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Xxxxxxxx Xxxxxx 2000/32/XX

xx xxx 19. května 2000,

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

(Xxxx s xxxxxxxx pro XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Smlouvu o xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx xx xxxxxxxx Xxxx 67/548/EHS ze xxx 27. xxxxxx 1967 x sbližování xxxxxxxx x správních xxxxxxxx xxxxxxxxxx se xxxxxxxxxxx, xxxxxx a xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], xxxxxxxxx xxxxxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Xxxx 1999/33/XX [3], a xxxxxxx xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx x xxxxx xxxxxxx:

(1) Příloha X směrnice 67/548/EHS xxxxxxxx xxxxxx nebezpečných xxxxx společně s xxxxxxxxxx údaji x xxxxxxxxxxx x xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxx, že xx xxx xxx xxxxxx xxxxxxxxxxxx xxxxx x uvedené xxxxxxx xxxxxxxxxxx. Xxxxxxx jazykové xxxxx xxxxxxxx vyžadují xxxxxx určitých xxxxxx xxxxxxxxx x tabulky X v xxxxxxx X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx xxxxxxxxxxx xxxxxx xxxxxxxxxx rizik xxxxxxxxx x xxxxxxxxxxxx xxxxxxx a xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx x xxxxxxxxxxxxxx xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxx xx klasifikaci x x označování xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx směrnice xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, XX x VI.

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

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

(5) Xxxxxxxx této směrnice xxxx v xxxxxxx xx xxxxxxxxxxx Výboru xxx xxxxxxxxxxxx technickému xxxxxxx xxxxxxx xxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxx na xxxxx xxxxxxxxxxxx látek x xxxxxxxxx,

XXXXXXX XXXX XXXXXXXX:

Xxxxxx 1

Směrnice 67/548/EHS xx xxxx xxxxx:

1. Xxxxxxx X xx xxxx takto:

a) odpovídající xxxxxxxx x xxxxxxxxx xx xxxxxxxxx poznámkou X x xxxxxxx 1X xxxx směrnice;

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

x) xxxxxxxxxxxx položky xx nahrazují xxxxxxxxx x příloze 1C xxxx xxxxxxxx;

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

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

3. Xxxxxxx XX xx xxxx takto:

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

x) odpovídající xxxxxx x příloze IV xx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx pokyny pro xxxxxxxx xxxxxxxxx x xxxxxxx 3X xxxx xxxxxxxx.

4. Xxxx X xxxxxxx V xx xxxx xxxxx:

x) xxxxxxxx X.10 se xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx směrnice;

b) xxxxxxxx B.11 xx xxxxxxxxx xxxxxx x xxxxxxx 4B xxxx xxxxxxxx;

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

x) xxxxxxxx X.13 x X.14 xx nahrazují textem x xxxxxxx 4X xxxx xxxxxxxx;

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

x) xxxxxxxx X.23 xx xxxxxxxxx textem x xxxxxxx 4F této xxxxxxxx. Název kapitoly X.23 xx vysvětlivce xx mění odpovídajícím xxxxxxxx;

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

5. Xxxxxxx xx xxxxxx xxxxxxx xxxxxxxx úvodu x xxxxx C xxxxxxx X.

6. Xxxxxxxxxxxx xxxxx x xxxxxxx XX xx nahrazují xxxxx x xxxxxxx 5 xxxx xxxxxxxx.

7. Xxxxxxx XX xx xxxx způsobem xxxxxxxx x příloze 6 xxxx směrnice.

Xxxxxx 2

1. Členské xxxxx uvedou v xxxxxxxx xxxxxx a xxxxxxx xxxxxxxx nezbytné xxx xxxxxxxx xxxxxxx x touto xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Neprodleně x xxxx xxxxxxx Xxxxxx.

Xxxx xxxxxxxx přijaté xxxxxxxxx xxxxx musí xxxxxxxxx odkaz xx xxxx směrnici nebo xxxx xxxxxx xxxxx xxx xxxxxx xxx xxxxxx úředním xxxxxxxxx. Xxxxxx xxxxxx xx xxxxxxx xxxxxxx xxxxx.

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

Xxxxxx 3

Xxxx xxxxxxxx xxxxxxxx x platnost xxxxxx dnem po xxxxxxxxx x Xxxxxxx xxxxxxxx Xxxxxxxxxx společenství.

Článek 4

Tato xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.

X Xxxxxxx xxx 19. května 2000.

Xx Xxxxxx

Xxxxxx Wallström

členka Xxxxxx


[1] Xxxxxxx po xxxxxxxxxxxx po xxxxxxx xxxxx.

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

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


XXXXXXX 1X

XXXXXXXXX X XXXXXXX X

Xxxxxxxxxx poznámek xxxxxxxxxx se xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx se českého 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 číslo

Chemický xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx 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; X50

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx

205–293–0

137–42–8

Xx; X22 X31 C; X34 R43 X; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

Xxxx. xxx. 3; X40 Xxxx. xxx. 3; R40 Xx; X22–48/22 N; X50–53

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

006–016–00–4

xxxxxxxx (XXX) 2- isopropoxyfenyl-N-methylkarbamát

204–043–8

114–26–1

T; X25 X; R50–53

T; X R: 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 T; X24 X; X50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; X24/25 X; X50–53

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

006–019–00–0

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

218–961–1

2303–16–4

Xxxx. xxx. 3; X40 Xx; X22 N; X50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xn; X22 X43 X; X50–53

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

006–023–00–2

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

217–991–2

2032–65–7

X; X25 N; R50–53

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

006–024–00–8

proxan-natrium (ISO) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx

205–443–5

140–93–2

Xx; X22 Xx; X38 X; X51–53

Xx; X R: 22–38–51/53 X: (2-)13-61

006–026–00–9

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 S: (1/2-)36/37–45–60–61

006–028–00-X

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

213–546–1

973–21–7

X; X25 X; R50–53

T; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

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

230–253–4

6988–21–2

X; R25 X; 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; R50–53

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

006–034–00–2

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

214–215–4

1114–71–2

Xx; X22 N; R51–53

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

006–037–00–9

promekarb (ISO) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–113–0

2631–37–0

X; X25 N; 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. xxx. 2; R45 Xx; X22 X; R50–53

T; X X: 45–22–50/53 X: 53–45–60–61

006–039–00-X

xxx-xxxxx (XXX) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx

218–962–7

2303–17–5

Xx; X22–48/22 X43 X; X50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; R40 Xx; R22 X; X50–53

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

006–043–00–1

monuron-TCA 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx

140–41–0

Xx; X36/38 Xxxx. xxx. 3; R40 X; X50–53

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

006–045–00–2

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

240–815–0

16752–77–5

X+; X28 N; X50–53

X+; X R: 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; R50–53

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

006–047–00–3

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

8065–36–9

X; X24/25 N; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xx; X22 X; R50–53

Xn; X X: 22–50/53 X: (2-)60-61

006–050–00–X

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

4482–55–7

Xx; 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 R: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; X28 Xx; X21 X; R50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; N X: 22–51/53 X: (2-)24-61

006–060–00–4

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 R:22–52/53 S: (2-)61

006–069–00–3

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

245–740–7

23564–05–8

Xxxx. xxx. 3; R40 X; X50–53

Xx; N X: 40–50/53 S: (2-)36/37–60–61

006–070–00–9

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

262–302–0

60568–05–0

Xxxx. kat. 3; R40 X; X50–53

Xx; N X: 40–50/53 X: (2-)36/37–60–61

006–088–00–7

xxxxxxxxxxx (XXX) xxxxx-X -[({[(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 T; X23/25 X; R34 X; X51–53

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

007–013–00–0

N,N-dimethylhydrazin 1,2-dimethylhydrazin

E

540–73–8

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

X; N X: 45–23/24/25–51/53 X: 53–45–61

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

009–003–00–1

xxxxxxxx xxxxxxxxxxxxxx … %

X

231–634–8

7664–39–3

X+; X26/27/28 X; R35

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

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

015–039–00–9

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

201–676–1

86–50–0

X+; X26/28 X; R24 R43 X; X50–53

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

015–048–00–8

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

200–231–9

55–38–9

Xxxx. xxx. 3; X40 X; X23–48/25 Xx; 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

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

220–147–6

2642–71–9

X+; X28 X; X24 X; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; X23/25 Xx; X21 N; X50–53

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

016–013–00-X

chlorid sirnatý

234–129–0

10545–99–0

R14 X; X34 X; X50

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

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

016–014–00–5

xxxxxxx xxxxxxxx

13451–08–6

X14 X; R34 X; 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; X36/37/38

016–023–00–4

xxxxxxxx-xxxxxx

X

201–058–1

77–78–1

Xxxx. xxx. 2; X45 Xxxx. xxx. 3; X40 X+; R26 X; X25 C; R34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

dimexano (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; X22 N; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

016–071–00–6

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

410–130–3

136248–03–8

X43

Xx X: 43 X: (2-)22–24–37

022–001–00–5

chlorid xxxxxxxxxx

231–441–9

7550–45–0

X14 C; X34

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

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

030–004–00–8

dimethylzinek [1] xxxxxxxxxxxx [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

X14 X; X17 X; X34 X; X50–53

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

050–002–00–0

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

236–049–1

13121–70–5

Xx; X20/21/22 X; R50–53

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

050–012–00–5

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

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

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

Xn; R20/21/22 X; R50–53

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

X ≥ 1 %: Xx; X20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

X+; R26 Xx; X36/38 X; 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) XX Xxxxxxx Xxxxxx 34 (XX 77603) XX xxxxxxxxxx žluť 34 (XX 77603)

215–693–7

1344–37–2

Xxxx. xxx. 3; R40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 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 xxxxxxxx) XX Xxxxxxx Xxx 104 (XX 77605) CI xxxxxxxxxx červeň 104 (XX 77605)

235–759–9

12656–85–8

Xxxx. kat. 3; X40 Xxxx. xxx. 1; R61 Xxxx. kat. 3; X62 X33 X; X50–53

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

1

601–024–00-X

kumen [1] xxxxxxxxxxxx [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

R10 Xx; X65 Xi; X37 N; X51–53

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

4

601–032–00–3

benzo[a]pyren benzo[def]chrysen

200–028–5

50–32–8

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

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

601–034–00–4

xxxxx[x]xxxxxxxxxxxxxxx

205–911–9

205–99–2

Xxxx. xxx.2; X45 N; X50–53

X; X R: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-xxxxxxxxxxxxx x-xxxxxxxxxxxxx

203–400–5

106–46–7

Xx; X36 X; R50–53

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

602–054–00–6

3-jodprop-1-en xxxxxxxxxx

209–130–4

556–56–9

X10 X; R34

C R: 10-34 X: (1/2-)7–26–45

603–076–00–9

xxx-2-xx-1,4-xxxx

203–788–6

110–65–6

X; X23/25 Xx; X21–48/22 X; X34

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

X ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ X &xx; 50 %: X; X21–23/25–36/38–48/22 10 % ≤ C &xx; 25 %: Xx; X20/22–48/22 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 Xx; X36

X; Xx R: 8–22–36 S: (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; R36 X52–53

Xx X:36–52/53 S: (2-)26-61

603–117–00–0

propan-2-ol xxxxxxxxxxxxxxxx isopropanol

200–661–7

67–63–0

F; R11 Xx; X36 X67

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

604–020–00–6

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

201–993–5

90–43–7

Xi; X36/37/38 X; R50

Xi; X X: 36/37/38–50 X: (2-)22-61

604–021–00–1

2-xxxxxxxxxx, xxxxx xxx xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx sodný xxxxxxx-xxxxxxx-2-xxxx

205–055–6

132–27–4

Xx; R22 Xx; X37/38–41 X; X50

Xx; X R: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

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

401–720–1

6807–17–6

Xxxx. xxx. 2; R60 Xx; X36 N; X50–53

X; X X: 60–36–50/53 X: 53–45–60–61

604–041–00–0

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

256–634–5 [1] 263–560–7 [2]

50594–66–6 [1] 62476–59–9 [2]

Xn; X22 Xx; X38–41 N; X50–53

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

604–043–00–1

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

203–083–3

103–16–2

Xi; X36 X43

Xx R: 36-43 X: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; R22 Xx; X36 X43

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

605–016–00–7

xxxxxxx… % xxxxxxxxx… %

X

203–474–9

107–22–2

Xxxx. kat. 3; X40 Xx; X20 Xx; R36/38 X43

Xx X: 20–36/38–40–43 X: (2-)36/37

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

606–016–00-X

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

201–462–8

83–26–1

X; X25–48/25 X; R50–53

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

606–018–00–0

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

204–210–5

117–80–6

Xx; X22 Xx; X36/38 X; R50–53

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

606–019–00–6

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

205–601–3

143–50–0

Xxxx. kat. 3; R40 T; X24/25 X; R50–53

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

606–034–00–8

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

244–209–7

21087–64–9

Xn; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

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

216–920–2

1698–60–8

X43 N; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

606–036–00–9

chinomethionát (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; X20/21/22–48/22 Xi; X36 X43 X; X50–53

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

606–037–00–4

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

256–103–8

43121–43–3

Xx; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

606–044–00–2

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

403–150–9

954–16–5

Xx; X22 Xx; R36 X; X50–53

Xx; N X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; X22 Xi; X41 X52–53

Xx; X X: 22–41–52/53 X: (2-)26-61

607–057–00–6

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

201–378–1

81–82–3

Xx; X48/22 X52–53

Xx X:48/22–52/53 X: (2-)37-61

607–058–00–1

kumafuryl (XXX) fumarin (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -chromen-2-on 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 R52–53

T X:25–48/25–52/53 S: (1/2-)37–45–61

607–079–00–6

xxxxxxx (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx 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; R51–53

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

607–097–00–4

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

209–008–0

552–30–7

Xi; X37–41 R42/43

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

607–143–00–3

pentanová xxxxxxxx valerová xxxxxxxx

203–677–2

109–52–4

X; X34 X52–53

X X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xn; X22 X; R51–53

Xn; X X: 22–51/53 X: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; R36/38 R52–53

Xi X:36/38–52/53 X: (2-)22-61

607–156–00–4

chlorfenson (XXX) 4-chlorfenyl-4-chlorbenzen-1-sulfonát

201–270–4

80–33–1

Xn; X22 Xx; X38 X; X50–53

Xx; N X: 22–38–50/53 X: (2-)37–60–61

607–158–00–5

sodná xxx chloroctové xxxxxxxx xxxxxxxxxx sodný

223–498–3

3926–62–3

T; X25 Xx; R38 X; X50

X; X X: 25–38–50 X: (1/2-)22–37–45–61

607–159–00–0

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

208–110–2

510–15–6

Xn; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

607–176–00–3

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

400–830–7

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; X51–53

Xx; X R: 43–51/53 X: (2-)24/37–61

607–209–00–1

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

403–030–6

Xx; R22 X43 X; R50–53

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

607–213–00–3

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

403–320–2

67567–23–1

X; X2 X; X7 X10 X; X51–53

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

607–217–00–5

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

403–960–2

X43 X53

Xx X: 43-53 X: (2-)24–37–61

607–243–00–7

xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] natrium-3,6-dichlor-o-anisát [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [3] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [3]

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

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

X52–53

X: 52/53 S: 61

607–248–00–4

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

205–073–4

132–67–2

Xx; X22

Xx X: 22 S: (2)

607–249–00-X

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

256–032–2

42978–66–5

Xi; X36/37/38 R43 X; X51–53

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

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

607–252–00–6

λ-xxxxxxxxxxx (XXX) Xxxx (1:1): (X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 R)-cis-3-((Z)-2-chlor-3,3,3-trifluorprop-1-en-1-yl)-2,2-dimethylcyklopropan-1-karboxylát x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx

415–130–7

91465–08–6

X+; R26 X; X25 Xx; X21 X; R50–53

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

607–255–00–2

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

69377–81–7

X52–53

X: 52/53 X: 61

608–003–00–4

xxxxxxxxxxxx

X X

203–466–5

107–13–1

X; Xxx Xxxx. kat. 2; R45 T; X23/24/25 Xx; X37/38–41 X43 N; X51–53

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

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

43

608–016–00–5

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

401–550–8

1897–41–2

X43 X; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. kat. 2; X61 X+; X28 X; R24 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; R45 Xxxx. xxx. 2; X61 Xx; R22 X; X50–53

X; X X: 45–61–22–50/53 X: 53–45–60–61

609–044–00–0

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

204–178–2

117–18–0

Xx; X22 X43 X; X50–53

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

611–008–00–4

4-aminoazobenzen 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. kat. 2; X45 X; R50–53

T; 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; R51–53

E; X R: 2–51/53 X: (2-)35-61

611–031–00-X

4,4'-[(4-xxxxxxxxxxxxxx-2,5-xxxx-1-xxxxxx)xxxxxxxx]xxxxxxxx-xxxxxxxxxxxx CI Xxxxx Red 9 XX xxxxxxx 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; R45 Xxxx. xxx. 3; X40 X; X23/24/25

X X: 45–23/24/25 X: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; R22 X; X50–53

X; N X: 45–22–50/53 X: 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; R45 Xxxx. xxx. 3; X40 X; X39/23/24/25Xx; X48/20/21/22 X43 N; 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, xxxx x-xxxxxxx, xxxx

X E

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Xxxx. xxx. 2; X45 Xx; X22 X; X51–53

X; X X: 45–22–51/53 X: 53–45–61

612–099–00–3

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

X

202–453–1

95–80–7

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

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

612–105–00–4

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

205–411–0

140–31–8

Xx; X21/22 C; R34 X43 R52–53

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

612–111–00–7

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

212–513–9

823–40–5

Xxxx. xxx. 3; X40 Xx; R21/22 X43 X; R51–53

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

612–125–00–3

2-methyl-p-fenylendiamin2-methyl-1,4-fenylendiamin2-methylbenzen-1,4-diamin 2,5-toluendiamin

202–442–1

95–70–5

T; 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 X; X50–53

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

612–151–00–5

xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. xxx. 2; X45 X; X25 Xx; X20/21 Xx; R36 R43 X; X51–53

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

613–018–00–4

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

7411–47–4

Xx; X22 Xi; X36/37/38 X52–53

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

613–031–00–5

xxxxxxxxx trichlorisokyanurová xxxxxxxx trichlor-1,3,5-triazintrion 1,3,5-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5X)-xxxxx

201–782–8

87–90–1

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

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

613–038–00–3

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

202–095–6

91–76–9

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

Xx; X20/22 N; X41 X; R50–53

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

613–043–00–0

xxxxxxxx-xxxxxx (ISO) 1-[2-(allyloxy)-2-(2,4-dichlorfenyl)ethyl]- 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 Xx; X41 N; R50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; X22 X; X50–53

Xx; X R: 22–50/53 X: (2-)60-61

613–091–00–2

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

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; X22 Xx; X36/37/38 X52–53

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

613–098–00–0

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

403–700–8

2687–94–7

X; X34 X; 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; R51–53

Xi; X X: 43–51/53 S: (2-)24–37–61

613–131–00–9

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

57369–32–1

Xx; X22 R52–53

Xn X:22–52/53 X: (2-)61

613–134–00–5

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

88671–89–0

Repr. xxx. 3; X63 Xx; R22 Xx; X36 X; R51–53

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

613–137–00–1

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

242–505–0

18691–97–9

X; R50–53

N R: 50/53 X: 60-61

613–139–00–2

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

74223–64–6

X; X50–53

X X: 50/53 S: 60-61

614–001–00–4

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

200–193–3

54–11–5

X+; X27 T; X25 X; X51–53

X+; 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 S: (1/2-)13–45–61

614–007–00–7

xxxxxx-xxxxxx [1] brucin-nitrát [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 X52–53

