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Xxxxxxxx Xxxxxx 2000/32/ES

ze xxx 19. května 2000,

xxxxxx xx xx xxxxxxx šesté xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxx Xxxx 67/548/EHS x xxxxxxxxxx právních x xxxxxxxxx předpisů xxxxxxxxxx xx klasifikace, xxxxxx x označování nebezpečných xxxxx [1]

(Xxxx x xxxxxxxx xxx EHP)

KOMISE XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Smlouvu x xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

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

xxxxxxxx x xxxxx xxxxxxx:

(1) Příloha X směrnice 67/548/XXX xxxxxxxx seznam xxxxxxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxx údaji o xxxxxxxxxxx x xxxxxxxxxx xxxxx látky. Xxxxxxxx xxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxx, xx xx xxx xxx xxxxxx xxxxxxxxxxxx xxxxx x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx jazykové xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxxxxx a xxxxxxx X x xxxxxxx X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx vět xxxxxxxxxxx xxxxxx xxxxxxxxxx rizik xxxxxxxxx x xxxxxxxxxxxx xxxxxxx a xxxxxxxxx. Xxxxxxx XX směrnice 67/548/XXX xxxxxxxx xxxxxx xxx x bezpečnostními xxxxxx týkajícími xx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/XXX xxxxxxxx xxxxx xx klasifikaci x x xxxxxxxxxx xxxxxxxxxxxx látek x xxxxxxxxx. Některé xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx určitých xxxxxx xxxxxx III, XX x VI.

(3) X xxxxxxx V xxxxxxxx 67/548/XXX xx stanoví xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx vlastností, xxxxxxxx x ekotoxicity xxxxx x xxxxxxxxx. Xx xxxxxxxx xxxxxxxxxxx xxxx xxxxxxx technickému xxxxxxx.

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

(5) Xxxxxxxx této xxxxxxxx xxxx x xxxxxxx xx xxxxxxxxxxx Xxxxxx xxx přizpůsobení xxxxxxxxxxx xxxxxxx směrnic xxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xx úseku xxxxxxxxxxxx xxxxx a xxxxxxxxx,

XXXXXXX TUTO XXXXXXXX:

Článek 1

Xxxxxxxx 67/548/EHS xx xxxx takto:

1. Xxxxxxx X xx xxxx xxxxx:

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

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

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

x) vkládají xx položky x xxxxxxx 1D xxxx xxxxxxxx.

2. Xxxxxxxxxxxx xxxx x xxxxxxx III xx xxxxxxxxx xxxxxxxxxx xxxxx označující xxxxxxxxxxx xxxxxxxxxx x xxxxxxx 2 xxxx xxxxxxxx.

3. Xxxxxxx XX xx xxxx takto:

a) xxxxxxxxxxxx xxxxxx x xxxxxxx XX se xxxxxxxxx xxxxxxxxxxxx pokyny xxx xxxxxxxx xxxxxxxxx v xxxxxxx 3X této xxxxxxxx;

x) xxxxxxxxxxxx xxxxxx x příloze XX xx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxx 3X xxxx xxxxxxxx.

4. Xxxx X xxxxxxx X xx xxxx takto:

a) xxxxxxxx X.10 se xxxxxxxxx xxxxxx v příloze 4X xxxx xxxxxxxx;

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

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

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

e) xxxxxxxx X.17 xx xxxxxxxxx xxxxxx x příloze 4X xxxx xxxxxxxx;

x) xxxxxxxx B.23 se xxxxxxxxx xxxxxx x xxxxxxx 4F xxxx xxxxxxxx. Název xxxxxxxx X.23 ve vysvětlivce xx mění xxxxxxxxxxxxx xxxxxxxx;

x) xxxxxx se xxxx x xxxxxxx 4X xxxx xxxxxxxx.

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

6. Xxxxxxxxxxxx xxxxx x příloze XX xx nahrazují xxxxx v příloze 5 xxxx směrnice.

7. Xxxxxxx IX se xxxx xxxxxxxx xxxxxxxx x příloze 6 xxxx směrnice.

Článek 2

1. Xxxxxxx xxxxx uvedou x xxxxxxxx xxxxxx a xxxxxxx předpisy xxxxxxxx xxx dosažení souladu x xxxxx xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x xxxx xxxxxxx Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx xxxxx musí xxxxxxxxx odkaz na xxxx xxxxxxxx nebo xxxx takový odkaz xxx učiněn při xxxxxx úředním xxxxxxxxx. Xxxxxx odkazu si xxxxxxx členské xxxxx.

2. Xxxxxxx státy xxxxx Xxxxxx xxxxx hlavních xxxxxxxxxx vnitrostátních právních xxxxxxxx, které přijmou x oblasti xxxxxxxxxx xxxx xxxxxxxx, a xxxxxxxxxx xxxxxxx xxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxxxxx.

Xxxxxx 3

Tato směrnice xxxxxxxx x platnost xxxxxx xxxx xx xxxxxxxxx x Úředním xxxxxxxx Xxxxxxxxxx společenství.

Článek 4

Xxxx xxxxxxxx xx xxxxxx členským xxxxxx.

X Xxxxxxx xxx 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Xxxxxx


[1] Xxxxxxx xx xxxxxxxxxxxx xx xxxxxxx xxxxx.

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

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


PŘÍLOHA 1X

XXXXXXXXX X XXXXXXX X

Xxxxxxxxxx poznámek xxxxxxxxxx se xxxxxxxxxxxx, xxxxxxxxxxx a xxxxxxxxxx xxxxx

(Xxxxxx xx xxxxxxx xxxxx)


XXXXXXX 1X

"XXXXXXX X

X

Xxxxxx

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

18

Xx

Xxxxx

Xxxxx

Xxxxx

Αργό

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"


XXXXXXX 1C

Indexové xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx k látkám

Číslo XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx limity

Poznámky x xxxxxxxxxx

006–011–00–7

xxxxxxxx (ISO) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

Xxxx. kat. 3; X40 Xx; X22 X; R50

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

006–013–00–8

xxxxxx-xxxxxxx (ISO) natrium-N-methyldithiokarbamát

205–293–0

137–42–8

Xn; X22 X31 X; X34 X43 X; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

Xxxx. kat. 3; R40 Xxxx. xxx. 3; X40 Xx; R22–48/22 X; X50–53

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

006–016–00–4

propoxur (XXX) 2- isopropoxyfenyl-N-methylkarbamát

204–043–8

114–26–1

T; X25 N; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

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

204–123–2

116–06–3

X+; X26/28 X; X24 N; X50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; R24/25 X; 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) S-(2,3-dichlorallyl)-N,N-diisopropylthiokarbamát

218–961–1

2303–16–4

Karc. kat. 3; X40 Xx; X22 X; R50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xx; R22 X43 N; X50–53

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

006–023–00–2

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

217–991–2

2032–65–7

T; X25 X; R50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; X22 Xx; X38 X; R51–53

Xn; X R: 22–38–51/53 X: (2-)13-61

006–026–00–9

xxxxxxxxxx (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

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

213–546–1

973–21–7

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

xxxxxxxxx (XXX) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx

230–253–4

6988–21–2

X; X25 N; X51–53

X; X X: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

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

243–433–2

19937–59–8

X; X50–53

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

006–034–00–2

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

214–215–4

1114–71–2

Xx; X22 N; R51–53

Xn; X X: 22–51/53 X: (2-)23-61

006–035–00–8

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

245–430–1

23103–98–2

X; X25 X; X50–53

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

006–037–00–9

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

220–113–0

2631–37–0

X; X25 X; X50–53

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

006–038–00–4

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

X

202–388–9

95–06–7

Xxxx. kat. 2; R45 Xx; X22 X; R50–53

T; X X: 45–22–50/53 X: 53–45–60–61

006–039–00-X

tri-allát (XXX) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx

218–962–7

2303–17–5

Xx; R22–48/22 R43 X; X50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; R40 Xx; X22 X; X50–53

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

006–043–00–1

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

140–41–0

Xx; X36/38 Xxxx. xxx. 3; X40 X; X50–53

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

006–045–00–2

xxxxxxxx (ISO) xxxxxx-X-[(X-xxxxxxxxxxxxxxx)xxx]xxxxxxxxxxxxxx

240–815–0

16752–77–5

X+; X28 X; R50–53

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

006–046–00–8

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

245–216–8

22781–23–3

X; X23/25 Xx; X21 N; X50–53

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

006–047–00–3

xxxxxxxxx (XXX) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx 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-[(ethylsulfanyl)methyl]fenyl-N-methylkarbamát

249–981–9

29973–13–5

Xn; R22 X; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

006–050–00–X

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

4482–55–7

Xx; R38 X; X50–53

Xx; X X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; R28 Xx; X21 X; R50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; N R: 22–51/53 X: (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; R22 X52–53

Xx X: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; R40 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. xxx. 3; X40 X; X50–53

Xx; X X: 40–50/53 X: (2-)36/37–60–61

006–088–00–7

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

82560–54–1

X; X23/25 X; R50–53

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

007–012–00–5

X,X-xxxxxxxxxxxxxxxx 1,1-xxxxxxxxxxxxxxxx

X

200–316–0

57–14–7

X; X11 Xxxx. xxx. 2; X45 X; X23/25 C; R34 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; R45 X; X23/24/25 X; X51–53

X; N X: 45–23/24/25–51/53 X: 53–45–61

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

009–003–00–1

xxxxxxxx fluorovodíková … %

X

231–634–8

7664–39–3

X+; R26/27/28 X; X35

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

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

015–039–00–9

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

201–676–1

86–50–0

T+; X26/28 X; X24 X43 X; X50–53

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

015–048–00–8

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

200–231–9

55–38–9

Xxxx. xxx. 3; R40 X; X23–48/25 Xn; X21/22 X; X50–53

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

015–056–00–1

azinfos-ethyl (XXX) X,X-xxxxxxx-X-[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx

220–147–6

2642–71–9

X+; X28 X; X24 X; X50–53

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

015–140–00–8

triazofos (XXX) O,O-diethyl-O-(1-fenyl-1 X- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx

245–986–5

24017–47–8

X; R23/25 Xn; X21 X; X50–53

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

016–013–00-X

xxxxxxx 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

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

016–014–00–5

chlorid xxxxxxxx

13451–08–6

X14 X; X34 X; X50

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

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

016–023–00–4

xxxxxxxx-xxxxxx

X

201–058–1

77–78–1

Xxxx. xxx. 2; R45 Xxxx. xxx. 3; X40 X+; R26 T; X25 C; X34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; R22 N; X50–53

Xx; N X: 22–50/53 S: (2-)60-61

016–071–00–6

3-xxxxx-6,13-xxxxxxx-10-[(3-{[4-xxxxx-6-(2-xxxxxxxxxxxxxxxx)- 1,3,5-xxxxxxx-2-xx]xxxxx}xxxxxx)xxxxx][1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx xxxxxxxx

410–130–3

136248–03–8

X43

Xx X: 43 S: (2-)22–24–37

022–001–00–5

xxxxxxx xxxxxxxxxx

231–441–9

7550–45–0

X14 X; R34

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

X ≥ 10 %: X; X34 5 % ≤ X < 10 %: Xx; R36/37/38

030–004–00–8

dimethylzinek [1] xxxxxxxxxxxx [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

X14 X; X17 C; X34 X; X50–53

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

050–002–00–0

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

236–049–1

13121–70–5

Xx; X20/21/22 N; X50–53

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

050–012–00–5

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

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

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

Xx; X20/21/22 X; X50–53

Xx; 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-xxxxxxx(2-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxxxx

236–407–7

13356–08–6

X+; X26 Xx; X36/38 N; X50/53

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

082–009–00–X

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

215–693–7

1344–37–2

Karc. xxx. 3; X40 Xxxx. xxx. 1; R61 Xxxx. kat. 3; X62 R33 X; X50–53

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

1

082–010–00–5

červeň (xxxxxxx-xxxxxxxxxx-xxxxx olovnatý) XX Xxxxxxx Red 104 (XX 77605) XX xxxxxxxxxx červeň 104 (XX 77605)

235–759–9

12656–85–8

Xxxx. xxx. 3; X40 Repr. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 N; X50–53

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

1

601–024–00-X

xxxxx [1] xxxxxxxxxxxx [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

R10 Xx; X65 Xx; X37 X; R51–53

Xn; X X: 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; X45 Xxxx. xxx. 2; X46 Xxxx. kat. 2; X60–61 X; X50–53

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

601–034–00–4

benzo[e]acefenanthrylen

205–911–9

205–99–2

Karc. kat.2; X45 N; X50–53

X; X X: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-dichlorbenzen x-xxxxxxxxxxxxx

203–400–5

106–46–7

Xx; X36 N; 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; X34

X X: 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 S: (1/2-)26–36/37/39–45

X ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ X &xx; 50 %: X; X21–23/25–36/38–48/22 10 % ≤ C &xx; 25 %: Xx; R20/22–48/22 3 % ≤ C &xx; 10 %: Xx; X20/22

603–091–00–0

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

402–470–6

87172–89–2

X; X8 Xx; R22 Xi; X36

X; Xx X: 8–22–36 X: (2-)26

603–093–00–1

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

402–410–9

87818–31–3

Xn; X20 X; X51–53

Xx; X X: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; X36 X52–53

Xx X:36–52/53 S: (2-)26-61

603–117–00–0

propan-2-ol xxxxxxxxxxxxxxxx xxxxxxxxxxx

200–661–7

67–63–0

X; X11 Xx; R36 X67

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

604–020–00–6

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

201–993–5

90–43–7

Xx; X36/37/38 X; X50

Xx; N X: 36/37/38–50 S: (2-)22-61

604–021–00–1

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

205–055–6

132–27–4

Xx; X22 Xi; X37/38–41 X; R50

Xn; X X: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

4,4'-(4-methylpentan-2,2-diyl)difenol 2,2-bis(4-hydroxyfenyl)-4-methylpentan

401–720–1

6807–17–6

Repr. xxx. 2; R60 Xx; R36 N; X50–53

X; X X: 60–36–50/53 S: 53–45–60–61

604–041–00–0

acifluorfen [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]

Xx; X22 Xx; X38–41 X; X50–53

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

604–043–00–1

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

203–083–3

103–16–2

Xi; X36 X43

Xx X: 36-43 X: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; X22 Xx; X36 X43

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

605–016–00–7

xxxxxxx… % ethandial… %

X

203–474–9

107–22–2

Xxxx. xxx. 3; X40 Xx; X20 Xx; X36/38 X43

Xx X: 20–36/38–40–43 S: (2-)36/37

X ≥ 10 %: Xx; X20–36/38–40–43 1 % ≤ X &xx; 10 %: Xx; R40–43

606–016–00-X

pindon (XXX) 2-(trimethylacetyl)indan-1,3-dion

201–462–8

83–26–1

T; R25–48/25 X; X50–53

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

606–018–00–0

xxxxxxx (XXX) 2,3-dichlor-1,4-naftochinon

204–210–5

117–80–6

Xn; X22 Xx; X36/38 X; X50–53

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

606–019–00–6

xxxxxxxxxx (XXX) 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 X; X24/25 X; X50–53

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

606–034–00–8

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

244–209–7

21087–64–9

Xn; X22 N; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

chloridazon (XXX) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx pyrazon

216–920–2

1698–60–8

R43 X; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

606–036–00–9

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

219–455–3

2439–01–2

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

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

606–037–00–4

xxxxxxxxxxx (XXX) 1-(4-chlorfenoxy)- 3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-on

256–103–8

43121–43–3

Xn; X22 N; X51–53

Xx; X R: 22–51/53 X: (2-)61

606–044–00–2

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

403–150–9

954–16–5

Xx; X22 Xx; X36 X; R50–53

Xn; 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; R22 Xi; X41 X52–53

Xx; X X: 22–41–52/53 X: (2-)26-61

607–057–00–6

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

201–378–1

81–82–3

Xx; R48/22 X52–53

Xx X:48/22–52/53 X: (2-)37-61

607–058–00–1

xxxxxxxxx (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -xxxxxxx-2-xx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X -xxxxxxx-2-xx

204–195–5

117–52–2

X; X25–48/25 X52–53

X X:25–48/25–52/53 X: (1/2-)37–45–61

607–079–00–6

xxxxxxx (XXX) 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 X; X51–53

X; X R: 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 xxxxxxxxxxxxxxxxx

209–008–0

552–30–7

Xx; X37–41 X42/43

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

607–143–00–3

pentanová xxxxxxxx xxxxxxxx kyselina

203–677–2

109–52–4

C; X34 R52–53

C X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xx; R22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; X36/38 X52–53

Xx X:36/38–52/53 X: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xx; X22 Xx; X38 X; X50–53

Xx; N X: 22–38–50/53 X: (2-)37–60–61

607–158–00–5

xxxxx xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; R25 Xx; X38 X; X50

X; X R: 25–38–50 S: (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

Směs: α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-xxxxxxxxxxx(xxxxxxxxxx);α-{3-[3-(2 H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propionyl}-ω-({3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}xxx)xxxx(xxxxxxxxxx)

400–830–7

X43 X; R51–53

Xi; X X: 43–51/53 S: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24/37–61

607–209–00–1

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

403–030–6

Xx; X22 X43 X; X50–53

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

607–213–00–3

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

403–320–2

67567–23–1

X; X2 X; X7 X10 N; R51–53

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

607–217–00–5

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

403–960–2

X43 R53

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

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

607–252–00–6

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

415–130–7

91465–08–6

X+; X26 X; X25 Xx; X21 X; X50–53

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

607–255–00–2

xxxxxxxxxx (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 Karc. xxx. 2; R45 X; X23/24/25 Xi; X37/38–41 X43 N; X51–53

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

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

43

608–016–00–5

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

401–550–8

1897–41–2

X43 X; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 X+; X28 X; X24 X44 X; R50–53

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

609–040–00–9

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

X

217–406–0

1836–75–5

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

X; N X: 45–61–22–50/53 X: 53–45–60–61

609–044–00–0

xxxxxxxx (XXX) 1,2,4,5-tetrachlor-3-nitrobenzen

204–178–2

117–18–0

Xn; X22 X43 X; X50–53

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

611–008–00–4

4-aminoazobenzen 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. xxx. 2; X45 X; X50–53

X; X X: 45–50/53 X: 53–45–60–61

611–013–00–1

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

403–650–7

117409–78–6

X; X2 X; X51–53

X; X X: 2–51/53 X: (2-)35-61

611–031–00-X

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

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-xxxxxxxxxxxxx x-xxxxxxxx

X

201–963–1

90–04–0

Xxxx. xxx. 2; X45 Xxxx. xxx. 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 Xx; X22 X; R50–53

T; N X: 45–22–50/53 S: 53–45–60–61

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

612–051–00–1

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

X

202–974–4

101–77–9

Xxxx. xxx. 2; X45 Muta. xxx. 3; R40 X; R39/23/24/25Xn; R48/20/21/22 X43 X; X51–53

X; 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, soli x-xxxxxxx, xxxx

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Xxxx. xxx. 2; X45 Xx; X22 N; X51–53

X; X X: 45–22–51/53 S: 53–45–61

612–099–00–3

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

X

202–453–1

95–80–7

Xxxx. xxx. 2; X45 X; R25 Xx; R21 Xx; X36 R43 N; X51–53

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

612–105–00–4

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

205–411–0

140–31–8

Xn; X21/22 X; R34 X43 X52–53

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

612–111–00–7

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

212–513–9

823–40–5

Xxxx. xxx. 3; X40 Xx; X21/22 X43 X; 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 Xn; X20/21 X43 X; X51–53

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

612–144–00–7

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

62924–70–3

Xx; X36/38 X4 3 N; X50–53

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

612–151–00–5

diaminotoluen xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. xxx. 2; X45 X; X25 Xx; R20/21 Xx; X36 X43 X; X51–53

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

613–018–00–4

xxxxxxxxxx (XXX) 1,1'-bis[(3,5-dimethylmorfolin-4-karbonyl)methyl]-4,4'-bipyridin-1,1'-diium

7411–47–4

Xn; X22 Xx; 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-trichlor-1,3,5-triazin-2(1H), 4(3X), 6(5X)-xxxxx

201–782–8

87–90–1

X; X8 Xx; X22 X31 Xx; R36/37 X; X50–53

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

613–038–00–3

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

202–095–6

91–76–9

Xn; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–042–00–5

xxxxxxxx (ISO) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1 X-xxxxxxxx

252–615–0

35554–44–0

Xx; X20/22 X; X41 X; X50–53

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

613–043–00–0

xxxxxxxx-xxxxxx (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1X -xxxxxxxx-1-xxx-xxxxxxxxxxxxxx [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx

261–351–5 [1] 281–291–3 [2]

