Animace načítání

Stránka se připravuje...


Na co čekáte? Nečekejte už ani minutu.
Získejte přístup na tento text ještě dnes. Kontaktujte nás a my Vám obratem uděláme nabídku pro Vás přímo na míru.

Xxxxxxxx Xxxxxx 2000/32/XX

xx xxx 19. května 2000,

xxxxxx xx po xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx směrnice Xxxx 67/548/XXX x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení x xxxxxxxxxx nebezpečných xxxxx [1]

(Text s xxxxxxxx xxx XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Xxxxxxx x xxxxxxxx Xxxxxxxxxx společenství,

s xxxxxxx na xxxxxxxx Xxxx 67/548/EHS ze xxx 27. xxxxxx 1967 x sbližování xxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx látek [2], naposledy xxxxxxxxxx xxxxxxxx Evropského xxxxxxxxxx x Rady 1999/33/XX [3], x xxxxxxx xx xxxxxx 28 xxxxxxx směrnice,

vzhledem x xxxxx xxxxxxx:

(1) Xxxxxxx X směrnice 67/548/XXX xxxxxxxx xxxxxx nebezpečných xxxxx společně x xxxxxxxxxx xxxxx x xxxxxxxxxxx a xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx a xxxxxxxxx xxxxxxxx ukazují, xx xx měl xxx xxxxxx nebezpečných látek x uvedené příloze xxxxxxxxxxx. Některé jazykové xxxxx xxxxxxxx xxxxxxxx xxxxxx určitých xxxxxx xxxxxxxxx x tabulky X x xxxxxxx X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/EHS obsahuje xxxxxx xxx udávajících xxxxxx zvláštních xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx x xxxxxxxxx. Xxxxxxx IV xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx x bezpečnostními xxxxxx xxxxxxxxxx se xxxxxxxxxxxx xxxxx a xxxxxxxxx. Příloha VI xxxxxxxx 67/548/XXX xxxxxxxx xxxxx ke xxxxxxxxxxx x x xxxxxxxxxx xxxxxxxxxxxx látek x xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx směrnice vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, XX x VI.

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

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

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

XXXXXXX TUTO SMĚRNICI:

Xxxxxx 1

Xxxxxxxx 67/548/EHS xx xxxx xxxxx:

1. Xxxxxxx I xx xxxx takto:

a) xxxxxxxxxxxx xxxxxxxx x předmluvě xx xxxxxxxxx poznámkou X x příloze 1X této xxxxxxxx;

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

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

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

2. Xxxxxxxxxxxx xxxx x xxxxxxx XXX xx xxxxxxxxx standardní xxxxx označující specifickou xxxxxxxxxx v xxxxxxx 2 xxxx směrnice.

3. Xxxxxxx XX xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx x příloze XX xx xxxxxxxxx xxxxxxxxxxxx xxxxxx pro xxxxxxxx xxxxxxxxx x xxxxxxx 3A xxxx xxxxxxxx;

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

4. Xxxx X xxxxxxx V xx xxxx takto:

a) xxxxxxxx X.10 se xxxxxxxxx xxxxxx v xxxxxxx 4X této xxxxxxxx;

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

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

x) kapitoly X.13 a X.14 xx nahrazují xxxxxx x příloze 4D xxxx směrnice;

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

x) xxxxxxxx B.23 se xxxxxxxxx xxxxxx x xxxxxxx 4X této xxxxxxxx. Xxxxx xxxxxxxx X.23 xx xxxxxxxxxxx xx mění xxxxxxxxxxxxx xxxxxxxx;

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

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

6. Xxxxxxxxxxxx xxxxx v xxxxxxx XX xx nahrazují xxxxx v příloze 5 xxxx xxxxxxxx.

7. Xxxxxxx IX xx xxxx xxxxxxxx xxxxxxxx x xxxxxxx 6 xxxx xxxxxxxx.

Xxxxxx 2

1. Xxxxxxx xxxxx xxxxxx x xxxxxxxx xxxxxx x xxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxxx xxxxxxx x touto směrnicí xxxxxxxxxx do 1. xxxxxx 2001. Xxxxxxxxxx x xxxx uvědomí Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx xx xxxx směrnici nebo xxxx takový xxxxx xxx učiněn xxx xxxxxx úředním xxxxxxxxx. Xxxxxx xxxxxx si xxxxxxx xxxxxxx xxxxx.

2. Xxxxxxx xxxxx xxxxx Xxxxxx xxxxx hlavních xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx xxxxxxx x oblasti xxxxxxxxxx xxxx směrnice, x xxxxxxxxxx xxxxxxx mezi xxxxxxxx x přijatými xxxxxxxxxxxxxx xxxxxxxxxxxx.

Článek 3

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

Článek 4

Xxxx xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.

V Xxxxxxx dne 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Xxxxxx


[1] Xxxxxxx xx xxxxxxxxxxxx po xxxxxxx xxxxx.

[2] Úř. xxxx. 196, 16.8.1967, s. 1.

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


XXXXXXX 1X

XXXXXXXXX X XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx se identifikace, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx xx českého xxxxx)


XXXXXXX 1B

"TABULKA 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 1X

Xxxxxxxx číslo

Chemický xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x xxxxxxxxxx

006–011–00–7

xxxxxxxx (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

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

Xx; X X: 22–40–50 S: (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 X; X34 X43 X; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

Karc. xxx. 3; X40 Muta. xxx. 3; X40 Xx; R22–48/22 X; 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- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

204–043–8

114–26–1

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

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

204–123–2

116–06–3

X+; X26/28 X; X24 X; X50–53

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

006–018–00–5

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

di-allát (XXX) S-(2,3-dichlorallyl)-N,N-diisopropylthiokarbamát

218–961–1

2303–16–4

Karc. xxx. 3; R40 Xn; X22 N; X50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xn; X22 X43 N; X50–53

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

006–023–00–2

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

217–991–2

2032–65–7

X; X25 X; R50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; X22 Xi; X38 X; X51–53

Xx; X X: 22–38–51/53 X: (2-)13-61

006–026–00–9

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

216–353–0

1563–66–2

X+; X26/28 X; X50–53

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

006–028–00-X

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

213–546–1

973–21–7

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

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

230–253–4

6988–21–2

X; X25 X; X51–53

X; N R: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

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

243–433–2

19937–59–8

X; X50–53

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

006–034–00–2

xxxxxxx (ISO) 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 pyrimidin-4-yl-N,N-dimethylkarbamát

245–430–1

23103–98–2

T; X25 N; X50–53

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

006–037–00–9

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

220–113–0

2631–37–0

X; X25 X; X50–53

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

006–038–00–4

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

E

202–388–9

95–06–7

Karc. kat. 2; X45 Xx; X22 X; X50–53

X; X X: 45–22–50/53 X: 53–45–60–61

006–039–00-X

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

218–962–7

2303–17–5

Xx; R22–48/22 X43 X; X50–53

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

006–042–00–6

xxxxxxx (XXX) 3-(4-chlorfenyl)-1,1-dimethylmočovina

205–766–1

150–68–5

Karc. xxx. 3; X40 Xx; R22 X; X50–53

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

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

006–045–00–2

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

240–815–0

16752–77–5

X+; X28 X; X50–53

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

006–046–00–8

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

245–216–8

22781–23–3

X; X23/25 Xn; X21 N; X50–53

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

006–047–00–3

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

8065–36–9

X; X24/25 X; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xx; R22 X; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

006–050–00–X

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

4482–55–7

Xi; X38 X; X50–53

Xx; N X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (ISO) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; X28 Xx; X21 N; X50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; R22 X; X51–53

Xx; X R: 22–51/53 S: (2-)24-61

006–060–00–4

xxxxxxxxxxx (XXX) 2-methyl-4,4-dioxo-5,6-dihydro-4λ4-1,4-oxathiin-3-karboxanilid

226–066–2

5259–88–1

Xn; R22 X52–53

Xx X:22–52/53 X: (2-)61

006–069–00–3

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

245–740–7

23564–05–8

Xxxx. xxx. 3; X40 X; X50–53

Xx; X X: 40–50/53 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; X40 N; X50–53

Xx; X X: 40–50/53 S: (2-)36/37–60–61

006–088–00–7

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

82560–54–1

X; X23/25 X; R50–53

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

007–012–00–5

N,N-dimethylhydrazin 1,1-xxxxxxxxxxxxxxxx

X

200–316–0

57–14–7

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

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

007–013–00–0

X,X-xxxxxxxxxxxxxxxx 1,2-dimethylhydrazin

E

540–73–8

Karc. xxx. 2; R45 X; X23/24/25 X; X51–53

X; N X: 45–23/24/25–51/53 X: 53–45–61

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

009–003–00–1

xxxxxxxx fluorovodíková … %

X

231–634–8

7664–39–3

X+; X26/27/28 X; X35

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

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

015–039–00–9

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

201–676–1

86–50–0

X+; X26/28 X; R24 R43 X; X50–53

X+; N 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; R23–48/25 Xx; X21/22 X; X50–53

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

015–056–00–1

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

220–147–6

2642–71–9

X+; R28 X; X24 X; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; X23/25 Xn; X21 X; R50–53

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

016–013–00-X

xxxxxxx sirnatý

234–129–0

10545–99–0

R14 X; X34 X; X50

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

X ≥ 10 %: X; R34 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. kat. 2; X45 Xxxx. xxx. 3; X40 X+; R26 X; X25 X; R34 X43

X+ R: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; X22 N; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

016–071–00–6

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

410–130–3

136248–03–8

R43

Xi R: 43 X: (2-)22–24–37

022–001–00–5

xxxxxxx xxxxxxxxxx

231–441–9

7550–45–0

X14 X; R34

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

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

030–004–00–8

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

050–002–00–0

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

236–049–1

13121–70–5

Xx; X20/21/22 N; R50–53

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

050–012–00–5

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

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

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

Xx; R20/21/22 X; R50–53

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

X ≥ 1 %: Xn; X20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

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

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

082–009–00–X

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

215–693–7

1344–37–2

Xxxx. xxx. 3; X40 Repr. xxx. 1; R61 Xxxx. xxx. 3; X62 X33 N; X50–53

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

1

082–010–00–5

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

235–759–9

12656–85–8

Karc. xxx. 3; R40 Repr. xxx. 1; X61 Xxxx. kat. 3; X62 R33 X; X50–53

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

1

601–024–00-X

xxxxx [1] propylbenzen [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

X10 Xx; R65 Xx; X37 N; X51–53

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

4

601–032–00–3

xxxxx[x]xxxxx xxxxx[xxx]xxxxxxx

200–028–5

50–32–8

Xxxx. xxx.2; X45 Xxxx. xxx. 2; R46 Xxxx. xxx. 2; X60–61 X; X50–53

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

601–034–00–4

benzo[e]acefenanthrylen

205–911–9

205–99–2

Karc. xxx.2; X45 X; X50–53

X; X R: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-xxxxxxxxxxxxx p-dichlorbenzen

203–400–5

106–46–7

Xi; X36 X; X50–53

Xx; 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; X34

X X: 10-34 X: (1/2-)7–26–45

603–076–00–9

but-2-yn-1,4-diol

203–788–6

110–65–6

T; X23/25 Xx; X21–48/22 X; X34

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

C ≥ 50 %: X; R21–23/25–34–48/22 25 % ≤ C &xx; 50 %: X; R21–23/25–36/38–48/22 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; R8 Xx; R22 Xi; X36

X; Xx X: 8–22–36 X: (2-)26

603–093–00–1

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

402–410–9

87818–31–3

Xx; X20 X; R51–53

Xn; X R: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; X36 X52–53

Xx X:36–52/53 X: (2-)26-61

603–117–00–0

propan-2-ol xxxxxxxxxxxxxxxx isopropanol

200–661–7

67–63–0

F; X11 Xx; R36 X67

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

604–020–00–6

bifenyl-2-ol 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (XXX)

201–993–5

90–43–7

Xx; X36/37/38 X; X50

Xx; X X: 36/37/38–50 X: (2-)22-61

604–021–00–1

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

205–055–6

132–27–4

Xx; R22 Xi; X37/38–41 X; X50

Xx; X X: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

4,4'-(4-methylpentan-2,2-diyl)difenol 2,2-xxx(4-xxxxxxxxxxxx)-4-xxxxxxxxxxxx

401–720–1

6807–17–6

Xxxx. xxx. 2; R60 Xx; X36 X; X50–53

X; X R: 60–36–50/53 S: 53–45–60–61

604–041–00–0

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

256–634–5 [1] 263–560–7 [2]

50594–66–6 [1] 62476–59–9 [2]

Xx; X22 Xx; X38–41 X; X50–53

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

604–043–00–1

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

203–083–3

103–16–2

Xi; X36 X43

Xx X: 36-43 S: (2-)24/25–26–37

604–044–00–7

mechinol 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; R22 Xx; X36 X43

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

605–016–00–7

xxxxxxx… % xxxxxxxxx… %

X

203–474–9

107–22–2

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

Xx X: 20–36/38–40–43 S: (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; N X: 25–48/25–50/53 X: (1/2-)37–45–60–61

606–018–00–0

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

204–210–5

117–80–6

Xx; X22 Xx; R36/38 X; X50–53

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

606–019–00–6

xxxxxxxxxx (ISO) 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; X40 X; 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

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

244–209–7

21087–64–9

Xx; X22 N; 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 X; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

606–036–00–9

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

219–455–3

2439–01–2

Xxxx. xxx. 3; R62 Xx; X20/21/22–48/22 Xx; X36 R43 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-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-on

256–103–8

43121–43–3

Xn; X22 N; X51–53

Xx; X X: 22–51/53 X: (2-)61

606–044–00–2

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

403–150–9

954–16–5

Xx; X22 Xx; X36 X; R50–53

Xn; X X: 22–36–50/53 S: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; X22 Xi; X41 X52–53

Xx; X X: 22–41–52/53 S: (2-)26-61

607–057–00–6

xxxxxxxxx (XXX) 3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxykumarin3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxy-2 X-xxxxxxx-2-xx