X+ X: 26/28–52/53 S: (1/2-)13–45–61

615–006–00–4

2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-methyl-m-fenylendiisokyanát [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] m-tolylidendiisokyanát [3] 5-methyl-1,3-fenylendiisokyanát [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [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+; R26 Xx; X36/37/38 X42/43 X52–53

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

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

2

616–010–00–9

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

204–854–7

127–65–1

Xx; X22 X31 X; R34 X42

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

616–034–00-X

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

246–419–4

24691–76–7

X52–53

X: 52/53 X: 61

616–035–00–5

xxxxxxxxx X -[(xxxxxxxxxx)xxxxxxxx]-2-xxxx-2-(xxxxxxxxxxxx)xxxxxxxx 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx

261–043–0

57966–95–7

Xx; X22 R43 X; X50–53

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

617–004–00–9

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

212–230–0

771–29–9

X; X7 Xn; X22 C; R34 X; X50–53

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

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

617–006–00-X

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

201–279–3

80–43–3

O; R7 Xx; R36/38 X; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; R2 Xi; X36 R43

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

650–007–00–3

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

228–200–5

6164–98–3

Xxxx. kat. 3; X40 Xx; X21/22 X; X50–53

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

650–008–00–9

xxxxxxxxxx (XXX) 4-[(2-chlorfenyl)hydrazono]-3-methylisoxazol-5(4 X)-xx

227–197–8

5707–69–7

X; X25 N; X50–53

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

650–009–00–4

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

243–269–1

19750–95–9

Xxxx. xxx. 3; 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) [(S)-(3-fenoxyfenyl)kyanmethyl]-(S)-2-(4-chlorfenyl)-3-methylbutanoát (X)-3-xxxxxx-α-xxxxxxxxxx-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx

66230–04–4

X; X23/25 R43 X; X50–53

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

650–041–00–9

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

82097–50–5

X; X50–53

X X: 50/53 S: 60-61


XXXXXXX 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx limity

Poznámky x xxxxxxxxxx

006–090–00–8

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

408–010–0

88558–41–2

Xx; X20 Xx; X41 R52–53

Xn X: 20–41–52/53 X: (2-)22–26–39–61

014–016–00–0

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

406–490–6

X; X51–53

X X: 51/53 X: 61

015–164–00–9

xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx xxxxxxxx

400–480–5

36669–85–9

X52–53

X:52/53 X: 61

015–165–00–4

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

404–986–7

Xi; X41 X; X50–53

Xx; 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-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; X41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; R50

N R: 50 S: 61

601–051–00–7

4-fenylbut-1-en

405–980–7

768–56–9

Xi; X38 N; X51–53

Xx; X X: 38–51/53 X: (2-)37-61

602–083–00–4

pentabromderivát xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; R48/21/22 R64 X; R50–53

Xn; N 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-terc-butoxypropan-2-ol

406–180–0

57018–52–7

R10 Xi; X41

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

603–130–00–1

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

406–325–8

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)39-61

603–131–00–7

Xxxx (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-deoxy-1-[methyl(1-oxotetradecyl)amino]-D-glucitol

407–290–1

Xi; R41

Xi 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 R52–53

Xi X:38–41–52/53 X: (2-)26–37/39–61

603–133–00–8

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

408–240–1

Xx; X22 X52–53

Xx R:22–52/53 S: (2-)22–36–61

603–134–00–3

Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx a xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (xxxxxxx a 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; R41 X; X51–53

Xx; X X: 41–51/53 S: (2-)26–39–61

603–136–00–4

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

410–910–3

104226–19–9

X43 X52–53

Xx R:43–52/53 X: (2-)24–37–61

603–137–00-X

Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx a 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-xxxxx-2-xxxxxxxxxxx

216–381–3

1570–64–5

X; X23 X; R 35 X; X50

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

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

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 X: 61

604–052–00–0

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

403–800–1

103597–45–1

X53

X:53 S: 61

604–053–00–6

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

410–760–9

157661–93–3

Xx; X38 X43 X; R50–53

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

604–054–00–1

Směs:2-methoxy-4-(4-methylidentetrahydropyran-2-yl)fenol a 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -pyran-2-yl)fenol

412–020–0

R43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

604–055–00–7

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

413–900–7

85954–11–6

Xxxx. Kat.3; R40

Xn X: 40 S: (2-)22–36–37

605–027–00–7

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

410–480–7

X43 X; X51–53

Xx; 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 xxxxxxxx

410–410–5

54574–82–2

X52–53

X:52/53 X: 61

607–272–00–5

xxxxxxxxxxx-xxxxxx (XXX) [1] xxxxxxxxxx-xxxxxxxxx (XXX) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-butoxy-1-methylethyl)-[(4-amino-3,5-dichlor-6-fluor-2-pyridyl)oxy]acetát [2]

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

X; X50–53

X X: 50/53 X: 60-61

607–273–00–0

xxxxxxx-7-{2,6-xxxxxxxx-8-[(2,2-xxxxxxxxxxxxxxxx)xxx]- 1,2,6,7,8,8x-xxxxxxxxx-1-xxxxxx}-3,5-xxxxxxxxxxxxxxxxxx

404–520–2

X52–53

X:52/53 X: 61

607–274–00–6

{2-[benzyl(methyl)amino]ethyl}-3-aminobut-2-enoát

405–350–1

54527–73–0

R43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–275–00–1

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

405–450–5

66531–87–1

X43

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

607–276–00–7

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

405–635–0

Xi; X38–41 N; X50–53

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

607–277–00–2

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

405–720–2

Xx; X22 Xx; X41 R43 N; 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 a xxxxxxxxxxxx)-3-[3-(2 X - benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty

405–760–0

Xi; X41 X43 X52–53

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

607–279–00–3

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

405–960–8

X43 X; R51–53

Xi; X X: 43–51/53 S: (2-)24–37–61

607–280–00–9

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

406–190–5

54322–20–2

Xn; X22 Xx; X36 X43

Xx R: 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 Xi; X38–41 R43 X; X50–53

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

607–284–00–0

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

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

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

410–065–0

X43

Xx X: 43 X: (2-)22–24–37

607–286–00–1

Xxxx:xxxxxx- x 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 R:43–52/53 X: (2-)22–24–37–61

607–287–00–7

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

410–140–8

X52–53

X:52/53 S: 61

607–288–00–2

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

410–160–7

148732–74–5

Xx; X36 R43 X52–53

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

607–288–00–8

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

410–370–9

105488–33–3

X53

X:53 X: 61

607–290–00–3

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

410–540–2

Xx; X38 R43 X; X50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx

410–630–1

104051–92–5

X53

X: 53 X: 61

607–292–00–4

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

410–640–6

Xx; X38–41 N; R50–53

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

607–293–00-XXxxx:

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

410–650–0

Xx; X41 X43 X; R51–53

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

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

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

410–800–5

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–296–00–6

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

410–830–9

R53

R: 53 X: 61

607–297–00–1

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

410–960–6

92761–26–7

Xx; X41

Xx R: 41 X: (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; X50–53

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

607–300–00–6

[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, d-sulfonatoftalocyanin]měďnatý xxxxxxx, xxxxxxxx xxx; a = 1,2,3 xxxx 4, x = 8, 9, 10 xxxx 11, x = 15, 16, 17 xxxx 18, x = 22, 23, 24 nebo 25

411–430–7

X43

Xx X: 43 X: (2-)22–24–37

607–301–00–1

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

411–860–5

Xx; X38–41 X43 X; X51–53

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

607–302–00–7

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

411–910–6

Xx; R38–41 X43 X; X51–53

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

607–303–00–2

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

413–760–7

93107–30–3

Xxxx. xxx.3; X62 X52–53

Xx X: 62–52/53 S: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; R50–53

N R: 50/53 X: 60-61

608–024–00–9

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

407–650–8

97460–76–9

X53

X:53 X: 61

608–025–00–4

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

410–970–0

117568–27–1

X53

X:53 X: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; X3 X; X8 Xxxx. xxx. 2; R45 X; X23/25 X43

X; X X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 X; X34 R43 X; X50–53

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

611–043–00–5

Xxxx (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx, [xxx{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx xxxxxxxx x[{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx

402–850–1

Xx R: 41–52/53 S: (2-)26–39–61

611–044–00–0

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

403–720–7

117527–94–3

X; 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; R25 Xn; X48/22 R43 N; X50–53

X; X 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 X: 61

611–048–00–2

Směs (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

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

400–720–9

R52–53

R: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; R41 N; X50–53

Xx; X R: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

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

410–780–8

Xx; X22–48/22 Xx; X41 X43 N; R51–53

Xn; 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 xxxxxxx a 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

X53

X: 53 X: 61

612–159–00–9

xxxxxxx xxxxxxxx xxxxx 2,2,4-xxxxxxxxx- x 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x xxxxxxx XXXXXX), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Epoxid 8) a 4-methylbenzen-1-sulfonové xxxxxxxx

410–880–1

Xx; R22 X; X34 N; X50–53

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

613–149–00–7

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

405–700–3

96489–71–3

X; X23/25 X; X50–53

X; N X: 23/25–50/53 S: (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 S: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-trichlorpyridin

407–270–2

16063–70–0

R52–53

R:52/53 X: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx X: 22 S: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; 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-xxxxx-5-xxxxxxxxxxxxx-4-xxxxxxxxxxx

410–260–0

83857–96–9

X43 N; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

613–157–00–0

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

410–330–0

54236–98–5

Xx; 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; X20/22 Xx; X41 X43 X; R51–53

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

613–159–00–1

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

410–580–0

120928–09–8

X; X25 Xn; X20 N; R50–53

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

613–160–00–7

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

411–000–9

125224–62–6

X43

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

615–022–00–1

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

410–550–7

79277–18–2

E; X2 R14 Xn; X48/22 X42/43

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

615–023–00–7

xxxxxxxxxxx 2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxxx kyselinymethyl-2-[(isokyanatosulfonyl)methyl]benzoát

410–900–9

83056–32–0

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

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

616–044–00–4

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

402–510–2

X; X51–53

X 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-xxxxx-7-xxxxxxxxxxxxxx[1,5-x][1,2,4]xxxxxxx-4-xx)xxxxxx]-2-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxxxxxx

406–390–2

X; X50–53

X X: 50/53 S: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - tetraalkyl(C16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x X, X′,X″,X′′′ - xxxxxxxxxx(X18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx

406–640–0

X43

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

616–048–00–6

3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx

406–740–4

1939–27–1

Xx; X48/22 N; X51–53

Xx; X X: 48/22–51/53 X: (2-)22–36–61

616–049–00–1

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

408–150–2

99141–89–6

R53

R:53 S: 61

616–050–00–7

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

410–690–9

103055–07–8

X43 N; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

Xxxx:3,3'-xxx(4-xxxxxxxxxxx)- 1,1'-(4-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; X2 X; X7 X; X50–53

X; N R: 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 R, 3 S)-, (2 X, 3 X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxx-1-(1X- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

94361–06–5

Xxxx. kat. 3; X63 Xn; R22 X; X50–53

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


PŘÍLOHA 2

POVAHA SPECIFICKÝCH XXXXX XXXXXXXXX S XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Komise 2001/59/XX,

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


XXXXXXX 3A

STANDARDNÍ POKYNY XXX XXXXXXXX XXXXXXXXX X NEBEZPEČNÝMI XXXXXXX X PŘÍPRAVKY

Viz směrnice Xxxxxx 2001/59/XX,

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


XXXXXXX 3X

XXXXXXXXXX POKYNY XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/XX,

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


XXXXXXX 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx u xxxxx xx xxxxx xx xxxxxxxxxxxxx činitele, xxxxx xxxxxxxxx xxxxxxxxxx chromozomové xxxxxxx x kultivovaných xxxxxxx xxxxx (1, 2, 3). Xxxxxxxxx xx dva xxxx xxxxxxxxxxxx xxxxxxx: chromozomové x chromatidové. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx typu, avšak xxxxxxxxxxxx xxxxxxx xx xxxxxx vyskytují. Xxxxxx xxxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx indukovat xxxxxxxxx aberace. Xxxx xxxxxx však není xxxxxx ke stanovení xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxx jevy jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx a x xxxx související xxxx xxxxxxxxxxx xxxxx v xxxxxxxxxx x x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx indukci xxxxxxxx u člověka x u xxxxxxxxx xxxxxx.

Xx xxxxxxx na xxxxxxxxxxxx xxxxxxx in xxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx, buněčné xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx. Použité buňky xxxx xxxxxxx na xxxxxxx schopnosti růstu x kultuře, xxxxxxxx xxxxxxxxx, počtu xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx vyžadují xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Je xxxxx xx zcela xxxxxxxxx xxxxxxxx, xxxxx xx vedly x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx k xxx xxxxx xxxxxx xX, xxxxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Xxxx zkouška xx xxxxxxx xx xxxxxxxx xxxxxxx mutagenů x xxxxxxxxxxx xxx xxxxx. Xxxxx sloučenin, xxx něž xx xxxx xxxxxxx xxxxxxxxx, xxxx xxx savce xxxxxxxxxxx; mezi xxxxx xxxxxxxx x karcinogenitou xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx touto xxxxxxxx, neboť xxxxxx xxxxxx jinými mechanismy xxx xxxxxx xxxxxxxxxx XXX.

Xxx xxxx Xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x podobě zlomu xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.

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

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

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

Xxxxxxxxx xxxxx : xxxxx xxxxx, xxxxx xx xxxxxxxxx x xxxxxxxx, x xxxxxxxxx xxxxx xxxxx v populaci; xxxxx xxxxxx proliferace xxxx populace.

Numerická xxxxxxx : odchylka xxxxx xxxxxxxxxx xx xxxxxxxxxx xxxxx obvyklého x xxxxxxxxx typu xxxxx.

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx jsou xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. V předem xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxx xx xx xxxxxxxxx xxxxxx xxxxx xxxxx zastavující xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx), kultury xx xxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xx zjistí xxxxxxxxxxxxxx xxxxxxxxxxx buněk.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx různé xxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxx lidských buněčných xxxxx (xxxx. xxxxxxxxxxx xxxxxx xxxxxxxx, xxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx měla xxx xxxxxxx vhodná xxxxxxxxxx xxxxx x inkubační xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, teplota x vlhkost). U xxxxxxxxxxxxxxx buněčných xxxxx x kmenů xx xxxx xxx rutinně xxxxxxxxxxxx xxxxxxxxx modální xxxxxxx xxxxx chromozomů x xxxx by xxx xxxxxxxxxxxx, xxx xxxxxx kontaminovány xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Pro xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx by měla xxx xxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx buněčné xxxxx x xxxxx: xxxxx xx xxxxxxx x xxxxxxxxx kultur, xxxxxx se do xxxxxxxxxxxx média x xxxxxx xxxxxxx, xxx xxxxxxxxx konfluence před xxxxxxxxx, x xxxxxxxx xx xxx 37 °X.

Xxxxxxxxx: xxxx xxxxxxxx xxxxxxxxxxxxxxx (xxxx. heparinem) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx probandů se xxxxxxx xx xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. fytohemaglutinin) x xxxxxxxx xx xxx 37 °C.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxxxxxx xxxxxxxx x xxx xx. Nejčastěji xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx postmitochondriální frakce (X9) připravená x xxxxx hlodavců zpracovaná xxxxxxxx indukujícím xxxxxx, xxxx xx Xxxxxxx 1254 (6, 7, 8 a 9), xxxx směs xxxxxxxxxxxxx x β-naftoflavonu (10, 11 x 12).

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

Řada xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx použitých xxxxxxxxx xxxxx xx xxxx být xxxxxxx xxxxxxxxxx (xxxx. důležitostí xxxxxxxxx cytochromu X450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx xxxx xxxxxxxx na xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx přidány přímo x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být xxxx xxxxxxxx zředěny. Xxxx by být xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxx, pokud xxxxx o stálosti xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx být xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx být xxxxxxxxxx x xxxxxxxx xxxxx x s xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx než známá xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx by xxxx xxx použita xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx přidáním molekulového xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Xxxxxxxxxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx x hlavním xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx integrity x xxxxx, jako xxxx stupeň xxxxxxxxxx, xxxxx životaschopných buněk xxxx xxxxxxxxx xxxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x předběžném xxxxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx by xxxx xxxx koncentrace xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx minimální xxxxxxxxx, případně žádnou xxxxxxxxx, což xxxxxxx xxxxxxx, xx xx xx xxxxxxxxxxx xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. X xxxxxxxx xxxxxxx xx měla xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx snížení xxxxxx xxxxxxxxxx, počtu xxxxx xxxx xxxxxxxxxxx xxxxxx (xxx o xxxx xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx xxxxxxxx měřítkem xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx a závisí xx době, která xxxxxxxx xx expozice. Xxxxxxxxx xxxxx je xxxx xxxxxxxxxx u xxxxxxxxxxx xxxxxx, x xxxxx xxxxx být xxxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx a xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx xxxxxxxxx cyklu, xxxxxxxxx xxxxxxxx generační xxxx (XXX), xxxxx xxx xxxxxxx xxxx xxxxxxxxx xxxxxxxxx. X xxxxxxx XXX xxxx xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx xxxxx xxxxxxx xx xxxxxxxxx zpožděných xxxxxxxxxxx, x x xxxx přírůstek xxxxxxxx xxxxxxxxx doby může xxx xx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx optimálního xxxxxxx xxxxxxx.

X případě xxxxxxxxx xxxxxxxxxxxxxxx látek by xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 M, xxxxx xxxx, xxxxx x xxxx xx xxxxxxxx.

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx toxické xxx xxxxxxxxxxxxx nižších, než xx jejich rozpustnost, xx měla xxx xxxxxxx xxxxxxxx dávka x koncentraci, xxx xx nad mezí xxxxxxxxxxxx x konečném xxxxxxxxxxx xxxxx xx xxxxx xxxx xxxxxxxx. X určitých xxxxxxxxx (xxxx. xxxxxxx-xx xx xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx, než xx xxxxxxxxxxx) xx xxxxxxxxxx xxxxxxxxx více xxxxxxxxxxx, xxx xxxxx xxxxxxx xx srážení. Xxxx být xxxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx a xx xxxxx xxxxxxxx, neboť xxxxxxxxxxx v testovacím xxxxxxx xx xxxx x xxxxxxx xxxxxxxx xxxxx x důsledku xxxxxxxxxxx buněk, xxxx X9 atd. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx měly xxx xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx). Xxx xxxxxxx xxxxxxxxxxx xxxxxxxx xx měla xxx xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxx vyžaduje aktivaci.

K xxxxxxxxx kontrole xx xxx xxx xxxxxx xxxxx xxxxxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx, xxxxx xxxxxxxx poskytnou xxxxxxxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx pozadí, xxxx xx xxxxxxx xxxxxxxxx xxxxxxxxxxx systému.

Koncentrace xxxxxxxxxxx xxxxxxx xx měly xxx xxxxxxx tak, xxx byl xxxxxx xxxxxxxx, ale aby xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxxxxxxxx x negativních xxxxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxx xxxxxx metabolické aktivace

methyl-methansulfonát

66–27–3

200–625–0

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

mitomycin X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X xxxxxx metabolickou xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

Xxx pozitivní xxxxxxxx xxxxx být xxxxxxx x xxxx xxxxxx xxxxx. Xxx xxxxxxxxx xxxxxxxx by xxxx xxx pokud xxxxx xxxxx x xxxxx použití xxxxxxxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx.