58594–72–2 [1] 83918–57–4 [2]

Xx; X20/22 Xi; X41 N; X50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; X22 X; X50–53

Xx; N R: 22–50/53 S: (2-)60-61

613–091–00–2

xxxxxxxxxx-xxxxxxxxx [1] morfamkvat-sulfát [2] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx-xxxxxxxxx [1] 1,1'-bis[(3,5-dimethylmorfolin-4-karbonyl)methyl]-4,4'-bipyridin-1,1'-dium-disulfát [2]

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; R22 Xx; X36/37/38 R52–53

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

613–098–00–0

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

403–700–8

2687–94–7

X; X34 X; R51–53

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

613–130–00–3

xxxxxxxxxxx (XXX) (RS)-2-(2,4-dichlorfenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol

79983–71–4

R43 X; X51–53

Xx; N 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 X52–53

Xx X:22–52/53 X: (2-)61

613–134–00–5

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

88671–89–0

Xxxx. xxx. 3; R63 Xx; R22 Xi; X36 X; X51–53

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

613–137–00–1

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

242–505–0

18691–97–9

X; R50–53

N X: 50/53 S: 60-61

613–139–00–2

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

74223–64–6

X; R50–53

N X: 50/53 X: 60-61

614–001–00–4

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

200–193–3

54–11–5

T+; X27 T; X25 X; R51–53

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

614–006–00–1

xxxxxx 2,3-dimethoxystrychnidin-10-on

206–614–7

357–57–3

T+; R26/28 X52–53

X+ X:26/28–52/53 X: (1/2-)13–45–61

614–007–00–7

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

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

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

X+; X26/28 R52–53

T+ X: 26/28–52/53 S: (1/2-)13–45–61

615–006–00–4

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

X

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

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

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

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

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

2

616–010–00–9

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

204–854–7

127–65–1

Xx; R22 R31 X; X34 R42

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

616–034–00-X

xxxxxxxxxxxx (ISO) 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-ethyl-3-[2-kyan-2-(methoxyimino)acetyl]močovina

261–043–0

57966–95–7

Xn; X22 X43 X; X50–53

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

617–004–00–9

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

212–230–0

771–29–9

X; X7 Xn; X22 C; X34 X; X50–53

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

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

617–006–00-X

xxx(α, α-dimethylbenzyl)peroxid xxx(2-xxxxxxxxxxx-2-xx)xxxxxxx xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx dikumylperoxid

201–279–3

80–43–3

O; R7 Xx; X36/38 N; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xx; X36 X43

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

650–007–00–3

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

228–200–5

6164–98–3

Xxxx. kat. 3; X40 Xn; R21/22 X; X50–53

Xx; N 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; N 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 X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx

243–269–1

19750–95–9

Xxxx. xxx. 3; X40 Xx; X22 X; X50–53

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

650–033–00–5

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

66230–04–4

T; X23/25 X43 X; X50–53

X; X 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-chlorethoxy)benzen-1-sulfonyl]-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)močovina

82097–50–5

N; X50–53

X X: 50/53 S: 60-61


PŘÍLOHA 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační xxxxxx

Xxxxxxxx x xxxxxxxxxx

006–090–00–8

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

408–010–0

88558–41–2

Xx; X20 Xx; X41 R52–53

Xn X: 20–41–52/53 S: (2-)22–26–39–61

014–016–00–0

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

406–490–6

X; X51–53

X X: 51/53 X: 61

015–164–00–9

kalcium-dihydrogen-(1-hydroxyethylen)bisfosfonát xxxxxxxx

400–480–5

36669–85–9

X52–53

X:52/53 X: 61

015–165–00–4

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

404–986–7

Xx; X41 X; R50–53

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

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 X: 61

015–167–00–5

3-[hydroxy(fenyl)fosfinoyl]propanová xxxxxxxx

411–200–6

14657–64–8

Xx; X41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; X50

X R: 50 S: 61

601–051–00–7

4-xxxxxxxx-1-xx

405–980–7

768–56–9

Xx; X38 X; X51–53

Xx; X X: 38–51/53 X: (2-)37-61

602–083–00–4

xxxxxxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; X48/21/22 X64 X; X50–53

Xx; 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 X: 52/53–59 X: 59-61

603–128–00–0

2-(xxxxxxxxxxxx)xxxxxxxx

405–490–3

613–62–7

X53

X:53 X: 61

603–129–00–6

1-xxxx-xxxxxxxxxxxx-2-xx

406–180–0

57018–52–7

X10 Xx; X41

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

603–130–00–1

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

406–325–8

Xx; R22 X52–53

Xx X:22–52/53 X: (2-)39-61

603–131–00–7

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 S: (2-)26-39

603–132–00–2

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

408–200–3

63187–91–7

Xx; R38–41 X52–53

Xx X:38–41–52/53 S: (2-)26–37/39–61

603–133–00–8

Směs:3-(4-amino-2-chlor-5-nitroanilino)propan-1,2-diol x 3,3'-[(2-chlor-5-nitro-1,4-fenylen)diimino]di(propan-1,2-diol)

408–240–1

Xn; X22 X52–53

Xx X:22–52/53 X: (2-)22–36–61

603–134–00–3

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

410–450–3

X53

X: 53 X: 61

603–135–00–9

bis[2-(2-methoxyethoxy)ethanolato]bis(2,2', 2-xxxxxxxxxxxxxxx-1-xxxxx-X,X)xxxxxxxxxx xxxxxxx

410–500–4

Xx; X41 N; X51–53

Xx; N R: 41–51/53 S: (2-)26–39–61

603–136–00–4

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

410–910–3

104226–19–9

X43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

603–137–00-X

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

411–130–6

Xx; X41

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

603–138–00–5

3-(2,2-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-xxxxxxxx-3-(3-xxxxxxxxxxx)xxxxxx-1-xx

403–140–4

103694–68–4

X52–53

X:52/53 X: 61

604–050–00-X

4-xxxxx-x-xxxxxx 4-chlor-2-methylfenol

216–381–3

1570–64–5

T; X23 C; X 35 N; R50

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

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

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 S: 61

604–052–00–0

2,2'-xxxxxxxxxxx[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -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 - butyl-2-methyl-6-(1-methylpentadecyl)fenol

410–760–9

157661–93–3

Xi; R38 X43 X; X50–53

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

604–054–00–1

Xxxx:2-xxxxxxx-4-(4-xxxxxxxxxxxxxxxxxxxxxxxxx-2-xx)xxxxx x 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -xxxxx-2-xx)xxxxx

412–020–0

X43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

604–055–00–7

4,4'-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, 4,5,6,7,7a-hexahydro-4,7-methano-1H - xxxxx-5-xxxxxxxxxxx

410–480–7

X43 N; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-xxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxx-1-xx

4–406–670–4

61203–83–6

X; X51–53

X X: 51/53 X: 61

606–052–00–6

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

410–410–5

54574–82–2

R52–53

R:52/53 X: 61

607–272–00–5

xxxxxxxxxxx-xxxxxx (XXX) [1] xxxxxxxxxx-xxxxxxxxx (ISO) [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]

N; X50–53

X X: 50/53 X: 60-61

607–273–00–0

amonium-7-{2,6-dimethyl-8-[(2,2-dimethylbutanoyl)oxy]- 1,2,6,7,8,8x-xxxxxxxxx-1-xxxxxx}-3,5-xxxxxxxxxxxxxxxxxx

404–520–2

X52–53

X:52/53 X: 61

607–274–00–6

{2-[xxxxxx(xxxxxx)xxxxx]xxxxx}-3-xxxxxxxx-2-xxxxx

405–350–1

54527–73–0

X43 X; X51–53

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

607–277–00–2

Xxxx:2-(xxxxxxxxxxxxx)xxxxxxxxx-xxxxxxxxxxxx x xxxxxxx-xxxxxxxxx

405–720–2

Xx; X22 Xx; X41 R43 X; X51–53

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

607–278–00–8

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

405–760–0

Xx; X41 X43 X52–53

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

607–279–00–3

Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) x (xxxxxxxxxxxxxx)xxxxxxxxx-(xxxxxxxx-xxxxxx)-(xxxxxxxx-xxxxxxxx)

405–960–8

X43 X; X51–53

Xx; 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; X36 X43

Xx X: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

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

407–000–3

127519–17–9

X; R51–53

N X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 S: 61

607–283–00–5

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

408–040–4

15121–89–8

Xx; X21/22 Xx; X38–41 X43 N; X50–53

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

607–284–00–0

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

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

Xxxx:7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxxx xxxxxxxx, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx x natrium-7-(3-aminobenzensulfonamido)naftalen-1,3-disulfonát

410–065–0

R43

Xi X: 43 S: (2-)22–24–37

607–286–00–1

Xxxx:xxxxxx- a natrium-7-[4-({4-[(2-hydroxy-1-naftyl)azo]fenyl}azo)benzensulfonamido]naftalen-1,3-disulfonát

410–070–8

141880–36–6

R43 X52–53

Xx X:43–52/53 X: (2-)22–24–37–61

607–287–00–7

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

410–140–8

X52–53

X:52/53 X: 61

607–288–00–2

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

410–160–7

148732–74–5

Xx; X36 X43 X52–53

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

607–288–00–8

3-[(3-{X —[4-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxx]xxxxxxxxx}-4-xxxxxxx-1-xxxxxx)xxxxxxxx]xxxxxxxxx xxxxxxxx

410–370–9

105488–33–3

X53

X:53 X: 61

607–290–00–3

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

410–540–2

Xx; R38 X43 X; R50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx

410–630–1

104051–92–5

X53

X: 53 X: 61

607–292–00–4

Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(xxxxx(X14)xxx)-1-(xxxxxxxxxxxxx)]xxxxxx 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-XSměs:

1-(2-aminoethyl)piperazin-1,4-diium-[(2,4,6-trimethylnonyl)fenoxy]benzendisulfonát a 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx

410–650–0

Xx; X41 X43 X; X51–53

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

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

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

410–800–5

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

607–296–00–6

Xxxx:xxxxxxxxxxx pentaerythritolu, xxxxxxxxx kyselina a 2-xxxxxxxxxxxxx xxxxxxxx

410–830–9

X53

X: 53 X: 61

607–297–00–1

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

410–960–6

92761–26–7

Xx; R41

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

607–298–00–7

[2-(xxxxxxxxxxxxxxx)xxxxx]-4-xxxxxxxxxxxxxxxx

411–010–3

X43

Xx X: 43 S: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; R22 X43 X; R50–53

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

607–300–00–6

[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, x-xxxxxxxxxxxxxxxxxxxx]xxxxxxx xxxxxxx, xxxxxxxx sůl; 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 X: 43 X: (2-)22–24–37

607–301–00–1

Xxxx:xxxxxxxxxx xxxxxxxx x dodekanoáty 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 xxxxxxxxxxxxxx xxxxx(1-7)xxxxxxx

411–910–6

Xx; X38–41 R43 X; X51–53

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

607–303–00–2

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

413–760–7

93107–30–3

Repr. xxx.3; X62 X52–53

Xx 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 S: 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 S: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; X3 X; X8 Xxxx. xxx. 2; X45 X; X23/25 R43

E; X X: 45–3–8–23/25–43 S: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; R22–48/22 C; X34 X43 X; X50–53

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

402–850–1

Xx X: 41–52/53 X: (2-)26–39–61

611–044–00–0

Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx x[(4(5)-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx) (3-nitro-5-pentylbenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx

403–720–7

117527–94–3

X; X51–53

Xx; X41 X52–53

611–045–00–6

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

404–830–8

X53

X:53 X: 61

X X: 51/53 X: 61

611–046–00–1

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

407–590–2

43151–99–1

X; X25 Xx; X48/22 R43 N; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

X53

X: 53 S: 61

611–048–00–2

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

407–900–6

111381–12–5

X53

X: 53 X: 61

611–049–00–8

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

408–000–6

118658–98–3

Xx; X48/22 X43 X52–53

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

611–051–00–9

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

411–110–7

136213–74–6

N; X50–53

X X: 50/53 X: 60-61

611–052–00–4

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

400–720–9

X52–53

X: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; X41 X; X50–53

Xx; X R: 41–50/53 S: (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 Xx; X41 X43 X; X51–53

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

612–158–00–3

Xxxx:[xxx(5-xxxxx(xxxxxxxxxx C12))-2-hydroxybenzaldoximato)]měďnatý xxxxxxx a 4-dodecyl-2-hydroxybenzaldoxim[bis(5-alkyl(rozvětvený X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx komplex x 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

X53

X: 53 S: 61

612–159–00–9

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

410–880–1

Xx; R22 C; X34 X; X50–53

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

613–149–00–7

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

405–700–3

96489–71–3

X; R23/25 X; X50–53

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

613–150–00–2

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

406–295–6

X53

X:53 X: 61

613–151–00–8

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

406–360–9

104218–44–2

X53

X:53 X: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 X; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-xxxxxxxxxxxxxxx

407–270–2

16063–70–0

X52–53

X:52/53 S: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx R: 22 X: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; X22 R52–53

Xn X: 10–22–52/53 X: (2-)23–36–61

613–156–00–5

2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-butyl-5-chlorimidazol-4-karbaldehyd

410–260–0

83857–96–9

R43 X; X51–53

Xx; X R: 43–51/53 S: (2-)24–37–61

613–157–00–0

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

410–330–0

54236–98–5

Xx; R22–48/22 Xi; X36

Xx R: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

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

410–340–5

69045–84–7

Xn; R20/22 Xx; R41 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 X; X50–53

X; X R: 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

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

410–550–7

79277–18–2

X; X2 R14 Xx; X48/22 R42/43

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

615–023–00–7

xxxxxxxxxxx 2-[(isokyanatosulfonyl)methyl]benzoové xxxxxxxxxxxxxx-2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxx

410–900–9

83056–32–0

X10 X14 Muta. kat. 3; X40 Xn; X20–48/22 Xx; X41 X42

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

616–044–00–4

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

402–510–2

X; R51–53

N X: 51/53 X: 61

616–045–00-X

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

405–190–2

122371–93–1

R43 X53

Xx X: 43-53 S: (2-)22–24–37–61

616–046–00–5

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

406–390–2

N; X50–53

X X: 50/53 X: 60-61

616–047–00–0

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

406–640–0

X43

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

616–048–00–6

3'-(trifluormethyl)isobutyranilid

406–740–4

1939–27–1

Xn; X48/22 X; X51–53

Xx; X X: 48/22–51/53 X: (2-)22–36–61

616–049–00–1

2-(2,4-xx-xxxx-xxxxxxxxxxx)-X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxx

408–150–2

99141–89–6

X53

X:53 X: 61

616–050–00–7

1-[2,5-xxxxxxx-4-(1,1,2,3,3,3-xxxxxxxxxxxxxxxx)xxxxx]-3-(2,6-xxxxxxxxxxxx)xxxxxxxx

410–690–9

103055–07–8

X43 N; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

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

xxx(4-xxxxxxxxxxxxx)xxxxxxx

407–950–9

895–85–2

X; R2 X; X7 N; X50–53

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

650–032–00-X

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

94361–06–5

Xxxx. xxx. 3; X63 Xn; X22 X; X50–53

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


XXXXXXX 2

POVAHA XXXXXXXXXXXX XXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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


PŘÍLOHA 3A

STANDARDNÍ POKYNY XXX XXXXXXXX ZACHÁZENÍ X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/ES,

Úř. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX ZACHÁZENÍ X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES,

Úř. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx na chromozomové xxxxxxx u xxxxx xx xxxxx má xxxxxxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx v xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Xxxxxxxxx xx dva xxxx xxxxxxxxxxxx aberací: chromozomové x chromatidové. U xxxxxxx chemických xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, avšak xxxxxxxxxxxx xxxxxxx se xxxxxx vyskytují. Nárůst xxxxxxxxxxx může znamenat, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxx však xxxx xxxxxx ke stanovení xxxxxxxxxxx aberací x xxxx x xxxxxx xxxxx xxxxxxx používána. Xxxxxxxxxxxx mutace a xxxxxxx xxxx jsou xxxxxxxx mnoha geneticky xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx x s xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx x v xxxxxx xxxxxxxxxxx buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx u xxxxxxx x x xxxxxxxxx xxxxxx.

Xx xxxxxxx na xxxxxxxxxxxx aberace xx xxxxx xxxxx xxx xxxxxxx stabilizované xxxxxxx xxxxx, xxxxxxx xxxxx xxxx primární xxxxxxx xxxxxxx. Použité xxxxx xxxx vybrány xx xxxxxxx xxxxxxxxxx xxxxx x xxxxxxx, xxxxxxxx xxxxxxxxx, počtu chromozomů, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx chromozomových xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx vyžadují xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx zcela napodobit xxxxxxxx xx xxxx x savců. Je xxxxx xx xxxxx xxxxxxxxx podmínek, které xx vedly x xxxxxxxxxx výsledkům, xxx xxxxxxxxxx xxxxxxx mutagenitu x může x xxx xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx úrovní cytotoxicity (4, 5).

Xxxx zkouška xx používá ke xxxxxxxx xxxxxxx mutagenů x karcinogenů xxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx xxx xxxxx xxxxxxxxxxx; xxxx touto xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx závisí xx xxxxxxxx třídě x xxxxxxxxx důkazy x xxx, že xxxxxxxx xxxxxxxxxxx, které xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx zřejmě xxxxxx xxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxxxxx XXX.

Xxx xxxx Xxxxxx xxxx, část X.

1.2 XXXXXXXX

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

Chromozomová xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx x xxxxxxx xxxx xxxxxxxxx x xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : xxxxxx, xxx xxxxxx x xxxxx po X-xxxx xxxxxxxxx XXX xxxxxxx x mitóze, xxxxx xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx xxxx chromozomy xx 4, 8, 16… xxxxxxxxxxxx.

Xxx : xxxxxxxxxxxx xxxx xxxxx xxx xxxxx xxxxx xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx chromatid.

Mitotický xxxxx : xxxxx xxxxx, xxxxx xx xxxxxxxxx x xxxxxxxx, x xxxxxxxxx xxxxx xxxxx v xxxxxxxx; xxxxx stupeň proliferace xxxx populace.

Numerická xxxxxxx : xxxxxxxx počtu xxxxxxxxxx od xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxx typu xxxxx.

Xxxxxxxxxxx : násobek haploidního xxxxx xxxxxxxxxxxxxx xxx (x), jiný xxx xxxxxxxxx (xx. 3 x, 4 n xxx.).

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx změny xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx dělení xx xxxxxx xxxxxxxx; xxxx xx xxxx delece x fragmenty, intrachromozomální xxxx xxxxxxxxxxxxxxxxxx změny.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, a xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. V předem xxxxxxxxxxx intervalech po xxxxxxxx látce xx xx xxxxxxxxx xxxxxx xxxxx xxxxx zastavující xxxxxxxx (xxxx. Xxxxxxxx® xxxx kolchicin), kultury xx sklidí, obarví x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xx zjistí xxxxxxxxxxxxxx xxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx různé xxxxxxx xxxxx, kmeny xxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxx lidských xxxxxxxxx xxxxx (např. xxxxxxxxxxx xxxxxx čínského, xxxxxxxxx xxxxxxxxx xxxx člověka xxxx jiných xxxxx).

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx xxx xxxxxxx xxxxxx kultivační xxxxx a xxxxxxxxx xxxxxxxx (kultivační xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). X xxxxxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxxx chromozomů x xxxx by xxx xxxxxxxxxxxx, zda xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx neměly xxx xxxxxxx. Xxx použité xxxxx x xxxxxxxxx xxxxxxxx xx měla xxx xxxxx normální xxxxx buněčného cyklu.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx x xxxxx: xxxxx xx xxxxxxx x xxxxxxxxx kultur, xxxxxx xx xx xxxxxxxxxxxx xxxxx v xxxxxx xxxxxxx, xxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx, a xxxxxxxx xx xxx 37 °X.

Xxxxxxxxx: xxxx xxxxxxxx xxxxxxxxxxxxxxx (např. xxxxxxxxx) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx probandů se xxxxxxx xx kultivačního xxxxx obsahujícího xxxxxxx (xxxx. fytohemaglutinin) x xxxxxxxx xx xxx 37 °X.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx měly xxx vystaveny xxxxxxxx xxxxx, x to x xxxxxxx metabolickou xxxxxxxx x xxx xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx z xxxxx hlodavců xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (6, 7, 8 x 9), xxxx xxxx fenobarbitonu x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx je x xxxxxxxx testovacím médiu xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx metabolického aktivačního xxxxxxx xxxx záviset xx xxxxx xxxxxxxx xxxxx, xxxxx je xxxxxxxx. V xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce.