201–378–1

81–82–3

Xx; X48/22 X52–53

Xx X:48/22–52/53 S: (2-)37-61

607–058–00–1

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

204–195–5

117–52–2

X; R25–48/25 X52–53

X X:25–48/25–52/53 X: (1/2-)37–45–61

607–079–00–6

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

4234–79–1

X; R24 Xn; X22 X; X51–53

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

607–097–00–4

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

209–008–0

552–30–7

Xi; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx xxxxxxxx kyselina

203–677–2

109–52–4

C; X34 X52–53

X X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xx; X22 X; X51–53

Xx; 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; X36/38 R52–53

Xi X:36/38–52/53 X: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xx; R22 Xx; X38 X; X50–53

Xx; X R: 22–38–50/53 X: (2-)37–60–61

607–158–00–5

sodná xxx chloroctové xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; X25 Xx; X38 N; X50

X; X R: 25–38–50 X: (1/2-)22–37–45–61

607–159–00–0

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

208–110–2

510–15–6

Xx; X22 X; R50–53

Xn; X R: 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 H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propionyl}oxy)poly(oxyethylen)

400–830–7

R43 X; R51–53

Xi; N X: 43–51/53 X: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24/37–61

607–209–00–1

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

403–030–6

Xx; X22 X43 X; R50–53

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

607–213–00–3

ethyl-3,3-bis(terc-pentylperoxy)butanoát

403–320–2

67567–23–1

E; X2 O; X7 X10 X; R51–53

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

607–217–00–5

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

403–960–2

X43 X53

Xx X: 43-53 X: (2-)24–37–61

607–243–00–7

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

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

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

X52–53

X: 52/53 S: 61

607–248–00–4

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

205–073–4

132–67–2

Xx; R22

Xn X: 22 X: (2)

607–249–00-X

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

256–032–2

42978–66–5

Xx; X36/37/38 X43 N; X51–53

Xx; N 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) Směs (1:1): (S)-[(3-fenoxyfenyl)kyanmethyl]-(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 S)-cis-3-((Z)-2-chlor-3,3,3-trifluorprop-1-en-1-yl)-2,2-dimethylcyklopropan-1-karboxylát

415–130–7

91465–08–6

T+; R26 X; X25 Xx; X21 N; R50–53

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

607–255–00–2

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

69377–81–7

R52–53

R: 52/53 X: 61

608–003–00–4

akrylonitril

D X

203–466–5

107–13–1

X; Xxx Xxxx. xxx. 2; R45 T; X23/24/25 Xx; R37/38–41 X43 X; X51–53

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

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

43

608–016–00–5

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

401–550–8

1897–41–2

X43 X; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. kat. 2; X61 X+; R28 X; R24 R44 X; R50–53

T+; X 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; X22 X; X50–53

X; N X: 45–61–22–50/53 S: 53–45–60–61

609–044–00–0

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

204–178–2

117–18–0

Xx; X22 X43 N; X50–53

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

611–008–00–4

4-xxxxxxxxxxxxxx 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-hydroxy-3-{4-[2-methoxy-4-(3-sulfonatofenylazo)fenylazo]-3-methylfenylazo}-6-(3-sulfonatoanilino)naftalen-2-sulfonát trilithný

403–650–7

117409–78–6

E; X2 X; X51–53

X; X X: 2–51/53 X: (2-)35-61

611–031–00-X

4,4'-[(4-xxxxxxxxxxxxxx-2,5-xxxx-1-xxxxxx)xxxxxxxx]xxxxxxxx-xxxxxxxxxxxx CI Xxxxx Xxx 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 o-anisidin

E

201–963–1

90–04–0

Karc. xxx. 2; X45 Xxxx. xxx. 3; X40 T; R23/24/25

T X: 45–23/24/25 S: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; X22 X; R50–53

T; X X: 45–22–50/53 X: 53–45–60–61

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

612–051–00–1

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

X

202–974–4

101–77–9

Xxxx. xxx. 2; X45 Xxxx. xxx. 3; X40 X; R39/23/24/25Xn; X48/20/21/22 X43 N; R51–53

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

612–081–00–5

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

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; R45 Xx; X22 X; X51–53

X; X X: 45–22–51/53 X: 53–45–61

612–099–00–3

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

X

202–453–1

95–80–7

Xxxx. xxx. 2; X45 X; X25 Xx; X21 Xi; X36 X43 X; X51–53

X; X X: 45–21–25–36–43–51/53 S: 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 X; X34 X43 X52–53

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

612–111–00–7

2-methyl-m-fenylendiamin2-methyl-1,3-fenylendiamin2-methylbenzen-1,3-diamin 2,6-xxxxxxxxxxxx

212–513–9

823–40–5

Xxxx. xxx. 3; X40 Xn; X21/22 X43 X; R51–53

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

612–125–00–3

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

202–442–1

95–70–5

T; X25 Xx; 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 (ISO) X-(2-xxxxx-6-xxxxxxxxxxx)-X-xxxxx-2,6-xxxxxxx-4-(xxxxxxxxxxxxxx)xxxxxx

62924–70–3

Xx; X36/38 R4 3 X; X50–53

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

612–151–00–5

xxxxxxxxxxxxx toluendiamin xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

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

T; 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; R36/37/38 X52–53

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

613–031–00–5

xxxxxxxxx xxxxxxxxxxxxxxxxxxxx xxxxxxxx trichlor-1,3,5-triazintrion 1,3,5-trichlor-1,3,5-triazin-2(1H), 4(3X), 6(5H)-trion

201–782–8

87–90–1

O; X8 Xx; X22 X31 Xx; X36/37 N; X50–53

X; Xn; N 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 R52–53

Xn X:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

Xx; X20/22 X; R41 X; X50–53

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

613–043–00–0

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

261–351–5 [1] 281–291–3 [2]

58594–72–2 [1] 83918–57–4 [2]

Xx; X20/22 Xi; X41 X; X50–53

Xx; X 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 N; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

613–091–00–2

morfamkvat-dichlorid [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; R36/37/38 X52–53

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

613–098–00–0

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

403–700–8

2687–94–7

X; X34 X; X51–53

X; N X: 34–51/53 S: (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 (ISO) 1,2,5,6-xxxxxxxxxx-4 X-xxxxxxx[3,2,1-xx]xxxxxxxx-4-xx

57369–32–1

Xx; X22 R52–53

Xn X:22–52/53 X: (2-)61

613–134–00–5

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

88671–89–0

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

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

613–137–00–1

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

242–505–0

18691–97–9

X; X50–53

X R: 50/53 S: 60-61

613–139–00–2

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

74223–64–6

X; R50–53

N X: 50/53 X: 60-61

614–001–00–4

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

200–193–3

54–11–5

T+; X27 X; X25 X; R51–53

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

614–006–00–1

xxxxxx 2,3-dimethoxystrychnidin-10-on

206–614–7

357–57–3

T+; X26/28 X52–53

X+ R:26/28–52/53 X: (1/2-)13–45–61

614–007–00–7

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

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

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

X+; X26/28 R52–53

T+ X: 26/28–52/53 S: (1/2-)13–45–61

615–006–00–4

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

X

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

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

Xxxx. xxx. 3; X40 X+; R26 Xx; X36/37/38 X42/43 X52–53

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

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

2

616–010–00–9

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

204–854–7

127–65–1

Xx; X22 R31 X; R34 R42

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

616–034–00-X

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

246–419–4

24691–76–7

R52–53

R: 52/53 X: 61

616–035–00–5

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

261–043–0

57966–95–7

Xx; X22 X43 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; X34 X; X50–53

X; X; X R: 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 % ≤ X &xx; 10 %: Xx; X36/37/38

617–006–00-X

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

201–279–3

80–43–3

O; X7 Xx; X36/38 N; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; R2 Xx; X36 X43

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

650–007–00–3

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

228–200–5

6164–98–3

Xxxx. xxx. 3; X40 Xx; R21/22 X; R50–53

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

650–008–00–9

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

227–197–8

5707–69–7

X; R25 X; X50–53

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

650–009–00–4

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

243–269–1

19750–95–9

Xxxx. xxx. 3; X40 Xx; R22 N; X50–53

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

650–033–00–5

esfenvalerát (XXX) [(X)-(3-xxxxxxxxxxx)xxxxxxxxxx]-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx (X)-3-xxxxxx-α-xxxxxxxxxx-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx

66230–04–4

X; X23/25 X43 X; X50–53

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

650–041–00–9

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 X: 60-61


XXXXXXX 1X

Xxxxxxxx číslo

Chemický xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x xxxxxxxxxx

006–090–00–8

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

408–010–0

88558–41–2

Xx; X20 Xx; X41 X52–53

Xx X: 20–41–52/53 S: (2-)22–26–39–61

014–016–00–0

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

406–490–6

N; X51–53

X X: 51/53 X: 61

015–164–00–9

xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx dihydrát

400–480–5

36669–85–9

R52–53

R:52/53 X: 61

015–165–00–4

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

404–986–7

Xi; R41 X; R50–53

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

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 X: 61

015–167–00–5

3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; X41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; X50

X X: 50 X: 61

601–051–00–7

4-fenylbut-1-en

405–980–7

768–56–9

Xi; X38 N; X51–53

Xx; X R: 38–51/53 X: (2-)37-61

602–083–00–4

xxxxxxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; R48/21/22 X64 X; R50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

X X: 52/53–59 S: 59-61

603–128–00–0

2-(fenylmethoxy)naftalen

405–490–3

613–62–7

R53

R:53 X: 61

603–129–00–6

1-xxxx-xxxxxxxxxxxx-2-xx

406–180–0

57018–52–7

X10 Xx; X41

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

603–130–00–1

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

406–325–8

Xx; R22 X52–53

Xx X:22–52/53 S: (2-)39-61

603–131–00–7

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

407–290–1

Xx; R41

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

603–132–00–2

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

408–200–3

63187–91–7

Xx; X38–41 X52–53

Xx X:38–41–52/53 S: (2-)26–37/39–61

603–133–00–8

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

408–240–1

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)22–36–61

603–134–00–3

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

Xx; X X: 41–51/53 X: (2-)26–39–61

603–136–00–4

3-{4-[bis(2-hydroxyethyl)amino]-2-nitroanilino}propan-1-ol

410–910–3

104226–19–9

R43 X52–53

Xx R:43–52/53 S: (2-)24–37–61

603–137–00-X

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

411–130–6

Xx; X41

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

603–138–00–5

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

403–140–4

103694–68–4

R52–53

R:52/53 X: 61

604–050–00-X

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

216–381–3

1570–64–5

X; X23 X; R 35 N; X50

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

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

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 X: 61

604–052–00–0

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

403–800–1

103597–45–1

X53

X:53 X: 61

604–053–00–6

4-xxxx - butyl-2-methyl-6-(1-methylpentadecyl)fenol

410–760–9

157661–93–3

Xi; R38 X43 N; R50–53

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

604–054–00–1

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

412–020–0

X43 R52–53

Xi X:43–52/53 X: (2-)24–37–61

604–055–00–7

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

413–900–7

85954–11–6

Xxxx. Xxx.3; R40

Xn X: 40 X: (2-)22–36–37

605–027–00–7

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

410–480–7

X43 N; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-xxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxx-1-xx

4–406–670–4

61203–83–6

X; X51–53

X R: 51/53 X: 61

606–052–00–6

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

410–410–5

54574–82–2

R52–53

R:52/53 X: 61

607–272–00–5

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

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

N; X50–53

X X: 50/53 X: 60-61

607–273–00–0

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

404–520–2

X52–53

X:52/53 X: 61

607–274–00–6

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

405–350–1

54527–73–0

X43 X; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

607–275–00–1

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

405–450–5

66531–87–1

R43

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

607–276–00–7

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

405–635–0

Xi; X38–41 X; X50–53

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

607–277–00–2

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

405–720–2

Xx; X22 Xx; X41 X43 X; X51–53

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

607–278–00–8

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

405–760–0

Xx; X41 X43 R52–53

Xi 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 X: (2-)24–37–61

607–280–00–9

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

406–190–5

54322–20–2

Xn; X22 Xx; X36 X43

Xx X: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

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

407–000–3

127519–17–9

N; X51–53

X X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 S: 61

607–283–00–5

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

408–040–4

15121–89–8

Xx; X21/22 Xi; X38–41 R43 X; X50–53

Xx; X X: 21/22–38–41–43–50/53 X: (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) x xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx)

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

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

410–065–0

R43

Xi 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 X: 61

607–288–00–2

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

410–160–7

148732–74–5

Xx; X36 X43 X52–53

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

607–288–00–8

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

410–370–9

105488–33–3

R53

R:53 X: 61

607–290–00–3

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

410–540–2

Xx; X38 X43 X; R50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx cyklohexyl)alkanoát

410–630–1

104051–92–5

R53

R: 53 X: 61

607–292–00–4

Směs:[2-(alkyl(C12)oxy)-1-(methoxymethyl)ethoxy]octová xxxxxxxx x [2-(alkyl(C14)oxy)-1-(methoxymethyl)]octová kyselina

410–640–6

Xi; X38–41 N; X50–53

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

607–293–00-XXxxx:

1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx x 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 X: (2-)26–36/37/39–61

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

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

410–800–5

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–296–00–6

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

410–830–9

X53

X: 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; R41

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

607–298–00–7

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

411–010–3

X43

Xx X: 43 X: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 R43 X; R50–53

Xn; 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, x-xxxxxxxxxxxxxxxxxxxx]xxxxxxx xxxxxxx, xxxxxxxx xxx; x = 1,2,3 xxxx 4, x = 8, 9, 10 xxxx 11, c = 15, 16, 17 xxxx 18, x = 22, 23, 24 xxxx 25

411–430–7

X43

Xx X: 43 X: (2-)22–24–37

607–301–00–1

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

411–860–5

Xx; X38–41 R43 N; X51–53

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

607–302–00–7

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

411–910–6

Xx; X38–41 R43 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 kyselina

413–760–7

93107–30–3

Repr. kat.3; X62 X52–53

Xx R: 62–52/53 X: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; X50–53

X X: 50/53 S: 60-61

608–024–00–9

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

407–650–8

97460–76–9

R53

R:53 X: 61

608–025–00–4

[2-nitro-4,5-bis(benzyloxy)fenyl]acetonitril

410–970–0

117568–27–1

R53

R:53 X: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; X3 O; X8 Karc. xxx. 2; R45 T; 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; R22–48/22 C; X34 X43 X; X50–53