X okamžiku xxxxxxxx xx xxxx xxx xxxxxxx negativní xxxxxxxx xxxxxxxxxx xx xx samotného rozpouštědla xxxx xxxxxxxx v xxxxxxxxxxx médiu x xxxxxxxxxx stejným xxxxxxxx xxxx xxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx žádné xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky se xxxxxxx zkoušené látce xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx něho. Xxxxxxxx xxxxxxxxx by xxxx být xxxxxxxx xxx 48 xxxxx xx mitogenní xxxxxxxxx.

1.4.3.2 Xxx xxxxxx koncentraci xx xxxx xxx xxxxxxx použity xxxxxxxxxx xxxxxxx, x xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx pro xxxxxxxxx kontrolu xxxx xxxxxxxx xxxxxxxxxxxx. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx duplicitními xxxxxxxxx xx xxxxxxxxx xxxxxx, xxxx xxx xxxxxxxxx xxxxxxx xxxxxx xxxxxxx.

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

1.4.3.3 Doba xxxxxxx kultur

V xxxxxx xxxxxxxxxxx xx xxxx xxx buňky xxxxxxxxx xxxxxxxx xxxxx, xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx ní, xx xxxx 3 — 6 xxxxx, x měly xx xxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného xxxxx (12). Jestliže xxxxx xxxxxx xxxx negativní xxxxxxxx xxx x xxxxxxxx, xxx bez xxxxxxxx, xxx xx xxx xxxxxxxx xxxxxxxxx xxxxxxxxxx bez aktivace x nepřetržitou expozicí xx do xxxxxx x xxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného cyklu. Xxxxxx chemické xxxxx xxx xxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxx xxx 1,5xxxxxxx xxxxx xxxxx. Xxxxxxxxx výsledky xxx xxxxxxxxxxx xxxxxxxx xxxx být xxxxxxxxx xxxxxx od xxxxxxx. X případech, xxx xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx za xxxxxxxx, xx xxxx xxx podáno zdůvodnění.

1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů

Do xxxxxxx xxxxxxx se obvykle 1-3 hodiny xxxx xxxxxxxxx xxxxx Xxxxxxxx® xxxx xxxxxxxxx. Xxx xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx xx xxxxx xxxxxxx kultura xxxxxx x zpracovává xxxxxx. Xxxxxxxx preparátů xxx xxxxxxx chromozomů xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x negativních xxxxxxx, xx xxxx xxx xxxx analýzou xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx fixaci xxxxx xxxxxxx xx xxxxx xxxxx xxxxx x xxxxxxxx x xx ztrátě xxxxxxxxxx, xxxx by vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx rovném xxxxxxx xxxxxxx ± 2 xxx xxxxxxx xxxx buněk. Xx xxxxxx xxxxxxxxxxx x xxxxxxxx xx mělo xxx xxxxxxxxx alespoň 200 xxxxx rozprostřených xxxxxxxx, případně xxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx velký xxxxx xxxxxxx.

Xxxxxx je účelem xxxxxxx detekovat xxxxxxxxxx xxxxxxxxxxxx aberace, xx xxxxxxxx xxxxxxxxxx polyploidii x endoreduplikace, xxxx-xx xxxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx x mělo xx xxxx xxx xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) vyjádřené x xxxxxxxxxx. Pro xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx chromozomových xxxxxxx s xxxxxx xxxxxx a xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx a xxxxxxx xx, xxx xxxxxxxxxx xx xx xxxxxxx xxxxxxxx xxxxxxx.

Xxxx xx xxx také xxxxxxxxxxx xxxxxxxx, která byla xxxxxxxxx pro stanovení xxxxxxxxxxxx x všech xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx kultur v xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

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

Xxxxxxx xxxxx xxxxxxxxx odpovědi xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx potvrdit negativní xxxxxxxx byla xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx parametrů studie x cílem xxxxxxxx xxxxxx posuzovaných podmínek xx xxxx být xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, které xx xxxxx být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x podmínky xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na xxxxxxxxxxx, nebo reprodukovatelný xxxxxx tohoto počtu. Xxxxxxxx xx měla xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx pomocný prostředek xxxxxxxxxxx metody (3, 13). Xxxxxxxxxxx významnost xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx.

Xxxxxx xxxxx polyploidie xxxxx xxxx xxxxxxxx, že xxxxxxxx látka xx xxxxxxxxx potlačit xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx chromozomové xxxxxxx. Xxxxxx počtu xxxxx x endoreduplikovanými xxxxxxxxxx xxxx znamenat, že xxxxxxxx xxxxx xx xxxxxxxxx potlačit xxxxxxxx xxxxxxxxx xxxxx (17, 18).

Xxxxxxxx xxxxx, xxxxx xxxxxxxx nesplňují xxxx xxxxxxx xxxxxxxx, xx x tomto xxxxxxx xxxxxxxx za xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx na xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx zkoušky xx xxxxxxxxxxxx xxxxxxx xx xxxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx strukturní xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.

3. ZPRÁVY

PROTOKOL X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxx:

- typ x xxxxx xxxxx,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx použitého xxxx xxxxx,

- popřípadě xxxxxxxxxxxx xxxxxxxxxxx,

- informace o xxxxx xxxxxxxxx cyklu,

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

- xxxxxxxx počet xxxxxx,

- případně xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxx hodnota počtu xxxxxxxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x počtu xxxxxx, xxxxxx xxxx. xxxxx x xxxxxxxxxxxx x xxxxxx xxxxxxxxxxxx, xxxx-xx x xxxxxxxxx,

- xxxxxxx xxxxx, případně xxxxxxxxxxx XX2,

- xxxxxxxxxxx zkoušené xxxxx,

- xxxxx xxxxxxxx x xxxxxxx zkoušené xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxx nasazení,

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

- xxxxxxxxx x xxxxxxxxx kontroly,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx aberací,

- počet xxxxxxxxxxxxx metafází,

- metody xxxxxxxxx toxicity,

- kritéria xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxxx xxxxxxx,

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

- definice xxxxxxx, xxxxxx xxxx,

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

- xxxxx xxxxxxx, xxxxx xxxx pozorovány,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

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

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, H. X. (1976), Cytological Xxxxxxx xxx Detecting Chemical Xxxxxxxx, in: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx and Xxxxxxx for xxxxx Xxxxxxxxx, Vol. 4, Xxxxxxxxxx, X. (xx) Xxxxxx Xxxxx, New Xxxx xxx Xxxxxx, 1-29.

2) Xxxxxxxx, X. Xx., Xxxxxx, X. (1985), Xxx In xxxxx Chromozomal Aberration Xxxx Using Xxxxxxx Xxxxxxx Lung (XXX) Xxxxxxxxxx Cells in Xxxxxxx, in: Xxxxxxxx xx Mutatation Xxxxxxxx, Xxx. 5, Xxxxx, X. xx xx., (xxx) Elsevier Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx York-Oxford, 427-432.

3) Galloway, X. X., Xxxxxxxxx, X. X., Reuben, X., Xxxxxx, S., Xxxxx, X., Xxxxxx, X., Xxxxx, A. D., Xxxxxxxx, X., Xxxxx, X., Duk, X., Xxxxx, J., Xxxxxxxx, X. X., Resnick, X. X., Xxxxxxxx, X., Xxxxxx X. (1978), Chromozome aberration xxx xxxxxx chromatic xxxxxxxxx xx Xxxxxxx xxxxxxx ovary xxxxx: Xxxxxxxxxx of 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (suppl. 10), 1-175.

4) Scott, X., Galloway, X. X., Xxxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxxxx, X., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx xxxxx Extreme Xxxxxxx Xxxxxxxxxx. X xxxxxx from ICPEMC Xxxx Group 9, Xxxxxxxxxx Xxx., 257, 147-204.

5) Morita, X., Xxxxxx, T., Fukuda, X., Xxxxxxx, K., (1992), Xxxxxxxxxxxxxx xx xxx xX to Xxxxxxx Cultured Mammalian Xxxxx, Mutatation Xxx., 268, 297-305.

6) Xxxx, X. X., McCann, X., Xxxxxxxx, X. (1975), Methods xxx Xxxxxxxxx Carcinogens xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Microsome Xxxxxxxxxxxx Xxxx, Mutation Xxx., 31, 347-364.

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

8) Xxxxxxxxx, X. X., Xxxxx, X. D., xxx Xxxx, P. P. X., Xxxxxxx, M., xx Xxxxx, N. (1976), Xxxxxxxxxxx Xxxxxxx xx Xxxxxxx/Xxxxxxxxxxx after Xxxxxxxxxx in a Xxxxxxxxxxx Xxxxxx In xxxxx, X. Xxxxxxxxx xx Chromozome Xxxxxxxxxxx xxx Xxxxxx Chromatid Xxxxxxxx by Xxxxxxxxxxxxxxxxxx (XXX) xxx Xxxxxxxxxxxxxxxxxxx (XXX) in XXX Xxxxx xx the Xxxxxxxx of Rat-Liver Xxxxxxxxxx, Xxxxxxxxxx Res., 37, 83-90.

9) Matsuoka, X., Hayashi, X., Xxxxxxxx, M. Jr. (1979), Xxxxxxxxxxx Xxxxxxxxxx Xxxxx xx 29 Xxxxxxxxx Xxxxxxxx xxxx X9 Mix Xx xxxxx, Xxxxxxxx Xxx., 66, 277-290.

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

11) Xxxxxxxxxx, X., Sawamura, X., Xxxx, K., Xxxxxxxx, T. (1976), X. Xxxx Substitute xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Systems, xx: xx Xxxxxx, F. X., Xxxxx, J. X. Xxxx, X. X., Xxxxxxx, X. X. (xxx), In xxxxx Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxx, X. X., Xxxxxxxx, X. X., Xxxxxx, X., Xxxxxxx, X., Xxxxxx, T. (1994), Xxxxxx xxxx Xxxxxxx Xxxxx on Xx vitro Xxxxx xxx Xxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Res., 312, 241-261.

13) Xxxxxxxxxx, X., Xxxxxxxx, X. A., Xxxxx, X. X., Xxxxxxxx, G., Xxxxxxx, X. X., Phillips, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx xxxxx Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. J., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

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

15) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, X. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Evaluation xx Xxxxx xxx Volatile Xxxxxxx, in: Xxxx, X. R., Costa, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Effects xx Xxxxxxxx Xxxxxx, New Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, X. O., Xxxxxx, X. X., Xx, X. X., Xxxxxx, X. X. (1983), Xxxxxxxxxx xx xx Exposure System Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Gels xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Xxxxxxxx Xxxxx, Xxxxxxxxxxxxx Mutagen., 5, 795-801.

17) Locke-Huhle, X. (1983), Xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx-xxxxxxxxx xxxxxxx G2 arrest, Xxxxxxxxxx Res., 119, 403-413.

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


XXXXXXX 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx aberace x xxxxx xx xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx aberací xxxxxxxxxxxx xxxxxxxxx látkou x xxxxxxx xxxxxx dřeně xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx — xxxxxxxxxxxx x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx může xxxxxxxx, xx chemická xxxxx xx schopnost xxxxxxxxx xxxxxxxxx xxxxxxx. V xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx typu, xxxxx chromozomové aberace xx xxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob u xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, xx chromozomové xxxxxx a xxxxxxxxxxx xxxx způsobující xxxxx x onkogenech x x xxxxxx somatických xxxxx tlumících xxxxxx, xxxx xxxxx na xxxxxxx rakoviny x xxxxxxx a v xxxxxxxxxxxxxxxx systémech.

Při xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxx xxxxx xx v xxxx zkoušce xxxxxx xxxx, xxxxxxxx je xxxxxx vaskularizovanou xxxxx x xxxxxxxx populaci xxxxx x rychlým xxxxxx, které xx xxxxxx izolují x xxxxxxxxxxxx. Xxxx xxxxx x cílové xxxxx xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx je xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx mutagenese, xxxxx umožňuje xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, farmakokinetiku a xxxxxxx reparace DNA, xxxxxxx xx mohou x xxxxxxx xxxxx x tkání xxxxx. Xxxxxxx xx vivo xx rovněž xxxxxxxx xxx další xxxxxx xxxxxxxxxxx účinků zjištěných xxxxxxxx xx vitro.

Jestliže xxxxxxxx xxxxx o xxx, xx se xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx cílové xxxxx, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 DEFINICE

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

Chromozomová xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx nebo xxxxx x xxxxxxx xxxx xxxxxxxxx x xxxxxx místě.

Endoreduplikace : xxxxxx, při xxxxxx x jádře xx X-xxxx xxxxxxxxx DNA xxxxxxx x xxxxxx, xxxxx následuje xxxxx X-xxxx. Výsledkem xxxx xxxxxxxxxx xx 4, 8, 16,… xxxxxxxxxxxx.

Xxx : xxxxxxxxxxxx léze xxxxx xxx xxxxx xxxxxxx chromatidu x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

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

Xxxxxxxxxx aberace : mikroskopicky xxxxxxxxxxxxx xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx dělení xx xxxxxx xxxxxxxx; xxxx xx jako xxxxxx x fragmenty, xxxxxxxxxxxxxxxxxx nebo xxxxxxxxxxxxxxxxxx xxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xxxx vystavena xxxxxxxx xxxxx vhodným xxxxxxxx x xx xxxxxxx xxxxxxxx po xxxxxxxx se usmrtí. Xxxx xxxxxxxxx xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx nebo Xxxxxxxx®). X buněk xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx chromozomů, xxxxxx se x xxxxxxxxx se chromozomové xxxxxxx buněk x xxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx zvířete

Běžně xx xxxxxxxx xxxxxx, myš x xxxxxx čínský, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx xx měla xxx xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx x xxxxxx xx x xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá pohlavně xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x skupinu, xxxxx xx xxxxxxx zkoušené xxxxx. Xxxxx by xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx jejich polohy xxxxxxxxxxxxx. Xxxxxxx se xxxxxxxxxxx xxxxxxxxxxxx. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxx

Xxxxx xxxxxxxx xxxxx xx měly být xxxx aplikací xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx být xxxx xxxxxxx zředěny. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x mělo xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx podloženo xxxxx o jejich xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx nejdříve xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí každého xxxxxxxxxxx xx měly xxx xxxxxxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx xxx obě xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx látky xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx identický xxxxxx jako xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx strukturní xxxxxxx xx xxxx xxx xxxxxxxxxxx úrovních, x xxxxx se xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx tak, xxx xxx účinek xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx xxxxx a xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx xxx jednou. Xxx pozitivní xxxxxxxx xxxxx xxx použity xxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x dispozici. Xxxxxxxx xxxxx xxx xxxxxxxxx kontrolu:

Látka

Číslo CAS

Číslo xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx C

50–07–7

200–008–6

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxxx odběru xx xxx xxx xxxxxxxx xxxxx x xxxxxxxxxxx xxxxxxx, xxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxx xxxxx podstupují xxxxxx proces jako xxxxxxxxxx skupiny, xxxxx xxxxxx z xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x variabilitě zvířat x xxxxxxxx xxxxx x xxxxxxxxxxxxxx aberacemi. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx jeden xxxxx, je nejvhodnějším xxxxxxxxx doba prvního xxxxxx. Xxxxx toho xx xxxx být xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává žádné xxxxxxx nebo xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x pohlaví zvířat

Každá xxxxxxxxxx a xxxxxxxxx xxxxxxx xx skládá x alespoň pěti xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx. Jestliže xxxx x xxxx xxxxxx k xxxxxxxxx xxxxx ze xxxxxx xx stejným xxxxxx x za xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx mezi xxxxxxxxx xxxxxx x toxicitě, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx určité xxxxxxx, xxxx xx xxxx xxxxxxxxx x některých xxxxxxxxxxxxxxx látek, xxxx xx být xxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx být xxxxx xxxxx xxxxxxxx jednorázově. Xxxxxxxx látky xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. xxx dávky x xxx den x rozmezí xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx podávání xxxxxxx xxxxxx xxxxxxxxx. Jiné xxxxxx xxxxxxxx by xxxx být vědecky xxxxxxxxxx.

Xxxxxx xx xxxx xxx odebrány xx xxxx různých intervalech xx xxxxxxxx xxxxxx x xxxxxx xxx. X xxxxxxxx xx xxxxx provádí xx xxxxxx xxxx xx xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (jenž xxxx xxxxxxx 12 — 18 x). Xxxxxxxx doba xxxxxxxx xxx xxxxxx a xxxxxxxxxxxx xxxxxxxx xxxxx x rovněž xxx xxxxxx xx kinetiku xxxxxxxxx cyklu xxxx xxx xxxx xx xxxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx se xxxxxxx xxxxx odběr xx 24 x od xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx do xxxx než xxxxxxx xxx, měl xx xxx xxxxx xxxxxxxx xx takové době xx poslední xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx xxxxxxxx xxxxx buněčného xxxxx.

Xxxx usmrcením xx xxxxxxxx xxxxxxxxxxxxxxxxx podá xxxxxx dávka xxxxx xxxxxxxxxxx metafázi (xxxx. Xxxxxxxx® xxxx kolchicin). Xxxx se xx xxxxxx xxxx provede x zvířat odběr. X xxxx je xxxx xxxx přibližně 3 — 5 x; u xxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx odeberou buňky x xxxxxxxxx xx xx xxxxxxxxxxxx xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx rozsahu dávek, xxxx xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx stejným xxxxxx, kmenem, xxxxxxxx x xx stejného xxxxxx expozice, jež xx použijí x xxxxxx xxxxxx (5). X xxxxxxx toxicity xx xxx první xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx a xxxxxxxx) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx být xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x xxxxxx xxxxx některé známky xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže zkouška x xxxxxx dávkou xxxxxxx 2000 mg/kg xxxxxxx hmotnosti podanou xxxxxxxxxxx nebo xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x není-li xx xxxxxxx xxxxx x látkách, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx studie xx xxxxx úrovněmi xxxxx xx xxxxxxxxx. X xxxx trvajících xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx xxx 14xxxxx aplikaci xx xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx expozice xxxxxxx xxxx znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx podávání xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx podán xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Použití xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx minimalizována xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

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

1.5.7 Xxxxxxx

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

X každého xxxxxxx xx xxxx xxx xxxxxxxxxxx alespoň 100 xxxxx. Tento xxxxx xxx xxxxxx, xx-xx xxxxxxxxx velký xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx kontrol xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx dochází xx xxxxxxxxxxxxxx xxxxxx xxxx xx ztrátě xxxxxxxxxx u xxxxx xxxxx v metafázi, xxxx xx xxxxxxxxxxx xxxxx obsahovat xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx xxxxxxxxxx xxxxxxx xx xxxx xxx zpracovány xx formě tabulky. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxx by xxx xxx xxxxxxxxxx počet xxxxx, počet aberací xx xxxxx x xxxxx xxxxx s xxxxxxxxxxxxx xxxxxxx (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxxx x xxxxxxxxx skupiny xx měly xxx xxxxxxx xxxxx typy xxxxxxxxxxxx chromozomových xxxxxxx x jejich počtem x četností. Xxxx xx xxxxxxxxxxxxx odděleně x xxxxxxx se, xxx xxxxxx xx xxxxxxxxxx do xxxxxxx xxxxxxxx xxxxxxx. Xxxxxxxxxx-xx xxxxx x rozdílu x odpovědi xxxx xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx relativního xxxxx buněk x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx na xxxxx xxxx jasný nárůst xxxxx buněk x xxxxxxxxx xxx xxxxxxx x xxxxxxx xxxxxx x x určitému xxxxxxxx xxxxxx. Xxxxxxxx xx měla být xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx jediným xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Dvojznačné výsledky xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx podmínek.

Nárůst xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Nárůst xxxxx buněk s xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, xx zkoušená xxxxx má xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (7, 8).

Zkoušená xxxxx, xxxxx výsledky xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx xxxxxxxx x tomto systému xx nemutagenní.