Řada xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx exprimujících specifické xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx xx xxxx xxx vědecky xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx být před xxxxxxxx na buňky xxxxxxxxxx nebo suspendovány xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx látky xxxxx xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx aplikací xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx být xxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx být slučitelné x xxxxxxxx xxxxx x s aktivitou X9. Xxxx-xx použita xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Xxxxxxxxxx xx xxxxx možno xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx nestálých xx vodě xx xxxx být xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx přidáním molekulového xxxx.

1.4.2.2 Expoziční koncentrace

Mezi xxxxxxxx, která xxxx xxx xxxxxxxxxx při xxxxxxxxx nejvyšší xxxxxxxxxxx, xxxxx cytotoxicita, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x xxxxx xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx by xxxx být xxxxxxxxx x metabolickou aktivací x xxx ní x xxxxxxx experimentu xx xxxxxxx xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, xxxx xxxx xxxxxx konfluence, xxxxx životaschopných xxxxx xxxx xxxxxxxxx xxxxx. Xxxx xxx xxxxxxx xxxxxxxx cytotoxicitu a xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx xx xxxx xxxx koncentrace xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx minimální xxxxxxxxx, případně žádnou xxxxxxxxx, xxx obvykle xxxxxxx, xx xx xx xxxxxxxxxxx xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. X xxxxxxxx xxxxxxx xx xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx snížení xxxxxx xxxxxxxxxx, počtu xxxxx xxxx xxxxxxxxxxx indexu (xxx x více xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx nepřímým xxxxxxxx xxxxxxxxxxxxx xxxx cytostatických xxxxxx x závisí xx xxxx, xxxxx xxxxxxxx od xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx xxxxxxxxxx u xxxxxxxxxxx kultur, x xxxxx xxxxx xxx xxxx xxxxxx stanovení xxxxxxxx obtížné x xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx buněčného xxxxx, xxxxxxxxx xxxxxxxx generační xxxx (XXX), mohou xxx xxxxxxx jako xxxxxxxxx informace. X xxxxxxx XXX však xxx x celkovou xxxxxxxxx hodnotu, x xxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, x x xxxx přírůstek xxxxxxxx xxxxxxxxx doby xxxx xxx xx následek xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx optimálního xxxxxxx xxxxxxx.

X xxxxxxx relativně xxxxxxxxxxxxxxx látek xx xxxx být xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, xxxxx x nich xx xxxxxxxx.

X případě relativně xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx xxxxxxx xxx xxxxxxxxxxxxx nižších, než xx xxxxxx rozpustnost, xx xxxx xxx xxxxxxx xxxxxxxx xxxxx x koncentraci, xxx xx nad xxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx médiu xx xxxxx xxxx aplikace. X xxxxxxxx případech (xxxx. xxxxxxx-xx xx xxxxxxxx xxxxx při xxxxxxx xxxxxxxxxxxxx, xxx xx rozpustnost) xx xxxxxxxxxx vyzkoušet xxxx xxxxxxxxxxx, při xxxxx xxxxxxx ke xxxxxxx. Xxxx xxx xxxxxxxx xxxxxxxx rozpustnost na xxxxxxx a xx xxxxx expozice, neboť xxxxxxxxxxx x xxxxxxxxxx xxxxxxx xx xxxx x xxxxxxx expozice xxxxx x důsledku xxxxxxxxxxx buněk, xxxx X9 xxx. Xxxxxxxxxxxxx xxx zjistit xxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx x pozitivní xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx být xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx). Xxx xxxxxxx metabolické xxxxxxxx xx xxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxx vyžaduje xxxxxxxx.

X xxxxxxxxx xxxxxxxx xx xxx xxx použit xxxxx elastogen x xxxxxxxxxxx xxxxxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x xxxxxxxxxxxxx nárůst xxx pozadí, xxxx xx prokáže citlivost xxxxxxxxxxx systému.

Koncentrace xxxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx nevyšla xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx x negativních xxxxxxx:

Xxxx metabolické xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx podle XXXXXX

Xxx xxxxxx metabolické xxxxxxxx

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X vnější xxxxxxxxxxxx xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Pro pozitivní xxxxxxxx xxxxx xxx xxxxxxx x xxxx xxxxxx xxxxx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx pokud xxxxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx.

X xxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx skládající se xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx x xxxxxxxxxxx xxxxx x xxxxxxxxxx stejným xxxxxxxx xxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx žádné xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené rozpouštědlo xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní účinky.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx se xxxxxxx xxxxxxxx xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx xxxxxxxxx by xxxx xxx xxxxxxxx xxx 48 hodin xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, a xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx xxx xxxxxxxxx xxxxxxxx nebo xxxxxxxx xxxxxxxxxxxx. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx údajů xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx xxxxxxxxx xx minimální xxxxxx, xxxx xxx přípustné xxxxxxx xxxxxx xxxxxxx.

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

1.4.3.3 Xxxx xxxxxxx xxxxxx

X xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, jak x xxxxxxxxxxxx xxxxxxxx, xxx xxx ní, xx xxxx 3 — 6 xxxxx, x xxxx by xxx odebrány xx xxxxxx době xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5násobku normální xxxxx xxxxxxxxx xxxxx (12). Xxxxxxxx xxxxx xxxxxx dává negativní xxxxxxxx xxx s xxxxxxxx, xxx bez xxxxxxxx, xxx xx xxx proveden dodatečný xxxxxxxxxx xxx aktivace x xxxxxxxxxxxx xxxxxxxx xx xx xxxxxx x xxxx, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx buněčného xxxxx. Xxxxxx xxxxxxxx xxxxx xxx xxxxx xxxxxxxxx xxx xxxxxx aplikace xxxx xxxxxx delších xxx 1,5násobek xxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx od xxxxxxx. X případech, xxx xx nepovažuje potvrzení xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, by xxxx xxx xxxxxx zdůvodnění.

1.4.3.4 Xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx

Xx buněčné xxxxxxx xx xxxxxxx 1-3 hodiny xxxx xxxxxxxxx přidá Colcemid® xxxx xxxxxxxxx. Pro xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx se xxxxx xxxxxxx kultura xxxxxx x xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxx buněk, xxxxxx a obarvení xxxxx.

1.4.3.5 Analýza

Všechny preparáty, xxxxxx xxxxxxxxx xxxxxxxxxxx x negativních xxxxxxx, xx xxxx být xxxx analýzou xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxx části buněk x xxxxxxxx a xx xxxxxx chromozomů, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x xxxxx xxxxxx xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx buněk. Xx xxxxxx xxxxxxxxxxx x xxxxxxxx by xxxx xxx hodnoceno xxxxxxx 200 dobře rozprostřených xxxxxxxx, případně rovnoměrně xxxxxxxxxxx mezi duplicitní xxxxxxx. Tento xxxxx xxx snížit, xx-xx xxxxxxxxx velký xxxxx xxxxxxx.

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

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxxxx jednotkou xx xxxxx a xxxx xx tedy být xxxxxxxxxxx množství buněk xx strukturní xxxxxxxxxxxxx xxxxxxx (aberacemi) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx a xxxxxxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxx různé xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx s xxxxxx xxxxxx a xxxxxxxx. Xxxx se xxxxxxxxxxxxx xxxxxxxx x uvádějí xx, xxx nezahrnují xx xx xxxxxxx xxxxxxxx aberací.

Měla xx xxx také xxxxxxxxxxx xxxxxxxx, která xxxx xxxxxxxxx xxx stanovení xxxxxxxxxxxx x všech xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

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

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Dvojznačné xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx byla xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx xxxxxxxxx studie x xxxxx rozšířit xxxxxx posuzovaných xxxxxxxx xx měla xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X parametrům xxxxxx, které xx xxxxx být změněny, xxxxx xxxxxxx koncentrací x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxxxxxxxx, nebo reprodukovatelný xxxxxx tohoto xxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Statistická xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím faktorem xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx potlačit xxxxxxxx xxxxxxxxx cyklu (17, 18).

Xxxxxxxx xxxxx, jejíž xxxxxxxx nesplňují výše xxxxxxx kritéria, xx x xxxxx xxxxxxx xxxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů poskytne xxxxx xxxxxxxxx nebo xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx na xx, kolikrát je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx výsledky xx zkoušky na xxxxxxxxxxxx aberace xx xxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx x kultivovaných xxxxxxxxxxx xxxxxxx xxxxx strukturní xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx neindukuje x xxxxxxxxxxxxx somatických xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx aberace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxx:

- typ x xxxxx xxxxx,

- xxxxxxxxxx xxxxxxxxx a xxxxxxxx xxxxxxxxx xxxx xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- informace o xxxxx buněčného xxxxx,

- xxxxxxx xxxxx krve, xxx byla použita xxxx xxxx nebo xxxxxxxxxx xxxxxxxxx, použitý xxxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- případně xxxxxx xxxxxxxxx buněčné xxxxxxx,

- xxxxxxx hodnota xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxx koncentrací x počtu xxxxxx, xxxxxx např. údajů x xxxxxxxxxxxx a xxxxxx rozpustnosti, jsou-li x dispozici,

- xxxxxxx xxxxx, případně xxxxxxxxxxx XX2,

- xxxxxxxxxxx zkoušené xxxxx,

- xxxxx vehikula x xxxxxxx zkoušené xxxxx,

- inkubační xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx při nasazení,

- xxx x složení xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxxxxxx,

- xxxxxxxxx a xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxxxxx,

- metody xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxx, xxxxx x buněčném xxxxx, počty xxxxx, xxxxxxxxx index,

- známky xxxxxxx,

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

- definice xxxxxxx, xxxxxx xxxx,

- xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx a xxxx xxxxxxx xxxxxx xxx xxxxxx xxxxxxxxxxx x xxxxxxxxx kulturu,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

2) Xxxxxxxx, X. Xx., Xxxxxx, T. (1985), The Xx xxxxx Chromozomal Xxxxxxxxxx Xxxx Xxxxx Chinese Xxxxxxx Lung (XXX) Xxxxxxxxxx Xxxxx xx Xxxxxxx, xx: Progress xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Xxxxx, X. et xx., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Xxxxxxxx, S. X., Xxxxxxxxx, X. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Cannon, X., Xxxxx, X. D., Xxxxxxxx, X., Ahmed, X., Duk, S., Xxxxx, X., Margolin, X. X., Xxxxxxx, X. X., Anderson, X., Xxxxxx X. (1978), Chromozome xxxxxxxxxx xxx sister chromatic xxxxxxxxx in Xxxxxxx xxxxxxx xxxxx cells: Xxxxxxxxxx of 108 xxxxxxxxx, Environ. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Xxxxx, X., Galloway, X. X., Xxxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxxxx, D., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx xxxxx Xxxxxxx Xxxxxxx Conditions. A xxxxxx from ICPEMC Xxxx Xxxxx 9, Xxxxxxxxxx Res., 257, 147-204.

5) Xxxxxx, T., Xxxxxx, T., Xxxxxx, X., Xxxxxxx, K., (1992), Xxxxxxxxxxxxxx xx xxx xX xx Xxxxxxx Xxxxxxxx Mammalian Xxxxx, Xxxxxxxxxx Xxx., 268, 297-305.

6) Xxxx, X. X., XxXxxx, X., Yamasaki, X. (1975), Xxxxxxx xxx Xxxxxxxxx Carcinogens xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Microsome Xxxxxxxxxxxx Xxxx, Xxxxxxxx Res., 31, 347-364.

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

8) Xxxxxxxxx, X. X., Xxxxx, X. X., xxx Xxxx, X. X. X., Xxxxxxx, M., xx Xxxxx, X. (1976), Cytogenetic Xxxxxxx xx Mutagen/Carcinogens after Xxxxxxxxxx xx x Xxxxxxxxxxx Xxxxxx Xx xxxxx, X. Xxxxxxxxx xx Xxxxxxxxxx Aberrations xxx Xxxxxx Xxxxxxxxx Xxxxxxxx by Xxxxxxxxxxxxxxxxxx (XXX) xxx Dimethylnitrosamine (XXX) xx XXX Xxxxx in xxx Xxxxxxxx xx Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Res., 37, 83-90.

9) Matsuoka, X., Xxxxxxx, M., Xxxxxxxx, M. Xx. (1979), Xxxxxxxxxxx Aberration Xxxxx on 29 Xxxxxxxxx Combined with X9 Mix Xx xxxxx, Xxxxxxxx Xxx., 66, 277-290.

10) Xxxxxx, X. M., Combes, X. X., Elcombe, X. R., Xxxxxxxxx, X. G., Xxxxxx, X. G., Xxxxxx, X. X., Xxxx, X. C. (1992), Xxxxxx of UK Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Party. Xxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 xx Xx xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, X., Xxxxxxxx, T. (1976), X. Safe Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. x. an Xxxxxxx of Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: xx Xxxxxx, F. X., Xxxxx, X. X. Xxxx, J. X., Philpot, X. X. (xxx), Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Testing, Xxxxxxxx, North-Holland, 85-88.

12) Xxxxxxxx, S. M., Xxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxx, X. X., Xxxxxxxx, D. J., Xxxxxx, X., Mosesso, X., Xxxxxx, X. (1994), Report xxxx Xxxxxxx Xxxxx on Xx xxxxx Xxxxx xxx Chromozomal Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 312, 241-261.

13) Xxxxxxxxxx, C., Xxxxxxxx, D. A., Xxxxx, J. X., Xxxxxxxx, X., Xxxxxxx, X. X., Xxxxxxxx, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx vitro Cytogenetic Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. X., (xx) Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, 141-154.

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

15) Xxxxx, D. X., Xxxxxx, X. X., XxXxxxx, X. T. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Evaluation of Xxxxx xxx Xxxxxxxx Xxxxxxx, in: Tice, X. R., Costa, X. L., Xxxxxxx, X. X. (eds), Xxxxxxxxx Effects of Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.

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

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

18) Xxxxx, X., Xxxxxx, C., Trosko, X. X. (1983), Xxxxxxxxxxx-xxxxxxx endoreduplication in Xxxxxxx xxxxxxx xxxxx, Xxxxxx Res., 43, 1362-1364."


XXXXXXX 4X

"X.11 MUTAGENITA–ZKOUŠKA XX XXXXXXXXXXXX ABERACE X XXXXXXX XXXXXX XXXXX XXXXX IN XXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx metody XXXX TG 475 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxxxx kostní xxxxx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx aberace x xxxxx xx xxxx xx používána xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx indukovaných xxxxxxxxx xxxxxx x xxxxxxx xxxxxx xxxxx xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx se xxx xxxx xxxxxxxxxxxx xxxxxxx — xxxxxxxxxxxx x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx chemická xxxxx xx schopnost indukovat xxxxxxxxx xxxxxxx. X xxxxxxx většiny xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx chromatidového typu, xxxxx xxxxxxxxxxxx xxxxxxx xx rovněž xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxx xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, že chromozomové xxxxxx x xxxxxxxxxxx xxxx způsobující změny x onkogenech x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx podíl xx xxxxxxx rakoviny u xxxxxxx x v xxxxxxxxxxxxxxxx systémech.

Při této xxxxxxx xxxx rutinně xxxxxxxxx xxxxxxxx. Cílovou xxxxx xx v xxxx zkoušce xxxxxx xxxx, poněvadž xx xxxxxx vaskularizovanou xxxxx x xxxxxxxx populaci xxxxx s rychlým xxxxxx, xxxxx xx xxxxxx xxxxxxx a xxxxxxxxxxxx. Xxxx xxxxx x xxxxxx tkáně xxxxxx předmětem této xxxxxx.

Xxxx zkouška xx xxxxxxxxxxxx xxxxxxx xx xxxxxxx xxxxxx x xxxxxxxxx nebezpečí xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx metabolismu in xxxx, farmakokinetiku x xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx x xxxxxxx druhů x xxxxx měnit. Xxxxxxx xx xxxx xx xxxxxx užitečná xxx xxxxx xxxxxx xxxxxxxxxxx účinků zjištěných xxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, že xx xxxxxxxx xxxxx nebo xxxxxxxxx metabolity xxxxxxxxxx xx cílové xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx také Xxxxxx úvod, část X.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : strukturní xxxxxxxxx xxxxxxxxxx v xxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx zlomu a xxxxxxxx xxxxxxx xxxxxxxxx.

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

Xxxxxxxxxxxxxxx : xxxxxx, xxx xxxxxx x xxxxx xx X-xxxx xxxxxxxxx XXX xxxxxxx x xxxxxx, xxxxx xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx jsou xxxxxxxxxx xx 4, 8, 16,… xxxxxxxxxxxx.

Xxx : achromatická léze xxxxx xxx šířka xxxxxxx xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

Xxxxxxxxxxx : xxxxxxx xxxxxxxxxxx počtu xxxxxxxxxxxxxx xxx (x), xxxx xxx diploidní (xx. 3 x, 4 x xxx.).

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx pozorovatelné xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx dělení xx xxxxxx metafáze; xxxx se jako xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx nebo xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx jsou xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xx xxxxxxx xxxxxxxx xx xxxxxxxx xx usmrtí. Xxxx usmrcením xx xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx kostní xxxxx se xxxx xxxxxxxx xxxxxxxxx chromozomů, xxxxxx xx x xxxxxxxxx xx chromozomové xxxxxxx xxxxx x xxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx xxxxxxxx potkan, myš x xxxxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx vhodný xxxxx xxxx. Xxxx xx xxx použity xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x hmotnosti xxxxxx minimální x xxxxxx xx u xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, xxxxx xx vystaví xxxxxxxx xxxxx. Xxxxx by xxxx xxx xxxxxxxxxx xxx, aby xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx se xxxxxxxxxxx identifikují. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx být xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx použitých xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx být xxxxxxxxx xxxxxxxxx, xx reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx použita jiná xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx podstoupit identický xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx kontroly xx xxxx xxxxxxxxxx strukturní xxxxxxx xx xxxx xxx xxxxxxxxxxx úrovních, x nichž se xxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx nad xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx xxx, xxx byl účinek xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx látka a xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxx xxxxx xx xxxxxx chemické xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx látek xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx EINECS

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

mitomycin X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X okamžiku xxxxxxx odběru xx xxx být xxxxxxxx xxxxx x negativních xxxxxxx, jimž xx xxxxxxxxxx pouze rozpouštědlo xxxx xxxxxxxxx x xxx xxxxx podstupují xxxxxx proces xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x dosavadních xxxxxxxxxxx údajů x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx jeden xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx kontroly použity xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Každá xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxxxx x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx. Xxxxxxxx xxxx v xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx druhem x xx použití xxxxxxxx způsobu xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx mezi pohlavími xxxxxx v xxxxxxxx, xxxx xxxxxxxxxxx zkoušení xxxxxxx pohlaví. Xx-xx xxxxxxxx člověka specifická xxx xxxxxx pohlaví, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx se xxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx by xxxx být pokud xxxxx podávány xxxxxxxxxxx. Xxxxxxxx látky mohou xxx xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. xxx dávky x xxx xxx x rozmezí ne xxxx xxx xxxxxxxx xxxxx, aby bylo xxxxxxxxx xxxxxxxx velkých xxxxxx materiálu. Xxxx xxxxxx podávání xx xxxx xxx vědecky xxxxxxxxxx.

Xxxxxx by xxxx xxx xxxxxxxx xx xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxxx x jednom xxx. X xxxxxxxx xx xxxxx xxxxxxx xx xxxxxx xxxx xx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu (xxxx xxxx obvykle 12 — 18 h). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x rovněž xxx xxxxxx xx xxxxxxxx xxxxxxxxx xxxxx může xxx xxxx xx xxxxxxxxx okamžik pro xxxxxxxxx chromozomových aberací, xxxxxxxxxx xx provést xxxxx xxxxx xx 24 x od xxxxxxx xxxxxx. Je-li xxxxxxxx xxxxxxxxx do xxxx než xxxxxxx xxx, měl by xxx odběr xxxxxxxx xx xxxxxx době xx xxxxxxxx xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx.

Xxxx xxxxxxxxx se xxxxxxxx intraperitoneálně podá xxxxxx xxxxx xxxxx xxxxxxxxxxx metafázi (např. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx době provede x xxxxxx xxxxx. X myši xx xxxx xxxx xxxxxxxxx 3 — 5 x; x křečka xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx odeberou xxxxx x xxxxxxxxx xx xx xxxxxxxxxxxx aberace.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx dávek, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx stejným xxxxxx, xxxxxx, pohlavím x za stejného xxxxxx expozice, xxx xx xxxxxxx x xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx pro první xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx použita xxxxx xxxxxxxx dávka. Xxxxxxxx dávka je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, že vyšší xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx podle xxxxxxxxx x letalitě. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx by xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx dávka xxxx xxx také xxxxxxxxxx jako dávka xxxxxxxxxxxx x kostní xxxxx některé xxxxxx xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx indexu).

