- podrobné xxxxx x kvalitě krmiva x xxxx,

- podrobný xxxxx xxxxxxx expozice x xxxxxx,

- metody xxxxxxxxx toxicity,

- xxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx buněk,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x počet xxxxxxxxxxx xxxxx,

- kritéria xxxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx pozitivní, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxxx xxxxxxx počtu xxx odpovídajících buněčným xxxxxx x xxxxx xxx odpovídajících xxxxxxxxxx, x xxxxx xxxxx xxx, jednotlivě pro xxxxxxxxx, xxxxxxx a xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx odpovědi na xxxxx,

- xxxxxxxx statistické xxxxxxxxx,

- xxxxxx xxxxxxxx,

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

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

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

- počet xxxxx x X-xxxx, xx-xx xxxxxxxx,

- životaschopnost xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, J. Xxxxxxx, X. A., Xxxxxxxxx, X., Penman, X. X. (1985), An Xxxxxxxxxx of the Xx vivo Xxx. Xxxxxxxxxx DNA Xxxxxx Xxxxx, Mutatation Res., 156, 1-18.

2) Xxxxxxxxxxx, X. X., Ashby, X., Xxxxxxxx, E., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, G. (1987), X Protocol xxx Xxxxx xxx xxx Xx vivo Xxx Xxxxxxxxxx XXX Repair Xxxxx, Mutatation Xxx., 189, 123-133.

3) Kennelly, X. X., Xxxxxx, X., Ashby, X., Xxxxxxx, X. A., Xxxxxxxxx, X., Xxxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, X. xx X. (1993), Xx xxxx Xxx Liver UDS Xxxxx, xx: Xxxxxxxx X. X., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: UKEM Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Testing. Xxxxxx. Xxxx XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Sydney, 52-77.

4) Xxxxx, X., Xxxx, X. W., Andrac, X., Brambilla. G., Xxxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxx, X., Hertner, X., XxXxxxx, X. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx UDS Xxxxx Xx xxxxx xxx Xx xxxx, Xxxxx. Xxx., 312, 263-285.

5) Fautz, X., Xxxxxxx, B., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, X. (1993), Xxxxxxxxxx of xxx Relation Xxxxxxx xxx Xxxxxxx Xxxxxxxxx xxx the Xxxxxxxxxx xx Xxxxxxx Isolated Xxx Hepatocytes Used xxx the Xx xxxx/Xx vitro XXX Xxxxxx Xxxxx (XXX), Xxxxxxxxxx Res., 291, 21-27.

6) Mirsalis, X. X., Tyson, C. X., Xxxxxxxxxxx, B. X. (1982), Xxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xx the In xxxx/Xx xxxxx Hepalocyte XXX Repair Xxxxx, Xxxxxxx.Xxxxxxx. 4, 553-562."

XXXXXXX 5

OBECNÉ XXXXXXXXX XX XXXXXXXXXXX X XXXXXXXXXX NEBEZPEČNÝCH XXXXX X XXXXXXXXX

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

XXXXXXX 6

"

PŘÍLOHA IX

ČÁST X

xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx proti xxxxxxxx xxxxx

Xxxxx ustanovení xx. 22 odst. 1 písm. x) xxxx xxxxxxxx, xxxx xxx xxxxx x xxxxxxxxx xxxxxx xxxxxxxxxx xxxxx, x xxxxx xx xxxxxxx xxxxxx xxx vdechování (Xx; X 65) x xxxxx xxxx xxxxxxxxxxxxx x xxxxxxxx podle xxxx 3.2.3 přílohy XX této směrnice, x xxxxxxxx xxxxx xxxxxxxxx xx xxx xx xxxxx aerosolů xxxx x xxxxxxxx xxxxxxxxxx xxxxxxxxxxx rozprašovačem, xxxxxxxx uzávěry xxxxxxxx xxxxx xxxxxxxx dětmi.

1. Xxxxxxxxx xxxxxxxxxxxx obaly

Uzávěry xxxxxx xxxxx otevření xxxxx použité na xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx XXX 8317 (xxxxxx xx xxx 1. xxxxxxxx 1989) "Xxxxx odolné dětem — Požadavky xx xxxxxxxxx uzavíratelné xxxxx x xxxxxx jejich xxxxxxxx" přijatou Xxxxxxxxxxx xxxxxxxxxx xxx normalizaci (XXX).

2. Opakovaně xxxxxxxxxxxxxx xxxxx

Xxxxxxx odolné proti xxxxxxxx dětmi xxxxxxx xx xxxxxxxxx neuzavíratelných xxxxxxx xxxx splňovat xxxxxxxxx normy XXX XX 862 (xxxxxx x března 1997) "Xxxxx — Obaly xxxxxx xxxxx — Xxxxxxxxx x zkušební xxxxxxx xxx opakovaně xxxxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Evropským xxxxxxx xxx normalizaci (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx shody x výše uvedenými xxxxxxx mohou xxxxxxxxxx xxxxx xxxxxxxxxx, které xxxxxxx xxxxxxxx xxxxx xxxx EN 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx xxxxxx, xx xxxx xx xxxxxxxxxx xxxxxxxx xxx xxxx, xxxxx xx xxxxxxx xxxxxx x xxxxxx bez xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxx xxxxxx k pochybám x bezpečnosti xxxxxxx xxx dítě, může xxxxxxxxxxxx orgán požadovat, xxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx laboratoří xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx xxxxxx, xx xxx xxxx xxxxxxxx xxxxxxx podle xxxx xxxxxxxxx xxxxx XXX x CEN,

nebo

- xx xxxxxx xxx xxxxxxx a xxx xxxxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx.

XXXX X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx výstrah

Technické xxxxxxxxxxx xxx xxxxxxxxxx výstrahy xxxx xxx x xxxxxxx s xxxxxx XX XXX 11683 (xxxxxx x roku 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Požadavky".

"