Ačkoli většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

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

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx, stáří x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx zvířat na xxxxxxx zkoušky, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx a negativní (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- údaje xx xxxxxx pro xxxxxxxx rozsahu, pokud xxxx provedena,

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, zda se xxxxxxxx xxxxx dostala xx krevního xxxxx xxxx xx xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx látky xxxxxxxxxxx xxxxxxxx, xxxx xxxxxxxxxxx a xxxxx xxxxxxxx,

- metody přípravy xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx xxxxx,

- xxx a xxxxx aberací uvedený xxxxxxxxxx xxx každé xxxxx,

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

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

- xxxxx xxxxxxx, pokud xxxx pozorovány,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

- dosavadní údaje x xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X. (1984), Xxxxxxxxxxx Tests xx Xxxxxxx, xx: Mutagenicity Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, X. Xxxxxx, X. X. Parry (xxx), XXX Press, Xxxxxx, Xxxxxxxxxx X. X., 275-306.

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

3) Xxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Gatehouse, X. X., Xxxxxxx, X., Henderson, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Testing. Report, Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx York, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

4) Tice, X. X., Xxxxxxx, X., XxxXxxxxxx, J. X., Xxxxxxxx, X., Xxxxxx, D. X., Xxxxxx, H. X., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., X. X., Xxxxxxxxxxxx, F., Xxxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, H., Xxxxx, X., Xxxxxxx, X. (1994), Xxxxxx xxxx the Working Xxxxx xx the xx xxxx Xxxxxxxxx Xxxx Marrow Xxxxxxxxxxx Xxxxxxxxxx Test, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, R. X., Xxxxx, J. A., Xxxxxx, A. X., Xxxxxx, X. X., Xxx, X., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Hodson-Walker, X., Xxxxxx, X. X., Kirkland, X. X., Xxxxxxx, M. (1992), Xxxxxx of Xxxxxxx Xxxxxxxxxx Society/UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Dose Xxxxxxx in Xx xxxx Mutagenicity Assays, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. P., Xxxxxxxx, X., Albanese, X., Xxxxxxxx, X. X., Clare, G., Xxxxxxxx, R., Richold, X., Papworth, X. X., Xxxxxx, X. X. K. (1989), Xxxxxxxxxxx Analysis of Xx vivo Cytogenetic Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, X. X. Kirkland (xx.) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 184-232.

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

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


XXXXXXX 4C

"B.12 MUTAGENITA–TEST XXXXXXX ERYTROCYTÁRNÍCH MIKROJADER XX XXXX

1. XXXXXX

Xxxx xxxxxx je replikou xxxxxx XXXX XX 474 — Xxxx xxxxxxx erytrocytárních xxxxxxxxxx xx xxxx (1997).

1.1 XXXX

Xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxx poškození chromozomů xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx, x xx xxxxxx xxxxxxx erytrocytů xxxxxxxxxx x kostní xxxxx x/xxxx buněk xxxxxxxxx xxxx, obvykle hlodavců.

Účelem xxxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx je identifikovat xxxxx, xxxxx způsobují xxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxx xx tvorba xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxx xxxxxxxxx xxxx celé xxxxxxxxxx.

Xxxx se erytroblast xxxxxx xxxxx xxxx xx polychromatický xxxxxxxxx, xxxxxx jádro je xxxxxxxx a xxxxxxxxxx, xxxxx xxx tom xxxxx xxxxxxxxx, zůstávají x xxxxxxxxxx, xxxxx xxxxx xxxxx neobsahuje. Xxxxxxxxxxxx mikrojader xx x xxxxxx xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx xxxxxx xxxxx. Xxxxxx výskytu xxxxxxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x exponovaných xxxxxxxxx xx známkou xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X tomto xxxxx xx rutinně xxxxxxxxx kostní xxxx xxxxxxxx, xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Stanovení xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx x periferní xxxx xx xxxxxxxxxx xxxxxxxxxx u xxxxxxxxxxx xxxxx, x něhož xxxx xxxxxxxxx neschopnost xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, nebo xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx aberace. Mikrojádra xxx xxxxxxxx řadou xxxxxxxx. Xx zahrnují xxxxxxxxxxxx přítomnosti xxxx xxxxxxxxxxxxx xxxxxxxxxxx (kinetochorní) XXX x xxxxxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx. Xxxxx xxxxxxx (normochromatických) xxxxxxxxxx x periferní xxxx, které xxxxxxxx xxxxxxxxxx, připadající xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx rovněž xxxxxx xxxx konečný xxxxxxxx xxxxxxx, xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxx xxxx.

Xxxxx test savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx zvláště xxxxxx x posouzení xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx DNA, třebaže xx mohou xxxxx x xxxxxxx xxxxx x xxxxx, xxxxx x x xxxxxxxxxxx xxxxxxxx. Zkouška xx xxxx xx xxxxxx xxxxxxxx xxx xxxxx xxxxxx mutagenních xxxxxx xxxxxxxxxx x systémech xx vitro.

Jestliže existuje xxxxx x xxx, xx xx xxxxxxxx xxxxx nebo reaktivní xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) xxxxxxxxxx, x níž (x xxxx) xx xxxxx xxxxxx xxxxx připojí xxxxxx vřeténko umožňující xxxxxxxxxx xxxxx dceřiných xxxxxxxxxx x xxxxx xxxxxxxxx xxxxx.

Xxxxxxxxxx : xxxx xxxxx existující xxxxxxxx od xxxxxxxx xxxxx a vedle xxxx, xxxxxxxxx xxxxx xxxxxxxx mitosy (xxxxxx) xxxxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx erytrocyt : zralý xxxxxxxxx xxxxxxxxxxxx xxxxxxxx, který xxx rozlišit od xxxxxxxxx xxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx selektivním xxx xxxxxxxx.

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx xxxxxxxxx ve xxxxxxxxx mezistadiu, který xxxxx obsahuje xxxxxxxx, x xxxx xxx xxxx xxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx xxxxx se xxxxxxx xx vhodném xxxxxxxx po xxxxxxxx xxxxxx, xxxxxxx se xxxxxx dřeň, připraví xx xxxxxxxxx x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx použití periferní xxxx xx xxxx xx xxxxxxx okamžiku xx expozici xxxxxxx, xxxxxxxxxx xx xxxxxxxx xxxxxxxx x xxxxxx xx (4, 8, 9, 10). Xxx xxxxxxxx x xxxxxxxxx xxxx xx xxxx xxxx xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxx xxxxxxxx xx xxxxxxxxx xxxx. Xxxxxxxxx jsou xxxxxxxxxxx xx xxxxxxxxxx xxxxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx zvířete

Při xxxxxxx xxxxxx dřeně se xxxx xxxxxxxxx zvíře xxxxxxxxxx xxx nebo xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxx xxxxxxx periferní krve xx doporučuje xxx. Xxx xxxx xxxxxx xxxxxxxx vhodný xxxx xxxxx xx xxxxxxxxxxx, xx xxx x xxxx, u xxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, xxxx xxxx xxxxxxxxxx dostatečnou xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx xxxxxxx. Měly xx xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx kmeny xxxxxxx zdravých pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx u xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx zvířata se xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, x xxx se provede xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx alespoň pět xxx aklimatizovat. Xxxxx xx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx by xxxx xxx před aplikací xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx nebo xxxxx xxx před xxxxxxx xxxxxxx. Xxxx xx xxx použity čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud údaje x jejich xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx nemělo xxx xxx xxxxxxxxx úrovních xxxxx toxické účinky x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx reaguje se xxxxxxxxx xxxxxx. Jsou-li xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být jejich xxxxxxxx podloženo údaji x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx nejdříve xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx a negativní (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx xxx xxxxxxx. X xxxxxxxx aplikace xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x nichž xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx xxxxxxxxxx xx xxxx při xxxxxxxxxxx xxxxxxxx, u xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, ale xxx xxx odečtu xxxxxxx ihned xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx přijatelné, xxx xxxxxxxxx kontrola xxxx xxxxxxxx jiným způsobem xxx xxxxxxxx xxxxx x xxx xxx xxxxx v xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx navíc xxxx xxx vzato v xxxxx xxxxxxx chemických xxxxx ze 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 X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx xxx být xxxxxxxx xxxxx u xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx aplikováno xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxx xxxxx podstupuje xxxxxx xxxxxx jako exponované xxxxxxx, pokud xxxxxx x dosavadních xxxxxxxxxxx xxxxx k dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx x xxxxxxxxxx. Provádí-li se xxx xxxxxxxxx xxxxxxxx xxxxx odběr, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Kromě xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud nebo xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx prokazující, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx krve xxxx xxx xxxx negativní xxxxxxxx xxxxxxxxxx také xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx x krátkých xxxxxx x xxxxxxxxx xxxx (např. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, xx xxxxxxxx xxxxx budou x xxxxxxx, xxxxx xx xx základě xxxxxxxxxxx kontrol xxxxxxx.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx xxxxxx

Xxxxx exponovaná x xxxxxxxxx skupina xx xxxx skládat x alespoň xxxx xxxxxxxxxxxxxxxx zvířat pro xxxxx pohlaví (11). Xxxxxxxx xxxx v xxxx studie x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx a za xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx v xxxxxxxx, xxxx postačující xxxxxxxx jednoho xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx pro určité xxxxxxx, xxxx xx xxxx například x xxxxxxxxx farmaceutických xxxxx, xxxx xx být xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx doporučit xxxxx standardní xxxx (xx. xxxxx, dvě xxxx xxx aplikace x intervalu 24 xxxxx). Xxxxxx ze xxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxxx xx x xxxxxx studií xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –x případě xxxxxxxxxxx studií — xxxxx xxxx xxxxxxxxx xxxxxxxx nebo byla xxxxxxxxx limitní xxxxx x podávání xxxxxxxxx xx xx xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, tzn. xxx xxxxx v týž xxx v xxxxxxx xx xxxx než xxxxxxxx hodin, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx xxx proveden xxxxx způsoby:

a) zkoušená xxxxx se xxxxxxxx xxxxxxxx xxxxxx. Xxxxxx xxxxxx xxxxx se xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx odběr xx xxxxxxx nejdříve 24 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx xxxxxxxx a x xxxxxxxxxx odstupem xxxx odběry. Xxxxx xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx být xxxxxxxxx. Xxxxxx xxxxxxxxx krve xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 36 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx xx xxxxxxxx x xx prvnímodběru xx dodrží xxxxxxxxxxxx xxxxxx. Je-li po xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, není xxxxx odběr xxxxx;

x) xxxx-xx xxxxxxxx dvě xxxx xxxx xxxxx xxxxx (např. dvě xxxx více xxxxx x intervalu 24 xxxxx), měly xx xxx xxxxxx xxx xxxxxxx xxxxxx xxxxx xxxxxxxx jednou po 18 xx 24 xxxxxxxx xx xxxxxxxx xxxxxxxx x xxx xxxxxxx xxxxxxxxx krve xxxxxx po 36 xx 48 hodinách xx xxxxxxxx xxxxxxxx (12).

Xxxxx xxxxxxx mohou xxx xxxxx xxxxxxx xxxx xxxx odběru.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx být xxxxxxxxx xx stejné xxxxxxxxxx, se xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx stejného xxxxxx expozice, jež xx xxxxxxx x xxxxxx xxxxxx (13). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx až xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx bude použita xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx xx vedly xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x letalitě. Látky xx specifickou biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x mitogeny) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx x xxxx by být xxxxxxxxx xxxxxx od xxxxxxx. Nejvyšší xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx x xxxxxx xxxxx xxxx x xxxxxxxxx krvi).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx dávkou x xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx toxické xxxxxx a xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx xxxxx xxxxxx xx třemi úrovněmi xxxxx za xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx a xxx xxxxx xxx 14xxxxx aplikaci je xxxxxxx xxxxxx 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx znamenat xxxxxxx xxxxxx v xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx obvykle xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxx xxxxxxxxx. Maximální objem xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxx sondou nebo xxxxxxxx, závisí na xxxxxxxxx testovacího xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx a žíravé xxxxx, které obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx zesílené xxxxxx, xx měla xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx se xxxxxxx získávají z xxxxxx xxxx tibie xxxxx po xxxxxxxx. Xxxxx se odeberou x xxxxxx xxxx xxxxx a xxxxxxxxxx xxxxxxxx xx xxxxxxxxx x obarví. Xxxxxxxxx xxxx se xxxxxxx x ocasní xxxx xxxx xxxx xxxxxx xxxxxx xxxx. Krevní xxxxx se xxxxx xxxxxxxxxxxx obarví (8, 9, 10), nebo xx xxxxxxxx xxxxxxxxx xxxxxxxx x xxxx xx xxxxxx. Xxxxxxxx xxxxxxx specifického xxx XXX (např. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 a xxxxxxx-X (15)) se xxx vyhnout xxxxxxxx xxxxxxxxxx spojeným x xxxxxxxx barviva xxxxxxxxxxxxxx xxx XXX. Tato xxxxxx xxxxxxx použití xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. xxxxxxxxxx kolona x xxxxxxxxxx buněk xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, xx xx xxxxxxxxx odpovídající xxxxxxxxx xxxxxx xxxxxxx xxx xxxxxxxxx mikrojader v xxxxxxxxxx.

1.5.7 Analýza

Pro xxxxx xxxxx se xxxxxxx xxxxx xxxxxxxxx erytrocytů x celkového (nezralé + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx se x xxxxxxx xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 xxxxxxxxxx x x případě xxxxxxxxx krve alespoň 1000 xxxxxxxxxx (17). Xxxxxxx preparáty xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx mikroskopem xxxxxxxxx xxxxxxxx. U xxxxxxx zvířete xx xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxxxxxxxx. Xxxxx informace xxxxx být xxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx. Xxx xxxxxxxxxxxxx xxxxxxx xx xxxxx xxx xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx nebo xxxx, xxx xxxx xxxxxxxx na výskyt xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx na xxxxx xxxxx. Xxxxxxx xxx automatickou xxxxxxx (xxxxxxx xxxxxx a xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxx) xxxx xx odpovídajícím xxxxxxxxxx x validaci přijatelnými xxxxxxxxxxxxx xxxxxxxxxx hodnocení.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx xxxxxxxxxx xxxxxxx xx xxxx být xxxxxxxxxx ve xxxxx xxxxxxx. Experimentální xxxxxxxxx xx zvíře. Xxx xxxxx xxxxxxxxxxx xxxxx xx xxx xxx xxxxxx xxxxx vyšetřených xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x xxxxx xxxxxxxxx erytrocytů x xxxxxxxxx množství erytrocytů. Xxxxxxxx xxxx zvířata xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx déle, xxxx xx xxx xxxx xxxxxxx údaje x xxxxxxx xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Pro xxxxx xxxxx se xxxxx xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx erytrocytů x xxxxxxxx množství xxxxxxxxxx x mikrojádry vyjádřené x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx o rozdílu x xxxxxxxx mezi xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx pro obě xxxxxxx xxxxxxxxxxxx.

2.2 HODNOCENÍ X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx počtu xxxxx x xxxxxxxxxx xxx xxxxxxx x určitou xxxxxx a x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Statistická xxxxxxxxxx xx xxxxxx být xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, se xxxxxxxx x tomto xxxxxxx xx nemutagenní.

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

Pozitivní xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx xxxxxxxxxx, xxx xxxx důsledkem xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx mitotického xxxxxxx xxxxxxxxxxxx testovacího xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxxx mikrojádra x xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x pohlaví zvířat,

- xxxxx, podmínky chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx zvířat xx xxxxxxx xxxxxxx, včetně xxxxxxx xxxxxxx hmotnosti, xxxxxxx xxxxxxx a xxxxxxxxxx odchylka pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

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

- zdůvodnění zvolených xxxxxx xxxxx,

- údaje x xxxxxxxx zkoušené xxxxx,

- údaje o xxxxxxxx zkoušené xxxxx,

- xxxxxxxxxx xxxxxxx podávání,

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

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx zkoušené xxxxx x krmivu nebo xxxx (xxx) na xxxxxxxxxxxx dávku (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x vody,

- xxxxxxxx popis xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx přípravy xxxxxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxx mikrojader x nezralých xxxxxxxxxxxx,

- xxxxx analyzovaných xxxxx xx xxxxx xxxxx,

- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, negativní xxxx dvojznačnou.

Výsledky:

- známky xxxxxxxx,

- podíl xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx erytrocytů,

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

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

- xxxxx možnosti závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy x xxxxxx,

- xxxxx x xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx o souběžné xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Heddle, X. X. (1973), X Xxxxx Xx xxxx Xxxx xxx Xxxxxxxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 18, 187-190.

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

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

4) Xxxxxxxxx, X. X., Xxxxxx, X. H., Xxxxxx, X. C., Xxxxxxxx, X. F., Xxxxxx, X. X. (1990), The Xx xxxx Xxxxxxxxxxxx Xxxxx xx Mammalian Xxxx Xxxxxx and Xxxxxxxxxx Xxxxx. X xxxxxx xx the X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Gene-Tox Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) MacGregor, X. X., Schlegel, X., Xxxx, X. X., Xxxx, X. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Erythrocytes: A Xxxxx Xxxxxx for Xxxxxxxxxxx Damage Xxxxxx Xxxxxxx Xxxxxxxx Xxxxxxx xx Xxxx, in: Xxxxxxxxxxxx xx Xxxxxxx xxx Practice xx Xxxxxxxxxx, xx. X. X. Xxxxx, R. X. Xxxxxxx, T. X. Xxxx. Elsevier, Xxxxxxxxx, 555-558.

6) MacGregor, X. T., Xxxxxx, X. X. Hite, X., Xxxxxxxx, X. X., Xxxxx, C., Xxxxxxxx, X. X., Xxxx, R. R., Xxxx, D. (1987), Xxxxxxxxxx xxx xxx Xxxxxxx of Xxxxxxxxxxxx Xxxxxx xx Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Res., 189, 103-112.

7) XxxXxxxxx, X. X., Wehr, X. X., Henika, X. X., Xxxxxx, X. X. (1990), Xxx xx vivo Erythrocyte Xxxxxxxxxxxx Xxxx: Measurement xx Xxxxxx Xxxxx Xxxxxxxxx Xxxxx Xxxxxxxxxx xxx Xxxxxxx Xxxxxxxxxxx xxxx Toxicity Xxxxxxx, Xxxxxx. Xxxx. Xxxxxxx. 14, 513-522.

8) Xxxxxxx, X., Xxxxxx, T., Xxxxxx, X., Xxxxxx, X., Ishidate, X. Xx. (1990), Xxx Xxxxxxxxxxxx Assay xxxx Xxxxx Xxxxxxxxxx Blood Xxxxxxxxxxxxx Using Xxxxxxxx Xxxxxx-Xxxxxx Xxxxxx, Mutatation Xxx., 245, 245-249.

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

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Test (XXXXX/XXXXX, XXX: The Mammalian Xxxxxxxxxxx Xxxxx Xxxxx xx the Xxxxxxxxxxxxx Xxxxxxx Society xx Xxxxx) (1995), Protocol xxxxxxxxxxx xxx xxx xxxxx-xxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Xxxx, X. X., XxxXxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, X. X., Kirsch-Volders, X., Xxxxxx, Xx. X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xx xxxx Rodent Xxxxxxxxxxx Micronucleus Xxxxx, Xxxxx. Res., 312, 293-304.

12) Higashikuni, X., Xxxxx, X. (1995), Xx xxxxxxx, xxxxxxxxxxx xxxxxxxx xxxx of 30 ± 6 x after xxxxxx xxxxxx xx the xxxxx xxxxxxxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 313-319.