1.5.4 Xxxxxxx zkouška

Jestliže zkouška x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx xxx nevykazuje xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx strukturu, xxxxxxxxx genotoxicita, nepovažuje xx xxxxx studie xx xxxxx xxxxxxxx xxxxx xx nezbytnou. X xxxx xxxxxxxxxx xxxxxx xx limitní xxxxxx xxx 14denní xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx a xxx xxxxx xxx 14xxxxx xxxxxxxx xx xxxxxxx dávkou 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx expozice člověka xxxx xxxxxxxx potřebu xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo vhodnou xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx x xxxxxxxxxxxx případech xxxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx xxxx injekčně, xxxxxx na xxxxxxxxx xxxxxxxxxxx zvířete. Objem xx neměl překročit 2 ml/100 g xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx xxx zdůvodněno. Xx xx xxxxxxxx x xxxxxx látky, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx minimalizována xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů xxx xxxxxxx chromozomů

Ihned po xxxxxxxx xx odebere xxxxxx xxxx, hypotonizuje xx x xxxxxx. Xxxxx xx nanesou xx xxxxxxxx xxxxxxx x xxxxxx se.

1.5.7 Xxxxxxx

Xxxx xxxxxxx xxxxxxxxxxxx xx xxx xxx x xxxxx xxxxxxxxxxxx xxxxxx (xxxxxx pozitivních xxxxxxx) x x xxxxxxxxxxxxxx xxxxxx xxx xxxxxxxxx xxxxxxxx stanoven xxxxxxxxx index, x xx xxxxxxx x 1000 xxxxx xx xxxxx xxxxx.

X xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx velký xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxx při xxxxxx xxxxx xxxxxxx xx chromozomálním xxxxxx xxxx xx xxxxxx xxxxxxxxxx x xxxxx xxxxx x xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx. Pro xxxxx xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx, xxxxx xxxxxxx xx buňku x xxxxx buněk x xxxxxxxxxxxxx xxxxxxx (chromozomovými xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx exponované x kontrolní xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx chromozomových aberací x xxxxxx xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx xxxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx. Neexistuje-li xxxxx x rozdílu x xxxxxxxx xxxx xxxxxxxxx, mohou být xxx statistickou xxxxxxx xxxxx xxx obě xxxxxxx zkombinovány.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx xxx xxxxxxx x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky mohou xxx xxxxxxx jako xxxxxxx xxxxxxxxxx statistické xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravami xxxxxxxxxxxxxxxx podmínek.

Nárůst xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, xx zkoušená xxxxx xx potenciál xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (7, 8).

Xxxxxxxx xxxxx, jejíž výsledky xxxxxxxxx výše uvedená xxxxxxxx, xx xxxxxxxx x xxxxx xxxxxxx xx nemutagenní.

Ačkoli většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x aktivitě xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx xxxxxx na xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

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

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx do xxxxxxxx xxxxx, xxxx xxxxxxxxxx xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x zkoušce xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x pohlaví zvířat,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

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

Zkušební podmínky:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x přípravě xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- popřípadě xxxxxx xxxxxxx, zda xx xxxxxxxx xxxxx dostala xx krevního xxxxx xxxx xx xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx krmiva x xxxx,

- xxxxxxxx popis xxxxxxx expozice x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx látky xxxxxxxxxxx xxxxxxxx, její xxxxxxxxxxx x délka xxxxxxxx,

- xxxxxx přípravy xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx analyzovaných xxxxx na xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx xxxxx,

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

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

- xxxxx buněk x xxxxxxxxx ve xxxxxxx xx středními xxxxxxxxx x xxxxxxxxxxxx odchylkami,

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

- dosavadní xxxxx x xxxxxxxxx kontrole x rozpětími, středními xxxxxxxxx a směrodatnými xxxxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X. (1984), Xxxxxxxxxxx Xxxxx xx Xxxxxxx, in: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, X. Xxxxxx, X. X. Xxxxx (xxx), XXX Xxxxx, Xxxxxx, Xxxxxxxxxx X. X., 275-306.

2) Xxxxxxx, X. J., Xxxx, X. X., Xxxxxxxx, X., Holden, X., XxXxx, A. X., Xxxxxx, M. (1987), Xxxxxxxxx In xxxx Xxxxxxxxxxx Assays: Analysis xx Xxxxxxxxxx Xxxxxxxxxxx xx Xxxx Xxxxxx Xxxxx, Mutatation Res., 189, 157-165.

3) Richold, X., Chandley, X., Xxxxx, J., Xxxxxxxxx, X. X., Bootman, X., Henderson, X. (1990), Xx xxxx Xxxxxxxxxxx Assays, xx: X. X. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx Xxxxx, UKEMS Recommended Xxxxxxxxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx X revised, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. X., Hayashi, X., XxxXxxxxxx, J. X., Xxxxxxxx, D., Xxxxxx, X. X., Xxxxxx, X. E., Xxxxxx-Xxxxxxx, M., Xxxxxx Xx., F. X., Xxxxxxxxxxxx, X., Xxxxxxx, X. J., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, S., Xxxxxxx, X. (1994), Xxxxxx xxxx xxx Working Xxxxx xx xxx xx vivo Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Mutatation Xxx., 312, 305-312.

5) Xxxxxxx, X. J., Xxxxx, X. X., Xxxxxx, A. R., Xxxxxx, X. X., Xxx, X., Esdaile, X. J., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, X. X., Xxxxxxx, M. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Society/UK Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx: Dose Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. P., Xxxxxxxx, X., Xxxxxxxx, X., Amphlett, G. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, D. X., Savage, X. X. X. (1989), Xxxxxxxxxxx Analysis of Xx vivo Xxxxxxxxxxx Xxxxxx, in: XXXXX Xxx-Xxxxxxxxx on Guidelines xxx Xxxxxxxxxxxx Testing, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Xxxx Data, X. X. Xxxxxxxx (xx.) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 184-232.

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

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


XXXXXXX 4X

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

1. METODA

Tato xxxxxx xx replikou xxxxxx XXXX XX 474 — Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx (1997).

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx používán xxx xxxxxxx poškození chromozomů xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, xxxxx je xxxxxxxxxx zkoušenou xxxxxx, x xx xxxxxx xxxxxxx xxxxxxxxxx odebraných x kostní dřeně x/xxxx xxxxx xxxxxxxxx xxxx, obvykle xxxxxxxx.

Xxxxxx xxxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx je xxxxxxxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, jehož xxxxxxxxx xx tvorba xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxx xxxxxxxxx nebo xxxx xxxxxxxxxx.

Xxxx xx erytroblast xxxxxx xxxxx xxxx xx xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxx xxxxx je xxxxxxxx x xxxxxxxxxx, xxxxx při xxx xxxxx xxxxxxxxx, xxxxxxxxx x cytoplasmě, která xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx xx x těchto buňkách xxxxxxxxx xxx, xx xxxxxxxxxx xxxxxx xxxxx. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx s mikrojádry x xxxxxxxxxxxx xxxxxxxxx xx xxxxxxx indukovaného xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx xx xxxxxxx xxxxxxxxx kostní xxxx xxxxxxxx, poněvadž xxxx xxxx produkuje polychromatické xxxxxxxxxx. Stanovení nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx v xxxxxxxxx xxxx xx xxxxxxxxxx xxxxxxxxxx u xxxxxxxxxxx xxxxx, x xxxxx xxxx prokázána xxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxxx xxx xxxxxxxx xxxxx xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx přítomnosti xxxx xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX x xxxxxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxxx nezralých (polychromatických) xxxxxxxxxx s mikrojádry. Xxxxx zralých (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxx xxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxxxxxxxx xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx jako xxxxxxx xxxxxxxx xxxxxxx, jestliže xxxx zvířata exponována xxxxx xxxxx xxxx xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx zvláště xxxxxx k xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx in vivo, xxxxxxxxxxxxxxx x procesy xxxxxxxx DNA, xxxxxxx xx mohou lišit x různých xxxxx x tkání, xxxxx x x genetického xxxxxxxx. Xxxxxxx xx xxxx xx rovněž xxxxxxxx pro xxxxx xxxxxx mutagenních účinků xxxxxxxxxx x xxxxxxxxx xx xxxxx.

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

Xxx také Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (kinetochor) : xxxxxx (xxxxxxx) xxxxxxxxxx, x níž (x xxxx) se během xxxxxx buněk xxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxx pohyb xxxxxxxxx xxxxxxxxxx k xxxxx xxxxxxxxx buněk.

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

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

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx erytrocyt ve xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx xxxxxxxx xxxxxxxx, x xxxx xxx xxxx xxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx xxxxx xx xxxxxxx xx vhodném xxxxxxxx xx xxxxxxxx xxxxxx, odebere se xxxxxx xxxx, xxxxxxxx xx xxxxxxxxx x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx xxxxxxxxx xxxx xx xxxx xx vhodném okamžiku xx expozici xxxxxxx, xxxxxxxxxx se xxxxxxxx xxxxxxxx x obarví xx (4, 8, 9, 10). Xxx xxxxxxxx s xxxxxxxxx xxxx by xxxx xxxx xxxxxxxx xxxxxxxx x xxxxxxxxx buněk xxxxxxxx xx xxxxxxxxx xxxx. Xxxxxxxxx xxxx xxxxxxxxxxx xx xxxxxxxxxx xxxxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx zvířete

Při použití xxxxxx xxxxx xx xxxx xxxxxxxxx xxxxx xxxxxxxxxx myš nebo xxxxxx, ačkoli xxx xxxxxx jakýkoli xxxxxx xxxxx xxxx. Xxx xxxxxxx xxxxxxxxx krve xx xxxxxxxxxx xxx. Xxx xxxx použít xxxxxxxx xxxxxx xxxx xxxxx za xxxxxxxxxxx, xx xxx x xxxx, x xxxxx xxxxxxx neodstraňuje xxxxxxxxxx x mikrojádry, xxxx xxxx vykazující xxxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické chromozomové xxxxxxx. Měly by xxx použity xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx zdravých pohlavně xxxxxxxxx zvířat. V xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx x xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx hodnoty hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx zvířata xx xxxxxxxx výběrem rozdělí xx kontrolní xxxxxxx x skupinu, x xxx xx xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Xxxxxxx xx v xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx. Xxxxx xx xxxxxxxxxx tak, xxx xxx vliv xxxxxx polohy minimalizován.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx nebo xxxxx xxx před podáním xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x jejich stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx mít xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx by xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx než xxxxx rozpouštědla/vehikula, xxxx xx xxx jejich xxxxxxxx podloženo xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každého experimentu xx xxxx xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx aplikace zkoušené xxxxx xx měla xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx ve xxxxxxxxx, x nichž xxxxx x expozici.

Pozitivní xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx in xxxx xxx xxxxxxxxxxx xxxxxxxx, u xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx pozadí. Xxxxx xxxxxxxxx kontroly by xxxx být xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx identifikace xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxxxxxxx xxxxxxxx byla xxxxxxxx xxxxx xxxxxxxx xxx zkoušená xxxxx x xxx xxx xxxxx x xxxxx xxxxxxx prováděn jen xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx xxxx xxx vzato x xxxxx xxxxxxx chemických xxxxx xx stejné xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx C

50–07–7

200–008–6

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx xxx být xxxxxxxx xxxxx u xxxxxxx negativní xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx rozpouštědlo xxxx xxxxxxxxx x která xxxxx podstupuje xxxxxx xxxxxx xxxx exponované xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx kontrolních xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxx. Provádí-li xx xxx xxxxxxxxx kontrolu xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx doba xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx dosud nebo xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx použití xxxxxxxxx xxxx xxxx xxx jako negativní xxxxxxxx přijatelný xxxx xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx x xxxxxxxx xxxxxx s xxxxxxxxx xxxx (xxxx. 1 — 3 xxxxxxxx) xx předpokladu, xx xxxxxxxx údaje budou x rozpětí, které xx xx základě xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx xxxxxxx x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx (11). Xxxxxxxx xxxx v xxxx xxxxxx x xxxxxxxxx údaje xx xxxxxx se xxxxxxx xxxxxx a xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx mezi xxxxxxxxx rozdíl x xxxxxxxx, xxxx postačující xxxxxxxx xxxxxxx pohlaví. Xx-xx expozice člověka xxxxxxxxxx xxx určité xxxxxxx, xxxx xx xxxx například x xxxxxxxxx farmaceutických látek, xxxx xx xxx xxxxxxx xxxxxxxxx se xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx xxxxxxxxx xxxxx standardní xxxx (xx. jednu, xxx xxxx tři aplikace x intervalu 24 xxxxx). Xxxxxx ze xxxxxx x prodlouženým xxxxxxx podávání xxxx xxxxxxxxxx, xxxxx xx x xxxxxx xxxxxx xxxxxxx pozitivní xxxxxxxx, xxxx –v xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx xxxx xxxxxxxxx xxxxxxxx xxxx xxxx xxxxxxxxx limitní xxxxx x xxxxxxxx pokračuje xx xx xxxxxxxx xxxxxx. Xxxxxxxx látky xxxxx xxx podávány xxxx xx xxxx xxxxxxx, xxx. xxx xxxxx x týž xxx x xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx usnadněno podávání xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx být proveden xxxxx xxxxxxx:

x) xxxxxxxx xxxxx xx aplikuje xxxxxxxx jednou. Vzorky xxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 24 hodin po xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 hodin xx xxxxxxxx x x xxxxxxxxxx odstupem xxxx xxxxxx. Odběr xxxxx než 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx xxxxxxxxx krve xx odeberou xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx se xxxxxxx xxxxxxxx 36 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx po aplikaci x xx xxxxxxxxxxxx xx xxxxxx xxxxxxxxxxxx xxxxxx. Xx-xx po xxxxxx xxxxxx pozorována xxxxxxxxx xxxxxxx, xxxx xxxxx xxxxx xxxxx;

x) xxxx-xx xxxxxxxx dvě xxxx xxxx dávek xxxxx (xxxx. xxx xxxx více dávek x xxxxxxxxx 24 xxxxx), xxxx xx xxx xxxxxx xxx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx xx 18 xx 24 xxxxxxxx po xxxxxxxx xxxxxxxx x xxx xxxxxxx periferní krve xxxxxx xx 36 xx 48 xxxxxxxx xx poslední aplikaci (12).

Xxxxx potřeby mohou xxx xxxxx xxxxxxx xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx rozsahu dávek, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx stejného xxxxxx expozice, xxx xx xxxxxxx x xxxxxx xxxxxx (13). X případě xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx tři xxxxxx dávky. Xxxx xxxxxx dávky xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx dávka je xxxxxxxxxx xxxx dávka xxxxxxxxxxxx takové známky xxxxxxxx, xx xxxxx xxxxx by vedly xxx stejném xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx x xxxx xx být xxxxxxxxx případ od xxxxxxx. Xxxxxxxx dávka xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x xxxxxx xxxxx některé xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx nezralých xxxxxxxxxx x celkového množství xxxxxxxxxx x xxxxxx xxxxx nebo v xxxxxxxxx xxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx dávkou o xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx toxické xxxxxx x není-li xx základě xxxxx x látkách, které xxxx xxxxxxxx strukturu, xxxxxxxxx genotoxicita, xxxx xxxxxxxxxx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx x xxx xxxxx než 14xxxxx xxxxxxxx xx xxxxxxx xxxxxx 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx se obvykle xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo xxxxxxx xxxxxxxxx kanylou, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx podávání jsou xxxxxxxxxx x xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx sondou xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx vyšších xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, které obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx zkušebního xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx získávají x xxxxxx xxxx xxxxx xxxxx po xxxxxxxx. Xxxxx xx odeberou x xxxxxx xxxx xxxxx x xxxxxxxxxx xxxxxxxx xx preparují x xxxxxx. Xxxxxxxxx xxxx se xxxxxxx x xxxxxx žíly xxxx xxxx xxxxxx xxxxxx cévy. Xxxxxx xxxxx xx ihned xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx xxxxxxxx xxxxxxxxx xxxxxxxx x poté xx xxxxxx. Xxxxxxxx xxxxxxx xxxxxxxxxxxx xxx XXX (xxxx. akridinová xxxxx (14) nebo Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx vyhnout některým xxxxxxxxxx xxxxxxxx s xxxxxxxx barviva xxxxxxxxxxxxxx xxx DNA. Xxxx xxxxxx nebrání použití xxxxxxxxxxx barviv (např. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. xxxxxxxxxx xxxxxx x xxxxxxxxxx buněk xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, xx se xxxxxxxxx odpovídající xxxxxxxxx xxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx se xxxxxxx xxxxx xxxxxxxxx erytrocytů x celkového (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx xx x xxxxxxx xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 xxxxxxxxxx x x xxxxxxx xxxxxxxxx xxxx xxxxxxx 1000 xxxxxxxxxx (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx před xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxxxxxxxx. Další informace xxxxx xxx získány xxxxxxxxxx zralých xxxxxxxxxx xx výskyt xxxxxxxxxx. Xxx mikroskopické xxxxxxx xx xxxxx být xxxxx nezralých xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx xxxxx xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx jsou xxxxxxx exponována xxxxxxxxxxx xxxxx týdny xxxx xxxx, lze xxxx xxxxxxxx na výskyt xxxxxxxxxx alespoň 2000 xxxxxxx xxxxxxxxxx na xxxxx xxxxx. Xxxxxxx xxx automatickou xxxxxxx (xxxxxxx obrazu x xxxxxxxxx cytometrická xxxxxxx xxxxxxx xxxxxxxx) jsou xx xxxxxxxxxxxxx zdůvodnění x xxxxxxxx přijatelnými xxxxxxxxxxxxx manuálního xxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx jednotlivá zvířata xx měly xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Pro xxxxx analyzované xxxxx xx měl být xxxxxx xxxxx xxxxxxxxxxx xxxxxxxxx erytrocytů, xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx nepřetržitě čtyři xxxxx nebo déle, xxxx by být xxxx uvedeny xxxxx x xxxxxxx erytrocytech, xxxx-xx xxxxxxxxxxxxx. Pro xxxxx xxxxx xx xxxxx xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx a xxxxxxxx xxxxxxxx erytrocytů x xxxxxxxxxx xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, mohou xxx xxx xxxxxxxxxxxx analýzu xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. nárůst xxxxx xxxxx x xxxxxxxxxx x xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx buněk x xxxxxxxxxx xxx xxxxxxx x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx by xxxx xxx xxxxxxx biologická xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný prostředek xxxxxxxxxxx xxxxxx (18, 19). Statistická xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx být xxxxxxxxx xxxxxx zkoušením, xxxxxxx x úpravou experimentálních xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx je xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx, že zkoušená xxxxx indukuje xxxxxxxxxx, xxx jsou xxxxxxxxx xxxxxxxxxxxxxx poškození xxxx xxxxxxxxx xxxxxxxxxxx aparátu xxxxxxxxxxxx xxxxxxxxxxx druhu. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxxx mikrojádra x xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx zkoušená xxxxx nebo xxxx xxxxxxxxxx dostanou do xxxxxxxx xxxxx, xxxx xxxxxxxxxx do xxxxxx xxxxx (xxxx. systémová xxxxxxxx).

3. ZPRÁVY

PROTOKOL O XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- počet, stáří x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx zvířat na xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx hmotnosti, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx pro xxxxxx skupinu.

Zkušební podmínky:

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

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- xxxxxxxxxx xxxxxxx podávání,

- xxxxxxxxx xxxxxx ověření, xxx xx xxxxxxxx xxxxx dostala do xxxxxxxx xxxxx nebo xx cílové xxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x krmivu xxxx xxxx (xxx) xx xxxxxxxxxxxx xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x kvalitě xxxxxx x vody,

- xxxxxxxx popis xxxxxxx xxxxxxxx x odběru,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx stanovení xxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,

- xxxxxxxx klasifikace xxxxxx xx pozitivní, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx,

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

- xxxxxxx xxxxxxx ± xxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx xx skupině,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx statistické xxxxxxx x metody,

- údaje x xxxxxxxx a xxxxxxxxx negativní xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Schmid, X. (1975), Xxx Xxxxxxxxxxxx Xxxx, Mutatation Xxx., 31, 9-15.

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

4) Xxxxxxxxx, K. X., Xxxxxx, X. H., Xxxxxx, X. C., Xxxxxxxx, X. X., Xxxxxx, X. X. (1990), Xxx Xx xxxx Xxxxxxxxxxxx Assay xx Xxxxxxxxx Bone Xxxxxx xxx Xxxxxxxxxx Xxxxx. X report xx xxx U. X. Environmental Xxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Xxx., 239, 29-80.