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

611–043–00–5

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

402–850–1

Xx X: 41–52/53 X: (2-)26–39–61

611–044–00–0

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

403–720–7

117527–94–3

X; R51–53

Xi; 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 Xx; X48/22 X43 X; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

R53

R: 53 S: 61

611–048–00–2

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

407–900–6

111381–12–5

R53

R: 53 X: 61

611–049–00–8

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, xxxxxxxx xxxxxx x xxxxxx xxxxxxxx (2:1:1)

408–000–6

118658–98–3

Xx; X48/22 X43 X52–53

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

611–051–00–9

2-({4-[xxxxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxx}xxx)-6-xxxxxxx-3-xxxxxxxxxxxxxxxxxxxxx-xxxxxxx

411–110–7

136213–74–6

X; X50–53

X X: 50/53 X: 60-61

611–052–00–4

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

400–720–9

X52–53

X: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; X41 X; 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; R41 X43 X; X51–53

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

612–158–00–3

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

410–820–4

X53

X: 53 S: 61

612–159–00–9

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

410–880–1

Xx; X22 X; X34 X; X50–53

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

613–149–00–7

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

405–700–3

96489–71–3

X; R23/25 X; R50–53

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

613–150–00–2

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

406–295–6

X53

X:53 X: 61

613–151–00–8

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

406–360–9

104218–44–2

X53

X:53 X: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 N; X51–53

Xx; 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 R: 22 X: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; X22 R52–53

Xn X: 10–22–52/53 S: (2-)23–36–61

613–156–00–5

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

410–260–0

83857–96–9

R43 X; X51–53

Xx; X R: 43–51/53 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 X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

2,3-xxxxxxx-5-(xxxxxxxxxxxxxx)xxxxxxx

410–340–5

69045–84–7

Xx; X20/22 Xx; X41 R43 X; 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 Xx; X20 X; X50–53

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

613–160–00–7

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

411–000–9

125224–62–6

R43

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

615–022–00–1

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

410–550–7

79277–18–2

X; X2 R14 Xx; X48/22 X42/43

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

615–023–00–7

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

410–900–9

83056–32–0

X10 X14 Muta. xxx. 3; X40 Xx; X20–48/22 Xi; X41 X42

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

616–044–00–4

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

402–510–2

N; X51–53

X X: 51/53 X: 61

616–045–00-X

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

405–190–2

122371–93–1

X43 R53

Xi X: 43-53 X: (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; R50–53

N X: 50/53 S: 60-61

616–047–00–0

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

406–640–0

X43

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

616–048–00–6

3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx

406–740–4

1939–27–1

Xx; X48/22 X; X51–53

Xx; X X: 48/22–51/53 X: (2-)22–36–61

616–049–00–1

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

408–150–2

99141–89–6

X53

X:53 X: 61

616–050–00–7

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

410–690–9

103055–07–8

X43 N; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

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

411–070–0

X53

X: 53 X: 61

617–015–00–9

xxx(4-xxxxxxxxxxxxx)xxxxxxx

407–950–9

895–85–2

X; X2 X; R7 N; X50–53

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

650–032–00-X

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

94361–06–5

Xxxx. kat. 3; X63 Xx; X22 X; X50–53

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


XXXXXXX 2

POVAHA XXXXXXXXXXXX XXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI A XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, s. 81.


XXXXXXX 3A

STANDARDNÍ POKYNY XXX BEZPEČNÉ ZACHÁZENÍ X NEBEZPEČNÝMI LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES,

Úř. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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


XXXXXXX 4X

"X.10 XXXXXXXXXX — XXXXXXX XX XXXXXXXXXXXX ABERACE X XXXXX XX VITRO

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxxx xx xxxxxxxxxxxxx činitele, které xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x chromatidové. X xxxxxxx xxxxxxxxxx mutagenů xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, avšak xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx xx xxxxxxxxx indukovat xxxxxxxxx aberace. Xxxx xxxxxx však není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx x xxxxxx xxxxx rutinně používána. Xxxxxxxxxxxx mutace x xxxxxxx xxxx xxxx xxxxxxxx xxxxx geneticky xxxxxxxxxxx xxxxxx x xxxxxxx x existuje xxxxx xxxxxx o xxx, že xxxxxxxxxxxx xxxxxx x s xxxx související xxxx xxxxxxxxxxx xxxxx v xxxxxxxxxx a v xxxxxx somatických buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x člověka x x xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx aberace in xxxxx mohou být xxxxxxx stabilizované xxxxxxx xxxxx, xxxxxxx xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx. Použité buňky xxxx xxxxxxx na xxxxxxx xxxxxxxxxx růstu x kultuře, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx chromozomů x xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

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

Xxxx xxxxxxx xx xxxxxxx ke xxxxxxxx xxxxxxx mutagenů x xxxxxxxxxxx xxx xxxxx. Mnoho xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx xxx xxxxx xxxxxxxxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx není absolutní xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx třídě x xxxxxxxxx důkazy x xxx, že xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx touto xxxxxxxx, neboť xxxxxx xxxxxx xxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxxxxx XXX.

Xxx xxxx Xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x podobě xxxxx xxxxxxxxxxxx xxxxxxxxx nebo xxxxx a opětného xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx aberace : xxxxxxxxxx poškození xxxxxxxxxx v podobě xxxxx nebo xxxxx x spojení xxxx xxxxxxxxx x xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : xxxxxx, xxx kterém x xxxxx xx X-xxxx xxxxxxxxx DNA xxxxxxx x mitóze, nýbrž xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx xxxx xxxxxxxxxx xx 4, 8, 16… xxxxxxxxxxxx.

Xxx : xxxxxxxxxxxx léze xxxxx xxx šířka xxxxx xxxxxxxxxx a x xxxxxxxxx xxxxxxxxx chromatid.

Mitotický xxxxx : xxxxx xxxxx, xxxxx xx xxxxxxxxx x metafázi, x celkového počtu xxxxx v xxxxxxxx; xxxxx xxxxxx xxxxxxxxxxx xxxx populace.

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

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

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx dělení ve xxxxxx xxxxxxxx; xxxx xx xxxx xxxxxx x xxxxxxxxx, intrachromozomální xxxx xxxxxxxxxxxxxxxxxx změny.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, x xx s metabolickou xxxxxxxx x bez xx. V předem xxxxxxxxxxx intervalech xx xxxxxxxx látce se xx xxxxxxxxx kultur xxxxx látka xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx), xxxxxxx xx sklidí, xxxxxx x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Mohou být xxxxxxx xxxxx buněčné xxxxx, kmeny nebo xxxxxxxx buněčné xxxxxxx, xxxxxx lidských xxxxxxxxx xxxxx (xxxx. fibroblasty xxxxxx čínského, xxxxxxxxx xxxxxxxxx xxxx člověka xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx a xxxxxxxxxx xxxxxxxx

Xxx udržování xxxxxx xx měla xxx xxxxxxx vhodná xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). U xxxxxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxx by xxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxx x mělo xx xxx xxxxxxxxxxxx, xxx xxxxxx kontaminovány mykoplasmaty; x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Pro xxxxxxx xxxxx x inkubační xxxxxxxx xx xxxx xxx xxxxx xxxxxxxx xxxxx buněčného xxxxx.

1.4.1.3 Xxxxxxxx kultur

Stabilizované buněčné xxxxx a xxxxx: xxxxx xx pomnoží x kmenových xxxxxx, xxxxxx xx xx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxxx, aby xxxxxxxxx konfluence xxxx xxxxxxxxx, x inkubují xx při 37 °X.

Xxxxxxxxx: xxxx ošetřená xxxxxxxxxxxxxxx (xxxx. heparinem) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxx se xxxxxxx xx xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. xxxxxxxxxxxxxxxx) x xxxxxxxx se xxx 37 °X.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx xxxxxxxxx zkoušené xxxxx, x to x xxxxxxx xxxxxxxxxxxx xxxxxxxx x xxx xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená x xxxxx xxxxxxxx zpracovaná xxxxxxxx xxxxxxxxxxx enzymy, xxxx je Xxxxxxx 1254 (6, 7, 8 x 9), xxxx xxxx xxxxxxxxxxxxx x β-naftoflavonu (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx používána v xxxxxxxxxxxxx 1 — 10 % obj. Xxxx metabolického aktivačního xxxxxxx může xxxxxxx xx třídě xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx použít více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx výsledků xxxxxx, včetně xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx endogenní xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx linií xx xxxx xxx xxxxxxx xxxxxxxxxx (xxxx. důležitostí xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx být xxxx xxxxxxxx xx xxxxx xxxxxxxxxx nebo suspendovány xx vhodných rozpouštědlech xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx přidány xxxxx x testovacím systémům x/xxxx xxxxx být xxxx xxxxxxxx zředěny. Xxxx xx být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx mělo být xxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx, x mělo xx být xxxxxxxxxx x xxxxxxxx xxxxx x s aktivitou X9. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Doporučuje xx pokud xxxxx xxxxxxxx zvážit použití xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx xxxxxxxxx xx vodě xx xxxx xxx xxxxxxx xxxxxxxxx rozpouštědla xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Expoziční koncentrace

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

Cytotoxicita xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx x xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx xxxxxxx integrity x xxxxx, xxxx xxxx xxxxxx xxxxxxxxxx, xxxxx životaschopných xxxxx xxxx xxxxxxxxx xxxxx. Xxxx xxx xxxxxxx xxxxxxxx cytotoxicitu x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx cytotoxicity by xxxx xxxx xxxxxxxxxxx xxxxxxxx rozmezí xxxx xxxxxxxxx xx minimální xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, což xxxxxxx xxxxxxx, že by xx koncentrace xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. V xxxxxxxx xxxxxxx by xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx snížení stupně xxxxxxxxxx, xxxxx xxxxx xxxx mitotického xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx nebo xxxxxxxxxxxxxx xxxxxx x závisí xx xxxx, xxxxx xxxxxxxx xx xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx přijatelný u xxxxxxxxxxx kultur, x xxxxx mohou být xxxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxxx. Informace x xxxxxxxx xxxxxxxxx cyklu, xxxxxxxxx průměrná xxxxxxxxx xxxx (XXX), mohou xxx xxxxxxx xxxx xxxxxxxxx xxxxxxxxx. X xxxxxxx XXX však xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, a x xxxx přírůstek průměrné xxxxxxxxx xxxx může xxx za xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

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

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx látek, xxxxx xxxxxx xxxxxxx xxx xxxxxxxxxxxxx xxxxxxx, xxx xx jejich rozpustnost, xx měla xxx xxxxxxx xxxxxxxx xxxxx x koncentraci, jež xx xxx xxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxx xxxxxxxx. X xxxxxxxx xxxxxxxxx (xxxx. projeví-li se xxxxxxxx xxxxx při xxxxxxx koncentracích, xxx xx rozpustnost) se xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, xxx xxxxx xxxxxxx ke xxxxxxx. Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx x na xxxxx expozice, xxxxx xxxxxxxxxxx v testovacím xxxxxxx se xxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx buněk, xxxx X9 atd. Xxxxxxxxxxxxx xxx zjistit xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x negativní xxxxxxxx (kontroly xxxxxxxxxxxx xxxx xxxxxxxx). Xxx xxxxxxx metabolické aktivace xx xxxx být xxx pozitivní kontrolu xxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx.

X xxxxxxxxx xxxxxxxx by xxx xxx xxxxxx xxxxx xxxxxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x detekovatelný xxxxxx xxx pozadí, xxxx xx xxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxx xxx zvoleny tak, xxx xxx xxxxxx xxxxxxxx, xxx aby xxx odečtu xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx aktivace

Látka

Číslo XXX

Xxxxx xxxxx EINECS

Bez xxxxxx metabolické xxxxxxxx

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X vnější xxxxxxxxxxxx xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Pro xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx x xxxx xxxxxx xxxxx. Pro xxxxxxxxx kontrolu xx xxxx být pokud xxxxx vzato x xxxxx použití xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx.

X xxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx skládající se xx samotného rozpouštědla xxxx vehikula x xxxxxxxxxxx xxxxx x xxxxxxxxxx xxxxxxx xxxxxxxx xxxx kultury. Xxxxx xxxx by měly xxx neexponované kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné zhoubné xxxx xxxxxxxxx účinky.

1.4.3 Xxxxxx

1.4.3.1 Expozice xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxxxxx zkoušené látce xxx za přítomnosti xxxxxxxxxxxxx aktivačního xxxxxxx, xxx xxx něho. Xxxxxxxx xxxxxxxxx xx xxxx být zahájena xxx 48 xxxxx xx xxxxxxxxx stimulaci.

1.4.3.2 Xxx xxxxxx koncentraci xx xxxx být xxxxxxx použity xxxxxxxxxx xxxxxxx, x xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx rozpouštědla. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx xxxxxxxxx xx minimální rozdíl, xxxx xxx xxxxxxxxx xxxxxxx xxxxxx kultury.

Plynné xxxx těkavé látky xx měly xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x xxxxx xxxxxxxxxx kultivačních xxxxxxxx (15, 16).

1.4.3.3 Doba xxxxxxx xxxxxx

X xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, jak x metabolickou aktivací, xxx bez xx, xx xxxx 3 — 6 hodin, x xxxx by xxx xxxxxxxx xx xxxxxx době xx xxxxxxxx aplikace, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx buněčného xxxxx (12). Jestliže xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx jak x xxxxxxxx, xxx bez xxxxxxxx, xxx xx xxx proveden dodatečný xxxxxxxxxx xxx xxxxxxxx x xxxxxxxxxxxx xxxxxxxx xx xx xxxxxx x xxxx, která xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx látky xxx snáze xxxxxxxxx xxx xxxxxx aplikace xxxx xxxxxx xxxxxxx xxx 1,5xxxxxxx délky xxxxx. Negativní xxxxxxxx xxx metabolické xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx od xxxxxxx. X xxxxxxxxx, kdy xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, by xxxx xxx xxxxxx xxxxxxxxxx.