13) Fielder, X. X., Xxxxx, X. X., Boobis, X. X., Xxxxxx, P. X., Xxx, J., Xxxxxxx, X. J., Xxxxxxxxx, D. G., Xxxxxx-Xxxxxx, G., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Toxicology Xxxxxxx/XX Environmental Mutagen Xxxxxxx Xxxxxxx Group: Xxxx Setting in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

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

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

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

17) Gollapudi, X., McFadden, X. X. (1995), Xxxxxx Xxxx for xxx Xxxxxxxxxx xx Xxxxxxxxxxxxx xx Xxxxxxxxxxxxxx Erythrocyte Xxxxx in xxx Xxxx Marrow Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 347, 97-99.

18) Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Henderson, X. (1990), Xx vivo Xxxxxxxxxxxx Xxxxx, in: X. J. Kirkland (xx.), Xxxxx Mutagenicity xxxxx, XXXXX Recommended Xxxxxxxxxx, XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx 1, revised, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx York, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. E., Xxxxx, X., Ferguson X., Richold, X., Xxxxxxxx, D. G., Xxxxxx, X. X. X. (1989), Staticical Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. J. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx XXX, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx York, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

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

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX XX 471 — Xxxxxxx na xxxxxxxx mutace s xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx na xxxxxxxx xxxxxx x bakteriemi xx používají bakteriální xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Salmonella xxxxxxxxxxx x Xxxxxxxxxxx xxxx, x xxxxxxx bodových xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxx x xxxxxx jednoho xxxx xxxxxxxx xxxx bází XXX (1, 2, 3). Xxxxxxxx této xxxxxxx xx reverzní xxxxxx s bakteriemi xxxxxxx x xxxxxxx xxxxxx, xxxxx xxxxxxxxx xxxxxx obsažené v xxxxxxxxxxx xxxxxxx a xxxxxxxx tak funkční xxxxxxxxx bakterií xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx xxxx xxx xxxxxxxxxx xxxx x xxxxxxxxxxxxx aminokyselin, které xxxx vyžadovány mateřským xxxxxxxxxx kmenem.

Bodové mutace x podobné xxxx xxxx příčinou xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x xxxxxxxx mnoho xxxxxx x xxx, xx xxxxxx xxxxxx x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx nádory xxxx xxxxx xx xxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx. Zkouška xx xxxxxxxx xxxxxx s xxxxxxxxxx xx xxxxxx, xxxxxxxxxx x xxxxxxxxx xxxxxx. Xxxxx testovacích xxxxx xx xxxx xxxxxxxxxx, xxxx xxxx xxxx citlivější xx xxxxxxx mutací, včetně xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx buněk xxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX nebo xxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxxxxxxxx x xxxxxx. Specifičnost xxxxxxxxxxx xxxxx může xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxx x typech xxxxxx, xxx jsou indukovány xxxxxxxxxxxxx činiteli. Xxx xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx k dispozici xxxxx xxxxxxxx databáze xxxxxxxx xxx širokou xxxxx struktur x xxxx byly xxxxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx chemických xxxxx, xxxxxx xxxxxxxx xxxxxxxxx, x různými xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx také xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx slouží x detekci xxxxxx x kmeni xxxxxxxxxxx xxxxxxxxxxxxx (xxxxxxxx xxxx. xxxxxxxxx), xxxxxxx xxxxxx xxxx xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx xxxx činitele, jež xxxxxxxxx změny v xxxxxx XXX. Xxx xxxxxxx xxxxxxxxxx xxxxxx xx xxxxx tyto xxxxx xxxxxxxxxx xx xxxxx xxxxxxx mutace xxxx xxxxx xxxxx xxxxxxxxxxxxx genomu.

Posunové xxxxxxxx xxxx xxxxxxxx, jež xxxxxxxxx adici nebo xxxxxx xxxxxxx xxxx xxxx párů xxxx XXX x posunují xxx xxxxx xxxxx XXX.

1.3 XXXXXXX ÚVAHY

Při xxxxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xx xxxxxxxxx prokaryotické xxxxx, které xx xxxx od xxxxx xxxxx xxxxxxx, xxxx xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx a xxxxxxxxx procesy XXX. Xxxxxxx xxxxxxxxx in xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx zcela xxxxxxxxx xxxxxxxx xx xxxx u xxxxx. Xxxxxxx tedy neposkytuje xxxxxx informaci o xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx látky xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxx xxx počáteční xxxxxxxxx xxxxxxxxxxx aktivity, x xxxxxxx xxxxxxxx vyvolávající xxxxxx mutace. Z xxxxxxxx xxxxxxxx xxxxxxx, xx xxxxx chemických xxxxx, xxxxx xxxx x xxxx xxxxxxx xxxxxxxxx, vykazuje xxxxxxxxx xxxxxxxx i x xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx nejsou xxxxxxxxxx xxxxx zkouškou. Xxxxxxx xxxxxx xxxxxxxxxxx xxx xxxxxxxxx xx xxxxxxxxxx xxxxxx detekovanéhokonečného xxxx, x rozdílech x xxxxxxxxxxx aktivaci xxxx x xxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx. Na xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx citlivost xxxxxxx xx xxxxxxxx xxxxxx xx xxxxxxxxxx, xxxxx xxxx x xxxxxxxxxxxx mutagenní xxxxxxxx.

Xxxxxxx xx reverzní mutace x xxxxxxxxxx nemusí xxx vhodná xxx xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx vysoce xxxxxxxxxxxx sloučeniny (např. xxxxxx antibiotika) x xxx chemické xxxxx, x xxxxx se xxxxxxxxxxx (nebo x xxxxx se xx), xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx xxxxx (např. xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). X xxxxxxxx xxxxxxxxx mohou být xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx mnoho xxxxxxxxx, pro něž xx xxxx xxxxxxx xxxxxxxxx, xx xxxxxxxxxxxx xxx savce, xxxx xxxxxxxx xxxxxxxxx. Závisí xx xxxxxxxx xxxxx x xxxxxxxx xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx xxxxx zkouškou, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxxx xxxxxxxxxxxxx xxxxx jsou xxxxxxxxx zkoušené látce, x to za xxxxxxxxxxx vnějšího metabolického xxxxxxxxxxx xxxxxxx x xxx xxxx. Xx xxxxxxxxxxx xxxxxxxx testu xx suspenze xxxxxxxx x vrchním xxxxxx x ihned xx xxxxxxx xx minimální xxxx. X xxxxxxxxxxxx xxxxxx xx xxxxxxxx xxxx xxxxxxxx x xxxx xx xxxx xxxxxxxxx na minimální xxxx smíchá x xxxxxxx xxxxxx. Xxx xxxx technikách se xx xxxx xxxx xxxxx dnech inkubace xxxxxxxxx xxxxxxx xxxxxxxxxx x provede se xxxxxxxx s xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

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

Zde xxxxxxx xxxxxxx se xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Každá x nich je xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx jak s xxxxxxxxxxxx xxxxxxxx, tak xxx xx. Xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxx za xxxxxxx xxxxxxxxxxxx metody. Xxxx xxxxx xxxxx xx xxxxxxxxxx xxxx, xx xxxxx patří xxxx xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, dvojvazné kovy, xxxxxxxx, xxxxxxxxxx x xxxxxxxxxx sloučeniny, pyrrolizidinové xxxxxxxxx, xxxxxxxx sloučeniny x xxxxxxxxxxxxxxx (3). Xxxxxx se připouští, xx xxxxxx třídy xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx xx standardní xxxxxxx test xxxx xxxxxxxxxxxx metoda. Xxxx xx být xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x x xxxxxx xxxxxxx xx xxxxxxx xxxxxxxxxx použít xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx tyto "xxxxxxxx xxxxxxx" (společně s xxxxxxxx xxxxxxx xxxxxx xxxxxxx): azobarviva x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx a těkavé xxxxxxxx látky (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx xx xxxxxxxxxxxx xxxxxxx musí xxx xxxxxxx xxxxxxxxxx.

1.5 XXXXX XXXXXXXX METODY

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx měly xxx kultivovány xx xxxxxx xxxxxxxxxxxxx xxxx xxxx do časné xxxxxxxxxxx xxxx xxxxx (xxxxxxxxx 109 buněk xx xx). Xxxxx x xxxxxx xxxxxxxxxxx xxxx xx neměly xxx xxxxxxx. Xx xxxxxxxx, aby xxxx xxxxxxx bakterie vysoký xxxx životaschopných xxxxxxxx. Xxxx xxxx xxx xxxxxxxx buď xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, nebo pro xxxxxx zkoušku xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx xxxxx xx miskách.

Doporučená xxxxxxxxx xxxxxxx je 37 °X.

Xxxx by být xxxxxxx xxxxxxx xxx xxxxx xxxxxxxx. Mezi xxxx xx xxxx xxx xxxxx xxxxx X. xxxxxxxxxxx (TA1535; XX1537 xxxx XX97x xxxx XX97; XX98 x XX100), jejichž xxxxxxx xx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxx spolehlivá a xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx S. xxxxxxxxxxx xxxx xxx bází XX xx xxxxxxxxx xxxxxxxxx xxxxx x xx známo, xx xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx určité oxidační xxxxxxxx, xxxxxxxx způsobující xxxxxxxxxx xxxxxx XXX x hydraziny. Xxxx xxxxx xxxxx být xxxxxxxxxx xxxxx X. xxxx XX2 xxxx X. xxxxxxxxxxx XX102 (19), xxxxx xxxx xx xxxxxxxxx xxxxxxxxx xxxxx xxx xxxx XX. Xxxxxxxxxx xxxxxxxxx xxxxx je tedy xxxx:

- X. xxxxxxxxxxx XX1535 x

- X. xxxxxxxxxxx XX1537 nebo XX97x a

- X. xxxxxxxxxxx XX98 x

- X. typhimurium XX100 x

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

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

Xxxx xx xxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx kmenové xxxxxxx, xxxxxxxxxx markeru x xxxxxxxxxx. Potřeba xxxxxxxxxxxxx xxx xxxx xx měla xxx xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx xxx xxxxx X. xxxxxxxxxxx a xxxxxxxxx xxx X. xxxx). Xxxxxxx by xxxx být xxxxxxxxxxxx xxxx xxxxxxxxxx charakteristiky, xxxxxxxxx xxxxx xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, XX100 x XX97x nebo XX97, XX2 uvrA x XX2 xxxX (xXX101) a xxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxx x xxxxx XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx mutací (xx. xxx xxxxxx x S. typhimurium xxxxxxxxxx na krystalovou xxxxxx x xxxX xxxxxx u X. xxxx nebo xxxX xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxxx) (2, 3). Kmeny by xxxx xxxxxx xxxxx xxxxx kolonií spontánních xxxxxxxxxx na misce x xxxxxxx xxxxxxxx xxxxxxxxxxx xx základě xxxxxxxxxxx xxxxx laboratorních xxxxxxx x xxxxxxx x xxxxxxx uvedeném x xxxxxxxxxx.

1.5.1.2 Xxxxxx

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

1.5.1.3 Metabolická xxxxxxxx

Xxxxxxxx xx xxxx xxx xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x xxx xxxx. Nejčastěji používaným xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx ošetřených xxxxxxxxxxx indukujícím xxxxxx, xxxx xx Aroclor 1254 (1, 2) xxxx fenobarbitonu a β-xxxxxxxxxxxx (18, 20, 21). Postmitochondriální xxxxxx xx xxxxxxx používána x xxxxxxxxxxxxx x xxxxxxx 5 až 30 % obj. xx směsi S9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx chemické xxxxx. V xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. U xxxxxxxxx x diazoniových xxxxxxxxx xxxx být xxxxxxxxx použití xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému (6, 13).

1.5.1.4 Xxxxxxxx xxxxx nebo xxxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx být před xxxxxxxx xx bakterie xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx látky, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx s xxxxxxxx xxxxxxxx a s xxxxxxxxx S9 (22). Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx nejdříve xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx xx xxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Zkušební xxxxx (viz 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx kritéria, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx patří xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx a xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx xxxx xxx xxxxxxxxxx snížením xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx zeslabením xxxxxxxxxxxxx xxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx xx může xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx aktivačních systémů. Xxxxxxxxxxxxx by xxxx xxx posouzena xx xxxxxxx xxxxxxxxxxx srážení x xxxxxxx xxxxx xx skutečných xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx zkušební xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx xx 5 mg/misku xxxx 5 μx/xxxxx. X xxxxxxxxxxxxxxx látek xxxxxxxxxxxxx xxx koncentracích 5 xx/xxxxx xxxx 5 μx/xxxxx xx xxxx xxx jedna xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, aby látky xxxx x xxxxxxx xxxxx pro xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxxxx xxx xxx koncentracích xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx, by měly xxx xxxxxxxx xx xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx xxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx pět různých xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, přičemž xxx xxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx xxxx xxxxxxxxxx xxxx xxxxx přibližně xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx xxxx vhodné x případě, xxx xx xxxxxxxxx křivka xxxxxxxxxx xxxxxxxx na xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx může xxx xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxx by xxxx xxx kmenově xxxxxxxxxx xxxxxxxxx x negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx s metabolickou xxxxxxxx a xxx xx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx vybrány xxxxxxxxxxx xxxxxxxxxxx účinnost každé xxxxxxx.

X případě zkoušek x použitím xxxxxxxxxxxxx xxxxxxxxxxx systému by xxxx xxx xxxxx (xxxxx) xxx pozitivní xxxxxxxx xxxxxxx (vybrány) xx základě xxxx xxxxxxxxx xxxxx bakterií.

Příkladem xxxxxx xxxxxxxxx kontroly x xxxxxxx x xxxxxxxxxxxx aktivací 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 xxxxxxxxxx

6055–19–2

Xxxx xxxxx je xxxxxxx xxxxxxxxx xxxxxxxxx pro xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

XX Xxxxxx Xxx 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx xx neměl xxx xxxxxx xxxx xxxxxx indikátor xxxxxxxxx xxxxx X9. Xxx xxxxxxx 2-xxxxxxxxxxxxxxx xx xxxx xxx každá xxxxx S9 xxxxxxxxxxxxxxxx xxxxxxxxx, xxxxx vyžaduje xxxxxxxxxxxx xxxxxxxx mikrosomálními xxxxxx, například xxxxx[x]xxxxx xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

Xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx u xxxxxxx bez xxxxxx xxxxxxxxxxx aktivace xxxx xxxx látky:

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

Xxxx

xxxx sodný

26628–22–8

247–852–1

TA1535 x TA100

2-nitrofluoren

607–57–8

210–138–5

TA98

9-aminoakridin

90–45–9

201–995–6

TA1537, XX97 x XX97x

XXX 191

17070–45–0

241–129–4

TA1537, XX97 a XX97x

Xxxxxxxxxxxxxxxxx

80–15–9

201–254–7

XX102

xxxxxxxxx X

50–07–7

200–008–6

XX2xxxX x TA102

1-methyl-3-nitro-1-nitrosoguanidin

70–25–7

200–730–1

WP2, XX2 xxxX x XX2 uvrA (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 xxxX x XX2 xxxX (pKM101)

α-[(5-nitro-2-furyl)methyliden]furan-2-acetamid (XX2)

3688–53–7

xxxxx obsahující plasmidy

Pro xxxxxxxxx xxxxxxxx xxxxx xxx použity jiné xxxxxx xxxxxxxxxx xxxxx. Xxx pozitivní xxxxxxxx xx mělo xxx xxxxx x xxxxx xxxxxxx chemických látek xx xxxxxx xxxxxxxx xxxxx, xxxx li x xxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx se xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula, xxx xxxxxxxx xxxxx, xxxxxxxxxx xxxxx stejným xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, neexistují-li xxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.

1.5.3 Xxxxxx

X xxxxxxxxxx xxxxxxx xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,05 xx nebo 0,1 xx xxxxxxxxxx roztoků, 0,1 xx čerstvé xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x 0,5 xx sterilního xxxxx x 2,0 xx xxxxxxxx xxxxx. X xxxxxxx xxxxxxx x xxxxxxxxxxxx aktivací se xxxxxxx smíchá 0,5 xx metabolické xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x xxxxxxx 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx xxxxx) x xxxxxxx xxxxxx (2,0 xx) x xxxxxxx x bakteriemi x xxxxxxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx. Obsah xxxxx zkumavky xx xxxxxxxx x xxxxxxx xxxx xxxxxx minimálního xxxxx xx xxxxx. Xxxx xxxxxxxx se xxxxx xxxxxx xxxx xxxxxxxx.

X preinkubační metody (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx xxxxxxxx xxxxxx xxxx xxxxxxxxx x vrchním agarem x xxxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx xxxxx obvykle 20 minut xxxx xxxx xxxxxxxxxxx s xxxxxxxxxx xxxxxx (obsahujícím xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x sterilním xxxxxx xxxx xxxxxxxxxxxx xxxxxxxxxx systémem (0,5 xx) při 30 — 37 °X. Xxxxxxx se xxxxxx 0,05 nebo 0,1 xx xxxxxxxx xxxxx xxxx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxxx x 0,5 ml xxxxx X9 nebo xxxxxxxxxx xxxxx x 2,0 ml xxxxxxxx xxxxx. Xxxxxxxx xx xxxx xxx během xxxxxxxx xxxxxxxxxxxxxx na xxxxxxxx.

X dostatečnému xxxxxx xxxxxxxx xx xxxx xxx xxx xxxxx xxxxxx dávky xxxxxxx 3 xxxxx. Použití xxxx misek xx xxxxxxxxxx xx vědeckém xxxxxxxxxx. Případná xxxxxx xxxxx nemusí znamenat xxxxxxxxxxxx xxxxxxx.

Xxxxxx xxxx xxxxxx xxxxx xx xxxx být zkoušeny xxxxxxxx metodami, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (12, 14, 15, 16).

1.5.4 Xxxxxxxx

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

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

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

Xxxxxxx xxxxx pozitivní xxxxxxxx xx nepožaduje. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxx experimentálních xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. Xxxxxxxx se potvrzení xxxxxxxxxxx xxxxxxxx nepovažuje xx xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx s xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx v xxxxxxxxxx experimentech. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx, metoda xxxxxxxxxx (xxxxxxxxxx misková xxxxxx xxxx preinkubace x xxxxxxxx xxxxx) a xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. nárůst xxxxx xxxxxxx xxxxxxxxxx xx misku nad xxxxxxxxx xxxxxx u xxxxxxx xxxxxxx xxxxx x xxxxxxxxxxxx aktivačním xxxxxxxx xxxx xxx xxxx, x xx x xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx xxxxxx xxxxx xxx jednu nebo xxxx koncentrací (23). Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx pomocný prostředek xxxxxxxxxxx metody (24). Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx nesplňují xxxx uvedená xxxxxxxx, xx xxxxxxxx x xxxxx xxxxxxx za xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx bez xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x xxxxxx kmenů Xxxxxxxxxx xxxxxxxxxxx a/nebo Xxxxxxxxxxx xxxx xxxxxx xxxxxx substitucí xxxx xxxx posunem čtecího xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že zkoušená xxxxx xxxx za xxxxxxxx xxxxxxx xxx xxxxxxxxx druhy mutagenní.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx xxxxx,

- počet xxxxx v xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxx xxxxx,

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

- postup xxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx xxxxx kolonií xxxxxxxxxx na xxxxx x xxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxx, X. N., McCann, X., Xxxxxxxx X. (1975), Xxxxxxx of Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx xxxx the Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx., 31, 347-364.

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

3) Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxx, L., Xxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, X. (1994), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx of Xxxxxxxxx Xxxxxxxx Xxxxxx, Xxxxxxxxxx Res., 312, 217-233.