5) MacGregor, X. X., Xxxxxxxx, R., Xxxx, W. N., Xxxx, X. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Screen xxx Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Toxicity Xxxxxxx xx Xxxx, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx of Xxxxxxxxxx, xx. A. X. Xxxxx, X. X. Schnell, X. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. X., Xxxxxx, X. X. Xxxx, X., Margolin, G. X., Xxxxx, C., Xxxxxxxx, X. X., Xxxx, X. R., Xxxx, X. (1987), Xxxxxxxxxx xxx xxx Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx xx Xxxxxxxxx Xxxx Marrow Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

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

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

9) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx xxx the Xxxxxxxxxxxx Xxxx (1992). Xxxxxxxxxxxx Xxxx xxxx Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx Supravital Staining: Xxx Xxxxxxx Xxxxxx xx xxx 5xx Xxxxxxxxxxxxx Study by XXXXX/XXXXX, MMS, Xxxxxxxxxx Xxx., 278, 83-98.

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: The Mammalian Xxxxxxxxxxx Xxxxx Xxxxx xx xxx Environmental Xxxxxxx Xxxxxxx xx Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx xxx the xxxxx-xxxx mouse peripheral xxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Tice, X. X., MacGregor, X. X., Xxxxxxxx, X., Xxxxxxx, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx, Xx. F. X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxxxx Xxxxx, Xxxxx. Xxx., 312, 293-304.

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

13) Fielder, R. X., Xxxxx, X. X., Boobis, X. X., Botham, X. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, D. X., Xxxxxx-Xxxxxx, G., Xxxxxx, X. X., Xxxxxxxx, X. X., Rochold, X. (1992), Xxxxxx xx Xxxxxxx Toxicology Xxxxxxx/XX Environmental Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx in Xx vivo Xxxxxxxxxxxx Xxxxxx, Mutagenesis, 7, 313-319.

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

15) XxxXxxxxx, J. X., Xxxx, X. M., Xxxxxxxx, X. X. (1983), X Simple Xxxxxxxxxxx Staining Procedure xxx Xxxxxxxxxxx xxx XXX in Xxxxxxxxxxxx Xxxxx Xxxxxxx 33258 xxx Pyromin Y, Xxxxxxxx Xxx., 120, 269-275.

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

17) Gollapudi, X., XxXxxxxx, L. X. (1995), Xxxxxx Xxxx xxx xxx Xxxxxxxxxx of Xxxxxxxxxxxxx xx Normochromatic Erythrocyte Xxxxx in xxx Xxxx Xxxxxx Xxxxxxxxxxxx Xxxx, Mutatation Res., 347, 97-99.

18) Richold, X., Ashby, X., Xxxxxxx, J., Chandley, X., Xxxxxxxxx, X. X., Henderson, L. (1990), Xx vivo Xxxxxxxxxxxx Xxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Mutagenicity xxxxx, XXXXX Recommended Xxxxxxxxxx, UKEMS Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, R., Xxxxxxxx, X. E., Xxxxx, X., Xxxxxxxx X., Richold, M., Xxxxxxxx, D. G., Xxxxxx, X. R. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Cytogenetic Xxxxxx, xx: D. J. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx of Mutagenicity Xxxx Data. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx XXX, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 184-232."


PŘÍLOHA 4X

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

1. METODA

Tato metoda xx xxxxxxxx xxxxxx XXXX XX 471 — Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx xx xxxxxxxx xxxxxx s bakteriemi xx používají xxxxxxxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Escherichia coli, x xxxxxxx xxxxxxxx xxxxxx, které xxxxxxxx xxxxxxxxxx, adici a xxxxxx jednoho xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Podstata xxxx xxxxxxx xx xxxxxxxx xxxxxx s bakteriemi xxxxxxx x xxxxxxx xxxxxx, xxxxx xxxxxxxxx xxxxxx xxxxxxxx x xxxxxxxxxxx kmenech x xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx reverzi xxxx xxxxxxxxxx díky své xxxxxxxxxx xxxx x xxxxxxxxxxxxx aminokyselin, které xxxx vyžadovány xxxxxxxxx xxxxxxxxxx kmenem.

Bodové mutace x xxxxxxx jevy xxxx xxxxxxxx xxxxx xxxxxxxxx podmíněných xxxxxx x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxx xxxxxx x xxxxxxxxxx x v xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxx na xxxxxx xxxxxxxx u xxxxxxx x x pokusných xxxxxx. Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxx, xxxxxxxxxx x xxxxxxxxx xxxxxx. Mnoho testovacích xxxxx má xxxx xxxxxxxxxx, xxxx xxxx xxxx xxxxxxxxxx xx xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx permeability xxxxx xxx velké xxxxxxxx x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX nebo xxxxxxxx xxxxxxxxxxx procesů XXX xxxxxxxxxx k xxxxxx. Specifičnost xxxxxxxxxxx xxxxx xxxx poskytnout xxxxxxx xxxxxxxx xxxxxxxxx x xxxxxx xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx činiteli. Pro xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx x dispozici xxxxx rozsáhlá xxxxxxxx xxxxxxxx xxx xxxxxxx xxxxx struktur x xxxx xxxx vyvinuty xxxxx vyzkoušené metody xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Mutageny xxxxxxxxxx xxxx xxxx xxxx činitele, xxx xxxxxxxxx xxxxx x xxxxxx XXX. Xxx xxxxxxx xxxxxxxxxx xxxxxx xx xxxxx xxxx xxxxx xxxxxxxxxx xx xxxxx xxxxxxx xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx genomu.

Posunové mutageny xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx nebo xxxxxx xxxxxxx nebo xxxx párů xxxx XXX x xxxxxxxx xxx čtecí xxxxx XXX.

1.3 VÝCHOZÍ XXXXX

Xxx xxxxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx využívají xxxxxxxxxxxxx xxxxx, xxxxx se xxxx od xxxxx xxxxx faktory, jako xxxx příjem, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx x xxxxxxxxx procesy XXX. Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx systémy xx xxxxx xxxxxxx xxxxx xxxxxxxxx podmínky xx xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx a karcinogenním xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxx xxx počáteční xxxxxxxxx xxxxxxxxxxx xxxxxxxx, x xxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxx xxxxxx. Z xxxxxxxx databáze vyplývá, xx xxxxx chemických xxxxx, které xxxx x xxxx zkoušce xxxxxxxxx, vykazuje xxxxxxxxx xxxxxxxx x v xxxxxx zkouškách. Xxxxxxxx xxxxxxxx xxxxxxxxxxx činitelů, xxxxx nejsou xxxxxxxxxx xxxxx xxxxxxxx. Příčiny xxxxxx skutečností lze xxxxxxxxx ve specifické xxxxxx xxxxxxxxxxxxxxxxxxxxx jevu, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx nebo x xxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx. Na xxxxx xxxxxx faktory, xxxxx xxxxxxx citlivost xxxxxxx xx xxxxxxxx xxxxxx xx xxxxxxxxxx, xxxxx vést k xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx reverzní xxxxxx x bakteriemi nemusí xxx xxxxxx xxx xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx xxxxxxxxxxx) x xxx xxxxxxxx látky, x xxxxx se xxxxxxxxxxx (xxxx x xxxxx xx ví), xx specificky zasahují xx replikačního xxxxxxx xxxxx savců (xxxx. xxxxxxx xxxxxxxxxx topoisomerasy x některé analogy xxxxxxxxxx). X xxxxxxxx xxxxxxxxx xxxxx být xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx mnoho xxxxxxxxx, xxx xxx xx xxxx zkouška xxxxxxxxx, xx xxxxxxxxxxxx xxx xxxxx, xxxx xxxxxxxx absolutní. Závisí xx xxxxxxxx třídě x xxxxxxxx xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx touto xxxxxxxx, xxxxx působí jinými, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx v xxxxxxxxxxxxx buňkách xxxxxxxxxx.

1.4 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxxx xxxxxxxxxxxxx buněk xxxx xxxxxxxxx xxxxxxxx xxxxx, x to xx xxxxxxxxxxx vnějšího metabolického xxxxxxxxxxx xxxxxxx x xxx něho. Xx xxxxxxxxxxx miskovém testu xx xxxxxxxx xxxxxxxx x xxxxxxx xxxxxx x ihned xx xxxxxxx xx minimální xxxx. X xxxxxxxxxxxx xxxxxx se xxxxxxxx xxxx inkubuje x xxxx xx před xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx. Xxx xxxx xxxxxxxxxx se xx xxxx xxxx xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxx xx xxxxxxxx x xxxxxx xxxxxxx xxxxxxxxxxx revertantů xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

Xx xxxxxxx xxxxxxx xxxxxxx provedení xxxxxxx xx reverzní xxxxxx x bakteriemi. Xxxx xxxxx xxxxxxxxx xxxxx standardní xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx xxxx (9, 10) x xxxxxxxxx xxxxxx (11). Xxxxxx pro zkoušení xxxxx a xxx xxxx popsány (12).

Xxx xxxxxxx xxxxxxx se xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx testu a xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx je xxxxxxxxxx pro provádění xxxxxxxxxxx xxx s xxxxxxxxxxxx aktivací, xxx xxx xx. Xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx metody. Tyto xxxxx xxxxx do xxxxxxxxxx tříd, xx xxxxx xxxxx mezi xxxxx xxxxxx alifatické xxxxxxxxxxx, xxxxxxxxx kovy, xxxxxxxx, azobarviva a xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, allylové sloučeniny x nitrosloučeniny (3). Xxxxxx se xxxxxxxxx, xx xxxxxx xxxxx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx xx standardní xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Měly xx xxx považovány xx "xxxxxxxx případy" x x xxxxxx xxxxxxx se xxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Je možné xxxxxxxxxxxxx xxxx "zvláštní xxxxxxx" (xxxxxxxx x xxxxxxxx postupů xxxxxx xxxxxxx): xxxxxxxxxx x xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx látky (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx xx xxxxxxxxxxxx xxxxxxx musí xxx vědecky zdůvodněna.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx xxxx xxx kultivovány do xxxxxx xxxxxxxxxxxxx fáze xxxx xx xxxxx xxxxxxxxxxx xxxx růstu (xxxxxxxxx 109 xxxxx xx xx). Xxxxx x pozdní xxxxxxxxxxx xxxx xx neměly xxx xxxxxxx. Xx xxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx xxxxxx xxxx životaschopných xxxxxxxx. Xxxx xxxx být xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx o xxxxxxx xxxxxx, nebo xxx xxxxxx xxxxxxx stanovením xxxxx životaschopných xxxxx xx miskách.

Doporučená inkubační xxxxxxx xx 37 °X.

Xxxx by xxx xxxxxxx xxxxxxx xxx xxxxx xxxxxxxx. Xxxx xxxx by xxxx xxx xxxxx kmeny X. xxxxxxxxxxx (XX1535; XX1537 nebo XX97x xxxx XX97; TA98 x TA100), jejichž xxxxxxx se xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx X. xxxxxxxxxxx xxxx xxx xxxx XX na primárním xxxxxxxxx místě a xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx vláken XXX x xxxxxxxxx. Xxxx xxxxx xxxxx xxx xxxxxxxxxx xxxxx X. xxxx XX2 xxxx X. xxxxxxxxxxx XX102 (19), xxxxx xxxx xx xxxxxxxxx reverzním xxxxx xxx xxxx XX. Xxxxxxxxxx kombinace xxxxx xx xxxx xxxx:

- X. xxxxxxxxxxx XX1535 x

- X. xxxxxxxxxxx TA1537 nebo XX97x a

- S. xxxxxxxxxxx TA98 a

- X. typhimurium TA100 x

- X. xxxx XX2 xxxX, xxxx X. coli XX2 xxxX (pKM101), nebo X. xxxxxxxxxxx XX102.

Xxx xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx DNA xxxx xxx xxxxxxxxx xxxxxxx XX102 xxxx xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx xxxxxxxx XXX, (xxxx. E. xxxx XX2 (xXX101)).

Xxxx xx xxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx kmenové xxxxxxx, xxxxxxxxxx xxxxxxx x xxxxxxxxxx. Xxxxxxx xxxxxxxxxxxxx pro xxxx xx xxxx být xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx xxx xxxxx X. typhimurium x xxxxxxxxx xxx X. xxxx). Podobně by xxxx xxx xxxxxxxxxxxx xxxx fenotypové xxxxxxxxxxxxxxx, xxxxxxxxx podle xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx rezistence x xxxxx TA98, TA100 x XX97x nebo XX97, WP2 xxxX x XX2 uvrA (xXX101) x xxxxxxxxxxxx x tetracyklinová xxxxxxxxxx x xxxxx TA102), xxxxxxxxxx charakteristických mutací (xx. rfa xxxxxx x S. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx xxxxxx a uvrA xxxxxx x X. xxxx xxxx uvrB xxxxxx x X. xxxxxxxxxxx citlivostí na xxxxxxxxxxxx xxxxxx) (2, 3). Xxxxx by xxxx rovněž dávat xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx na misce x xxxxxxx četností xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx x nejlépe x rozmezí xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx xxxxxxxxx xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx E (Xxxxx-Xxxxxx) x xxxxxxx) x xxxxxx agar xxxxxxxxxx xxxxxxxx a xxxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx xxxx být xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx systémem xxxxxxxxxxx xxxxxxxx x xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je xxxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx z xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx indukujícím enzymy, xxxx xx Xxxxxxx 1254 (1, 2) xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (18, 20, 21). Postmitochondriální frakce xx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx x xxxxxxx 5 až 30 % xxx. xx xxxxx X9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx xxxx xxxxxxx na xxxxx xxxxxxxx chemické xxxxx. X xxxxxxxxx xxxxxxxxx xxxx být xxxxxx použít xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. X xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx může být xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx mohou xxx xxxx aplikací xxxxxxx. Xxxx by být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx údaje o xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx reaguje xx xxxxxxxxx xxxxxx, x xxxx xx být xxxxxxxxxx s přežitím xxxxxxxx a x xxxxxxxxx X9 (22). Xxxx-xx použita xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx nestálých xx xxxx xx xxxx xxx xxxxxxx organická xxxxxxxxxxxx xxxxxxxxxxxx vodu.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Zkušební xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Xxxx xxx xxxxxxxx xxxxxxxx toxicitu x xxxxxxxxxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx xxxx xxx xxxxxxxxxx snížením xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx zeslabením xxxxxxxxxxxxx podkladu xxxx xxxxxxxx stupně xxxxxxx xxxxxxxxxxxx xxxxxx. Cytotoxicita xxxxx xx může xxxxxx v přítomnosti xxxxxxxxxxxxx aktivačních xxxxxxx. Xxxxxxxxxxxxx xx měla xxx xxxxxxxxx xx xxxxxxx viditelného srážení x konečné směsi xx xxxxxxxxxx zkušebních xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx zkušební xxxxxxxxxxx pro rozpustné xxxxxxxxxxxxx xxxxx xx 5 mg/misku xxxx 5 μx/xxxxx. U xxxxxxxxxxxxxxx látek xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx xx xxxx xxx jedna xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, xxx xxxxx xxxx v xxxxxxx xxxxx pro xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxxxx xxx při koncentracích xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, by xxxx xxx zkoušeny až xx cytotoxické xxxxxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

Mělo xx xxx xxxxxxx xxxxxxx pět různých xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, přičemž při xxxxxx xxxxxxxxxxx xx xxxx xxx intervaly xxxx xxxxxxxxxx body xxxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxx stupnice (xx. Ö10). Xxxxx xxxxxxxxx jsou xxxxxx x případě, xxx xx xxxxxxxxx xxxxxx xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Zkoušení xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx xxx xxxxxxx při xxxxxxxxx xxxxx obsahujících xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Negativní x xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxx xx měly xxx kmenově xxxxxxxxxx xxxxxxxxx x negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx s metabolickou xxxxxxxx x xxx xx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X případě zkoušek x xxxxxxxx metabolického xxxxxxxxxxx xxxxxxx by xxxx xxx xxxxx (xxxxx) pro xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxx) xx základě xxxx xxxxxxxxx kmene xxxxxxxx.

Xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx s xxxxxxxxxxxx xxxxxxxx xxxx xxxx xxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Tato xxxxx je xxxxxxx xxxxxxxxx kontrolou pro xxxxxx redukční xxxxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

XX Xxxxxx Red 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx xx neměl xxx xxxxxx xxxx xxxxxx xxxxxxxxx xxxxxxxxx xxxxx S9. Při xxxxxxx 2-xxxxxxxxxxxxxxx by xxxx xxx každá xxxxx S9 charakterizována xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxx mikrosomálními xxxxxx, xxxxxxxxx xxxxx[x]xxxxx xxxx 7,12-dimethylbenzo[a]anthracen.

Příkladem xxxxxxxxxxxxxxxxx xxxxxxxxx kontroly x xxxxxxx xxx xxxxxx xxxxxxxxxxx aktivace jsou xxxx xxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx EINECS

Kmen

azid sodný

26628–22–8

247–852–1

TA1535 x XX100

2-xxxxxxxxxxxx

607–57–8

210–138–5

XX98

9-xxxxxxxxxxxx

90–45–9

201–995–6

XX1537, XX97 x XX97x

XXX 191

17070–45–0

241–129–4

TA1537, XX97 x XX97x

Xxxxxxxxxxxxxxxxx

80–15–9

201–254–7

XX102

xxxxxxxxx X

50–07–7

200–008–6

XX2xxxX x XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 uvrA x XX2 xxxX (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 xxxX a XX2 xxxX (xXX101)

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

3688–53–7

xxxxx xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxxxx mohou xxx použity jiné xxxxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxxx kontrolu xx mělo být xxxxx v xxxxx xxxxxxx xxxxxxxxxx látek xx stejné xxxxxxxx xxxxx, xxxx xx x xxxxxxxxx.

Xxxx xx xxx použity xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula, xxx xxxxxxxx xxxxx, xxxxxxxxxx xxxxx stejným xxxxxxxx xxxx exponované xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5.3 Xxxxxx

X standardní miskové xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 ml xxxxxxx xxxxxxxxxxx kultury (obsahující xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x 0,5 xx xxxxxxxxxx xxxxx x 2,0 xx xxxxxxxx xxxxx. V xxxxxxx zkoušky x xxxxxxxxxxxx xxxxxxxx se xxxxxxx smíchá 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxx přiměřené xxxxxxxx postmitochondriální frakce (x xxxxxxx 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx xxxxx) s xxxxxxx agarem (2,0 xx) x xxxxxxx x xxxxxxxxxx x xxxxxxxxx látkou nebo xxxxxxxxx roztokem. Xxxxx xxxxx xxxxxxxx xx xxxxxxxx x xxxxxxx xxxx povrch minimálního xxxxx xx xxxxx. Xxxx xxxxxxxx xx xxxxx vrchní xxxx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx (2, 3, 5, 6) se xxxxxxxx xxxxx xxxx xxxxxxxx xxxxxx xxxx smícháním x vrchním xxxxxx x přelitím xxxx xxxxxx minimálního xxxxx xx misce obvykle 20 xxxxx xxxx xxxx xxxxxxxxxxx s xxxxxxxxxx xxxxxx (xxxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) a xxxxxxxxx xxxxxx nebo metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) xxx 30 — 37 °C. Xxxxxxx se smíchá 0,05 xxxx 0,1 xx zkoušené látky xxxx zkušebního xxxxxxx, 0,1 xx xxxxxxxx x 0,5 ml xxxxx X9 xxxx xxxxxxxxxx pufru s 2,0 ml vrchního xxxxx. Zkumavky xx xxxx xxx xxxxx xxxxxxxx provzdušňovány na xxxxxxxx.

X dostatečnému odhadu xxxxxxxx xx měly xxx xxx xxxxx xxxxxx dávky xxxxxxx 3 misky. Xxxxxxx xxxx misek xx xxxxxxxxxx po xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxxxx xxxxx nemusí xxxxxxxx xxxxxxxxxxxx zkoušky.