1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

Xx buněčné xxxxxxx xx obvykle 1-3 hodiny před xxxxxxxxx xxxxx Colcemid® xxxx xxxxxxxxx. Xxx xxxxxxxx xxxxxxxxx pro xxxxxxx xxxxxxxxxx se xxxxx buněčná kultura xxxxxx x zpracovává xxxxxx. Xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Analýza

Všechny preparáty, xxxxxx preparátů xxxxxxxxxxx x negativních xxxxxxx, xx měly xxx xxxx xxxxxxxx xxx xxxxxxxxxxx nezávisle kódovány. Xxxxxxxx xxx fixaci xxxxx xxxxxxx xx xxxxx části buněk x xxxxxxxx x xx xxxxxx chromozomů, xxxx xx vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxx xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx xxxxx. Na xxxxxx xxxxxxxxxxx x xxxxxxxx xx mělo xxx hodnoceno xxxxxxx 200 dobře xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx rovnoměrně xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Tento xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx počet xxxxxxx.

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

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx x xxxx xx tedy xxx xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx chromozomovou xxxxxxx (xxxxxxxxx) vyjádřené x xxxxxxxxxx. Pro xxxxxxxxx a experimentální xxxxxxx by xxxx xxx uvedeny xxxxx xxxx strukturních chromozomových xxxxxxx s xxxxxx xxxxxx x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx xxxxxxxxxx xx do xxxxxxx xxxxxxxx xxxxxxx.

Xxxx by xxx xxxx zaznamenána xxxxxxxx, která byla xxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx kultur x xxxxxxxx xxxxxxxxxxxxx s xxxxxxxxx.

Xxxx xx být xxxxxxx údaje xxx xxxxxxxxxx xxxxxxx. Dále xx xxxx být xxxxxxx údaje xxxxxxx xx formě tabulky.

Ověření xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x xxxxxxxx experimentálních podmínek. Xxxxxxxxxx potvrdit negativní xxxxxxxx byla diskutována x bodu 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x xxxxx rozšířit xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx by xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro stanovení xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, např. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx xxxxxx xxxxx. Xxxxxxxx by měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Při xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx metody (3, 13). Statistická xxxxxxxxxx xx neměla xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, se x xxxxx xxxxxxx xxxxxxxx xx nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx o xxxxxxxx zkoušené látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, kolikrát xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx znamenají, že xxxxxxxx látka za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxxx somatických xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx aberace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx musí obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Buňky:

- xxx x zdroj xxxxx,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx použitého typu xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- xxxxxxxxx x xxxxx buněčného xxxxx,

- xxxxxxx xxxxx xxxx, xxx byla xxxxxxx xxxx xxxx nebo xxxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx,

- případně xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx výběru xxxxxxxxxxx x počtu kultur, xxxxxx xxxx. údajů x xxxxxxxxxxxx x xxxxxx xxxxxxxxxxxx, xxxx-xx x dispozici,

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- koncentrace xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x přidané xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- xxxxxxxx hustota xxxxx xxx nasazení,

- xxx a xxxxxxx xxxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,

- xxxxxxxxx a xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx aberací,

- počet xxxxxxxxxxxxx metafází,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxxx xxxxxxx,

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

- xxxxxxxx xxxxxxx, xxxxxx gapů,

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

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx analýzy,

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

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

Xxxxxx výsledků.

Závěry.

4. LITERATURA

1) Xxxxx, X. X. (1976), Xxxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, in: Chemical Xxxxxxxx, Principles xxx Xxxxxxx for their Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, X. (ed) Xxxxxx Xxxxx, New Xxxx and Xxxxxx, 1-29.

2) Ishidate, M. Xx., Sofumi, X. (1985), The Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Using Xxxxxxx Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Xxxxx xx Xxxxxxx, in: Progress xx Xxxxxxxxxx Research, Xxx. 5, Xxxxx, X. et xx., (xxx) Elsevier Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Xxxxxxxx, X. X., Xxxxxxxxx, M. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Cannon, X., Xxxxx, X. X., Xxxxxxxx, X., Xxxxx, X., Duk, S., Xxxxx, J., Xxxxxxxx, X. X., Resnick, X. X., Xxxxxxxx, X., Zeiger E. (1978), Chromozome aberration xxx xxxxxx xxxxxxxxx xxxxxxxxx in Xxxxxxx xxxxxxx xxxxx cells: Xxxxxxxxxx xx 108 xxxxxxxxx, Xxxxxxx. Molec. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Scott, X., Xxxxxxxx, X. X., Marshall, X. X., Xxxxxxxx, X. Xx., Xxxxxxx, X., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx xxxxx Extreme Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Xxxx Group 9, Xxxxxxxxxx Res., 257, 147-204.

5) Xxxxxx, T., Xxxxxx, X., Xxxxxx, X., Xxxxxxx, X., (1992), Xxxxxxxxxxxxxx xx xxx pH xx Xxxxxxx Cultured Xxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 268, 297-305.

6) Xxxx, X. X., XxXxxx, X., Yamasaki, E. (1975), Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx the Xxxxxxxxxx/Xxxxxxxxx Microsome Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 31, 347-364.

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

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

9) Xxxxxxxx, X., Xxxxxxx, M., Xxxxxxxx, M. Xx. (1979), Chromozomal Aberration Xxxxx xx 29 Xxxxxxxxx Xxxxxxxx xxxx X9 Xxx In xxxxx, Xxxxxxxx Res., 66, 277-290.

10) Xxxxxx, X. X., Xxxxxx, X. X., Elcombe, X. X., Xxxxxxxxx, X. X., Gibson, X. X., Mackay, X. X., Wolf, X. X. (1992), Xxxxxx of XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 in In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

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

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

13) Xxxxxxxxxx, X., Xxxxxxxx, D. A., Xxxxx, X. X., Xxxxxxxx, G., Xxxxxxx, X. O., Phillips, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx vitro Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Kirkland, X. X., (ed) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

14) Soper, X. A., Galloway, X. X. (1994), Xxxxxxxxx Xxxxxx xxx xxx Xxxxxxxxx xxx Xx xxxxx Xxxxxxxxxx Xxxxxxxxxx Xxxxxx xx XXX Cells, Xxxxxxxxxx Xxx., 312, 139-149.

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

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

17) Xxxxx-Xxxxx, X. (1983), Endoreduplication xx Xxxxxxx xxxxxxx xxxxx xxxxxx alpha-radiation xxxxxxx G2 arrest, Xxxxxxxxxx Xxx., 119, 403-413.

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


PŘÍLOHA 4X

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

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx metody XXXX XX 475 — Xxxxxxx xx xxxxxxxxxxxx aberace x xxxxxxx xxxxxx dřeně xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxx xx používána xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx látkou v xxxxxxx xxxxxx dřeně xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Rozlišují xx xxx typy strukturních xxxxxxx — chromozomové x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx může znamenat, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx aberace. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx vyskytují. Xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx jevy jsou xxxxxxxx mnoha geneticky xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx xxxxxx o xxx, xx xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx způsobující xxxxx x xxxxxxxxxx a x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx podíl na xxxxxxx xxxxxxxx x xxxxxxx a v xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Cílovou xxxxx xx x xxxx xxxxxxx kostní xxxx, poněvadž je xxxxxx xxxxxxxxxxxxxxxx xxxxx x obsahuje xxxxxxxx xxxxx x xxxxxxx xxxxxx, které xx xxxxxx xxxxxxx x xxxxxxxxxxxx. Xxxx xxxxx x cílové xxxxx xxxxxx xxxxxxxxx této xxxxxx.

Xxxx xxxxxxx na xxxxxxxxxxxx aberace je xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx umožňuje xxxxxxxxx xxxxxxx metabolismu xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx x xxxxxxx xxxxx x tkání xxxxx. Xxxxxxx in vivo xx rovněž xxxxxxxx xxx další xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx in xxxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, že xx xxxxxxxx látka xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx cílové xxxxx, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxx také Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Chromozomová xxxxxxx : strukturní xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx a xxxxxxx xxxx chromatid v xxxxxx xxxxx.

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

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

Xxxxxxxxx aberace : xxxxxxxx počtu xxxxxxxxxx xx normální xxxxxxx xxxxxxx u xxxxxxxxx xxxxx.

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx struktury xxxxxxxxxx xxx buněčném xxxxxx xx stadiu metafáze; xxxx xx xxxx xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxxxx xxxxxxxx látce vhodným xxxxxxxx x xx xxxxxxx xxxxxxxx xx xxxxxxxx se usmrtí. Xxxx xxxxxxxxx se xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx nebo Xxxxxxxx®). X xxxxx kostní xxxxx se xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx a xxxxxxxxx se xxxxxxxxxxxx xxxxxxx xxxxx v xxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx xxxxxxxx potkan, xxx x xxxxxx čínský, xxxxxx xxx použít xxxxxxxx vhodný savčí xxxx. Měly xx xxx xxxxxxx xxxxx xxxxxxx laboratorní kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. V xxxxxxxx zahájení xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx x xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx zvířata se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, xxxxx xx xxxxxxx xxxxxxxx xxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, aby byl xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata se xxxxxxxxxxx xxxxxxxxxxxx. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxx

Xxxxx zkoušené látky xx xxxx být xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx podáním xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx při xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx vyloučeno xxxxxxxxx, xx xxxxxxx xx zkoušenou látkou. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by být xxxxxx xxxxxxxx podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx a xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx xxx obě xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx zvířata xxxxxxxxx xxxxxxx podstoupit xxxxxxxxx xxxxxx xxxx zvířata xx xxxxxxxxx, v xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, xxx aby xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx xxx xxxxx x xxxxx případě xxxxxxxx xxx jednou. Xxx xxxxxxxxx kontrolu xxxxx xxx xxxxxxx xxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx látek pro xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxxx odběru xx xxx xxx xxxxxxxx xxxxx u negativních xxxxxxx, jimž xx xxxxxxxxxx pouze xxxxxxxxxxxx xxxx xxxxxxxxx x xxx jinak podstupují xxxxxx proces xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x dosavadních xxxxxxxxxxx xxxxx k xxxxxxxxx přijatelné xxxxx x xxxxxxxxxxx zvířat x xxxxxxxx xxxxx x chromozomovými xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx doba prvního xxxxxx. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x pohlaví xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxxxx x xxxxxxx pěti xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx. Xxxxxxxx xxxx v době xxxxxx k xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x za xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x toxicitě, xxxx postačující xxxxxxxx xxxxxxx pohlaví. Xx-xx xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je tomu xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx být xxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx dvou dávkách, xxx. dvě xxxxx x xxx xxx x rozmezí xx xxxx než několika xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx xxxxxx podávání by xxxx být xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx odebrány xx xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxxx x xxxxxx xxx. X xxxxxxxx se xxxxx xxxxxxx xx xxxxxx xxxx od xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx normální délky xxxxxxxxx xxxxx (xxxx xxxx xxxxxxx 12 — 18 h). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx pro xxxxxx na kinetiku xxxxxxxxx xxxxx xxxx xxx xxxx xx xxxxxxxxx xxxxxxx pro xxxxxxxxx chromozomových xxxxxxx, xxxxxxxxxx xx provést xxxxx odběr xx 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx rozložena xx xxxx než jednoho xxx, xxx xx xxx xxxxx xxxxxxxx xx takové době xx poslední xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx xxxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx podá xxxxxx xxxxx látky xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® nebo xxxxxxxxx). Xxxx xx xx xxxxxx době xxxxxxx x xxxxxx xxxxx. X xxxx xx xxxx doba xxxxxxxxx 3 — 5 x; x křečka xxxxxxxx xx tato xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx odeberou xxxxx x xxxxxxxxx xx xx chromozomové xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx dostupných xxxxx xxxxxx pro xxxxxxxx xxxxxxx xxxxx, xxxx xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, se stejným xxxxxx, xxxxxx, pohlavím x xx stejného xxxxxx xxxxxxxx, jež xx použijí v xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx pro první xxxxx xxxxxxx xxx xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx pokrývat rozpětí xxxx xxxxxxxxx x xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxx stejném xxxxxx xxxxxxxxx xxxxx očekávání x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx dávkách (např. xxxxxxx x xxxxxxxx) xxxxxx kritériím stanovení xxxxx vyhovovat x xxxx by být xxxxxxxxx případ xx xxxxxxx. Xxxxxxxx dávka xxxx xxx také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x xxxxxx xxxxx některé xxxxxx xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, nepovažuje xx xxxxx xxxxxx xx třemi xxxxxxxx xxxxx za xxxxxxxxx. X déle xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx než 14xxxxx xxxxxxxx xx xxxxxxx xxxxxx 1000 xx/xx xxxxxxx hmotnosti/den. Xxxxxxxxx expozice xxxxxxx xxxx znamenat xxxxxxx xxxxxx x limitní xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx nebo xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx podávání xxxx x odůvodněných xxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx na velikosti xxxxxxxxxxx zvířete. Xxxxx xx neměl překročit 2 ml/100 g xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být zdůvodněno. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx obvykle xxx xxxxxxx koncentracích vykazují xxxxxxxx xxxxxx, by xxxx xxx variabilita xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx koncentrace zajišťující xxxxxxxxxx objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů xxx xxxxxxx chromozomů

Ihned xx xxxxxxxx xx odebere xxxxxx xxxx, hypotonizuje xx x xxxxxx. 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 xxx xxxxxxxxx kontrolu xxxxxxxx xxxxxxxxx xxxxx, x xx xxxxxxx x 1000 buněk xx xxxxx xxxxx.

X xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx. Tento xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx kontrol by xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xx ztrátě xxxxxxxxxx x xxxxx xxxxx x xxxxxxxx, xxxx by xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x počtu odpovídajícímu xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx. Xxx každé xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx, xxxxx xxxxxxx xx buňku a xxxxx buněk x xxxxxxxxxxxxx xxxxxxx (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx xxxxx typy xxxxxxxxxxxx chromozomových xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx odděleně x xxxxxxx xx, xxx xxxxxx xx xxxxxxxxxx do xxxxxxx xxxxxxxx xxxxxxx. Neexistuje-li xxxxx x xxxxxxx x odpovědi xxxx xxxxxxxxx, mohou xxx xxx xxxxxxxxxxxx analýzu xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst relativního xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx pro skupinu x xxxxxxx dávkou x x xxxxxxxx xxxxxxxx xxxxxx. Nejdříve xx xxxx být xxxxxxx biologická xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx použity jako xxxxxxx xxxxxxxxxx statistické xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx podmínek.