4) Xxxx, X. X., Xxxxxxx X. X., Xxxxxxx, X. X., Von Xxxxx, X. X., Xxxxx, X. X., Simmon, X. F., Dunkel, X., XxXxxx, X., Xxxxxxxxxx, X., Prival, X., Xxx, X. X., Xxx V. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Xxxxxx of xxx X. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, T., Degawa, X., Xxxxx, X. X., Xxxxxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, Y. (1975), Mutagenicity xx Xxxxxxxxxx Xxx Xxxx xxx xxxxx Derivatives, Xxxxxx Xxxx. 1, 91-96.

6) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Microbial Xxxxx, in: Short-term Xxxx Xxxxxxx for Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx K. X., Xxxxxx, R. C., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx York, 273-285.

7) Xxxxxxxxx, X. X., Rowland, X. X., Xxxxxx, X., Xxxxxxxxx, R. D., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Assays, xx: Xxxxx Xxxxxxxxxxxx Xxxxx: XXXXX Xxxx 1 Revised, xx. X. X. Xxxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, 13-61.

8) Aeschacher, X. X., Xxxxxx, X., Xxxxxxx, X. (1987), Xxxxxx Preincubation Mutagenicity Xxxx for Xxxxx, X. Food Safety., 8, 167-177.

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

10) Hubbard, X. X., Xxxxx, X. X. X., Xxxxxxxxx, D., Bridges, X. X. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, xx: Xxxxxxxx of Mutagenicity Xxxx Procedures, 2. xxx., Kilbey, X. X., Legator, M., Xxxxxxx, X., Xxxxx, X. (eds.), Elsevier, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, X. X., Xxxxxxx, X. J. (1981), An Xxxxxxxxxxx xx xxx Quantitative Xxxxxxxxxx Xxxxx for Xxxxxxxxxxx with Strains xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxxxxxxxxx Mutagenesis, 3, 453-465.

12) Araki, X., Xxxxxxx, X., Kato, X., Xxxxxxxxxx, X. (1994), Xxxxxxxx Method xxx Mutagenicity Testing xx Gaseous Compounds xx Using x Xxx Sampling Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

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

14) Xxxxxx, X., Xxxxxxxx, X. E., Haworth, X., Xxxxxx, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Mutagenicity Xxxxx. X. Xxxxxxx xxxx xxx Xxxxxxx xx 311 Xxxxxxxxx, Environ. Xxx. Xxxxxxx., 19, 2-141.

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

16) Xxxxxx, X. X., Xxxxxxx, X. M., Xxxxxxxx, X. X., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Technique xx Xxxxxxx Mutagenic Xxxxxxxx xx Volatile Organic Xxxxxxxxx xx the Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, T., Xxxxxxxxx, X., Shirai, X., Xxxxxxxx, M., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx xxx Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxx Xxx., 39, 3780-3782.

18) Xxxxxx, X., Xxxx, X., Ferro-Luzzi, A., Xxxx, X. N. (1980), Fecalase: A Xxxxx xxx Activation xx Xxxxxxx Glycosides xx Xxxxxxxx xx Xxxxxxxxxx Xxxxx, Xxxx. Xxxx. Acad. Xxx. X. X. X, 77, 4961-4965.

19) Wilcox, X., Xxxxxx, X., Xxxx, X. J., Xxxxxxxxx, D. X. (1990), Comparison of Xxxxxxxxxx xxxxxxxxxxx XX 102 xxxx Escherichia xxxx WP2 Xxxxxx xxxxxxx, Mutagenesis, 5, 285-291.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Activation Systems, xx: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Testing, xxx. X. J. xx Xxxxxx xx xx. Xxxxxxxx, North Xxxxxxx, 85-88.

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

22) Xxxxx, X., Katzenellenbogen, X., Xxxx, X. X. (1981), Xxxxxxxxxxxxx xx Organic Solvents xxxx the Salmonella/Microsome Xxxx, Mutatation Res., 88, 343-350.

23) Xxxxxxx, X. X., Allen, X., Xxxxxxx, X., Xxxxxxxxxx, K., Xxxxxxxx, X., Xxxxxx, X. (1987), Xxxxx xxx xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Xxxxxxxxxxxx, Mutatation Xxx., 189, 83-91.

24) Xxxxx, G. X. X., Green, X. X. L., Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, X. J. (1989), Analysis xx Xxxx xxxx Microbial Xxxxxx Assays, in: XXXXX Sub-Committee xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Part XX. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, xx. Xxxxxxxx, D. X., Xxxxxxxxx University Xxxxx, 28-65."


PŘÍLOHA 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx xx xxxxx lze xxxxxx xxx detekci xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xxxxxx buněčné xxxxx xxxxx xxxxx lymfomu X5178X xxxx, xxxxxxx xxxxx XXX, XXX-XX52 x X79 křečka xxxxxxxx x xxxxxxxxxxxxxxx xxxxx XX6 xxxxxxx (1). X těchto xxxxxxxxx linií xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx xxxxxx xxxx xxx thymidinkinasu (TK) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x xxxxxxxx xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Zkoušky xx xxxxxx XX, XXXX x XXXX detekují xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX x XPRT xxxx umožnit xxxxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxx xxxxxx), xxxxx xxxxx detekovat x XXXX lokusu xx X chromozomech (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx savců xx xxxxx xxx použít xxxxxxx xxxxxxxxxx linií xxxxx xxxx xxxxxxx xxxxx. Xxxxx xx xxxxxxxx xxxxx xxxxxxxxxx xxxxx v xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx mutací.

Zkoušky prováděné xx xxxxx obecně xxxxxxxx použití vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx nemůže zcela xxxxxxxxx podmínky xx xxxx x savců. Xx xxxxx xx xxxxx vyvarovat podmínek, xxxxx by vedly x xxxxxxxxxx výsledkům, xxx xxxxxxxxxx vlastní xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx mutagenitu, xxxx xxxxx změnou pH, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx xx xxxxxxx xx zjištění možných xxxxxxxx a xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx je xxxx xxxxxxx pozitivní, xxxx xxxxxxxxxxx xxxxx; xxxx xxxxx xxxxxxxx x karcinogenitou xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx třídě x xxxxxxxxx xxxxxx x xxx, že xxxxxxxx xxxxxxxxxxx, které xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx působí xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx buňkách xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Přímá xxxxxx : xxxxxx xxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxxxxxx aktivity xxxxxxxxxx xxxxxxxx.

Xxxxxxxx substituce xxxx xxxx : látky, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxx více xxxx xxxx x XXX.

Xxxxxxxx xxxxxxxx : xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxx xxxx více xxxx xxxx v xxxxxxxx XXX.

Xxxx xxxxxxx xxxxxxxx : xxxx, xxxxx xxx xxxxxx x nově mutovaných xxxxx xxxxxxxxx genové xxxxxxxx.

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

Relativní celkový xxxx : nárůst xxxxx xxxxx x xxxx xx srovnání x kontrolní xxxxxxxx xxxxx; xxxxxxx xx xxxx xxxxxx xxxxxx xxxxxxxxx růstu v xxxxxxxx x x xxxxxxxxx xxxxxxxx x xxxxxxxxx účinnosti xxxxxxxxx xxxxxxxx x negativní xxxxxxxx.

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

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

Xxxxxxx : xxxxxxxx xxxxxxxxx buněk xxx xxxxxxxx xx xxxxx xx konci xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx xxxxxxxxx x xxxxxx x xxxxxxx xxxxxxxxx populace xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx XX+/-® XX— /- neobsahují xxxxxxxxxxxxxx (XX) xxxx xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxx pyrimidinu xxxxxxxxxxxxxxxxx (XXX). Xxxxx xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx na XXX, xxx způsobuje xxxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxx xxxxx xxxxxxx xxxxxx. Xxxxxxxx buňky xxxx xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxxxxx XXX, xxxxxxx normální xxxxx, xxxxx obsahují xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Podobně xxx x xxxxx x xxxxxxxxxxxx XXXX xxxx XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx rezistence x 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (XX). Xxxxxxxxxx xxxxxxxx látky xx xxxx být xxxxxxx xxxxxxx, xxxxxxxx je xx xxxxxxx na xxxxxx mutace x xxxxxxx xxxxx zkoušen xxxxxx báze xxxx xxxxxxxxxx xxxxxxx selekčnímu xxxxxxx. Xxxx xx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx podezření xx xxxxxxxxxx toxicitu xxxxxxxx xxxxx pro mutantní xxxx xxxxxxxxxx xxxxx. Xxx zkoušení chemických xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx činidlo, musí xxxx xxx potvrzena xxxxxxxx xxxxxxx xxxx xxxxxxx xxx xxxxxxx (8).

Xxxxx x suspenzní xxxx jednovrstevné xxxxxxx xxxx xxxxxxx dobu xxxxxxxxx xxxxxxxx xxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, x xxxxxxxxxxxxxx xx účelem xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx exprese xxxxxxxx xxxx xxxxxxx mutantů (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx obvykle xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (přežití) nebo xxxxxxxxxx relativního xxxxxxxxx xxxxx xxxxxx po xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx kultury xx xxxxxxx v růstovém xxxxx po xxxxxxx xxxx xxxxxxxxxxxxxxxxx xxx xxxxx xxxxxxx xxxxx x xxx xxxxx, xxx xxxxxxx přibližně xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx se xxxxxxx xxx, že xx xxxxxx známý počet xxxxx xx xxxxx xxxxxxxxxxxx selekční činidlo xxx xxxxxxx xxxxxxxxxx xxxxx x xx xxxxx bez xxxxxxxxxx xxxxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Xx vhodné xxxxxxxxx xxxx se xxxxxxxxx xxxxxxx. Četnost xxxxxxx xx xxxxxxx x počtu xxxxxxxxxx xxxxxxx x selekčním xxxxx a xxxxx xxxxxxx v xxxxx xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx použití x této xxxxxxx xxxx x xxxxxxxxx xxxxx typy xxxxx, xxxxxx xxxxxxxx buněk X5171X, XXX, XXX-XX52, X79 xxxx XX6. Xxxx xxxxx v xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxxxx, zda nejsou xxxxxxxxxxxxx mykoplasmaty, a x xxxxxxx xxxxxxxxxxx xx neměly být xxxxxxx.

Xxxxxxx xx xxxx xxx xxxxxxxx xxx, xxx xxxx xxxxxx xxxxxxxxxx xxxxxxxxx a xxxx. Xxxxx xxxxxxxxx xxxxx, xxxxxx x xxxxxxxxxxx zkoušené xxxxx xx xxx xxxx xxxxxxxxxx xxxxxxxxx odrážet (14). Xxxxxxxxx počet xxxxx, xxxxx xxxxxxx xxxxxxxx a které xxxxx použity x xxxxxx stadiu xxxxxxx, xx xxx xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx xx, xxx xxx xxxxxx počet xxxxx, xxxxx je xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx spontánních xxxxxx. Xx však doporučeno, xxx bylo použito xxxxxxx 106 buněk. Xxxx by být x xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx doložena xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.

1.4.1.2 Média a xxxxxxxxxx xxxxxxxx

Xxx udržování xxxxxx by xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx média x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x vlhkost). Xxxxx xx xxxx xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx a xxxx xxxxx xxxxxxxxx xxx zkoušce. Xx xxxxxxx xxxxxxxx, aby xxxxxxxxxx xxxxxxxx byly xxxxxxx xxx, aby xxxx xxxxxxxxx xxxxxxxxx xxxx xxxxx xxxxx xxxxxx xxxxxxx a xxxxxxxxx xxx mutovaných, xxx nemutovaných buněk xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx by xxxx xxx získávány z xxxxxxxxx xxxxxx, xxxxxxxx xx xxxxxxxxxxxx xxxxx x inkubovány při 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx může xxx xxxxxxxx xxxxxxxxx x xxxxxxx xxx přítomné xxxxxxxx xxxxx.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx by xxxx xxx vystaveny xxxxxxxx xxxxx, x to x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx a xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (S9) xxxxxxxxxx x jater xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (15, 16, 17 x 18), xxxx xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (19, 20).

Postmitochondriální xxxxxx xx v xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x koncentracích 1 — 10 % obj. Xxxxx x stav metabolického xxxxxxxxxxx systému xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxx, která xx xxxxxxxx. V xxxxxxxxx případech xxxx xxx vhodné xxxxxx xxxx než xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, včetně xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx linií xxxxxxxxxxxxx xxxxxxxxxx aktivační enzymy, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx aktivaci. Xxxxx xxxxxxxxx buněčných linií xx měla být xxxxxxx xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Příprava xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx před aplikací xx buňky rozpuštěny xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a popřípadě xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx přímo k xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, pokud xxxxx x stálosti xxxxxxxxxxx možnost skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx, x mělo xx být xxxxxxxxxx x xxxxxxxx buněk x x aktivitou X9. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx údaji x xxxxxx kompatibilitě. Doporučuje xx xxxxx možno xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx látek xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

Xxxx xxxxxxxx, která xxxx xxx zohledněna xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx cytotoxicita, xxxxxxxxxxx x testovacím xxxxxxx x xxxxx pH xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx být xxxxxxxxx x metabolickou aktivací x xxx xx x hlavním xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx xxxxxxx integrity x růstu, xxxx xxxx relativní xxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxx xxxxxxx růst. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx alespoň xxxxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a minimální xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx bude xxxxxxx xxxxxxxx, xx xx se koncentrace xxxx xxxxx xxxxxxxx 2 xx Ö10. Xx-xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx cytotoxicity, xxxx by xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) xxxxxxx (relativní xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx celkový růst. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx maximální xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 mg/ml xxxx 0,01 M, xxxxx toho, xxxxx x xxxx xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx látky xx měly být xxxxxxxx xx x xxxx rozpustnosti xx xxxxxxxxxxxx podmínek, xxxx xx xx xxxx xxx. Xxxx xx xxx xxxxxxxxx případná xxxxxxxxxxxxx x xxxxxxxx xxxxx, ve kterému xxxx xxxxx xxxxxxxxxx. Xxxx xxx výhodné xxxxxxxx xxxxxxxxxxx xx xxxxxxx x xx xxxxx aplikace, neboť xxxxxxxxxxx se xxxx x průběhu xxxxxxxx x xxxxxxxxxx systému xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, X9 xxxx, xxx. Xxxxxxxxxxxxx xxx zjistit vizuálně. Xxxxxxxxx by xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx měly xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx nebo vehikulum) xxxxxxxx xxx s xxxxxxxxxxxx aktivací, tak xxx xx. Xxx xxxxxxx xxxxxxxxxxx xxxxxxxx xx měla být xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, xxxxx k xxxxxxxxx xxxxxxxx vyžaduje xxxxxxxx.

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxx xxxxx:

Xxxx metabolické xxxxxxxx

Xxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

Xxx xxxxxx xxxxxxxxxxx xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx a xxxxx xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X xxxxxx xxxxxxxxxxxx xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (malé a xxxxx xxxxxxx)

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxx[x]xxxxx

50–32–8

200–028–5

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–5

XXXX

X-xxxxxxxxxxxxxxxxxxx (xxx xxxxxx xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx být xxxxxxx xxxx jiné referenční xxxxx xxx pozitivní xxxxxxxx, např. xx-xx xxxxxxxxx xxxxxxxx dosavadních xxxxx x 5-brom-2′-deoxyuridinu (XXX 59–14–3, XXXXXX 200–415–9), xxxx xxx xxxx referenční xxxxx xxxxxx použita. Xxx xxxxxxxxx kontrolu xx xxxx xxx xxxxx x xxxxx použití xxxxxxxxxx xxxxx pokud xxxxx ze xxxxxx xxxxxxxx xxxxx.

Xxxx by xxx použity xxxxxxxxx xxxxxxxx xxxxxxx médiem xxxxxxxxxxx samotné rozpouštědlo xxxx xxxxxxxxx x xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx exponované xxxxxxx. Xxxxx xxxx xx měly být xxxxxxxxxxxx kontroly použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx xxx xx přítomnosti xxxxxxxxxxxxx aktivačního xxxxxxx, xxx xxx xxxx. Xxxxxxxx xx xxxx xxxxx xxxxxxx dobu (xxxxxxx xx účinná xxxx 3 xx 6 xxxxx). Xxxxxxxxx xxxx xxxx být xxxxxxxxxxx xx xxxxx xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx mohou být xxxxxxx xxxxxxxxxx xxxxxxx xxxx jedna xxxxxxxxxx xxxxxxx. Je-li použita xxxxx xxxxxxx, xxx xx být počet xxxxxxxxxxx xxxxxx xxx, xxx xxx xxxxxxxx xxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxx (xxxx. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx xx xxx použity duplicitní xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx xxxxxxxxxxxx).

Xxxxxx xxxx xxxxxx xxxxx xx xxxx xxx xxxxxxxx xxxxxxxx metodami, např. x xxxxx xxxxxxxxxx xxxxxxxxxxxx nádobách (21, 22).

1.4.3.2 Xxxxxxxxx přežití, xxxxxxxxxxxxxxxx x četnosti xxxxxx

Xx xxxxx expoziční xxxx se buňky xxxxxxx a kultivují xx xxxxxx xxxxxxxxx xxxxxxx x xx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxx prostřednictvím xxxxxxxxx relativní účinnosti xxxxxxxxx (přežití) xxxx xxxxxxxxxxx celkového xxxxx xxxxxx xx xxxxxxx xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx lokus má xxxxxxxxxx minimální xxxxxx xxxxxx, aby xxxxxxx xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (XXXX x XXXX xxxxxxxx alespoň 6 xx 8 xxx, XX xxxxxxx xxx xxx). Xxxxx xxxx xxxxxxxxxxx x xxxxx xx selekčním xxxxxxxx (xxxxxxxxxx činidly) x bez něho (xxx xxxx) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx x klonovací xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx četnosti mutantů) xx xxxxxxx xx xxxxx xxxx xxxxxxx xxxxxxxxx na misku xxx selekčního xxxxxxx.

Xx-xx xxxxxxxx xxxxx xxxxxxxxx xx xxxxxxx X5178X XX+/-, mělo by xxx xxxxxxxxx xxxxxxx xx jedné xx xxxxxxxxxx xxxxxx (x xxxxxxxx pozitivní koncentrací) x xx xxxxxxxxxxx x xxxxxxxxxxx kontrolách xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií. Je-li xxxxxxxx xxxxx xx xxxxxxx X5178X XX+/- xxxxxxxxx, mělo xx xxx rozdělení kultury xxxxx xxxxxxxxx xxxxxxx xxxxxxxxx na xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx za xxxxxxx XX6 XX+/- xxxx xxx xxxx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xx měly xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x xxxxxxxx mutantů xxx xxxxxxxxxx x xxxxxxxxx kultury. V xxxxxxx pozitivní xxxxxxxx xx zkoušku X5178X XX+/- se xxxxxxx xxxxxxxxx alespoň u xxxxx xxxxxxxxxxx zkoušené xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x x xxxxxxxxx x pozitivní xxxxxxxx xx použití xxxxxxxx malá kolonie — velká xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxx xxxxxxx, xxx mutantů xxxxxxxxx xxxx kolonie byla xxxxxxxx zkoumána (23, 24). Xx xxxxxxx XX+/- xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxx (xxxxx) x kolonie x xxxxxxx xxxxxx (malá) (25). X xxxxxxxxxx xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx genetické xxxxxxxxx, xx xxxxxxxxxxx doby xxxxxxxx, x tvoří xxxx xxxx xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx xx xxxxx xxxxxx xxxx xx xx xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Indukce xxxxxxx xxxxxxxxx xxxx xxxxxxx xx xxxxxxx x xxxxxxxxxx xxxxxxx, xxxxx indukují silné xxxxxxxxxxxx aberace (26). Xxxx závažně postižené xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxx buňky a xxxxx velké xxxxxxx.