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

1.5.4 Xxxxxxxx

Xxxxxxx xxxxx x xxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xxx 37 °X xx 48 –72 xxxxxxxx. Po uplynutí xxxxxxxxx xxxx se xxxxxx xxxxx kolonií xxxxxxxxxx na xxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ VÝSLEDKŮ

Předloženými xxxxx xx měly xxx xxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xx xxxxx. Xxx xx xxx xxxxxx uveden xxxxx xxxxxxx revertantů xxx xx miskách x xxxxxxxxx xxxxxxxxx (xxxxxxxx xxxxxxxxxxxx x xxxxxxxx neexponovaná kontrola), xxx na xxxxxxx x xxxxxxxxx xxxxxxxxx. Xxxxx xx xxxxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx revertantů xx xxxxx a xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxx x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Xxxxxxxxxx výsledky by xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx výsledků xxxxxxxxxx xx nezbytné, xxxx xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx by měla xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx studie, které xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx misková metoda xxxx xxxxxxxxxxx v xxxxxxxx médiu) x xxxxxxxx metabolické xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx stanovení pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx nad xxxxxxxxx xxxxxx u xxxxxxx jednoho xxxxx x xxxxxxxxxxxx aktivačním xxxxxxxx nebo bez xxxx, x to x xxxxxxxxxx xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx xxxxxx xxxxx xxx xxxxx nebo xxxx xxxxxxxxxxx (23). Xxxxxxxx xx xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx být použity xxxx xxxxxxx prostředek xxxxxxxxxxx metody (24). Xxxxxxxxxxx významnost by xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx odpověď.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx xxxxxxxxx výsledky, x ojedinělých případech xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx výrok x aktivitě xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxx xxxxx Xxxxxxxxxx typhimurium x/xxxx Xxxxxxxxxxx coli xxxxxx xxxxxx xxxxxxxxxx xxxx xxxx posunem čtecího xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx xxxxxxxx xxxxx xxxx za xxxxxxxx xxxxxxx pro xxxxxxxxx druhy xxxxxxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx xxxxx,

- počet xxxxx x xxxxxxx,

- xxxxxxxxxxxxxxx kmene.

Zkušební podmínky:

- xxxxxxxx xxxxxxxx xxxxx xx xxxxx (xx/xxxxx xxxx μx/xxxxx) s xxxxxxxxxxx xxxxxx xxxxx x xxxxx xxxxx xx xxxxxxxxxxx,

- xxxxxxx xxxxx,

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

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

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

- xxxxx možnosti závislost xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Ames, X. X., XxXxxx, X., Yamasaki X. (1975), Methods xx Xxxxxxxxx Carcinogens and Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Res., 31, 347-364.

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

3) Xxxxxxxxx, D., Xxxxxxx, S., Cebula, X., Xxxxx, X., Xxxx, X., Matsushima, X., Xxxxxxx, C., Xxxxx, X., Venitt, X., Xxxxxx, X. (1994), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx of Xxxxxxxxx Xxxxxxxx Assays, Xxxxxxxxxx Xxx., 312, 217-233.

4) Xxxx, X. X., Xxxxxxx X. X., Auletta, X. X., Von Xxxxx, X. S., Xxxxx, X. M., Simmon, X. F., Xxxxxx, X., XxXxxx, J., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, X. X., Xxx X. (1986), Xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Assay: X Xxxxxx xx xxx U. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, T., Xxxxxx, X., Xxxxx, Y. X., Xxxxxxxxxx, T., Xxxxx, M., Xxxxxxxx, X., Xxxxxxxxx, X. (1975), Mutagenicity xx Xxxxxxxxxx Xxx Dyes xxx their Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

6) Xxxxxxxxxx, X., Xxxxxxxx, T., Xxxxx, X., Xxxxxx, T., Xxxxxx, A., Sawamura, X. (1980), Factors Xxxxxxxxxx Xxxxxxxxxxxx Microbial Xxxxx, xx: Xxxxx-xxxx Xxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx, ed. Xxxxxxx K. X., Xxxxxx, X. C., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

7) Gatehouse, X. X., Xxxxxxx, I. X., Xxxxxx, X., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Mutation Xxxxxx, xx: Basic Xxxxxxxxxxxx Xxxxx: UKEMS Xxxx 1 Xxxxxxx, xx. X. J. Xxxxxxxx, Xxxxxxxxx University Xxxxx, 13-61.

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

9) Xxxxx, X. X. L., Xxxxxx, X. J., Xxxxxxx, X. A. (1976), Xxx xx x simplified xxxxxxxxxxx xxxx to xxxxxx xxx xxxxxx xx xxxxxxxx, Xxxxxxxxxx Xxx., 38, 33-42.

10) Hubbard, X. X., Green, X. X. X., Xxxxxxxxx, D., Xxxxxxx, X. W. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, in: Xxxxxxxx xx Mutagenicity Xxxx Procedures, 2. xxx., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (xxx.), Elsevier, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, E. X., Xxxxxxx, P. X. (1981), Xx Xxxxxxxxxxx xx xxx Quantitative Xxxxxxxxxx Assay xxx Xxxxxxxxxxx with Xxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Xxxxx, X., Xxxxxxx, X., Xxxx, X., Matsushima, T. (1994), Improved Method xxx Xxxxxxxxxxxx Xxxxxxx xx Xxxxxxx Compounds xx Xxxxx a Xxx Sampling Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

13) Xxxxxx, M. X., Bell, X. X., Xxxxxxxx, V. X., Reipert, X. X., Xxxxxxx, X. X. (1984), Mutagenicity xx Benzidine and Xxxxxxxxx-Xxxxxxxx Dyes xxx Xxxxxxxx Xxxxxxx Xxxx xx x Xxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, X., Xxxxxxxx, X. X., Haworth, X., Xxxxxx, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx xxxx xxx Xxxxxxx of 311 Xxxxxxxxx, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

15) Xxxxxx, X., Xxxxxxxx, K., Tardiff, X. G. (1977), Xxxxxxxxx Activity of Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxx Water, in Xxxxxxxx in Xxxxxxx Xxxxxxxxxx, D. Xxxxx, X. Xxxxxxx, X. Xxxxxx (xxx.) Elsevier, Xxxxxxxxx, 249-258.

16) Xxxxxx, X. X., Xxxxxxx, X. M., Xxxxxxxx, X. G., Claxton, X. X. (1987), Xxxxxxxxxxxx Technique to Xxxxxxx Mutagenic Activity xx Xxxxxxxx Xxxxxxx Xxxxxxxxx xx the Xxxx/Xxxxxxxxxx Assay, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, X., Xxxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, M., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx xxx Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx xxx Synthetic Xxxxxxxxxxx Xxxxxxx Xxxxxxxxxx in Xxxxxxxxxx typhimurium, Cancer Xxx., 39, 3780-3782.

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

19) Xxxxxx, X., Naidoo, A., Xxxx, X. J., Xxxxxxxxx, X. X. (1990), Xxxxxxxxxx xx Xxxxxxxxxx typhimurium XX 102 xxxx Xxxxxxxxxxx xxxx XX2 Tester xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), X Xxxx Xxxxxxxxxx for Xxxxxxxxxxxxxxx Xxxxxxxxx a. s. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, xx: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx in Xxxxxxxxxxx Xxxxxxx, eds. X. X. xx Xxxxxx xx xx. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.

21) Xxxxxx, X. X., Combes, X. X., Xxxxxxx, X. X., Gatehouse, X. X., Gibson, X. X., Xxxxxx, X. X., Xxxx, R. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx in xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, D., Xxxxxxxxxxxxxxxx, X., Ames, X. X. (1981), Xxxxxxxxxxxxx xx Xxxxxxx Solvents xxxx xxx Salmonella/Microsome Xxxx, Mutatation Res., 88, 343-350.

23) Xxxxxxx, X. D., Xxxxx, X., Auletta, A., Xxxxxxxxxx, X., Xxxxxxxx, X., Zeiger, E. (1987), Guide xxx xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, G. X. X., Xxxxx, X. X. X., Middleton, X., Xxxxxxx, I., Xxxxxxxx, X. X., Xxxxxx, X. X. (1989), Analysis xx Xxxx xxxx Xxxxxxxxx Xxxxxx Assays, in: XXXXX Sub-Committee xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Xxxx II. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, xx. Kirkland, X. X., Xxxxxxxxx University Xxxxx, 28-65."


XXXXXXX 4X

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

1. METODA

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

1.1 XXXX

Xxxxxxx xx xxxxxx xxxxxx x buňkách xxxxx xx xxxxx xxx xxxxxx xxx xxxxxxx xxxxxxxx mutací indukovaných xxxxxxxxxx látkami. Xxxx xxxxxx buněčné linie xxxxx xxxxx xxxxxxx X5178X myší, xxxxxxx xxxxx XXX, CHO-AS52 x X79 xxxxxx xxxxxxxx x lymfoblastoidní xxxxx XX6 člověka (1). X xxxxxx xxxxxxxxx linií xxxx xxxxxxxxxxxxxxx xxxxx genetických xxxxxx xxxxxx xxxx xxx xxxxxxxxxxxxxx (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (HPRT) x transgen xanthin-guaninfosforibosyltransferasy (XXXX). Zkoušky xx xxxxxx XX, XXXX x XXXX detekují xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX x XPRT xxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx xxxxxx), xxxxx xxxxx detekovat x XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx nebo buněčné xxxxx. Xxxxx se xxxxxxxx xxxxx xxxxxxxxxx xxxxx x xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx mutací.

Zkoušky prováděné xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx aktivace. Xxxxx metabolický xxxxxxxxx xxxxxx nemůže xxxxx xxxxxxxxx podmínky xx xxxx x xxxxx. Xx xxxxx se xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx neodrážejí xxxxxxx xxxxxxxxxx. K pozitivním xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx mutagenitu, xxxx xxxxx xxxxxx pH, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx xx používá xx xxxxxxxx možných xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx karcinogeny xxxxx; xxxx touto zkouškou x karcinogenitou xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx na xxxxxxxx xxxxx x xxxxxxxxx xxxxxx o xxx, že existují xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, které x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx (6).

Viz také xxxxxx xxxx, část X.

1.2 XXXXXXXX

Xxxxx xxxxxx : genová xxxxxx xxxxxxxxx typu mutované xxxxx, která způsobuje xxxxx xxxx ztrátu xxxxxxxxxxx xxxxxxxx kódovaných xxxxxxxx.

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

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

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

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

Xxxxxxxxx celkový xxxx : xxxxxx xxxxx xxxxx x xxxx ve srovnání x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx se xxxx xxxxxx poměru xxxxxxxxx xxxxx v xxxxxxxx a v xxxxxxxxx kontrole a xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxx x xxxxxxxx : xxxxxx xxxxx buněk v xxxxxxx exprese vzhledem x negativní xxxxxxxx.

Xxxxxxxxxxxxxxx : xxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx na misku xx selektivních xxxxxxxx xx expresi.

Přežití : xxxxxxxx klonování xxxxx xxx xxxxxxxx xx xxxxx xx xxxxx xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx vyjádřeno x xxxxxx x xxxxxxx xxxxxxxxx xxxxxxxx xxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (TK) xxxx xxxxxxxxxxx k xxxxxxxxxxxx xxxxxxx xxxxxxx pyrimidinu xxxxxxxxxxxxxxxxx (XXX). Xxxxx xxxxxxxxxxx thymidinkinasu xxxx xxxxxxx na TFT, xxx způsobuje inhibici xxxxxxxxx xxxxxxxxxxx a xxxxxxxxx xxxxx xxxxxxx xxxxxx. Xxxxxxxx buňky xxxx xxxx schopny xxxxxxxxxxx xx xxxxxxxxxxx XXX, zatímco xxxxxxxx xxxxx, které xxxxxxxx xxxxxxxxxxxxxx tuto schopnost xxxxxx. Xxxxxxx xxx x xxxxx x xxxxxxxxxxxx XXXX nebo XXXX provést selekci xxxxxxxxxxxxxxx xxxxxxxxxx x 6-xxxxxxxxxxx (XX) nebo 8-xxxxxxxxxx (XX). Vlastnosti xxxxxxxx xxxxx by xxxx být pečlivě xxxxxxx, xxxxxxxx xx xx zkoušce na xxxxxx xxxxxx v xxxxxxx savců xxxxxxx xxxxxx báze xxxx xxxxxxxxxx podobná xxxxxxxxxx xxxxxxx. Xxxx xx xxx například xxxxxxxxx xxxxxxxx xxxxxxxxx xx xxxxxxxxxx xxxxxxxx zkoušené xxxxx pro xxxxxxxx xxxx xxxxxxxxxx xxxxx. Xxx zkoušení xxxxxxxxxx xxxxx, které xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx činidlo, musí xxxx xxx potvrzena xxxxxxxx systému nebo xxxxxxx xxx xxxxxxx (8).

Xxxxx x xxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxx xxxx vhodnou xxxx xxxxxxxxx zkoušené xxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, x xxxxxxxxxxxxxx xx účelem xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (přežití) xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxxx doby expozice. Xxxxxxxxxx kultury se xxxxxxx x xxxxxxxx xxxxx xx xxxxxxx xxxx xxxxxxxxxxxxxxxxx xxx xxxxx zvolený xxxxx x typ buněk, xxx nastala xxxxxxxxx xxxxxxxxx fenotypová exprese xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx xx xxxxxxx xxx, že xx xxxxxx xxxxx xxxxx xxxxx xx média xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx xxxxxxx mutantních xxxxx x xx xxxxx xxx xxxxxxxxxx xxxxxxx, xxx xxxx xxxxxxxxx účinnost xxxxxxxxx (xxxxxxxxxxxxxxx). Po vhodné xxxxxxxxx xxxx se xxxxxxxxx kolonie. Xxxxxxx xxxxxxx se vypočte x xxxxx mutantních xxxxxxx x xxxxxxxxx xxxxx a xxxxx xxxxxxx x xxxxx xxx xxxxxxxxxx činidla.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx xxxxxxx x xxxx zkoušce xxxx x dispozici xxxxx xxxx xxxxx, xxxxxx subklonů xxxxx X5171X, XXX, XXX-XX52, X79 xxxx XX6. Xxxx buněk x xxxx zkoušce by xxxx xxxxxxxxx citlivost x xxxxxxxxx mutagenům, xxxxxxx klonovací schopnost x xxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxxxx, zda xxxxxx xxxxxxxxxxxxx mykoplasmaty, x x xxxxxxx xxxxxxxxxxx xx xxxxxx být xxxxxxx.

Xxxxxxx xx xxxx xxx xxxxxxxx xxx, xxx xxxx předem xxxxxxxxxx xxxxxxxxx x xxxx. Počet xxxxxxxxx xxxxx, xxxxxx a xxxxxxxxxxx xxxxxxxx xxxxx xx měl xxxx xxxxxxxxxx parametry odrážet (14). Xxxxxxxxx xxxxx xxxxx, xxxxx xxxxxxx xxxxxxxx a xxxxx xxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx, xx xxx xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx xx, xxx xxx xxxxxx xxxxx xxxxx, který xx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx však xxxxxxxxxx, xxx xxxx xxxxxxx xxxxxxx 106 xxxxx. Xxxx xx xxx x xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxxxx, xxx byla xxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx podmínky

Pro xxxxxxxxx xxxxxx by měla xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x vlhkost). Xxxxx xx xxxx xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx x xxxx buněk použitých xxx zkoušce. Je xxxxxxx xxxxxxxx, xxx xxxxxxxxxx podmínky xxxx xxxxxxx tak, xxx xxxx xxxxxxxxx optimální xxxx xxxxx xxxxx xxxxxx xxxxxxx x xxxxxxxxx xxx xxxxxxxxxx, xxx xxxxxxxxxxxx xxxxx xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

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

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

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

Postmitochondriální xxxxxx xx x konečném xxxxxxxxxx médiu xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxxx x xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx na xxxxx xxxxxxxx xxxxx, která xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx může xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx aktivaci. Xxxxx xxxxxxxxx buněčných linií xx xxxx být xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx isoenzymu cytochromu X450 xxx metabolismus xxxxxxxx látky).

1.4.1.5 Xxxxxxxx xxxxxxxx látky

Pevné xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx přímo k xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Měly xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx xxx xxxx xxxxxxxxx, že xxxxxxx xx zkoušenou xxxxxx, x xxxx xx xxx slučitelné x xxxxxxxx xxxxx x s xxxxxxxxx X9. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx látek nestálých xx vodě xx xxxx být použitá xxxxxxxxx rozpouštědla xxxxxxxxxxxx xxxx. Vodu xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

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

Cytotoxicita xx xxxx být stanovena x metabolickou xxxxxxxx x bez xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, jako xxxx relativní xxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx být xxxxxxx xxxxxxxx cytotoxicitu a xxxxxxxxxxx x předběžném xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx toxicity by xxxx tyto koncentrace xxxxxxxx xxxxxxx xxxx xxxxxxxxx x minimální xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx, xx xx xx xxxxxxxxxxx xxxx lišit faktorem 2 xx Ö10. Xx-xx maximální koncentrace xxxxxxxx xx cytotoxicity, xxxx xx být xxxxxxxxx přibližně 10 — 20 % (xxx nejméně 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx klonování) nebo xxxxxxxxx xxxxxxx xxxx. X případě relativně xxxxxxxxxxxxxxx látek by xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, xxxxx x nich xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx měly xxx xxxxxxxx xx k xxxx xxxxxxxxxxxx za xxxxxxxxxxxx xxxxxxxx, nebo xx za tuto xxx. Xxxx xx xxx xxxxxxxxx případná xxxxxxxxxxxxx x konečném xxxxx, xx kterému xxxx xxxxx exponovány. Xxxx xxx xxxxxxx xxxxxxxx rozpustnost xx xxxxxxx x xx xxxxx xxxxxxxx, neboť xxxxxxxxxxx se xxxx x xxxxxxx expozice x xxxxxxxxxx xxxxxxx xxxxx x důsledku xxxxxxxxxxx buněk, S9 xxxx, atd. Xxxxxxxxxxxxx xxx xxxxxxx vizuálně. Xxxxxxxxx by neměla xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx xxx s xxxxxxxxxxxx aktivací, xxx xxx xx. Xxx xxxxxxx metabolické xxxxxxxx xx měla xxx xxxxxxxxx kontrolou xxxxxxxx xxxxx, xxxxx x xxxxxxxxx odpovědi vyžaduje xxxxxxxx.

Xxxxxxxxx xxxxxxxxx kontroly xxxxx xxx tyto xxxxx:

Xxxx xxxxxxxxxxx aktivace

Lokus

Látka

Číslo XXX

Xxxxx xxxxx Einecs

Bez xxxxxx xxxxxxxxxxx xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx x velké xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X 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 xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx xxx použity xxxx jiné xxxxxxxxxx xxxxx pro pozitivní xxxxxxxx, např. xx-xx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxx x 5-brom-2′-deoxyuridinu (XXX 59–14–3, XXXXXX 200–415–9), xxxx xxx xxxx xxxxxxxxxx xxxxx xxxxxx xxxxxxx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx vzato x úvahu použití xxxxxxxxxx xxxxx pokud xxxxx xx xxxxxx xxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx samotné rozpouštědlo xxxx vehikulum x xxxxxxxxxx jinak stejným xxxxxxxx xxxx exponované xxxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx nevyvolává žádné xxxxxxx nebo mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx látce

Proliferující buňky xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, xxx xxx něho. Xxxxxxxx by měla xxxxx xxxxxxx dobu (xxxxxxx xx xxxxxx xxxx 3 až 6 xxxxx). Expoziční xxxx xxxx xxx xxxxxxxxxxx xx xxxxx xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx mohou xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx exponovaná xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, měl xx být xxxxx xxxxxxxxxxx xxxxxx xxx, xxx xxx zajištěn xxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxx (např. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Měly by xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx xxxxxxxxxxxx).

Xxxxxx xxxx xxxxxx látky xx xxxx xxx xxxxxxxx xxxxxxxx metodami, xxxx. x těsně xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Xxxxxxxxx xxxxxxx, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx konci xxxxxxxxx xxxx xx buňky xxxxxxx a kultivují xx xxxxxx xxxxxxxxx xxxxxxx a za xxxxxx xxxxxxxx exprese xxxxxxxx mutantu. Xx xxxxxxxxxx cytotoxicity xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxxx celkového xxxxx xxxxxx xx započne xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, xxx umožnil xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx xxxx indukovaných xxxxxxx (XXXX x XXXX xxxxxxxx alespoň 6 xx 8 xxx, XX xxxxxxx xxx dny). Xxxxx xxxx xxxxxxxxxxx x xxxxx xx xxxxxxxxx xxxxxxxx (xxxxxxxxxx činidly) x xxx něho (xxx nich) xx xxxxxx stanovení počtu xxxxxxx a klonovací xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx pro xxxxxxx xxxxxxxx xxxxxxx) xx xxxxxxx xx xxxxx xxxx xxxxxxx xxxxxxxxx na xxxxx xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx xxxxx pozitivní xx zkoušce L5178Y XX+/-, mělo by xxx provedeno xxxxxxx xx xxxxx xx xxxxxxxxxx xxxxxx (s xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x xx negativních x xxxxxxxxxxx kontrolách xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxx. Je-li xxxxxxxx látka xx xxxxxxx X5178X XX+/- xxxxxxxxx, xxxx xx xxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií xxxxxxxxx na xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx za xxxxxxx XX6 XX+/- xxxx být xxxx xxxxxxxxx rozdělení kultury xxxxx velikosti xxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xx xxxx zahrnovat xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, počtu kolonií x xxxxxxxx xxxxxxx xxx xxxxxxxxxx x xxxxxxxxx kultury. X xxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxx L5178Y XX+/- se xxxxxxx xxxxxxxxx xxxxxxx x xxxxx koncentrace xxxxxxxx xxxxx (xxxxxxxx pozitivní xxxxxxxxxxx) x x xxxxxxxxx x xxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx malá xxxxxxx — velká xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx velké xxxxxxx, xxx mutantů xxxxxxxxx xxxx xxxxxxx xxxx xxxxxxxx zkoumána (23, 24). Xx xxxxxxx XX+/- xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx kolonie x xxxxxxxxx xxxxxx (xxxxx) x kolonie s xxxxxxx růstem (malá) (25). U xxxxxxxxxx xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx prodloužily xxxx xxxxxxxx, x tvoří xxxx xxxx xxxxxxx. Xxxxxxxxx xx obvykle xxxxxx xx xxxxx xxxxxx xxxx xx xx xxxxxxxxxxxx viditelné xxxxxxxxxxxx aberace. Indukce xxxxxxx xxxxxxxxx malé xxxxxxx xx xxxxxxx x xxxxxxxxxx látkami, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx aberace (26). Xxxx závažně xxxxxxxxx xxxxx mutantů xxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxx xxxxx x xxxxx xxxxx kolonie.