Nárůst xxxxxxxxxxx xxxx znamenat, že xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx chromozomy xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx potenciál xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (7, 8).

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

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

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx znamenají, xx xxxxxxxx xxxxx za xxxxxxxx zkoušky neindukuje x xxxxxx dřeni xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

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

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx o zkoušce xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx zvířat,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

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

Xxxxxxxx podmínky:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- xxxxx xx studie pro xxxxxxxx xxxxxxx, pokud xxxx xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, zda xx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx xx cílové xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx a xxxx,

- podrobný xxxxx xxxxxxx expozice x xxxxxx,

- xxxxxx stanovení xxxxxxxx,

- identifikace xxxxx xxxxxxxxxxx metafázi, její xxxxxxxxxxx x délka xxxxxxxx,

- xxxxxx přípravy xxxxxxxxx,

- xxxxxxxx hodnocení xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx na xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx každé xxxxx,

- celkový xxxxx xxxxxxx ve skupině xx xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx buněk s xxxxxxxxx ve skupině xx středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx pozorovány,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx analýzy,

- údaje x souběžné xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx kontrole x rozpětími, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

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

3) Xxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxxxxx, X. G., Bootman, X., Henderson, L. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx I xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. R., Xxxxxxx, X., XxxXxxxxxx, X. X., Anderson, D., Xxxxxx, X. X., Xxxxxx, X. E., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., F. X., Xxxxxxxxxxxx, F., Preston, X. J., Romagna, X., Shimada, X., Xxxxx, X., Xxxxxxx, X. (1994), Report xxxx xxx Working Xxxxx on xxx xx xxxx Mammalian Xxxx Marrow Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, P. X., Xxx, J., Esdaile, X. X., Gatehouse, X. X., Hodson-Walker, X., Xxxxxx, D. X., Kirkland, D. X., Richold, X. (1992), Xxxxxx of Xxxxxxx Xxxxxxxxxx Society/UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx in Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. P., Xxxxxxxx, X., Xxxxxxxx, X., Amphlett, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxx, X., Papworth, D. X., Savage, X. X. X. (1989), Xxxxxxxxxxx Analysis of Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Part III. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, X. X. Kirkland (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.

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

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


XXXXXXX 4X

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

1. METODA

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

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxx xxxxxxxxx chromozomů xxxx mitotického xxxxxxx xxxxxxxxxxxx, xxxxx je xxxxxxxxxx zkoušenou xxxxxx, x xx pomocí xxxxxxx xxxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx x/xxxx xxxxx xxxxxxxxx xxxx, xxxxxxx hlodavců.

Účelem xxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx je xxxxxxxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxx xx xxxxxx xxxxxxxxxx obsahujících nereplikující xx (xxxxxxx) chromozomové xxxxxxxxx xxxx xxxx xxxxxxxxxx.

Xxxx xx erytroblast xxxxxx xxxxx xxxx xx polychromatický xxxxxxxxx, xxxxxx jádro xx xxxxxxxx a mikrojádra, xxxxx při xxx xxxxx vzniknout, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx jádra xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx je x xxxxxx buňkách xxxxxxxxx xxx, xx xxxxxxxxxx hlavní jádro. Xxxxxx xxxxxxx polychromatických xxxxxxxxxx x xxxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xx známkou xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx xx xxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxxxx xxxx xxxx xxxxxxxxx polychromatické xxxxxxxxxx. Xxxxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx x periferní xxxx xx rovnocenně xxxxxxxxxx x kteréhokoli xxxxx, x xxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Mikrojádra xxx xxxxxxxx xxxxx xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx nebo xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX v mikrojádře. Xxxxxxxxx xx zejména xxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x mikrojádry. Xxxxx xxxxxxx (normochromatických) xxxxxxxxxx v xxxxxxxxx xxxx, které obsahují xxxxxxxxxx, xxxxxxxxxxx xx xxxxxx xxxxx zralých xxxxxxxxxx lze rovněž xxxxxx xxxx konečný xxxxxxxx xxxxxxx, jestliže xxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx nebo xxxx.

Xxxxx xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx je xxxxxxx xxxxxx k posouzení xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx xx mohou xxxxx x xxxxxxx druhů x tkání, xxxxx x x genetického xxxxxxxx. Zkouška in xxxx xx xxxxxx xxxxxxxx pro další xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx x xxxxxxxxx xx xxxxx.

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

Xxx také Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) chromozomu, x xxx (x xxxx) xx během xxxxxx buněk připojí xxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxx xxxxx.

Xxxxxxxxxx : xxxx xxxxx xxxxxxxxxx xxxxxxxx od xxxxxxxx xxxxx a xxxxx xxxx, xxxxxxxxx xxxxx xxxxxxxx xxxxxx (xxxxxx) xxxxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx erytrocyt : xxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxx, který xxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx selektivním xxx xxxxxxxx.

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx xxxxxxxxx ve xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx xxxxxxxx ribozomy, 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 použití xxxxxx xxxxx xx xxxxxxx xx xxxxxxx xxxxxxxx po expozici xxxxxx, xxxxxxx se xxxxxx xxxx, xxxxxxxx xx preparáty x xxxxxx se (1, 2, 3, 4, 5, 6, 7). Xxx použití xxxxxxxxx xxxx xx krev xx xxxxxxx okamžiku xx xxxxxxxx xxxxxxx, xxxxxxxxxx xx připraví xxxxxxxx x xxxxxx xx (4, 8, 9, 10). Při xxxxxxxx x xxxxxxxxx xxxx xx xxxx xxxx poslední expozicí x xxxxxxxxx xxxxx xxxxxxxx co nejkratší xxxx. Xxxxxxxxx jsou xxxxxxxxxxx xx xxxxxxxxxx xxxxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx xxxxxxx xxxxxx xxxxx xx xxxx xxxxxxxxx xxxxx xxxxxxxxxx myš xxxx xxxxxx, ačkoli xxx xxxxxx jakýkoli xxxxxx xxxxx xxxx. Xxx xxxxxxx periferní xxxx xx doporučuje xxx. Xxx xxxx xxxxxx xxxxxxxx vhodný xxxx xxxxx za xxxxxxxxxxx, xx xxx o xxxx, x něhož xxxxxxx xxxxxxxxxxxx erytrocyty x xxxxxxxxxx, xxxx xxxx xxxxxxxxxx dostatečnou xxxxxxxxx detekovat činitele, xxxxx xxxxxxxxx strukturní xxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx by x xxxx xxxxxxx překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx výběrem rozdělí xx xxxxxxxxx skupinu x xxxxxxx, x xxx se xxxxxxx xxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx. Xxxxx xx uspořádají xxx, xxx byl xxxx xxxxxx xxxxxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xxxxxxxx rozpuštěny xxxx xxxxxxxxxxxx ve vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx podávány xxxxx nebo xxxxx xxx xxxx xxxxxxx xxxxxxx. Měly xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxx stálosti xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých úrovních xxxxx toxické xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou. Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx být jejich xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx nejdříve xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každého experimentu xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx pohlaví. X xxxxxxxx aplikace xxxxxxxx xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx mikrojádra xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Xxxxx xxxxxxxxx kontroly by xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx přijatelné, xxx xxxxxxxxx kontrola xxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x aby byl xxxxx x tomto xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx může xxx xxxxx v xxxxx použití chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou-li x dispozici. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx xxx xxx xxxxxxxx odběr u xxxxxxx xxxxxxxxx kontroly, xxxxx xx xxxxxxxxxx xxxxx rozpouštědlo nebo xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako exponované xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx k dispozici xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx a xxxxxxxx buněk x xxxxxxxxxx. Xxxxxxx-xx se xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx okamžikem xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx publikovány xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx nebo xxxxxxxxx účinky.

Při xxxxxxx xxxxxxxxx krve xxxx xxx xxxx negativní xxxxxxxx xxxxxxxxxx xxxx xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx x xxxxxxxx xxxxxx x xxxxxxxxx xxxx (xxxx. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, xx xxxxxxxx údaje xxxxx x xxxxxxx, které xx na xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx zvířat

Každá xxxxxxxxxx x xxxxxxxxx skupina xx musí xxxxxxx x alespoň pěti xxxxxxxxxxxxxxxx xxxxxx pro xxxxx xxxxxxx (11). Xxxxxxxx xxxx v xxxx xxxxxx x xxxxxxxxx údaje ze xxxxxx se xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx postačující xxxxxxxx jednoho xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, jako xx xxxx například x xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx by xxx xxxxxxx provedena se xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxx (xx. xxxxx, xxx xxxx xxx aplikace x xxxxxxxxx 24 xxxxx). Xxxxxx xx xxxxxx s prodlouženým xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxxx xx x těchto xxxxxx xxxxxxx pozitivní xxxxxxxx, xxxx –v xxxxxxx xxxxxxxxxxx studií — xxxxx byla prokázána xxxxxxxx xxxx xxxx xxxxxxxxx limitní dávka x xxxxxxxx pokračuje xx xx okamžiku xxxxxx. Zkoušené xxxxx xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, tzn. dvě xxxxx x týž xxx v rozmezí xx xxxx xxx xxxxxxxx xxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx xxx xxxxxxxx xxxxx xxxxxxx:

x) xxxxxxxx xxxxx se xxxxxxxx xxxxxxxx xxxxxx. Xxxxxx xxxxxx xxxxx se xxxxxxxx xxxxxxx dvakrát, xxxxxxx první xxxxx xx xxxxxxx xxxxxxxx 24 xxxxx po xxxxxxxx a xxxxxxxx xxxxxxxxxx 48 hodin xx xxxxxxxx a x xxxxxxxxxx odstupem xxxx odběry. Xxxxx xxxxx než 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx periferní krve xx odeberou xxxxxxx xxxxxxx, xxxxxxx první xxxxx se xxxxxxx xxxxxxxx 36 hodin xx aplikaci a xxxxxxxx nejpozději 72 xxxxx po xxxxxxxx x xx prvnímodběru xx xxxxxx xxxxxxxxxxxx xxxxxx. Xx-xx xx xxxxxx xxxxxx pozorována xxxxxxxxx odpověď, není xxxxx xxxxx nutný;

b) xxxx-xx podávány xxx xxxx xxxx dávek xxxxx (xxxx. xxx xxxx xxxx xxxxx x xxxxxxxxx 24 xxxxx), xxxx by xxx xxxxxx xxx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx xx 18 až 24 xxxxxxxx xx poslední xxxxxxxx x při xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx poslední xxxxxxxx (12).

Xxxxx xxxxxxx xxxxx xxx xxxxx použity xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx rozsahu xxxxx, xxxx by být xxxxxxxxx xx xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x za xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí v xxxxxx xxxxxx (13). X xxxxxxx toxicity xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Tyto xxxxxx xxxxx by xxxx xxxxxxxx xxxxxxx xxxx maximální až xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx specifickou biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx být xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx být také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx xxxxxxx známky xxxxxxxx (např. snížení xxxxxx xxxxxxxxx erytrocytů x celkového množství xxxxxxxxxx x xxxxxx xxxxx nebo x xxxxxxxxx xxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška s xxxxxx xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx v xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx toxické xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, které xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx úplná xxxxxx xx xxxxx úrovněmi xxxxx xx xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx je limitní xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx a xxx xxxxx xxx 14xxxxx xxxxxxxx je xxxxxxx xxxxxx 1000 xx/xx xxxxxxx hmotnosti/den. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx v limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx podávání jsou xxxxxxxxxx v xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx xxxx xxx xxxxxxxx podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx a xxxxxx xxxxx, které obvykle xxx vyšších koncentracích xxxxxxxx zesílené účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx xxxxxxxxx x xxxxxx xxxx tibie xxxxx xx xxxxxxxx. Xxxxx xx xxxxxxxx x femuru nebo xxxxx x zavedenými xxxxxxxx xx preparují x xxxxxx. Xxxxxxxxx xxxx se xxxxxxx x xxxxxx xxxx xxxx jiné xxxxxx xxxxxx xxxx. Xxxxxx xxxxx se ihned xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx xxxxxxxx xxxxxxxxx xxxxxxxx x poté xx xxxxxx. Xxxxxxxx xxxxxxx xxxxxxxxxxxx xxx XXX (xxxx. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx xxxxxxx xxxxxxxx xxxxxxxxxx spojeným x xxxxxxxx barviva xxxxxxxxxxxxxx xxx DNA. Tato xxxxxx nebrání použití xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. xxxxxxxxxx xxxxxx x xxxxxxxxxx buněk xxxxxxxxxxxx jádra (16)) xxx xxxxxx za xxxxxxxxxxx, xx xx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx xx stanoví xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx (nezralé + xxxxx) xxxxxxxx xxxxxxxxxx, přičemž se x xxxxxxx xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 erytrocytů x x případě xxxxxxxxx xxxx xxxxxxx 1000 xxxxxxxxxx (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx být xxxx xxxxxxxx xxx mikroskopem xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx se xxxxxxx xxxxxxx 2000 xxxxxxxxx erytrocytů xx xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Xxxxx informace xxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx mikrojader. Xxx mikroskopické xxxxxxx xx neměl xxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx xxxxx než 20 % xxxxxxxxx xxxxxxx. Jestliže xxxx xxxxxxx xxxxxxxxxx nepřetržitě xxxxx týdny xxxx xxxx, lze také xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx erytrocytů xx xxxxx xxxxx. Systémy xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx a xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxx) jsou xx xxxxxxxxxxxxx zdůvodnění x validaci xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx hodnocení.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx formě xxxxxxx. Experimentální xxxxxxxxx xx xxxxx. Xxx xxxxx analyzované xxxxx xx xxx být xxxxxx xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, počet xxxxxxxxx erytrocytů s xxxxxxxxxx a počet xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx. Xxxxxxxx jsou zvířata xxxxxxxxxx nepřetržitě xxxxx xxxxx xxxx xxxx, xxxx xx xxx xxxx xxxxxxx xxxxx x zralých xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx xxxxx xx xxxxx podíl xxxxxxxxx xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x procentech. Xxxxxxxxxx-xx xxxxx x rozdílu x xxxxxxxx mezi xxxxxxxxx, mohou být xxx statistickou analýzu xxxxx pro obě xxxxxxx zkombinována.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx s xxxxxxxxxx x xxxxxxxxxx na xxxxx nebo jasný xxxxxx xxxxx buněk x mikrojádry pro xxxxxxx x určitou xxxxxx a k xxxxxxxx okamžiku odběru. Xxxxxxxx by xxxx xxx xxxxxxx biologická xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx odpověď. Xxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxx experimentálních xxxxxxxx.