Xxxx xx xxx udáno xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx xxxxxxx růst. Xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxx jako xxxxx xxxxxxx x xxxxx přeživších xxxxx.

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

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx musí xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxx, xxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxx, xx třeba xxxxx zdůvodnění. Změna xxxxxxxxx studie s xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, xxx xxx xxxxxxxxx výsledky. X xxxxxxxxxx xxxxxx, které xx xxxxx xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx pozitivního výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxx xx koncentraci, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení výsledků xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost xx xxxxxx xxx xxxxxxx xxxxxxxxx faktorem pro xxxxxxxxx odpověď.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní výsledky, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx konečný výrok x aktivitě zkoušené xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx savců xx xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx. Reprodukovatelná pozitivní xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx xx velmi xxxxxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx xxxxxxxx xxxxx za podmínek xxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx buňkách xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby rozpouštědla/vehikula,

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

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxx buněčných xxxxxx,

- xxxxxxxx počet xxxxxx,

- případně xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx podmínky:

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

- složení xxxxx, xxxxxxxx koncentrace XX2,

- koncentrace zkoušené xxxxx,

- xxxxx vehikula x přidané zkoušené xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- případně xxxxxxx xxxxx během xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- xxxxx xxxx xxxxxxx (případně xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx x xxxxxx xxxxx),

- xxxxxxxx xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx buněk,

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

Xxxxxxxx:

- známky toxicity,

- xxxxxx srážení,

- xxxxx x pH a xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxx látce, pokud xxxx stanoveny,

- xxxxxxxx xxxxxxx, byla-li vyšetřována, xxxxxxx xxx negativní x xxxxxxxxx xxxxxxxx,

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

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

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

- xxxxxxx mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. M., XxXxxxxx, X. X., DeSerres, X. X., Xxxxxx, X. R. (xxx.) (1987), Xxxxxxx Xxxxxx 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Cold Spring Xxxxxx Xxxxxxxxxx, Xxx Xxxx.

2) Chu, E. X. X., Xxxxxxx X. V. (1968), Xxxxxxxxx Cell Xxxxxxxx. XX. Chemical Xxxxxxxxx xx Specific Xxxxx Xxxxxxxxx xx Xxxxxxx Xxxxxxx Xxxxx Xx xxxxx, Xxxx. Xxxx. Xxxx. Sci. U. X. X, 61, 1306-1312.

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

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

5) Xxxxx, X. S., Xxxxxxxxxx, Xx. X. X., (1989), Comparison of xxx XX52/XXXX xxx xxx CHO/HPRT Assays: Xxxxxxxxxx xx Xxx Xxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx. 223, 121-128.

6) Xxxxx, C. X., Xxxxxxxxxx, X., Xxxxx, X. X., Xxxxx, X., Nishi, X., Xxxxxxxxxx, Jr. X. X., Xxxxxx, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Report. Xxxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxxx xx Standardisation xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Xxxxx, X., Galloway, X. X., Xxxxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, X., Ashby, X., Xxxx, X. X. (1991), Genotoxicity Xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. A xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

8) Xxxxx, D., XxXxxx, X., Xxxxxxx, J. X. X., Xxxxx, X., Xxxxxxxxx, X. X. (1983), Xxxxxxxx Xxxx Xxxxxxxxx in X5178X Cells xx Xxxxxxx. X Report xx the U. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Res., 115, 225-251.

9) Xx, X. X., Gupta, X. X., Xxxxxxx, X. X., Xxxxxx, X. X. (1988), X Xxxxxx xxx Xxxxxxxx xx the Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Xxxxxxxxx xxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx: A Xxxxxx xx Xxxxx III xx xxx X. X. Xxxxxxxxxxxxx Protections Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, A. X., Carver, X. X., Xxxx, W. X., Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. X., O'Νeill, J. X., Riddle, J. X., Xxxxxxxxxx, L. X. Jr., Xxxx, X. X. (1987), X Guide xxx xxx Xxxxxxxxxxx xx xxx Chinese Hamster Xxxxx Cell/Hypoxanthine-Guanine Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Mutatation Res., 189, 135-141.

11) Liber, X. X., Yandell, X. W., Little, X. X. (1989), X Comparison xx Xxxxxxxx Induction at xxx XX xxx XXXX Loci xx Xxxxx Xxxxxxxxxxxxxx Cells: Xxxxxxxxxxxx Xxxxxxxxxxx are Xxx to xx Xxxxxxxxxx Xxxxx xx Xxxxxxxxx xx xxx Xxxxxxxxx TK Xxxxx, Xxxxxxxxxx Xxx., 216, 9-17.

12) Xxxxxxxxxx, L. X. Jr., Xxxxxx, X. X., Xxxx, X. X. (1986), Xxxxxxxxxxxx and Xxxxxxxxx Xxxxxxxx xx Ethyl Xxxxxxxxxxxxxxxxx xxx XXX 191-Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Ethyl Xxxxxxxxxxxxxxxxx xxx ICR 191 Xxxxxxx Xxxxxxxx in XX52 Xxxxx, Xxxxxxxxxx Xxx., 160, 133-147.

13) Xxxxxx, X. T., Xxxxxx, A. G., Xxxxx, D. (1984), Xxxxxxxxx for the X5178X/XX+/--XX+/- Xxxxx Lymphoma Xxxx Xxxxxxxxxxxx Xxxxx, xx: Xxxxxx, X. X. xx al (xxx.) Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, Xxxxxxxx Science Xxxxxxxxxx, Xxx Xxxx, 239-268.

14) Xxxxxx, C. F., Xxxxx, X. M., Xxxxxx, X. X., Xxxxx, M. X. X., Xxxx, J., XxXxxxxx, X. X., Xxxxxxx X. X. (1989), Mammalian Xxxx Xxxx Mutation Xxxxxx Xxxxx upon Xxxxxx Xxxxxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Kirkland, X. J., xx., Xxxxxxxxx Xxxxxxxxxx Press, 66-101.

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

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

17) Xxxxx, D., Xxxxxxx, X. O., Xxxxxxx, X. F. S., Xxxxxx X. G., Xxxxx X. X. X. (1979), Xxxxxxxxxx xxx Characterisation of xxx L5178Y/TK+/--Mouse Lymphoma Xxxxxxx Xxxxx Xxxxxx, Xxxxx. Xxx. 59, 61-108.

18) Xxxxx, X. X., Ames, X. X. (1983), Xxxxxxx Xxxxxxx for xxx Xxxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx. 113, 173-215.

19) Xxxxxxx, B. X., Xxxxxx, R. X., Elcombe, X. X., Gatehouse, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-Xxxxxxx X9 xx: Xx xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, X: Xx vitro Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, de Serres, X. X., Fouts, X. R., Bend, X. X., Philpot, X. X. (xxx), Xxxxxxxx, North-Holland, 85-88.

21) Xxxxx, X. X., Xxxxxx, X. C., XxXxxxx, X. X. (1982), XXX/XXXXX Mutation Xxxxx: Xxxxxxxxxx of Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Costa, X. X., Xxxxxxx, X. X. (eds), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, New Xxxx, Plenum, 91-103.

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

23) Applegate, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxxxxx of Mutations xx the Heterozygous Xxxxxxxxx Kinase Locus xx Mouse Lymphoma Xxxxx, Xxxx. Xxxx. Xxxx. Xxx. U. X. X, 87, 51-55.

24) Xxxxx, X. X., Xxxxx, X., Xxxxxx, X. X., Xxxxxx, B. X., Xxxxxx, X. X., Xxxxxx, N. T., Xxxxxx, X. (1985), Xxxxxxxx of Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (TFT+) Xxxxxxx xx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx. 151, 161-174.

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

26) Xxxxx, X. X., Xxxxx, X. L. (1990), Xxxxxxxxxx of Xxxxxxxxxx Aberration Frequency xxx Xxxxx Colony XX-Xxxxxxxxx Xxxxxx Xxxxxxxxx xx X5178X/XX+/- 3.7.2X Xxxxx Lymphoma Xxxxx, Xxxxxxxxxxx, 5, 609-614."


XXXXXXX 4X

"X.23 ZKOUŠKA XX XXXXXXXXXXXX XXXXXXX XX SPERMATOGONIÍCH XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxx xxxxxxx na chromozomové xxxxxxx xx xxxxxxxxxxxxxxx xxxxx xx vivo xx xxxxxxxxxxxxx takové xxxxx, xxxxx způsobují xxxxxxxxxx xxxxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x chromatidové. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxx xxxxxx xx xxxxxxxxx numerických xxxxxxx x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxx xxxx jsou xxxxxxxx xxxxx geneticky xxxxxxxxxxx xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx ve xxxxxxxxxxxxxxx a xxxxxxxxxxx xx xxxx, xx xxxx xxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx dědičných xxxxxx v xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Touto cytogenetickou xxxxxxxx xx xxxx xx xxxxxxxx xxxxxxxxxxxx xxxxxxx xxx xxxxxx xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx xx spermatogoniích by xxxx xxx — xxxxx než xxxxx xx xxxxxx xxxx — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx dělení, xxxxx xxxxxxxxx xx xxxxxxxx. Další informace x xxxxxxxxxxxx spermatogoniálních xxxxxxxxx buněk xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx aberací xxxxxxxxxxxxxx xxxx v xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx xx xxxxxxxx xxx vyšetření, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx je xxxx xxxxxxx se xxxxxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx zohlednit faktory xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a procesy xxxxxxxx XXX.

Xx xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxxx s xxxxxx xxxxxxxxxx na xxxxxxxx xxxxxxxx látce. Xxxxxxxxxx xxxxxxx tedy xxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxxxxxxx diferencovanými xxxxxxxxxxxxxxx. X xxxxxxxxxx xx xxx poloze xx xxxxxxxxx, xxxxx xxxx xxxxxx být xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx x důsledku xxxxxxxxx a xxxxxxxxxxxx xxxxxxx Sertoliho xxxxx x xxxxxxx mezi xxxxxxx xxxxxx a xxxxxxx.

Xxxxxxxx existuje xxxxx x xxx, xx xx xxxxxxxx látka xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx cílové xxxxx, xxxx xxxxxx xxxx zkoušku xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

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

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

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

Xxxxxxxxxxx : xxxxxxx haploidního xxxxx xxxxxxxxxxxxxx xxx (x), jiný než xxxxxxxxx (tj. 3 x, 4 x xxx.).

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx látce a xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx. Xxxx usmrcením se xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx připraví xxxxxxxxx xxxxxxxxxx, xxxxxx xx a xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xxxx xxxxxxxxx samci xxxxxx xxxxxxxx x xxxx; xxx xxxx xxxxxx samce jakéhokoli xxxxxx vhodného druhu xxxxx. Xxxx by xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx minimální a xxxxxx xx překročit ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx se xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, xxxxx xx xxxxxxxx. Klece xx xxxx být xxxxxxxxxx xxx, xxx xxx xxxx jejich xxxxxx minimalizován. Xxxxxxx xx jednoznačně identifikují. Xxxx xxxxxxxxx xxxxxx xx nechají x xxxxxxxxxxxxx podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx by xxxx xxx před xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx nebo xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by xxx použity xxxxxxx xxxxxxxxxx zkoušené chemické xxxxx, pokud údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx mít při xxxxxxxxx hladinách xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx zvážit použití xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx experimentu xx xxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly. X xxxxxxxx aplikace xxxxxxxx xxxxx xx měla xxxxxxx kontrolní xxxxxxx xxxxxxxxxx identický xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx xxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xx xxxx při xxxxxxxxxxx xxxxxxxx, x nichž xx xxxxxxxxxxx, xx xxxxxxxxx detekovatelný xxxxxx xxx xxxxxx.

Xxxxx pozitivní xxxxxxxx by xxxx xxx zvoleny tak, xxx xxx účinek xxxxxxxx, xxx aby xxx xxxxxx nevyšla xxxxx xxxxxx kódovaná xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx způsobem než xxxxxxxx látka a xxx xxx odběr x xxxxx případě xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxx xxx xxxxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx látek xx stejné xxxxxxxx xxxxx, jsou-li k xxxxxxxxx. Xxxxxxxx látek 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 C

50–07–7

200–008–6

akrylamid (monomer)

79–06–1

201–173–7

2,4,6-tris(aziridin-1-yl)-1,3,5-triazin

51–18–3

200–083–5

V xxxxxxxx každého odběru xx xxx být xxxxxxxx xxxxx u xxxxxxx xxxxxxxxx kontroly, xxxxx xx xxxxxxxxxx xxxxx rozpouštědlo xxxx xxxxxxxxx a xxxxx xxxxx podstupuje xxxxxx xxxxxx xxxx exponované xxxxxxx, pokud xxxxxx x dosavadních xxxxxxxxxxx xxxxx k dispozici xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Kromě xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx kontrolní xxxxx prokazující, že xxxxxxx rozpouštědlo/vehikulum xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 POSTUP

1.5.1 Xxxxx xxxxxx

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

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx nebo xxxxxxxxx (xx. při xxxxx xxxxxxxx nebo xxxx xxxxxxxxxx). Xxxxxxxx látky xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, xxx. xxx xxxxx x xxx xxx x rozmezí xx xxxx xxx xxxxxxxx hodin, aby xxxx xxxxxxxxx podávání xxxxxxx objemů xxxxxxxxx. Xxxx xxxxxx podávání xx měly xxx xxxxxxx zdůvodněny.

Ve xxxxxxx x xxxxxxxx dávkou xx měly xxx xx xxxxxxxx xxxxxxxxx xxx odběry. Xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx xxxx být zkoušenou xxxxxx xxxxxxxxx, provede xx jeden xxxxx xxxxx a jeden xxxxxxxx odběr přibližně 24 x 48 xxxxx xx expozici. X xxxxxxx xxxx xxx xxxxxxxx xxxxx xx měl xxx xxxxx xxxxxxxx po 24 xxxxx xxxx xx xxxxxx xxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx délky xxxxxxxxx xxxxx, xxxxx xxxx xxxxx xxxx vhodnější xxxx xxx xxxxxxx xxxxxx (6).

Xxxxx xxxxx xxx odběry xxxxxxxxx xxxx v xxxx xxxx. Například x xxxxxxx xxxxxxxxxx xxxxx, xxxxx mohou xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) xxxxxxxxxx nebo xxxxx xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx být xxxxxxxxx xxxxxxxx xxxxx (1).

Vhodnost xxxxx opakované xxxxxxxx xxxx xxx xxxxxx xxxxxx xx xxxxxxx. X xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx usmrcena 24 xxxxx (1,5násobek délky xxxxx) po poslední xxxxxxxx. Xxxxx xxxxxxx xxxxx být xxxxxxxxx xxxxx xxxxxx x xxxx době.

Před xxxxxxxxx xx xxxxxxxx intraperitoneálně xxxx vhodná xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Colcemid® xxxx xxxxxxxxx). Poté xx xx vhodné xxxx xxxxxxx x xxxxxx xxxxx. X xxxx xx tato xxxx xxxxxxxxx 3 — 5 hodin; x xxxxxx xxxxxxxx xx xxxx xxxx přibližně 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx neexistenci xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx zjištění rozsahu, xxxx xx být xxxxxxxxx xx stejné xxxxxxxxxx, se stejným xxxxxx a kmenem x xx xxxxxxxx xxxxxx xxxxxxxx, xxxxx xx použije x xxxxxx studii (7). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx odběru xxxxx, xxxx xxxx xxxxxxx xxxxx nejvyšší dávka. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx by xxxxx xxxxx vedly xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x letalitě.

Látky se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx dávka xxxx xxx xxxx xxxxxxxxxx xxxx dávka vyvolávající xx spermatogoniích xxxxxxx xxxxxx toxicity (xxxx. xxxxxxx počtu xxxxxxxxxxxxx x mitose xxxxxxxx x xxxxx a xxxxx xxxxxxxxx xxxxxxxx; xxxx xxxxxxx xx xxxxxx překročit 50 %).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x jednom dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx základě xxxxx o látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx se xxxxx xxxxxxxx xxxxx za xxxxxxxxx. Očekávaná xxxxxxxx xxxxxxx xxxx znamenat xxxxxxx použít x xxxxxxx zkoušce xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx látka xx xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx sondou xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxx sondou nebo xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, musí xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, které obvykle xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx všech úrovních xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx xxxxxxx chromozomů

Ihned xx xxxxxxxx xx x xxxxxxx xxxx xxxx xxxxxx xxxxx xxxxxxx xxxxxxxx, hypotonizuje xx x fixuje. Xxxx xx xxxxxx xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx mělo být xxxxxxxxxxx xxxxxxx 100 xxxxx x xxxxx xxxxxxxxxxxx xxxxxxxx (xx. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Xxxxx xxxxx xxx snížit, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Všechny xxxxxxxxx včetně xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx měly xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx nebo xxxxxx xxxxxxxxxx x xxxxx xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx pro jednotlivá xxxxxxx by xxxx xxx zpracovány xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx xxxxx xxxxx xx měl xxx xxxxxxxxxx xxxxx buněk xx strukturními chromozomovými xxxxxxxxx a počet xxxxxxxxxxxxxx xxxxxxx na xxxxx. Pro exponované x xxxxxxxxx xxxxxxx xx xxxx být xxxxxxx xxxxx xxxx xxxxxxxxxxxx chromozomových xxxxxxx x xxxxxx počtem x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx obecně xx xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, xxx by xxx xxx xxxxxxxxx xxxxxxx cytotoxických účinků xxxx xxxx cytotoxicity xxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx x xxxxxx sloužících jako xxxxxxxxx kontrola xxxxx xxxxxxxxxxxxx v xxxxxx xxxxxxxx x xxxxx x xxxxx meiotické xxxxxxxx, x xx x xxxxxxxx xxxxxx 100 dělících xx xxxxx xx jedno xxxxx. Pokud xx xxxxxxxxx pouze xxxxxx, xxxxxxx x 1000 xxxxxxx xx zvíře xx xxx být xxxxxxxx xxxxxxxxx xxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx xx xxxxx xxxx xxxxx nárůst xxxxx buněk s xxxxxxxxx xxx skupinu x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx dalším zkoušením, xxxxxxx x úpravami xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor údajů xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx experiment opakován.

Pozitivní xxxxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx xx xxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x germinálních xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx neindukuje x xxxxxxxxxxxx buňkách xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx musí obsahovat xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

- rozpustnost x stálost zkoušené xxxxx v rozpouštědle/vehikulu, xx-xx známa.

Testovací xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx x stáří xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

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

Zkušební podmínky:

- xxxxx ze studie xxx xxxxxxxx rozsahu, xxxxx xxxx xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- zdůvodnění xxx xxxxxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx krmiva x xxxx,

- podrobný xxxxx xxxxxxx expozice x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxxxx, xxxx koncentrace a xxxxx xxxxxxxx,

- metody xxxxxxxx preparátů,

- xxxxxxxx xxxxxxxxx aberací,

- počet xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxxxxx index,

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

- xxx a xxxxx xxxxxxx xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- xxxxxxx počet xxxxxxx xx xxxxxxx,

- xxxxx buněk s xxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx na dávce,

- xxxxxxxx statistické xxxxxxx,

- xxxxx o souběžné xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx odchylkami,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- změny xxxxxxx, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Potential xx Xxxxx Xxxxxxxxxxxxx of Xxxxxxxx Xxxxxxxx Related xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Genetic Xxxxxxxxxx xx Xxxxxxxxxxxxx Xxxxxxxxx, Part X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Xxxxxxx, X., Xxxxxxxxx, X. (xxx) Xxxx, Xxx Xxxx, 477-484.