Mělo xx xxx xxxxx xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. Xxxxxxx xxxxxxx by xxxx xxx xxxxxxxxx xxxx xxxxx xxxxxxx x xxxxx přeživších xxxxx.

Xxxx xx xxx xxxxxxx xxxxx xxx jednotlivé xxxxxxx. Xxxx xx xxxx být xxxxxxx xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Tam, xxx xxxx potvrzení xxxxxxxxxxx xxxxxxxx xxxxxxxxxx za xxxxx, xx xxxxx xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx studie x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx podmínek xx xxxx xxx zvážena x xxxxxxxxxx xxxxxxxxxxxxx xxx pro xxxxxxxxxx xxxxxxxx, xxx xxx xxxxxxxxx xxxxxxxx. X xxxxxxxxxx xxxxxx, které xx mohly xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx a podmínky xxxxxxxxxxx aktivace.

2.2 HODNOCENÍ X INTERPRETACE VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik kritérií, xxxx. xxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx této xxxxxxxx. Xxxxxxxx xx xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx xxxxxxxxxx by xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx konečný výrok x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx dvojznačné nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x použitých xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx je xxxxx xxxxxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx neindukuje x xxxxxxxxx xxxxxxxxxxxxx buňkách xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby xxxxxxxxxxxx/xxxxxxxx,

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

Buňky:

- xxx a zdroj xxxxx,

- počet buněčných xxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx kultury,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x xxxxx xxxxxx, xxxxxx např. údajů x cytotoxicitě x xxxxxx xxxxxxxxxxxx, jsou-li x xxxxxxxxx,

- xxxxxxx xxxxx, případně koncentrace XX2,

- koncentrace zkoušené xxxxx,

- objem xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx doba,

- délka xxxxxxxx,

- xxxxxxxx hustota xxxxx xxxxx expozice,

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

- pozitivní x xxxxxxxxx xxxxxxxx,

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

- selekční xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx nebo dvojznačnou,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx a xxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxx xxxxx xxxxxxxxx x xxxx (xxxxxxxx xxxxxx xxxxxxxx xxx "xxxx" a "xxxxx" xxxxxxx).

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

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

- xxxxxxxx xxxxxxx, xxxx-xx xxxxxxxxxxx, xxxxxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxxxx,

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

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

- xxxxxxx xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., DeMarini, X. X., XxXxxxxx, X. J., Tindal, X. X. (xxx.) (1987), Xxxxxxx Report 28; Xxxxxxxxx Cell Xxxxxxxxxxx, Xxxx Spring Xxxxxx Xxxxxxxxxx, New Xxxx.

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

3) Liber, X. X., Xxxxxx, X. X. (1982), Mutation Xxxxx xx the Xxxxxxxxx Xxxxxx Xxxxx xx Diploid Xxxxx Xxxxxxxxxxxx, Mutation Xxx. 94, 467-485.

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

5) Xxxxx, X. X., Stankowski, Xx. X. F., (1989), Xxxxxxxxxx of xxx AS52/XPRT xxx xxx XXX/XXXX Assays: Xxxxxxxxxx of Xxx Xxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx. 223, 121-128.

6) Xxxxx, C. X., Xxxxxxxxxx, X., Xxxxx, X. X., Xxxxx, X., Xxxxx, X., Xxxxxxxxxx, Xx. L. X., Theiss, J., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Gene Xxxxxxxx Xxxxxx Working Xxxxx Report. Xxxxxx xx xxx International Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxxx, X. X., Ishidate, M., Xxxxxxx, X., Ashby, X., Myhr, X. X. (1991), Genotoxicity Xxxxx Extreme Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Mutation Xxx. 257, 147-204.

8) Xxxxx, X., XxXxxx, X., Spector, J. X. X., Xxxxx, X., Xxxxxxxxx, X. X. (1983), Xxxxxxxx Xxxx Xxxxxxxxx xx X5178X Xxxxx xx Xxxxxxx. X Xxxxxx xx xxx X. X. Environmental Xxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Res., 115, 225-251.

9) Xx, A. X., Xxxxx, X. X., Xxxxxxx, R. X., Xxxxxx, X. X. (1988), X Xxxxxx xxx Analysis xx xxx Chinese Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Determine xxx Xxxxxxxxxxxx of Chemical Xxxxxx: X Report xx Phase XXX xx the X. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Li, A. X., Carver, X. X., Xxxx, X. X., Hsie, X. X., Xxxxx, X. X., Loveday, X. X., X'Νxxxx, X. X., Xxxxxx, J. X., Stankowski, L. X. Jr., Xxxx, X. L. (1987), X Xxxxx for xxx Xxxxxxxxxxx xx xxx Chinese Hamster Xxxxx Cell/Hypoxanthine-Guanine Xxxxxxxxxxxxxx Xxxxxxxxxxx Gene Xxxxxxxx Xxxxx, Mutatation Xxx., 189, 135-141.

11) Liber, X. X., Yandell, X. X., Xxxxxx, X. X. (1989), X Xxxxxxxxxx of Xxxxxxxx Xxxxxxxxx xx xxx TK xxx XXXX Xxxx xx Xxxxx Xxxxxxxxxxxxxx Xxxxx: Xxxxxxxxxxxx Xxxxxxxxxxx xxx Xxx xx xx Xxxxxxxxxx Class xx Xxxxxxxxx xx xxx Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Res., 216, 9-17.

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

13) Xxxxxx, X. T., Xxxxxx, A. X., Xxxxx, X. (1984), Xxxxxxxxx for the X5178X/XX+/--XX+/- Mouse Xxxxxxxx Xxxx Xxxxxxxxxxxx Xxxxx, xx: Xxxxxx, B. X. et al (xxx.) Xxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, Xxxxxxxx Xxxxxxx Publishers, Xxx Xxxx, 239-268.

14) Xxxxxx, X. F., Xxxxx, X. X., Xxxxxx, X. X., Xxxxx, X. X. X., Cole, J., XxXxxxxx, D. B., Xxxxxxx S. X. (1989), Xxxxxxxxx Cell Xxxx Mutation Assays Xxxxx upon Xxxxxx Xxxxxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, Kirkland, X. X., xx., Xxxxxxxxx Xxxxxxxxxx Press, 66-101.

15) Xxxxxxxxxxxx, A., Xxxxxxx, S., Xxxxx, X., Xxxxxx, X., Xxxxxxxx, X., Mazzaccoro, X. (1977), Xxxxxxxxx xx 6-Thioguanine-Resistant Mutants xx V79 Xxxxxxx Xxxxxxx Xxxxx xx Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Dimethylnitrosamine, Xxxxxxxxxx Res. 46, 365-373.

16) Xxxx, B. X., McCann, J., Xxxxxxxx, E. (1975), Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx xxx Mutagens xxxx the Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx. 31, 347-364.

17) Xxxxx, X., Xxxxxxx, X. X., Xxxxxxx, X. F. X., Xxxxxx X. X., Xxxxx M. X. X. (1979), Validation xxx Xxxxxxxxxxxxxxxx xx xxx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxxxx Xxxxx System, Xxxxx. Res. 59, 61-108.

18) Xxxxx, X. X., Xxxx, X. X. (1983), Revised Xxxxxxx xxx xxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res. 113, 173-215.

19) Xxxxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, X. X., Gatehouse, D. X., Xxxxxx, X. X., Mackay, X. X., Xxxx, X. X. (1992), Alternatives xx Xxxxxxx 1254-Xxxxxxx X9 xx: Xx xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, T., Sawamura, X., Xxxx, K., Xxxxxxxx, T. (1976), X Xxxx Substitute xxx Polycholrinated Xxxxxxxxx x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, X: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Mutagenesis Xxxxxxx, de Serres, X. X., Xxxxx, X. X., Xxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. X., Xxxxxx, F. X., XxXxxxx, X. X. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Xxxxxxxxxx of Xxxxx xxx Xxxxxxxx Xxxxxxx, in: Ticc, X. X., Xxxxx, X. L., Schaich, X. X. (eds), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

22) Xxxxxx, X. X., Xxxxxx, X. X., Xx, X. P., Xxxxxx, A. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx System Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Gels xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Mutation Xxxxx, Environ. Xxxxxxxxxxx, 5, 795-801.

23) Xxxxxxxxx, X. X., Moore, X. M., Broder, X. X., Xxxxxxx, X., Hozier, X. X. (1990), Molecular Xxxxxxxxxx xx Xxxxxxxxx xx the Xxxxxxxxxxxx Xxxxxxxxx Kinase Xxxxx xx Mouse Lymphoma Xxxxx, Xxxx. Natl. Xxxx. Xxx. X. X. X, 87, 51-55.

24) Xxxxx, M. X., Xxxxx, D., Xxxxxx, X. C., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. T., Xxxxxx, X. (1985), Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (TFT+) Xxxxxxx xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Res. 151, 161-174.

25) Xxxxxxx, X. W., Dryja, X. P., Xxxxxx, X. B. (1990), Xxxxxxxxx Genetic Analysis xx Recessive Xxxxxxxxx xx a Xxxxxxxxxxxx Xxxxxxxxx Xxxxx in Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.

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


PŘÍLOHA 4X

"X.23 XXXXXXX XX XXXXXXXXXXXX ABERACE XX SPERMATOGONIÍCH SAVCŮ

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX XX 483 — Xxxxxxx na chromozomové xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1997).

1.1 ÚVOD

Účelem xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx xx xxxx xx identifikovat xxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx aberace xx spermatogoniích xxxxx (1, 2, 3, 4, 5). Rozlišují xx xxx typy xxxxxxxxxxxx aberací: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Tato xxxxxx xxxx xxxxxx xx xxxxxxxxx numerických xxxxxxx a xxxx x tomuto xxxxx xxxxxxx používána. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx xxxxx geneticky xxxxxxxxxxx xxxxxx x člověka.

Touto xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx xx xxxxxxxxxxxxxxx x předpokládá xx xxxx, xx xxxx xxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx v xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx používáni xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx xx vivo xx detekují chromozomové xxxxxxx xxx xxxxxx xxxxxxxxxxxxx. Xxxx cílové xxxxx xxxxxx předmětem xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx xx xxxxxxxxxxxxxxx xx xxxx xxx — xxxxx xxx dojde xx xxxxxx xxxx — xxxxxxxxx první xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx xx xxxxxxxx. Xxxxx informace x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxx chromozomového xxxx x xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx zkouška in xxxx xx navržena xxx xxxxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx aktivní xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx xx xxxx xxxxxxx xx spermatogoniemi xxxxxxxx pro xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx x procesy xxxxxxxx XXX.

Xx xxxxxxxxx xx přítomna xxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxxxx na xxxxxxxx xxxxxxxx látce. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx souhrnnou xxxxxxx xxxxxxxxxx xxxxxxxx spermatogonií x xxxxxxxxxxxxxx diferencovanými xxxxxxxxxxxxxxx. X závislosti xx xxx xxxxxx xx xxxxxxxxx, mohou xxxx xxxxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx v xxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx xxxxx x xxxxxxx mezi xxxxxxx xxxxxx x xxxxxxx.

Xxxxxxxx existuje xxxxx x tom, že xx zkoušená xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, není xxxxxx xxxx zkoušku xxxxxx.

Xxx xxxx xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu x xxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxx nebo zlomu x xxxxxxxx xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození chromozomu x xxxxxx xxxxx xxxx xxxxx x xxxxxxx obou chromatid x tomtéž místě.

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

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

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx změny xxxxxxxxx xxxxxxxxxx při xxxxxxxx xxxxxx xx xxxxxx metafáze xxx xxxxxxxxxxx, xxxx xx xxxx xxxxxx x xxxxxxxxx, intrachromozomální nebo xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX METODY

Zvířata xxxx xxxxxxx způsobem exponována xxxxxxxx xxxxx x xx xxxxxx době xx xxxxxxxx xxxxxxxx. Xxxx xxxxxxxxx se xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx xxxx Xxxxxxxx®). X germinálních xxxxx xx xxxx připraví xxxxxxxxx chromozomů, xxxxxx xx x analyzují xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xxxx xxxxxxxxx samci xxxxxx xxxxxxxx a xxxx; xxx však xxxxxx samce xxxxxxxxxx xxxxxx vhodného druhu xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx studie xx měla být xxxxxxxx v xxxxxxxxx xxxxxx minimální x xxxxxx by překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx mladí pohlavně xxxxxxx xxxxx xx xxxxxxxx xxxxxxx rozdělí xx kontrolní xxxxxxx x skupinu, xxxxx xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx minimalizován. Xxxxxxx xx jednoznačně xxxxxxxxxxxx. Xxxx xxxxxxxxx xxxxxx xx xxxxxxx x xxxxxxxxxxxxx podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx by měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x popřípadě zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx nebo xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxxxx mít při xxxxxxxxx xxxxxxxxx dávek xxxxxxx xxxxxx x xxxx xx být xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Jsou-li xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx experimentu by xxxx být souběžné xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx aplikace xxxxxxxx xxxxx xx xxxx xxxxxxx kontrolní xxxxxxx xxxxxxxxxx identický proces xxxx xxxxxxx ve xxxxxxxxx, x xxxxx xxxxx x expozici.

Pozitivní xxxxxxxx xx měly xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx in xxxx při expozičních xxxxxxxx, u xxxxx xx předpokládá, xx xxxxxxxxx detekovatelný nárůst xxx pozadí.

Dávky pozitivní xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xxx účinek xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx byla xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx kontrolu xxxx být navíc xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx kontrolu:

Látka

Číslo XXX

Xxxxx xxxxx Xxxxxx

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxx (xxxxxxx)

79–06–1

201–173–7

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

51–18–3

200–083–5

X xxxxxxxx xxxxxxx xxxxxx xx měl xxx xxxxxxxx odběr x xxxxxxx xxxxxxxxx kontroly, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a která xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx nejsou x dosavadních xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 POSTUP

1.5.1 Xxxxx xxxxxx

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

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx měly být xxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxx nadvakrát (xx. xxx xxxxx xxxxxxxx xxxx xxxx xxxxxxxxxx). Zkoušené xxxxx xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, tzn. dvě xxxxx x týž xxx x xxxxxxx xx xxxx než xxxxxxxx xxxxx, aby xxxx xxxxxxxxx podávání xxxxxxx xxxxxx xxxxxxxxx. Xxxx režimy xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x xxxxxxxx xxxxxx xx xxxx xxx xx expozici provedeny xxx xxxxxx. Poněvadž xxxxxxxx xxxxxxxxx xxxxx xxxx být xxxxxxxxx xxxxxx ovlivněna, xxxxxxx xx xxxxx časný xxxxx a xxxxx xxxxxxxx xxxxx xxxxxxxxx 24 x 48 xxxxx xx expozici. X případě xxxx xxx xxxxxxxx dávky xx měl být xxxxx xxxxxxxx po 24 xxxxx xxxx xx xxxxxx xxxx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx není xxxxx xxxx xxxxxxxxx xxxx pro detekci xxxxxx (6).

Xxxxx xxxxx xxx xxxxxx provedeny xxxx x xxxx xxxx. Xxxxxxxxx v xxxxxxx xxxxxxxxxx látek, xxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (lagging) xxxxxxxxxx nebo mohou xxxxxxxxxx S-nezávislé xxxxxx, xxxx xxx xxxxxxxxx xxxxxxxx odběr (1).

Xxxxxxxx xxxxx opakované expozice xxxx být určena xxxxxx xx xxxxxxx. X případě plánu x xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx xxxxxxxx 24 xxxxx (1,5násobek xxxxx xxxxx) xx xxxxxxxx xxxxxxxx. Xxxxx potřeby xxxxx být xxxxxxxxx xxxxx xxxxxx x xxxx době.

Před xxxxxxxxx xx zvířatům intraperitoneálně xxxx vhodná xxxxx xxxxx xxxxxxxxxxx metafázi (xxxx. Xxxxxxxx® nebo xxxxxxxxx). Poté xx xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. X xxxx xx xxxx doba xxxxxxxxx 3 — 5 xxxxx; x xxxxxx čínského xx xxxx xxxx přibližně 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx údajů studie xxx xxxxxxxx xxxxxxx, xxxx xx být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx x kmenem x xx stejného xxxxxx xxxxxxxx, xxxxx xx použije v xxxxxx studii (7). X případě xxxxxxxx xx xxx první xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx xxxxxxxx xxxxxxx xxxx maximální a xxxxxxxxx toxicitou, xxxxxxxx xxxxxx toxicitou. Při xxxxxxxxx xxxxxx xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx by xxxxx xxxxx xxxxx xxx stejném xxxxxx xxxxxxxxx podle xxxxxxxxx x xxxxxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (např. hormony x xxxxxxxx) xxxxxx xxxxxxxxx stanovení dávky xxxxxxxxx x xxxx xx xxx hodnoceny xxxxxx xx případu. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx toxicity (xxxx. xxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxxx metafázi; xxxx xxxxxxx xx xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx s jednou xxxxxx alespoň 2000 xx/xx tělesné hmotnosti xxxxxxx jednorázově nebo xx xxxx xxxxxxx x jednom xxx xxxxxxxxxx xxxxx pozorovatelné xxxxxxx účinky x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx mají xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx se úplná xxxxxx xx xxxxx xxxxxxxx xxxxx za xxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx může znamenat xxxxxxx xxxxxx v xxxxxxx zkoušce vyšší xxxxxx xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx látka se xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx způsoby podávání xxxx xxxxxxxxxx, jsou-li xxxxxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx může xxx xxxxxxxx podán xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 ml/100 x tělesné hmotnosti. Xxxxxxx xxxxxxx objemů, xxx je xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx zesílené účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx konstantní objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava xxxxxxxxx xx analýzu chromozomů

Ihned xx usmrcení xx x jednoho xxxx xxxx varlat xxxxx xxxxxxx xxxxxxxx, hypotonizuje xx a xxxxxx. Xxxx xx nanese xx podložní xxxxxxx x xxxxxx se.

1.5.7 Xxxxxxx

X každého zvířete xx xxxx xxx xxxxxxxxxxx alespoň 100 xxxxx x xxxxx xxxxxxxxxxxx xxxxxxxx (tj. xxxxxxxxx 500 xxxxxxxx xx skupinu). Xxxxx xxxxx lze xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx mikroskopickou xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx při xxxxxx xxxxx dochází xx xxxxxxxxxxxxxx xxxxxx nebo xxxxxx xxxxxxxxxx x xxxxx xxxxxxxx, měly xx vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx odpovídajícímu xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx každé zvíře xx měl být xxxxxxxxxx xxxxx buněk xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x počet xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx xxxxxxxxxx x kontrolní xxxxxxx xx xxxx xxx xxxxxxx různé xxxx xxxxxxxxxxxx chromozomových xxxxxxx x xxxxxx počtem x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x uvádějí se, xxx obecně xx xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, xxx xx xxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxxxxx účinků xxxx míra xxxxxxxxxxxx xxxxxxxx x všech xxxxxxxxxxxx xxxxxx a xxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxxx xxxxxxxx, x to x xxxxxxxx vzorku 100 xxxxxxxx xx xxxxx xx jedno xxxxx. Pokud je xxxxxxxxx xxxxx xxxxxx, xxxxxxx x 1000 xxxxxxx na xxxxx xx xxx být xxxxxxxx mitotický xxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje několik xxxxxxxx, např. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx s xxxxxxxxx xxx xxxxxxx x xxxxxxx dávkou x x určitému xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Dvojznačné výsledky xx měly xxx xxxxxxxxx dalším zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx kritéria, xx v xxxxx xxxxxxx xxxxxxxx za xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx soubor údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx savců in xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx aberace. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxx x germinálních xxxxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.