Xxxxxxxx látka, jejíž xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, se xxxxxxxx v xxxxx xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, v xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx ohledu xx xx, kolikrát je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx mikrojádra, xxx xxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx látka xx xxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx erytrocytech xxxxxxxxxxx xxxxx.

Xxxx xx být xxxxxxxxxxx pravděpodobnost, x xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx dostanou xx xxxxxxxx xxxxx, nebo xxxxxxxxxx xx xxxxxx xxxxx (např. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění volby xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- počet, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- individuální xxxxxxxx xxxxxx xx xxxxxxx zkoušky, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx odchylka pro xxxxxx xxxxxxx.

Xxxxxxxx podmínky:

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

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

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- xxxxx x přípravě zkoušené xxxxx,

- údaje x xxxxxxxx zkoušené xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, xxx xx zkoušená xxxxx dostala xx xxxxxxxx xxxxx xxxx xx cílové xxxxx,

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

- xxxxxxxx xxxxx o kvalitě xxxxxx x vody,

- xxxxxxxx popis xxxxxxx xxxxxxxx x odběru,

- xxxxxx přípravy xxxxxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- xxxxxxxx hodnocení xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx analyzovaných xxxxx xx xxxxx zvíře,

- xxxxxxxx klasifikace studie xx pozitivní, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxx nezralých xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx,

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

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy x xxxxxx,

- xxxxx x souběžné x xxxxxxxxx xxxxxxxxx kontrole,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

3) Xxxxxx, X. A., Xxxxxxxx, X. X., Xxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X., XxxXxxxxx, X. X., Xxxxxx, X. X. (1983), Xxx Xxxxxxxxx xx Micronuclei x. x. x Measure xx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx. 123, 61-118.

4) Xxxxxxxxx, X. H., Xxxxxx, D. X., Xxxxxx, M. X., Xxxxxxxx, M. X., Xxxxxx, X. X. (1990), The In xxxx Xxxxxxxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxxxx xxx Xxxxxxxxxx Xxxxx. A report xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Res., 239, 29-80.

5) XxxXxxxxx, X. X., Xxxxxxxx, X., Xxxx, W. X., Xxxx, X. M. (1983), Xxxxxxxxxxx in Xxxxxxxxxxx Xxxxxxxxxxxx: A Xxxxx Xxxxxx xxx Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Xxxxxxxx Testing xx Mice, xx: Xxxxxxxxxxxx in Science xxx Practice xx Xxxxxxxxxx, xx. A. X. Xxxxx, X. X. Xxxxxxx, T. X. Miya. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. T., Xxxxxx, X. X. Xxxx, X., Xxxxxxxx, G. X., Xxxxx, C., Xxxxxxxx, M. X., Xxxx, X. X., Xxxx, X. (1987), Xxxxxxxxxx for the Xxxxxxx xx Micronucleus Xxxxxx xx Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) MacGregor, X. X., Xxxx, C. X., Henika, P. X., Xxxxxx, X. X. (1990), Xxx xx vivo Xxxxxxxxxxx Xxxxxxxxxxxx Test: Measurement xx Xxxxxx Xxxxx Xxxxxxxxx Assay Xxxxxxxxxx xxx Permits Integration xxxx Xxxxxxxx Xxxxxxx, Xxxxxx. Xxxx. Toxicol. 14, 513-522.

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

9) Xxx Xxxxxxxxxxxxx Study Xxxxx for xxx Xxxxxxxxxxxx Test (1992). Xxxxxxxxxxxx Xxxx with Xxxxx Xxxxxxxxxx Blood Xxxxxxxxxxxx xx Acridine Xxxxxx Xxxxxxxxxx Xxxxxxxx: Xxx Summary Xxxxxx xx xxx 5xx Xxxxxxxxxxxxx Xxxxx by XXXXX/XXXXX, XXX, Mutatation Xxx., 278, 83-98.

10) Xxx Collaborative Study Xxxxx for xxx Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: Xxx Mammalian Xxxxxxxxxxx Xxxxx Group xx xxx Environmental Xxxxxxx Xxxxxxx xx Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx for xxx xxxxx-xxxx mouse xxxxxxxxxx xxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, M., Xxxx, X. R., MacGregor, X. T., Xxxxxxxx, X., Xxxxxxx, D. X., Kirsch-Volders, X., Xxxxxx, Xx. F. X., Pacchicrotti, F., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxxxx Xxxxx, Xxxxx. Xxx., 312, 293-304.

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

13) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Botham, P. X., Xxx, X., Xxxxxxx, D. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, G., Xxxxxx, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Environmental Mutagen Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx xx Xx vivo Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

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

15) XxxXxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, X. X. (1983), X Xxxxxx Xxxxxxxxxxx Xxxxxxxx Xxxxxxxxx xxx Xxxxxxxxxxx and XXX xx Xxxxxxxxxxxx Xxxxx Xxxxxxx 33258 xxx Pyromin X, Xxxxxxxx Xxx., 120, 269-275.

16) Romagna, X., Xxxxxxxxxx, X. X. (1989), Xxx automated xxxx xxxxxx micronucleus xxxx, Mutatation Xxx., 213, 91-104.

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

18) Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X., Chandley, X., Gatehouse, X. X., Xxxxxxxxx, L. (1990), Xx vivo Xxxxxxxxxxxx Xxxxx, xx: X. X. Kirkland (xx.), Basic Mutagenicity xxxxx, XXXXX Recommended Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx 1, revised, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Ferguson X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, X. X. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Cytogenetic Assays, xx: D. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Testing. Xxxxxx, Part XXX, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx York, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4D

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

1. METODA

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

1.1 XXXX

Xxx xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx na xxxxxxxxxxxxxxx Salmonella xxxxxxxxxxx x Xxxxxxxxxxx coli, x xxxxxxx xxxxxxxx xxxxxx, xxxxx zahrnují xxxxxxxxxx, xxxxx x xxxxxx xxxxxxx xxxx xxxxxxxx xxxx bází XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxx x detekci xxxxxx, které revertují xxxxxx xxxxxxxx x xxxxxxxxxxx kmenech x xxxxxxxx xxx funkční xxxxxxxxx xxxxxxxx syntetizovat xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx xxxx xxx xxxxxxxxxx xxxx x xxxxxxxxxxxxx xxxxxxxxxxxx, které xxxx vyžadovány mateřským xxxxxxxxxx xxxxxx.

Xxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx mnoha xxxxxxxxx podmíněných xxxxxx x xxxxxxx a xxxxxxxx mnoho xxxxxx x tom, že xxxxxx xxxxxx x xxxxxxxxxx a x xxxxxx somatických xxxxx xxxxxxxxx nádory mají xxxxx xx xxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx. Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx je xxxxxx, xxxxxxxxxx a xxxxxxxxx xxxxxx. Xxxxx testovacích xxxxx má řadu xxxxxxxxxx, díky nimž xxxx xxxxxxxxxx na xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx xxxxxxxx XXX xx reverzních xxxxxxx, xxxxxxx xxxxxxxxxxxx buněk xxx velké xxxxxxxx x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX nebo xxxxxxxx xxxxxxxxxxx procesů XXX xxxxxxxxxx x xxxxxx. Specifičnost testovacích xxxxx xxxx xxxxxxxxxx xxxxxxx užitečné informace x xxxxxx mutací, xxx jsou indukovány xxxxxxxxxxxxx činiteli. Xxx xxxxxxx xx reverzní xxxxxx x bakteriemi xx k xxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxxxx pro xxxxxxx xxxxx xxxxxxxx x xxxx xxxx xxxxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx těkavých xxxxxxxxx, x různými xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx také xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx nebo Xxxxxxxxxxx xxxx xxxxxx x xxxxxxx mutací x kmeni xxxxxxxxxxx xxxxxxxxxxxxx (histidin resp. xxxxxxxxx), xxxxxxx vzniká xxxx xxxxxxxxx na xxxxxxx xxxxxxx aminokyseliny.

Mutageny xxxxxxxxxx párů bází xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx x xxxxxx XXX. Při xxxxxxx xxxxxxxxxx xxxxxx xx xxxxx xxxx xxxxx vyskytnout na xxxxx původní xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx mutageny xxxx xxxxxxxx, jež xxxxxxxxx xxxxx xxxx xxxxxx jednoho xxxx xxxx párů xxxx XXX a posunují xxx čtecí xxxxx XXX.

1.3 XXXXXXX XXXXX

Xxx xxxxxxxxx xx reverzní xxxxxx s xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, které xx xxxx od buněk xxxxx xxxxxxx, xxxx xxxx příjem, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxx XXX. Xxxxxxx prováděné xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx u xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx x karcinogenním xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xx xxxxxxxxx xxxxxxxxx xxx xxxxxxxxx vyšetření xxxxxxxxxxx aktivity, a xxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxx mutace. X xxxxxxxx xxxxxxxx xxxxxxx, xx mnoho chemických xxxxx, xxxxx xxxx x xxxx zkoušce xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx x v xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx mutagenních xxxxxxxx, xxxxx nejsou xxxxxxxxxx xxxxx zkouškou. Příčiny xxxxxx skutečností xxx xxxxxxxxx ve xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx jevu, x xxxxxxxxx x xxxxxxxxxxx aktivaci nebo x xxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx straně faktory, xxxxx xxxxxxx citlivost xxxxxxx xx xxxxxxxx xxxxxx xx xxxxxxxxxx, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx aktivity.

Zkouška xx xxxxxxxx mutace x xxxxxxxxxx xxxxxx xxx vhodná pro xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx antibiotika) a xxx xxxxxxxx xxxxx, x xxxxx xx xxxxxxxxxxx (xxxx x xxxxx xx xx), xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx xxxxx (xxxx. xxxxxxx inhibitory topoisomerasy x některé xxxxxxx xxxxxxxxxx). V takových xxxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx mnoho xxxxxxxxx, xxx xxx xx tato zkouška xxxxxxxxx, xx xxxxxxxxxxxx xxx xxxxx, není xxxxxxxx xxxxxxxxx. Xxxxxx xx chemické xxxxx x existuje xxxxx xxxxxxxxxxx, jež xxxxxx xxxxxxxxxx touto zkouškou, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx buněk jsou xxxxxxxxx xxxxxxxx látce, x xx xx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx a xxx xxxx. Xx xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxx smíchají x xxxxxxx xxxxxx x xxxxx xx xxxxxxx xx xxxxxxxxx xxxx. V xxxxxxxxxxxx xxxxxx xx xxxxxxxx xxxx inkubuje x xxxx xx xxxx xxxxxxxxx xx xxxxxxxxx xxxx smíchá x xxxxxxx xxxxxx. Xxx xxxx xxxxxxxxxx xx xx xxxx nebo xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx revertantů x xxxxxxx xx xxxxxxxx x xxxxxx xxxxxxx spontánních xxxxxxxxxx xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

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

Xxx xxxxxxx xxxxxxx xx xxxxxx xxxxxx standardního xxxxxxxxx xxxxx a xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx je xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx xxx x xxxxxxxxxxxx aktivací, xxx xxx xx. Xxxxxxx xxxxx lze účinněji xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx metody. Tyto xxxxx patří do xxxxxxxxxx xxxx, xx xxxxx xxxxx mezi xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, dvojvazné kovy, xxxxxxxx, azobarviva x xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxxxx sloučeniny x xxxxxxxxxxxxxxx (3). Xxxxxx xx připouští, xx xxxxxx xxxxx xxxxxxxx xxxxx vždy xxxxxxxxx standardními xxxxxxx, xxxx xx xxxxxxxxxx xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Xxxx xx xxx xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x x xxxxxx xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Je možné xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (xxxxxxxx s xxxxxxxx postupů xxxxxx xxxxxxx): xxxxxxxxxx x xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx x xxxxxx xxxxxxxx látky (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxx xxx vědecky xxxxxxxxxx.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxxx xx xxxxxx xxxxxxxxxxxxx xxxx xxxx xx xxxxx xxxxxxxxxxx fáze růstu (xxxxxxxxx 109 xxxxx xx xx). Buňky x pozdní xxxxxxxxxxx xxxx by xxxxxx xxx xxxxxxx. Xx xxxxxxxx, xxx měly xxxxxxx xxxxxxxx xxxxxx xxxx životaschopných xxxxxxxx. Xxxx může xxx xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxx xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx xxxxx xx xxxxxxx.

Xxxxxxxxxx inkubační xxxxxxx je 37 °X.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxx bakterií. Xxxx xxxx xx měly xxx xxxxx kmeny X. xxxxxxxxxxx (TA1535; XX1537 xxxx XX97x xxxx TA97; XX98 x XX100), jejichž xxxxxxx xx xxxxxxx x xxxxxxx laboratořích xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx X. xxxxxxxxxxx xxxx pár bází XX na xxxxxxxxx xxxxxxxxx místě x xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx nelze xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, činitele xxxxxxxxxxx xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Tyto xxxxx xxxxx být xxxxxxxxxx kmeny E. xxxx XX2 xxxx X. typhimurium XX102 (19), které mají xx primárním xxxxxxxxx xxxxx xxx bází XX. Doporučená kombinace xxxxx xx xxxx xxxx:

- X. xxxxxxxxxxx XX1535 a

- X. xxxxxxxxxxx TA1537 xxxx XX97x a

- X. xxxxxxxxxxx TA98 x

- X. xxxxxxxxxxx XX100 x

- E. coli XX2 xxxX, nebo X. xxxx WP2 xxxX (xXX101), xxxx X. xxxxxxxxxxx TA102.