2) Xxxxx, X. X., (1984), Xxxxxxxxxxx xxxxx xx Mammals, xx: Mutagenicity Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, (xx.) S. Xxxxxx, X. X. Xxxxx, XXX Press, Xxxxxx, Xxxxxxxxxx XX, 275-306.

3) Xxxxx, X. X., Xxxxxxx, X., Ford, X. E. (1964), Xx Xxx-xxxxxx Xxxxxx xxx Xxxxxxx Xxxxxxxxxxxx xxxx Xxxxxxxxx Xxxxxx, Xxxxxxxxxxxx Cell Xxxxxxxx, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, A., Xxxxxxxxx, X. X., Henderson, X. (1990), In xxxx Cytogenetic Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx. Xxxxxx. Xxxx I xxxxxxx, Cambridge Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, I. X., Xxxxxx M. X., Xxxxxxx, J., Favor, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Shibuya, X., Xxxxxx X. (1994), International Xxxxxxxx xx Xxxxxxxxxxxxxxx of Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Xxxxxx of xxx Xxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.

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

8) Xxxxxx, D. X., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, G. X., Clarc, G., Xxxxxxxx, X., Richold, X., Xxxxxxxx, X. X., Xxxxxx X. X. X. (1989), Xxxxxxxxxxx Analysis of Xx vivo Cytogenetic Xxxxxx, in: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Subcommittee on Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Cambridge University Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

"X.39 ZKOUŠKA XX XXXXXXXXXXXX SYNTÉZU XXX (XXX) V XXXXXXXXX XXXXXXX SAVCŮ XX VIVO

1. XXXXXX

Xxxx xxxxxx je xxxxxxxx xxxxxx XXXX XX 486 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx XXX (XXX) x xxxxxxxxx buňkách savců xx xxxx (1997).

1.1 XXXX

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

Xxxx xxxxxxx xx vivo xxxxxxxxx metodu vyšetření xxxxxxxxxxxxx účinků xxxxxxxxxx xxxxx x játrech. Xxxxxxxxxxx jev xx xxxxxxxxxx xxxxxxxxx XXX x xxxxxxxx reparace x xxxxxxxxx xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx místem, xxx xxxx xxxxxxxxxxx sloučeniny xxxxxxxxxxxxxx. Jsou tedy xxxxxxx xxxxxx pro xxxxxxxxx míry xxxxxxxxx XXX in xxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, xx xx xxxxxxxx látka nedostane xx xxxxxx tkáně, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx XXX (XXX) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxxxxxxxxxx xxxxxxxxx inkorporace xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx xxxxxxx xx XXX xx xxxx xx xxxxxxxxxx xxxxxxxxx xxxxx xxxxxxx. Xxxx xxxxx xxx játra xxxxx xxx xxxxxx xxxxxxx, xxxxxx xxxx xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx XXX závisí xx počtu xxxx XXX xxxxxxxxxxx a xxxxxxxxxxx v xxxxx xxxxxxxxx. Zkouška na XXX je xxxx xxxxxx xxxxxxx pro xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx repair") (20 xx 30 xxxx) xxxxxxxxxxxx látkou. Xxxxxx xxxxxx ("xxxxx-xxxxx xxxxxx") (xxxxx xx tři xxxx) jsou naproti xxxx detekovány x xxxxxx menší xxxxxxxxxx. Xxxxx xxxx důsledkem xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxxxx lézí XXX xxxxx x xxxxxxxxxx xxxxxxxxx. Xxxxxx odpovědi XXX neposkytuje xxxxxx xxxxxxxxx x věrnosti xxxxxxxxxxx procesů. Xxxxx xx možné, xx xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx reparací. Xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxx, xxxxx xxxx xxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxx, xx vyvážen xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxx, xxxxx xx vyšetřován x xxxxx genomu.

Viz xxxx xxxxxx úvod, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : čistý xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX), xxxxx xxx xxxxxxxxxx xxxxxxx stanovená xxxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxx počet xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (NNG) : xxxxxxxxxxxxx míra XXX xxxxxxxx xxxxx v xxxxxxxxxxxxxxxxx zkoušce xx XXX, vypočtená odečtením xxxxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (XX) xxxxxxxxxxxxxx xxxxxx xx xxxxx zrn xxxxxxxxxxxxxx buněčným xxxxxx (XX): XXX = XX — XX. Xxxxxxx XXX xx xxxxxxx xxx xxxxxxxxxx xxxxx, xxxx xxxxxxxx xxx buňky x xxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxx.

Xxxxxxxxxxx syntéza XXX (UDS) : Xxxxxxx xxxxxxxx DNA xx vyštěpení a xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xx XXX x jaterních xxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx. Zkouška xx obvykle založena xx inkorporaci 3H-TdR xx DNA jaterních xxxxx, kde xx xxxx xxxxxxx buněk x X-xxxx buněčného xxxxx. Inkorporace 3X-XxX xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx xxxx xxx xxxxxxx na xxxx X-xxxx xxxxx jako xxxx. xxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 POPIS XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xx používán xxxxxx, ačkoli lze xxxxxx xxxxxxxx vhodný xxxx savce. Xxxx xx xxx xxxxxxx xxxxx xxxxxxxxx laboratorní xxxxx mladých xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx by xxxx xxx odchylka v xxxxxxxxx zvířat minimální x neměla by xxxxxxxxx ± 20 % střední xxxxxxx xxxxxxxxx xxx xxx xxxxxxx.

1.4.1.2 Podmínky xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx zvířat

Zdravá pohlavně xxxxxxx xxxxxxx xx xxxxxxxx výběrem rozdělí xx kontrolní xxxxxxx x xxxxxxx, která xx xxxxxxxx. Klece xx xxxx xxx xxxxxxxxxx xxx, aby xxx vliv jejich xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx x před započetím xxxxxx xx 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 látky mohou xxx podávány xxxxx xxxx xxxxx xxx xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx neprokazují možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx vyloučeno xxxxxxxxx, že reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Doporučuje se xxxxxxxx xxxxxx xxxxxxx xxxxx možno vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxx pozitivní x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X výjimkou xxxxxxxx xxxxxxxx látky xx měla zvířata xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxx ve xxxxxxxxx, x xxxxx xxxxx x expozici.

Pozitivními xxxxxxxxxx xx xxxx xxx xxxxx, x nichž xx xxxxx, že xxxxxx xxxxxxxx v xxxxxxxxxxx expozičních koncentracích xxxx x nárůstu XXX detekovatelnému xxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx x dávkách xxxxxxxxxxxx xxxxxx xxxxxxx (4). Xxxxx mohou xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx preparátu. Xxxxxxxx xxxxx xxx pozitivní xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

Xxxxx doby xxxxxx (2 až 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx doby xxxxxx (12 xx 16 h)

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

53–96–3

200–188–6

Xxxxx xxx použity xxxx xxxx xxxxx xxx xxxxxxxxx xxxxxxxx. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxx xxxxx xxxxxxxx, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx xxxxxx

Xxx xx xxx použit xxxxxxxxxx xxxxx xxxxxx, xxx xxxx zohledněno xxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx. Xxxxx xxxxxxx xx se xxxx xxxxxxx alespoň xx xxx analyzovatelných xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx dostatečné xxxxxxxxx xxxxx, xx xxx xxxxxxxxx x pozitivní xxxxxxxxx xxxxxxx nezbytné xxxxx jedno až xxx zvířata.

Jestliže xxxx x době studie x dispozici xxxxx xx xxxxxx xx xxxxxxx xxxxxx a xx xxxxxxx stejného xxxxxxx expozice, jež xxxxxxxxx, xx neexistuje xxxx pohlavími rozdíl x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, nejlépe xxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, jako xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx xx xxx xxxxxxx provedena xx xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx expozice

Zkoušené xxxxx xxxx xxxxxxxxx podávány xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx xxxxxxxxxx xxxxxxxx xx používají xxxxxxx dvě xxxxxx xxxxx. Xxxxxxxx xxxxx xx definována jako xxxxx vyvolávající xxxxxx xxxxxx toxicity, xx xxxxx dávky by xxxxx xxxxx očekávání xxx stejném xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx xx xxxx xxx xxxxxxxxx 50 % až 25 % xxxxx xxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx aktivitou xxx xxxxxxx netoxických dávkách (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x xxxx by xxx hodnoceny xxxxxx xx případu. Provádí-li xx xxxxx neexistenci xxxxxxxx xxxxxxxxxx údajů xxxxxx xxx xxxxxxxx xxxxxxx, měla xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, xxxxxxxx a xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí x hlavní xxxxxx.

Xxxxxxxx xxxxx může xxx xxxxxxxxxx také jako xxxxx vyvolávající známky xxxxxxxx v xxxxxxx (xxxx. xxxxxxxxxx xxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x jednou dávkou x xxxxxxx 2000 xx/xx tělesné hmotnosti xxxxxxx jednorázově xxxx xx xxxx xxxxxxx x xxxxxx dni xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx a xxxx-xx na základě xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, očekávána xxxxxxxxxxxx, xxxxxx xxx úplná xxxxxx xxxxxxxx. Očekávaná xxxxxxxx xxxxxxx xxxx xxxxxxxx potřebu xxxxxx x xxxxxxx xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx látka xx obvykle xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx xxxx xxxxx, xxx-xx xx zdůvodnit. Xxxxxxxx xxxxxxxxxxxxxxxxx se xxxx xxxxxxxxxxxx, xxxxx xx xxxxx mohla xxx xxxxxxxxxx xxxxxxxx xxxxx přímo x xxxxxx prostřednictvím oběhového xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx je xxxxxxx xxxxx, musí být xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx všech úrovních xxxxx.

1.5.6 Příprava jaterních xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx x exponovaných xxxxxx xxxxxxxxx 12 xx 16 hodin xx podání xxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (xxxxxx xxx xx čtyři hodiny xx xxxxxxxx) xx xxxxxxxx, xxxx-xx xx 12 xx 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx xxxxxxx xxxx xxxx odběru, xxxx-xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx údajů.

Krátkodobé kultury xxxxxxxxx xxxxx xxxxx xx zpravidla zakládají xxxxxxx xxxxx xxxxxxxxxxx xx situ x xxxxxx xx, xxx xx xxxxxxx xxxxxxxxxxx xxxxxxx buňky zachytily xx xxxxxxx povrchu. Xxxxxxx xxxxx z xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxx životaschopnost (5) xxxxxxx 50 %.

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx jaterní buňky xxxxx xx obvykle xxxxxxx dobu, xxxx. xxx xx xxx xxxxx, xxxxxxxx x xxxxxx obsahujícím 3X-XxX. Xx xxxxx xxxxxxxxx xxxx xx xxxx xxx xxxxxx x xxxxx xxxxxxxxxx a xxxxx xxxx mohou xxx xxxxxxxxxx s xxxxxx obsahujícím xxxxxxxx xxxxxxxxxxx xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx xx xxxx xxxxxxx, xxxxxx x xxxxxx. Při xxxxx xxxxxxxxx xxxx nemusí xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Preparáty se xxxxxx xx xxxxxxxxxxxxxxxxx xxxxxx, exponují xx x xxxxx (xxxx. x chladu 7 xx 14 xxx), xxxxxxxx xx, obarví x spočítají xx xxxxxxxxxx xxxx stříbra. X xxxxxxx xxxxxxx xx xxxxxxxx xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxx počet xxxxxxxxxxxx normálních buněk, xxx xxxx xxxxxxxxx XXX xxxxxxxxx xxxxxxx. Xxxxxxxxx xx pod xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxx xxxxxxxxxxxx (xxxx. na pyknosu, xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx).

Xxxx počítáním xxx by xxxx xxx xxxxxxxxx kódovány. Xxxxxxxxx xx xxxxxxxxx 100 xxxxx xx xxxxx zvíře xxxxxxx xx xxxx preparátů; xxxxxxxxx xxxx než 100 xxxxx/xxxxx xx xxxx být zdůvodněno. Xxx počítání xxx xx xxxxx v X-xxxx xxxxxxxxxxx, xxx xxxxx xxxxx x X-xxxx xxxx xxx xxxxxxxxxx.

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

Xxxxx xxxxx xx xxxxxxx x xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (xx) x z prŭměrného xxxxx zrn x xxxxxxxxxxxxxxxxx xxxxxxxxx (cg) xxxxxxxxxxxxxx jádrŭm. jako xxxxxxx cg se xxxxxxx xxx xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx oblast xxxxxxxxxx, xxxx xxŭxxxxx xxxxxxx xxxx až xxx xxxxxxx vybraných oblastí x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxx. po xxxxxxxxxxxxx zdŮvodnění mohou xxx xxxxxxx x xxxx postupy stanovení xxxxx buněk (např. xxxxxxxx celých buněk) (6).

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx by xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx x xxxxxxx. Xxxxx xx xxxx být xxxx xxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX xx hodnoty XX by měl xxx vypočten xxx xxxxxx xxxxx, xxx xxxxx xxxxx x xxx xxxxxx dávku x xxx xxxxx xxxxx xxx odpovídajících xxxxxxxx jádrům (NNG). Xxxxxxxx jsou počítány "xxxxxxxxxx" xxxxx, xxxx xx xxx xxxxxxxx xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx odůvodněna x xxxxxxxx na xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x negativních xxxxxxxxxx. Xxxxxxxxx výsledky mohou xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx xxx xxxxxxx, xxxx xx xxx xxxxxxxxxxx testy xxxxxxx x xxxxxxxxxx xxxx xxxxxxxxxx studie.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx příklady kritérií xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx

x)

xxxxxxx XXX leží xxx xxxxxxxx xxxxxx, která xx xxxxxxxxxx xx xxxxxxx dosavadních údajů xxxxxxxxxx;

xxxx

xx)

xxxxxxx NNG xx xxxxxxxx xxxxx než xxxxxxx xxx xxxxxxxxx xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx NNG xxxx xx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxx xx;

xxxx

xx)

xxxxxxx NNG xxxx xxxxxxxx xxxxx než xxxxxxx xxx souběžnou xxxxxxxx.

Xxxx xx být xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx. xxxx xx xxx vzaty x xxxxx xxxxxxxxx, xxxx jsou variabilita xxxxxx, xxxxx dávky x xxxxxxxx a xxxxxxxxxxxx. Při hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx.

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na XXX v jaterních xxxxxxx savců xx xxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx buňkách xxxxx xx xxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx XXX in xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx poškození XXX, xxxxx xxx xxxxxxxxx xxxxx xxxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s jakou xx zkoušená xxxxx xxxxxxx xx krevního xxxxx popř. xx xxxxxx xxxxx (např. xxxxxxxxx toxicita).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx druh/kmen,

- počet, xxxxx a xxxxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

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

Zkušební xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxxxxxx podávání,

- xxxxxxxxx xxxxxx xxxxxxx, zda xx xxxxxxxx látka xxxxxxx xx xxxxxxxx xxxxx nebo do xxxxxx tkáně,

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

- podrobné xxxxx x xxxxxxx krmiva x vody,

- xxxxxxxx xxxxx rozvrhu expozice x odběru,

- metody xxxxxxxxx toxicity,

- xxxxxx xxxxxxxx x kultivace xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx technika,

- xxxxx xxxxxxxxx x počet xxxxxxxxxxx xxxxx,

- kritéria xxxxxxxxx,

- xxxxxxxx klasifikace xxxxxx na pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxx možnosti xxxxxxxxx odpovědi na xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxx,

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

- xxxxxxxxx xxxxx o xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx x rozmezími, xxxxxxxxx hodnotami x xxxxxxxxxxxx xxxxxxxxxx,

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

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

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, J. Xxxxxxx, X. X., Burlinson, X., Penman, M. X. (1985), Xx Xxxxxxxxxx of xxx Xx xxxx Xxx. Xxxxxxxxxx XXX Xxxxxx Xxxxx, Mutatation Res., 156, 1-18.

2) Xxxxxxxxxxx, X. E., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxx, D., Mirsalis, X., Xxxxxx, X., Xxxxxxxx, X. (1987), X Xxxxxxxx xxx Xxxxx xxx the Xx vivo Xxx Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 123-133.

3) Xxxxxxxx, X. X., Waters, X., Ashby, X., Xxxxxxx, X. A., Xxxxxxxxx, X., Xxxxxxx, X. X., Xxxx, X. X., Mitchell, X. xx X. (1993), Xx xxxx Xxx Xxxxx XXX Xxxxx, xx: Xxxxxxxx X. J., Xxx X., (eds), Supplementary Xxxxxxxxxxxx Tests: XXXX Xxxxxxxxxxx Procedures. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx. Xxxx XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Xxxx, X. X., Andrac, X., Brambilla. G., Xxxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, T., XxXxxxx, C. X., Xxxx, H. (1993), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx xx XXX Xxxxx In vitro xxx Xx xxxx, Xxxxx. Xxx., 312, 263-285.

5) Xxxxx, R., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, C. (1993), Xxxxxxxxxx of xxx Relation Xxxxxxx xxx Initial Xxxxxxxxx xxx the Attachment xx Freshly Xxxxxxxx Xxx Hepatocytes Xxxx xxx the Xx xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (UDS), Xxxxxxxxxx Xxx., 291, 21-27.

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


XXXXXXX 5

XXXXXX XXXXXXXXX XX KLASIFIKACI A XXXXXXXXXX XXXXXXXXXXXX XXXXX X XXXXXXXXX

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


XXXXXXX 6

"

PŘÍLOHA IX

ČÁST X

xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx proti xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 xxxx. 1 xxxx. x) xxxx xxxxxxxx, xxxx xxx xxxxx x xxxxxxxxx xxxxxx xxxxxxxxxx xxxxx, s xxxxx xx xxxxxxx xxxxxx xxx xxxxxxxxxx (Xn; X 65) x xxxxx jsou xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx xx xxx xx xxxxx xxxxxxxx xxxx x xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx, xxxxxxxx uzávěry odolnými xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx uzavíratelné obaly

Uzávěry xxxxxx xxxxx otevření xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx požadavky xxxxx XXX 8317 (xxxxxx xx xxx 1. xxxxxxxx 1989) "Xxxxx xxxxxx xxxxx — Xxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxx xxxxxxxx" xxxxxxxx Xxxxxxxxxxx xxxxxxxxxx pro normalizaci (XXX).

2. Xxxxxxxxx xxxxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx xx opakovaně neuzavíratelných xxxxxxx xxxx splňovat xxxxxxxxx xxxxx XXX XX 862 (xxxxxx x března 1997) "Xxxxx — Xxxxx xxxxxx xxxxx — Xxxxxxxxx a zkušební xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx obaly xxxxxx xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Evropským xxxxxxx xxx normalizaci (CEN).

3. Xxxxxxxx

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

2. Xxxxxxxxxx xxxxxxx

Xx-xx xxxxxx, xx obal xx xxxxxxxxxx xxxxxxxx xxx xxxx, xxxxx se xxxxxxx xxxxxx x xxxxxx xxx xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx provedena.

Ve xxxxx xxxxxxxxx případech a xxxxx existují oprávněné xxxxxx x xxxxxxxx x bezpečnosti xxxxxxx xxx xxxx, xxxx xxxxxxxxxxxx orgán požadovat, xxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx xx xxx předložila xxxxxxxxxx vydaný laboratoří xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx xxxxxx, xx jej xxxx xxxxxxxx zkoušet xxxxx xxxx uvedených norem XXX x XXX,

xxxx

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

XXXX X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx výstrah

Technické specifikace xxx xxxxxxxxxx výstrahy xxxx xxx v xxxxxxx x xxxxxx XX XXX 11683 (xxxxxx x roku 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Xxxxxxxxx".

"