Xxxx by xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx xxxxxxxx xxxxx nebo xxxx xxxxxxxxxx xxxxxxxx xx xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Testovací xxxxxxx:

- xxxxxxx druh/kmen,

- počet x xxxxx xxxxxx,

- xxxxx, podmínky chovu, xxxxxx xxx.,

- individuální xxxxxxxx xxxxxx xx xxxxxxx zkoušky, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx hodnoty x xxxxxxxxxx odchylky xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxx xx studie xxx xxxxxxxx xxxxxxx, xxxxx byla xxxxxxxxx,

- xxxxxxxxxx zvolených úrovní xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

- xxxxx x xxxxxxxx zkoušené látky,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxx xxxxxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- podrobný xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx toxicity,

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

- metody xxxxxxxx preparátů,

- xxxxxxxx xxxxxxxxx aberací,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky toxicity,

- xxxxxxxxx xxxxx,

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

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx každé xxxxx,

- xxxxxxx xxxxx xxxxxxx xx xxxxxxx,

- xxxxx buněk s xxxxxxxxx ve xxxxxxx,

- xxxxx možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- změny ploidie, xxxxx xxxx pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Adler, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx in Xxxxx Xxxxxxxxxxxxx xx Xxxxxxxx Xxxxxxxx Xxxxxxx xx their Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxxx Xxxxxxxxx, Xxxx X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Xxxxxxx, X., Xxxxxxxxx, J. (xxx) Xxxx, Xxx Xxxx, 477-484.

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

3) Xxxxx, X. X., Xxxxxxx, G., Xxxx, X. X. (1964), Xx Air-drying Xxxxxx xxx Meiotic Preparations xxxx Xxxxxxxxx Xxxxxx, Xxxxxxxxxxxx Cell Xxxxxxxx, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, J., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxx Xxxxxx, xx: D. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx I xxxxxxx, Cambridge University Xxxxx, Cambridge, New Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

5) Xxxxxxxx, K., Xxxxxxx, X. (1978), X Xxx Xxxxxx xxx Xxxxxxxxxxx of Xxxxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 52, 207-209.

6) Xxxxx, X. D., Xxxxxx X. X., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, W., Xxxxxxxxxxxx, F., Xxxxxxx, X., Xxxxxx X. (1994), International Xxxxxxxx xx Xxxxxxxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxx Xxxxxx xx xxx Working Xxxxx xx Mammalian Xxxx Xxxx Xxxxx, Mutatation Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, J. X., Xxxxxx, X. R., Xxxxxx, P. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Xxxxxx of Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Society Xxxxxxx Group: Xxxx Xxxxxxx xx Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, D. X., Xxxxxxxx, D., Albanese, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, R., Richold, X., Papworth, D. X., Savage X. X. K. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, in: D. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data. XXXXX Subcommittee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Sydney, 184-232."


XXXXXXX 4X

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

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx OECD TG 486 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx XXX (XXX) x xxxxxxxxx buňkách xxxxx xx vivo (1997).

1.1 XXXX

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

Tato xxxxxxx xx xxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx účinků xxxxxxxxxx xxxxx x xxxxxxx. Xxxxxxxxxxx jev je xxxxxxxxxx poškození DNA x xxxxxxxx reparace x jaterních xxxxxxx. Xxxxx jsou xxxxxxx xxxxxxx místem, xxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Xxxx xxxx xxxxxxx xxxxxx pro xxxxxxxxx xxxx xxxxxxxxx XXX xx xxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx nedostane xx cílové tkáně, xxxx vhodné xxxx xxxxxxx použít.

Rozsah xxxxxxxxxxx xxxxxxx XXX (XXX) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx syntézou XXX (S-fází). Xxxxxxxxxxxxxxx xxxxxxxxx xx autoradiografické xxxxxxxxx xxxxxxxxxxx thymidinu xxxxxxxxx xxxxxxx (3X-XxX). Xxx xxxxxxx xx XXX xx vivo xx xxxxxxxxxx xxxxxxxxx xxxxx xxxxxxx. Xxxx xxxxx než xxxxx xxxxx xxx rovněž xxxxxxx, xxxxxx však xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx XXX závisí xx xxxxx bází XXX vyštěpených a xxxxxxxxxxx x xxxxx xxxxxxxxx. Xxxxxxx xx XXX je tedy xxxxxx zvláště pro xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 bází) xxxxxxxxxxxx látkou. Krátké xxxxxx ("xxxxx-xxxxx xxxxxx") (xxxxx xx xxx xxxx) jsou xxxxxxx xxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxx. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, chybné xxxxxxxx xxxx xxxxxx xxxxxxxxx xxxx XXX xxxxx x xxxxxxxxxx xxxxxxxxx. Xxxxxx odpovědi XXX neposkytuje xxxxxx xxxxxxxxx x věrnosti xxxxxxxxxxx procesů. Navíc xx možné, xx xxxxxxx reaguje x XXX, xxx poškození XXX xxxx opraveno xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxx, xxxxx xxxx xxxxxxx poskytuje x xxxxxxxxx xxxxxxxx, xx xxxxxxx potenciální xxxxxxxxxx xxxxxx xxxx, xxxxx xx xxxxxxxxxx x xxxxx xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Opravované xxxxx : xxxxx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (NNG), xxxxx než xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx xxxx UDS xxxxxxxx buněk v xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxx xxx x cytoplasmatických xxxxxxxxx (XX) odpovídajících jádrům xx počtu xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): XXX = XX — XX. Xxxxxxx XXX xx xxxxxxx pro xxxxxxxxxx xxxxx, xxxx společně xxx xxxxx x xxxxxxx, x paralelních xxxxxxxxx xxx.

Xxxxxxxxxxx xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx xxxxxxxxx a xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx region x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xx XXX x xxxxxxxxx buňkách xxxxx in vivo xxxxxxxx syntézu xxxxxxxx XXX xx vyštěpení x odstranění úseku XXX obsahujícího region x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx xxxxxxxx xx inkorporaci 3H-TdR xx XXX jaterních xxxxx, xxx xx xxxx xxxxxxx buněk x S-fázi buněčného xxxxx. Xxxxxxxxxxx 3X-XxX xx xxxxxxx stanoveno xxxxxxxxxxxxxxx, xxxxxxx tato xxxxxxxx xxxx xxx xxxxxxx na xxxx X-xxxx buněk jako xxxx. kapalná xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx je používán xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxxxx laboratorní xxxxx xxxxxxx zdravých xxxxxxxx dospělých xxxxxx. X xxxxxxxx zahájení xxxxxx xx xxxx xxx odchylka x xxxxxxxxx zvířat xxxxxxxxx x xxxxxx by xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx xxx obě xxxxxxx.

1.4.1.2 Podmínky xxxxx x xxxxxx

Xxxxx obecné xxxxxxxx xxxxx xxxxxxxx xxxxx x části X, xxxxxxx xx xxxx být xxxxxxxx xxxxxxxx vzduchu 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, která xx exponuje. Klece xx xxxx být xxxxxxxxxx xxx, aby xxx xxxx jejich xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují x xxxx xxxxxxxxx xxxxxx se nechají x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx zkoušené xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx zvířatům xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx zředěny. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx zvážit xxxxxxx xxxxx možno xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxx xxxxxxxxx prováděné části xxxxxxxxxxx by xxxx xxx souběžné xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx měla xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx proces xxxx xxxxxxx xx xxxxxxxxx, x xxxxx dojde x expozici.

Pozitivními kontrolami xx xxxx xxx xxxxx, o xxxxx xx xxxxx, xx xxxxxx podávání v xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx aktivaci xx xxxx xxx xxxxxxx v xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Xxxxx mohou xxx xxxxxxx tak, xxx byl účinek xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx CAS

Číslo xxxxx Xxxxxx

Xxxxx xxxx xxxxxx (2 xx 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx doby xxxxxx (12 až 16 x)

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

53–96–3

200–188–6

Xxxxx xxx použity xxxx xxxx látky xxx xxxxxxxxx xxxxxxxx. Je xxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxx jiným způsobem, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Měl xx xxx xxxxxx xxxxxxxxxx xxxxx xxxxxx, xxx xxxx xxxxxxxxxx přirozené xxxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx. Každá xxxxxxx xx xx xxxx xxxxxxx xxxxxxx xx tří xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, je xxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx skupiny nezbytné xxxxx xxxxx až xxx zvířata.

Jestliže xxxx x xxxx xxxxxx x xxxxxxxxx údaje xx xxxxxx se xxxxxxx xxxxxx a xx xxxxxxx stejného xxxxxxx xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, nejlépe samců. Xx-xx expozice xxxxxxx xxxxxxxxxx xxx určité xxxxxxx, xxxx je xxxx například x xxxxxxxxx farmaceutických xxxxx, xxxx by xxx xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx expozice

Zkoušené xxxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx.

1.5.3 Dávkování

Za xxxxxxxxxx xxxxxxxx xx xxxxxxxxx xxxxxxx dvě úrovně xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx dávky xx xxxxx podle xxxxxxxxx xxx xxxxxxx režimu xxxxxxxxx x letalitě. Xxxxx dávka xx xxxx xxx xxxxxxxxx 50 % xx 25 % xxxxx xxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx netoxických dávkách (xxxx. hormony x xxxxxxxx) nemusí xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x měly by xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx xxxxxxx, měla xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx xxxxxxx druhem, xxxxxx, xxxxxxxx x za xxxxxxxx režimu xxxxxxxx, xxx xx xxxxxxx x hlavní studii.

Nejvyšší xxxxx xxxx xxx xxxxxxxxxx xxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxxxx x xxxxxxx (xxxx. pyknotická xxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx žádné pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx být xxxxx xxxxxx nezbytná. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx potřebu xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx látka xx obvykle podává xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx xxxxxxx intubační xxxxxxx. Xxxx způsoby xxxxxxxx jsou možné, xxx-xx xx xxxxxxxxx. Xxxxxxxx intraperitoneálně xx xxxx xxxxxxxxxxxx, xxxxx xx xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxx xxxxx přímo x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který může xxx xxxxxxxx xxxxx xxxxxxxxx sondou nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx je xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx jaterních xxxxx

Xxxxxxx xxxxx se xxxxxxxxxx z exponovaných xxxxxx xxxxxxxxx 12 xx 16 hodin xx xxxxxx dávky. Xxxxxxxxxx dřívější xxxxxxxx xxxxxx (obecně xxx xx xxxxx xxxxxx xx xxxxxxxx) xx xxxxxxxx, xxxx-xx xx 12 xx 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx xxxxxxx jiné xxxx xxxxxx, xxxx-xx xxxxxxxxxx xx základě xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx kultury xxxxxxxxx xxxxx xxxxx xx xxxxxxxxx zakládají xxxxxxx jater kolagenasou xx xxxx x xxxxxx xx, xxx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxx zachytily xx xxxxxxx xxxxxxx. Xxxxxxx xxxxx z xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxx xxxxxxxxxxxxxxx (5) alespoň 50 %.

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx jaterní xxxxx xxxxx xx xxxxxxx xxxxxxx xxxx, např. xxx xx osm xxxxx, xxxxxxxx x xxxxxx obsahujícím 3H-TdR. Xx xxxxx inkubační xxxx xx mělo xxx xxxxxx x xxxxx odstraněno x xxxxx poté mohou xxx xxxxxxxxxx x xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx, xxx xxxx xxxxxxx neinkorporovaná xxxxxxxxxxxxx ("cold xxxxx"). Xxxxx se xxxx xxxxxxx, xxxxxx x xxxxxx. Xxx xxxxx xxxxxxxxx xxxx xxxxxx xxx snížení xxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx se xxxxxx do autoradiografické xxxxxx, xxxxxxxx xx x temnu (např. x xxxxxx 7 xx 14 xxx), xxxxxxxx xx, xxxxxx x xxxxxxxxx xx xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxxx xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

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

Xxxx počítáním xxx by měly xxx preparáty xxxxxxxx. Xxxxxxxxx xx xxxxxxxxx 100 xxxxx na xxxxx xxxxx xxxxxxx xx xxxx preparátů; xxxxxxxxx xxxx xxx 100 xxxxx/xxxxx by xxxx xxx xxxxxxxxxx. Xxx xxxxxxxx xxx xx xxxxx x X-xxxx xxxxxxxxxxx, xxx xxxxx xxxxx x X-xxxx xxxx být xxxxxxxxxx.

Xxxxxxxx 3H-TdR xxxxxxxxxxxxxxx xx xxxxx x xxxxxxxxxx morfologicky xxxxxxxxxx xxxxx doložené xxxxxxxxxxx xxx xxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxx.

Xxxxx xxxxx xx xxxxxxx x xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (xx) x x xxŭxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (xx) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx xx se xxxxxxx buď xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx xxxxxx cytoplasmy, xxxx xxŭxxxxx xxxxxxx xxxx až xxx xxxxxxx xxxxxxxxx oblastí x blízkosti dotyčných xxxxxxxxx xxxxx. xx xxxxxxxxxxxxx xxXxxxxxxx mohou xxx xxxxxxx x xxxx xxxxxxx xxxxxxxxx xxxxx xxxxx (xxxx. xxxxxxxx celých buněk) (6).

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxx xx být xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx a xxxxxxx. Údaje xx xxxx xxx xxxx xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX od hodnoty XX xx xxx xxx xxxxxxxx xxx xxxxxx xxxxx, xxx xxxxx xxxxx a xxx každou xxxxx x xxx xxxxx xxxxx zrn odpovídajících xxxxxxxx xxxxxx (XXX). Xxxxxxxx xxxx počítány "xxxxxxxxxx" xxxxx, měla xx xxx kritéria xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx odůvodněna x xxxxxxxx na xxxxxxxxxxx xxxx souběžných xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx mohou xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx být xxxxxxx, xxxx xx xxx xxxxxxxxxxx xxxxx xxxxxxx x odůvodněny xxxx xxxxxxxxxx xxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx odpověď patří:

pozitivní

i)

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

xxxx

xx)

xxxxxxx NNG je xxxxxxxx vyšší xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx XXX leží xx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxx xx;

xxxx

xx)

xxxxxxx NNG xxxx xxxxxxxx vyšší xxx xxxxxxx pro souběžnou xxxxxxxx.

Xxxx xx xxx xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx. měly xx xxx vzaty x xxxxx xxxxxxxxx, xxxx xxxx variabilita xxxxxx, xxxxx dávky x xxxxxxxx x xxxxxxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost xx však neměla xxx jediným určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx XXX x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x xxxxxxxxx xxxxxxx xxxxx xx vivo xxxxxxxxx DNA, xxxxx xxx opravit xxxxxxxxxxxx xxxxxxxx XXX xx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že zkoušená xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx poškození XXX, které lze xxxxxxxxx xxxxx xxxxxxxx.

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

3. ZPRÁVY

PROTOKOL X ZKOUŠCE

Protokol x xxxxxxx musí obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx hmotnost xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, střední xxxxxxx x xxxxxxxxxx odchylky xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- xxxxx xx studie xxx xxxxxxxx rozsahu, xxxxx byla xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx podávání,

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

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

- xxxxxxxx xxxxx x xxxxxxx krmiva x vody,

- xxxxxxxx xxxxx rozvrhu expozice x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxx,

- použitá xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx a počet xxxxxxxxxxx buněk,

- kritéria xxxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx pozitivní, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxxx xxxxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx a xxxxx xxx xxxxxxxxxxxxxx cytoplasmě, x xxxxx xxxxx xxx, xxxxxxxxxx xxx xxxxxxxxx, xxxxxxx a xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- případné xxxxxxxxxxx xxxxxxxxx,

- xxxxxx toxicity,

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

- xxxxxxxxx xxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) a xxxxxxxxx xxxxxxxx x rozmezími, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx odchylkami,

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

- xxxxx xxxxx v X-xxxx, xx-xx xxxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. Lefevre, X. A., Burlinson, X., Xxxxxx, M. X. (1985), Xx Xxxxxxxxxx xx xxx Xx xxxx Xxx. Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.

2) Butterworth, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, G., Xxxxxxxx, G. (1987), X Xxxxxxxx and Xxxxx xxx xxx Xx xxxx Xxx Xxxxxxxxxx XXX Repair Xxxxx, Xxxxxxxxxx Xxx., 189, 123-133.

3) Xxxxxxxx, X. C., Xxxxxx, X., Xxxxx, X., Xxxxxxx, P. X., Xxxxxxxxx, X., Xxxxxxx, X. J., Dean, X. W., Mitchell, X. de X. (1993), Xx xxxx Xxx Xxxxx XXX Xxxxx, xx: Xxxxxxxx X. X., Fox X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: UKEM Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Mutagenicity Testing. Xxxxxx. Part XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Xxxx, X. X., Andrac, X., Xxxxxxxxx. G., Xxxxxxxxx, X., Doolittle, X. J., Furihata, X., Xxxxxxx, T., XxXxxxx, C. A., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx the Xxxxxxxxxxx of UDS Xxxxx Xx xxxxx xxx Xx vivo, Xxxxx. Xxx., 312, 263-285.

5) Fautz, R., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, X. (1993), Xxxxxxxxxx xx xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Viability xxx xxx Xxxxxxxxxx xx Xxxxxxx Xxxxxxxx Xxx Xxxxxxxxxxx Xxxx xxx the Xx xxxx/Xx xxxxx XXX Xxxxxx Assay (XXX), Xxxxxxxxxx Res., 291, 21-27.

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


XXXXXXX 5

OBECNÉ XXXXXXXXX XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX LÁTEK X PŘÍPRAVKŮ

Viz xxxxxxxx Xxxxxx 2001/59/XX, Xx. xxxx. L 332, 28. 12. 2000, x. 81.


XXXXXXX 6

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PŘÍLOHA XX

XXXX X

xxxxxxxx týkající se xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 xxxx. 1 xxxx. x) xxxx xxxxxxxx, xxxx xxx obaly x xxxxxxxxx objemu xxxxxxxxxx xxxxx, x nimiž xx xxxxxxx xxxxxx xxx xxxxxxxxxx (Xx; X 65) x xxxxx xxxx xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 přílohy XX této xxxxxxxx, x výjimkou xxxxx xxxxxxxxx xx trh xx xxxxx xxxxxxxx xxxx x nádobách xxxxxxxxxx xxxxxxxxxxx rozprašovačem, xxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx uzavíratelné xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx obalech xxxx xxxxxxxx xxxxxxxxx xxxxx ISO 8317 (xxxxxx xx xxx 1. července 1989) "Xxxxx xxxxxx xxxxx — Xxxxxxxxx na xxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxx jejich xxxxxxxx" přijatou Xxxxxxxxxxx xxxxxxxxxx xxx normalizaci (XXX).

2. Opakovaně neuzavíratelné xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx CEN XX 862 (vydání x března 1997) "Xxxxx — Obaly xxxxxx dětem — Xxxxxxxxx x xxxxxxxx xxxxxxx pro opakovaně xxxxxxxxxxxxxx xxxxx xxxxxx xxx farmaceutických xxxxxxx" xxxxxxxx Evropským výborem xxx xxxxxxxxxxx (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx xxxxx x xxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxx laboratoře, které xxxxxxx xxxxxxxx xxxxx xxxx XX 45000.

2. Xxxxxxxxxx případy

Je-li xxxxxx, xx obal je xxxxxxxxxx bezpečný pro xxxx, xxxxx xx xxxxxxx dostat k xxxxxx bez xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx případech a xxxxx xxxxxxxx oprávněné xxxxxx k pochybám x xxxxxxxxxxx xxxxxxx xxx xxxx, xxxx xxxxxxxxxxxx orgán požadovat, xxx xxxxx odpovědná xx xxxxxxx xxxxxxx xx xxx předložila xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx xxxxxx, xx xxx xxxx xxxxxxxx xxxxxxx podle xxxx xxxxxxxxx xxxxx XXX x XXX,

xxxx

- xx xxxxxx xxx xxxxxxx x xxx xxxxxxx xxxxxxxxxxx podle xxxx xxxxxxxxx norem.

ČÁST X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx specifikace xxx xxxxxxxxxx xxxxxxxx xxxx xxx x xxxxxxx x normou XX XXX 11683 (xxxxxx z roku 1997) "Xxxxx — Xxxxxxxxxx výstrahy xxxx xxxxxxxxxx — Požadavky".

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