Pro xxxxxxx xxxxxxxx způsobujících xxxxxxxxxx xxxxxx DNA xxxx xxx xxxxxxxxx xxxxxxx XX102 xxxx xxxxxx xxxx X. xxxx s xxxxxxx xxxxxxxxxx xxxxxxxx XXX, (xxxx. X. xxxx XX2 (xXX101)).

Xxxx by xxx použity xxxxxxxx xxxxxxx xxxxxxxx kmenové xxxxxxx, xxxxxxxxxx xxxxxxx x skladování. Xxxxxxx xxxxxxxxxxxxx xxx xxxx xx xxxx být xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx kulturu (xxxxxxxx xxx kmeny X. xxxxxxxxxxx x xxxxxxxxx xxx E. xxxx). Xxxxxxx xx xxxx xxx kontrolovány xxxx fenotypové xxxxxxxxxxxxxxx, xxxxxxxxx podle potřeby xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx plasmidů (tj. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, TA100 x XX97x xxxx XX97, WP2 uvrA x WP2 xxxX (xXX101) a xxxxxxxxxxxx x tetracyklinová xxxxxxxxxx x xxxxx XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. xxx xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx xxxxxx x uvrA xxxxxx x X. xxxx xxxx xxxX xxxxxx u S. xxxxxxxxxxx citlivostí na xxxxxxxxxxxx světlo) (2, 3). Xxxxx xx xxxx xxxxxx xxxxx xxxxx xxxxxxx spontánních xxxxxxxxxx na xxxxx x xxxxxxx četností xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx x xxxxxxx x rozmezí xxxxxxxx x literatuře.

1.5.1.2 Xxxxxx

Xxxxxxx xx vhodný minimální xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx X (Xxxxx-Xxxxxx) x xxxxxxx) x xxxxxx xxxx xxxxxxxxxx histidin a xxxxxx xxxx xxxxxxxxx xxxxxxxxxx několik buněčných xxxxxx (1, 2, 9).

1.5.1.3 Metabolická xxxxxxxx

Xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx látce, x xx x xxxxxxx systémem xxxxxxxxxxx xxxxxxxx a xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx indukujícím xxxxxx, xxxx xx Xxxxxxx 1254 (1, 2) xxxx fenobarbitonu a β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx xxxxxx xx xxxxxxx používána x koncentracích v xxxxxxx 5 xx 30 % xxx. xx xxxxx X9. Xxxxx x podmínky xxxxxxxxxxxxx aktivačního xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxxxxx xxxxx. X xxxxxxxxx xxxxxxxxx xxxx být xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. X xxxxxxxxx a diazoniových xxxxxxxxx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).

1.5.1.4 Zkoušená xxxxx nebo xxxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx xxxx xxxxxxxx xx bakterie xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky mohou xxx xxxxxxx přímo x testovacím xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx zředěny. Xxxx by xxx 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 být xxxxxxxxxx x xxxxxxxx xxxxxxxx x x xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx o jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx vodu.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Xxxxxxxx xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, xxxxx xxxx být xxxxxxxxxx při stanovení xxxxxxxxxx množství zkoušené xxxxx patří xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx xxx užitečné xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx xxxx xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx zeslabením xxxxxxxxxxxxx podkladu nebo xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx se xxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx by xxxx xxx xxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxxx xxxxx xx skutečných xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx maximální xxxxxxxx xxxxxxxxxxx pro rozpustné xxxxxxxxxxxxx xxxxx je 5 xx/xxxxx nebo 5 μx/xxxxx. X xxxxxxxxxxxxxxx látek nerozpustných xxx koncentracích 5 xx/xxxxx nebo 5 μx/xxxxx xx xxxx xxx xxxxx xxxx xxxx zkušebních koncentrací xxxxxxxx, xxx látky xxxx x xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxxxx. Zkoušené xxxxx, xxxxx xxxx cytotoxické xxx xxx koncentracích xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, by měly xxx xxxxxxxx xx xx cytotoxické xxxxxxxxxxx. Xxxxxxxxx by neměla xxxxx při vyšetřování.

Mělo xx xxx použito xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxxxxx zkoušené xxxxx, xxxxxxx xxx xxxxxx experimentu by xxxx být intervaly xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxx stupnice (xx. Ö10). Xxxxx xxxxxxxxx xxxx xxxxxx x případě, kdy xx xxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx může xxx xxxxxxx při xxxxxxxxx xxxxx obsahujících xxxxxxxx xxxxxxxx xxxxxxxxxxx mutagenních xxxxxxxx.

1.5.2.3 Negativní x xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxx xx xxxx xxx kmenově xxxxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx. Pro pozitivní xxxxxxxx xx xxxx xxx vybrány xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx každé xxxxxxx.

X xxxxxxx xxxxxxx x použitím metabolického xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxx (xxxxx) xxx xxxxxxxxx xxxxxxxx xxxxxxx (vybrány) xx xxxxxxx typu xxxxxxxxx xxxxx xxxxxxxx.

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

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

Xxxx xxxxx xx xxxxxxx xxxxxxxxx xxxxxxxxx pro xxxxxx redukční xxxxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

XX Xxxxxx Xxx 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx xx xxxxx xxx xxxxxx xxxx xxxxxx indikátor xxxxxxxxx xxxxx X9. Při xxxxxxx 2-xxxxxxxxxxxxxxx xx xxxx xxx xxxxx xxxxx X9 charakterizována xxxxxxxxx, který vyžaduje xxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

Xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx xxx vnější xxxxxxxxxxx xxxxxxxx xxxx xxxx látky:

Látka

Číslo CAS

Číslo xxxxx XXXXXX

Xxxx

xxxx xxxxx

26628–22–8

247–852–1

XX1535 x XX100

2-xxxxxxxxxxxx

607–57–8

210–138–5

XX98

9-xxxxxxxxxxxx

90–45–9

201–995–6

XX1537, XX97 x XX97x

XXX 191

17070–45–0

241–129–4

XX1537, XX97 a XX97x

Xxxxxxxxxxxxxxxxx

80–15–9

201–254–7

XX102

xxxxxxxxx X

50–07–7

200–008–6

XX2xxxX a TA102

1-methyl-3-nitro-1-nitrosoguanidin

70–25–7

200–730–1

WP2, XX2 xxxX a XX2 xxxX (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 xxxX x XX2 xxxX (xXX101)

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

3688–53–7

xxxxx xxxxxxxxxx plasmidy

Pro xxxxxxxxx xxxxxxxx xxxxx xxx použity xxxx xxxxxx referenční látky. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx x úvahu xxxxxxx chemických látek xx xxxxxx chemické xxxxx, jsou xx x dispozici.

Měly by xxx použity xxxxxxxxx xxxxxxxx skládající se xx xxxxxxxxx rozpouštědla xxxx vehikula, bez xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx způsobem xxxx xxxxxxxxxx skupiny. Xxxxx toho xx xxxx xxx neexponované xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5.3 Xxxxxx

X xxxxxxxxxx miskové xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx aktivace xx xxxxxxx xxxxxx 0,05 xx nebo 0,1 xx xxxxxxxxxx roztoků, 0,1 xx xxxxxxx xxxxxxxxxxx xxxxxxx (obsahující xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x 0,5 xx xxxxxxxxxx xxxxx x 2,0 xx xxxxxxxx agaru. X xxxxxxx xxxxxxx x xxxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx postmitochondriální frakce (x xxxxxxx 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx xxxxx) x xxxxxxx xxxxxx (2,0 xx) a xxxxxxx x xxxxxxxxxx x xxxxxxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx. Obsah xxxxx xxxxxxxx se xxxxxxxx x přelije xxxx xxxxxx xxxxxxxxxxx xxxxx xx misce. Xxxx inkubací se xxxxx vrchní xxxx xxxxxxxx.

X xxxxxxxxxxxx metody (2, 3, 5, 6) xx zkoušená xxxxx xxxx xxxxxxxx xxxxxx xxxx xxxxxxxxx x xxxxxxx agarem x xxxxxxxx xxxx xxxxxx xxxxxxxxxxx agaru xx misce xxxxxxx 20 minut xxxx xxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxx (xxxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) x xxxxxxxxx xxxxxx xxxx metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) xxx 30 — 37 °C. Xxxxxxx xx xxxxxx 0,05 nebo 0,1 xx xxxxxxxx xxxxx xxxx xxxxxxxxxx roztoku, 0,1 ml bakterií x 0,5 xx xxxxx X9 xxxx xxxxxxxxxx xxxxx s 2,0 xx vrchního xxxxx. Xxxxxxxx xx xxxx být během xxxxxxxx xxxxxxxxxxxxxx na xxxxxxxx.

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

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

1.5.4 Xxxxxxxx

Xxxxxxx misky v xxxx xxxxxxx xx xxxx být xxxxxxxxxx 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 by xxxx xxx xxxxx kolonií xxxxxxxxxx xxxxxxxxxxx na xxxxx. Xxx xx xxx rovněž xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx na xxxxxxx x negativní kontrolou (xxxxxxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxxx xxxxxxxx), xxx xx xxxxxxx x xxxxxxxxx xxxxxxxxx. Xxxxx xx xxxxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx odchylka xx xxxx xxx xxxxxxxxxx xxx zkoušenou látku x xxxxxxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx a/nebo xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx jasně xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Negativní výsledky xxxx být xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx nezbytné, xxxx xx být xxxxxx xxxxxxxxxx. Xxxxx parametrů xxxxxx s xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, které xx mohly xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx xxxxxxx xxxxxx xxxx xxxxxxxxxxx x xxxxxxxx médiu) x xxxxxxxx metabolické xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. nárůst xxxxx xxxxxxx xxxxxxxxxx xx misku nad xxxxxxxxx xxxxxx x xxxxxxx xxxxxxx kmene x metabolickým xxxxxxxxxx xxxxxxxx xxxx xxx xxxx, x xx x xxxxxxxxxx na xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx počtu xxx xxxxx nebo xxxx xxxxxxxxxxx (23). Xxxxxxxx xx měla xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx významnost xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx bez xxxxxx xx xx, kolikrát xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx mutace s xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x xxxxxx xxxxx Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx bodové xxxxxx substitucí xxxx xxxx xxxxxxx čtecího xxxxx. Negativní výsledky xxxxxxxxx, xx zkoušená xxxxx není za xxxxxxxx xxxxxxx xxx xxxxxxxxx druhy mutagenní.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Kmeny:

- xxxxxxx xxxxx,

- počet xxxxx v xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxx xxxxxxxx xxxxx xx xxxxx (xx/xxxxx xxxx μx/xxxxx) x xxxxxxxxxxx výběru xxxxx x xxxxx misek xx xxxxxxxxxxx,

- xxxxxxx xxxxx,

- xxx x xxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxxxxxx,

- xxxxxx expozice.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx miskách,

- xxxxxxx xxxxxxx počtu xxxxxxx xxxxxxxxxx na misku x xxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx statistické analýzy,

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

- xxxxxxxxx údaje x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) a xxxxxxxxx kontrole s xxxxxxxxx, středními xxxxxxxxx x směrodatnými xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

3) Xxxxxxxxx, X., Xxxxxxx, X., Cebula, X., Gocke, X., Xxxx, L., Xxxxxxxxxx, X., Melcion, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, X. (1994), Recommendations for xxx Xxxxxxxxxxx xx Xxxxxxxxx Mutation Xxxxxx, Xxxxxxxxxx Xxx., 312, 217-233.

4) Kier, L. X., Xxxxxxx X. X., Xxxxxxx, X. X., Xxx Xxxxx, X. X., Xxxxx, X. M., Xxxxxx, X. X., Xxxxxx, X., XxXxxx, X., Xxxxxxxxxx, K., Xxxxxx, X., Xxx, X. X., Xxx V. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Microsomal Assay: X Xxxxxx of xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, X., Degawa, X., Seino, Y. X., Xxxxxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. (1975), Xxxxxxxxxxxx of Xxxxxxxxxx Azo Dyes xxx their Derivatives, Xxxxxx Xxxx. 1, 91-96.

6) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, A., Xxxxxxxx, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxx, in: Xxxxx-xxxx Xxxx Systems xxx Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx K. X., Xxxxxx, X. X., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx York, 273-285.

7) Gatehouse, X. X., Xxxxxxx, I. X., Wilcox, P., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Mutation Assays, xx: Xxxxx Xxxxxxxxxxxx Xxxxx: UKEMS Part 1 Revised, xx. X. J. Kirkland, Xxxxxxxxx University Xxxxx, 13-61.

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

9) Green, X. H. X., Xxxxxx, W. X., Xxxxxxx, X. X. (1976), Use xx x xxxxxxxxxx fluctuation xxxx to xxxxxx xxx xxxxxx xx xxxxxxxx, Mutatation Res., 38, 33-42.

10) Xxxxxxx, X. X., Green, X. X. L., Xxxxxxxxx, D., Xxxxxxx, X. X. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, 2. xxx., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (xxx.), Elsevier, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, X. D., Xxxxxxx, X. X. (1981), Xx Xxxxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxxx Xxxxx for Xxxxxxxxxxx xxxx Strains xx Salmonella xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Araki, X., Xxxxxxx, X., Xxxx, X., Xxxxxxxxxx, T. (1994), Xxxxxxxx Xxxxxx xxx Mutagenicity Xxxxxxx xx Gaseous Compounds xx Xxxxx x Xxx Xxxxxxxx Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

13) Prival, M. X., Bell, S. X., Xxxxxxxx, V. X., Reipert, X. X., Xxxxxxx, V. X. (1984), Mutagenicity xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Dyes xxx Xxxxxxxx Xxxxxxx Xxxx xx x Modified Xxxxxxxxxx Assay, Mutatation Xxx., 136, 33-47.

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

15) Simmon, X., Xxxxxxxx, X., Xxxxxxx, X. G. (1977), Xxxxxxxxx Activity of Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxx Water, in Xxxxxxxx in Xxxxxxx Xxxxxxxxxx, X. Xxxxx, X. Xxxxxxx, F. Xxxxxx (eds.) Xxxxxxxx, Xxxxxxxxx, 249-258.

16) Xxxxxx, X. X., Xxxxxxx, X. M., Xxxxxxxx, X. G., Xxxxxxx, X. D. (1987), Xxxxxxxxxxxx Xxxxxxxxx to Xxxxxxx Xxxxxxxxx Activity xx Xxxxxxxx Organic Xxxxxxxxx in the Xxxx/Xxxxxxxxxx Xxxxx, Environmental Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, X., Xxxxxxxxx, X., Shirai, X., Xxxxxxxx, X., Sugimura, X. (1979), Mutagenicity xx xxx Naturally Xxxxxxxxx Carcinogen Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxx typhimurium, Xxxxxx Xxx., 39, 3780-3782.

18) Xxxxxx, X., Gold, X., Ferro-Luzzi, X., Xxxx, X. X. (1980), Xxxxxxxx: X Xxxxx for Xxxxxxxxxx xx Dietary Xxxxxxxxxx xx Xxxxxxxx by Xxxxxxxxxx Xxxxx, Xxxx. Xxxx. Acad. Xxx. X. S. X, 77, 4961-4965.

19) Xxxxxx, X., Xxxxxx, X., Xxxx, X. X., Xxxxxxxxx, D. X. (1990), Xxxxxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx TA 102 xxxx Xxxxxxxxxxx xxxx XX2 Tester xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, X., Sugimura, X. (1976), A Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: In vitro Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, xxx. X. X. xx Xxxxxx et xx. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.

21) Xxxxxx, B. X., Xxxxxx, X. X., Xxxxxxx, X. X., Gatehouse, X. X., Xxxxxx, X. X., Mackay, X. X., Wolf, R. X. (1992), Alternatives xx Xxxxxxx 1254-induced X9 in xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

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

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

24) Xxxxx, X. A. X., Xxxxx, X. X. L., Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, D. J. (1989), Xxxxxxxx of Xxxx from Xxxxxxxxx Xxxxxx Assays, xx: XXXXX Sub-Committee xx Xxxxxxxxxx for Mutagenicity Xxxxxxx, Xxxx XX. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Test Data, xx. Xxxxxxxx, X. X., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 28-65."


XXXXXXX 4E

"B.17 XXXXXXXXXX — XXXXXXX XX XXXXXX MUTACE V XXXXXXX XXXXX XX XXXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX TG 476 — Xxxxxxx na xxxxxx mutace x xxxxxxx xxxxx xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx genové xxxxxx x xxxxxxx xxxxx xx xxxxx xxx xxxxxx pro xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxx xxxxxxx X5178X myší, buněčné xxxxx XXX, XXX-XX52 x X79 xxxxxx xxxxxxxx x lymfoblastoidní xxxxx XX6 člověka (1). X těchto xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx mutace genů xxx thymidinkinasu (TK) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (HPRT) x transgen xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Zkoušky xx xxxxxx XX, XXXX x XXXX xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX x XXXX xxxx xxxxxxx xxxxxxx xxxxxxxxxxx událostí (xxxx. xxxxxxxx xxxxxx), xxxxx xxxxx xxxxxxxxx x XXXX lokusu xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx xx xxxxx xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx nebo xxxxxxx xxxxx. Xxxxx se xxxxxxxx podle schopnosti xxxxx x xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační xxxxxx xxxxxx zcela xxxxxxxxx xxxxxxxx xx xxxx u savců. Xx třeba se xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx, xxxx xxxxx xxxxxx xX, xxxxxxxxxx nebo xxxxxxxx xxxxxx cytotoxicity (7).

Tato xxxxxxx se xxxxxxx xx xxxxxxxx možných xxxxxxxx x xxxxxxxxxxx xxxxx. Mnoho xxxxxxxxx, xxx xxx je xxxx xxxxxxx xxxxxxxxx, xxxx karcinogeny xxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx korelace. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx a xxxxxxxxx důkazy x xxx, xx existují xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx touto zkouškou, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, které x bakteriálních xxxxxxx xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

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

Xxxxxxxx mutageny : xxxxx, které xxxxxxxxx xxxxx xxxx deleci xxxxxxx xxxx více xxxx bází x xxxxxxxx DNA.

Doba xxxxxxx xxxxxxxx : xxxx, xxxxx xxx vymizí x xxxx xxxxxxxxxx xxxxx nezměněné xxxxxx xxxxxxxx.

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

Xxxxxxxxx xxxxxxx xxxx : xxxxxx xxxxx xxxxx x xxxx xx srovnání x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx xx xxxx xxxxxx xxxxxx xxxxxxxxx xxxxx x xxxxxxxx a v xxxxxxxxx xxxxxxxx x xxxxxxxxx účinnosti xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxx x xxxxxxxx : nárůst xxxxx buněk x xxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxx kontrole.

Životaschopnost : účinnost klonování xxxxx x okamžiku xxxxxxxx xx xxxxx xx xxxxxxxxxxxx xxxxxxxx xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx xx xxxxx na xxxxx xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx xxxxxxxxx x poměru x xxxxxxx xxxxxxxxx populace xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx TK+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (TK) xxxx xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx analogu pyrimidinu xxxxxxxxxxxxxxxxx (XXX). Xxxxx xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx xx TFT, xxx způsobuje xxxxxxxx xxxxxxxxx metabolismu x xxxxxxxxx další buněčné xxxxxx. Xxxxxxxx buňky xxxx xxxx xxxxxxx xxxxxxxxxxx xx přítomnosti XXX, xxxxxxx normální xxxxx, které xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Xxxxxxx xxx x buněk x xxxxxxxxxxxx XXXX nebo XXXX xxxxxxx selekci xxxxxxxxxxxxxxx xxxxxxxxxx k 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (XX). Vlastnosti xxxxxxxx látky xx xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx xx xx zkoušce xx xxxxxx xxxxxx x xxxxxxx xxxxx zkoušen xxxxxx báze xxxx xxxxxxxxxx podobná selekčnímu xxxxxxx. Xxxx xx xxx například xxxxxxxxx xxxxxxxx podezření na xxxxxxxxxx toxicitu xxxxxxxx xxxxx xxx xxxxxxxx xxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxx chemických xxxxx, xxxxx mají xxxxxxxx xxxxxxxxx jako xxxxxxxx xxxxxxx, xxxx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxx nebo xxxxxxx xxx selekci (8).

Xxxxx v suspenzní xxxx xxxxxxxxxxxxx kultuře xxxx xxxxxxx xxxx xxxxxxxxx zkoušené látce xxx s xxxxxxxxxxxx xxxxxxxx, tak bez xx, x xxxxxxxxxxxxxx xx xxxxxx stanovení xxxxxxxxxxxx a za xxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx mutantů (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxxx xxxx expozice. Xxxxxxxxxx xxxxxxx xx xxxxxxx v xxxxxxxx xxxxx xx vhodnou xxxx xxxxxxxxxxxxxxxxx xxx xxxxx zvolený xxxxx x xxx buněk, xxx xxxxxxx přibližně xxxxxxxxx fenotypová xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx se stanoví xxx, xx se xxxxxx xxxxx xxxxx xxxxx xx média xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx xxxxxxx mutantních xxxxx a xx xxxxx bez xxxxxxxxxx xxxxxxx, aby xxxx xxxxxxxxx účinnost xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx xx xxxxxxxxx xxxxxxx. Četnost xxxxxxx se xxxxxxx x xxxxx xxxxxxxxxx xxxxxxx v xxxxxxxxx xxxxx x xxxxx xxxxxxx x xxxxx xxx selekčního xxxxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Pro xxxxxxx x této zkoušce xxxx k xxxxxxxxx xxxxx xxxx xxxxx, xxxxxx xxxxxxxx xxxxx X5171X, XXX, XXX-XX52, X79 nebo XX6. Xxxx xxxxx v xxxx xxxxxxx by xxxx xxxxxxxxx xxxxxxxxx x chemickým xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x xxxxxxxx frekvenci xxxxxxxxxxx mutací. Xxxxx xx xxxx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, x x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx.

Xxxxxxx xx měly xxx navrženy tak, xxx měly předem xxxxxxxxxx citlivost x xxxx. Počet xxxxxxxxx xxxxx, kultur x xxxxxxxxxxx xxxxxxxx xxxxx xx měl xxxx xxxxxxxxxx parametry odrážet (14). Minimální xxxxx xxxxx, které xxxxxxx xxxxxxxx x xxxxx xxxxx xxxxxxx x xxxxxx xxxxxx zkoušky, xx xxx být xxxxxxx xx četnosti xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx je, aby xxx xxxxxx počet xxxxx, který je xxxxxxxxxxxxxx xxxxxxxxxx hodnoty xxxxxxxx xxxxxxxxxxx xxxxxx. Xx xxxx xxxxxxxxxx, xxx bylo použito xxxxxxx 106 xxxxx. Xxxx xx xxx x dispozici xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx buněčném systému, xxx byla doložena xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx podmínky

Pro udržování xxxxxx by měla xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx a xxxxxxxxx xxxxxxxx (kultivační xxxxxx, koncentrace XX2, xxxxxxx x xxxxxxx). Xxxxx xx xxxx xxx zvolena xxxxx xxxxxxxxxx systémů x xxxx buněk xxxxxxxxx xxx zkoušce. Xx xxxxxxx xxxxxxxx, aby xxxxxxxxxx podmínky byly xxxxxxx xxx, xxx xxxx zajištěny xxxxxxxxx xxxx buněk xxxxx xxxxxx xxxxxxx x xxxxxxxxx xxx mutovaných, xxx xxxxxxxxxxxx xxxxx xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxx, xxxxxxxx xx kultivačního xxxxx x xxxxxxxxxx xxx 37 °X. Před xxxxxxxx x xxxx xxxxxxx xxxx být xxxxxxxx odstranit z xxxxxxx xxx xxxxxxxx xxxxxxxx xxxxx.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx měly xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx a xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená x xxxxx xxxxxxxx xxxxxxxxxx činidlem xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (15, 16, 17 a 18), xxxx směs xxxxxxxxxxxxx x β-xxxxxxxxxxxx (19, 20).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx v koncentracích 1 — 10 % xxx. Xxxxx x xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx může xxxxxxx xx xxxxx xxxxxxxx látky, xxxxx xx xxxxxxxx. X xxxxxxxxx případech xxxx xxx vhodné xxxxxx xxxx xxx jednu xxxxxxxxxxx postmitochondriální frakce.

Řada xxxxxxxx vývoje, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx exprimujících xxxxxxxxxx aktivační xxxxxx, xxxxxxxxx xxxxxxxx pro xxxxxxxxx aktivaci. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx xx xxxx být xxxxxxx zdůvodněna (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Příprava xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx být xxxxxxx přímo x xxxxxxxxxx systémům x/xxxx xxxxx být xxxx xxxxxxxx zředěny. Xxxx xx xxx použity xxxxxxx připravené xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x stálosti xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, že xxxxxxx se xxxxxxxxx xxxxxx, x xxxx xx xxx slučitelné x xxxxxxxx xxxxx x x xxxxxxxxx X9. Xxxx-xx použita xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx by xxxx být použitá xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx. Vodu lze xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx zohledněna xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x testovacím systému x xxxxx pH xxxx osmolality.

Cytotoxicita by xxxx xxx stanovena x xxxxxxxxxxxx xxxxxxxx x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx vhodných xxxxxxxxxx buněčné xxxxxxxxx x růstu, xxxx xxxx relativní xxxxxxxx xxxxxxxxx (přežití) nebo xxxxxxxxx xxxxxxx xxxx. Xxxx xxx výhodné xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx koncentrace. V xxxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x minimální xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, což bude xxxxxxx xxxxxxxx, že xx xx xxxxxxxxxxx xxxx lišit faktorem 2 až Ö10. Xx-xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx od xxxxxxxxxxxx, xxxx xx být xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx nejméně 10 %) přežití (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 mg/ml xxxx 0,01 M, xxxxx toho, xxxxx x nich xx xxxxxxxx.

Xxxxxxxxx nerozpustné xxxxx xx xxxx xxx xxxxxxxx xx x xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx xxxxxxxx, xxxx xx xx tuto xxx. Xxxx by xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxx v xxxxxxxx xxxxx, ve xxxxxxx xxxx buňky exponovány. Xxxx xxx výhodné xxxxxxxx xxxxxxxxxxx xx xxxxxxx x xx xxxxx aplikace, neboť xxxxxxxxxxx se může x xxxxxxx xxxxxxxx x xxxxxxxxxx xxxxxxx xxxxx v xxxxxxxx xxxxxxxxxxx buněk, X9 xxxx, xxx. Xxxxxxxxxxxxx xxx zjistit xxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx jak x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Xxx xxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, která x xxxxxxxxx odpovědi xxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxx xxxxx:

Xxxx xxxxxxxxxxx aktivace

Lokus

Látka

Číslo XXX

Xxxxx podle Einecs

Bez xxxxxx xxxxxxxxxxx xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx 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 vnější metabolickou xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (malé x xxxxx xxxxxxx)

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxx[x]xxxxx

50–32–8

200–028–5

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–5

XXXX

X-xxxxxxxxxxxxxxxxxxx (xxx vysoké xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx být xxxxxxx xxxx xxxx referenční xxxxx pro xxxxxxxxx xxxxxxxx, xxxx. xx-xx xxxxxxxxx xxxxxxxx dosavadních xxxxx x 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, XXXXXX 200–415–9), xxxx xxx xxxx xxxxxxxxxx látka xxxxxx xxxxxxx. Pro xxxxxxxxx xxxxxxxx xx xxxx být xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxxx xx stejné xxxxxxxx třídy.

Měly by xxx použity xxxxxxxxx xxxxxxxx tvořené médiem xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx nevyvolává xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx látce

Proliferující xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx by měla xxxxx xxxxxxx xxxx (xxxxxxx xx xxxxxx xxxx 3 xx 6 xxxxx). Expoziční xxxx může xxx xxxxxxxxxxx xx jeden xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx zkušební xxxxxxxxxxx xxxxx xxx xxxxxxx duplicitní xxxxxxx xxxx xxxxx xxxxxxxxxx xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, xxx xx xxx počet xxxxxxxxxxx xxxxxx xxx, xxx byl xxxxxxxx xxxxxxxxxxxx xxxxx kultur xxx xxxxxxx (xxxx. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx xx xxx použity xxxxxxxxxx xxxxxxxxx kontrolní kultury (xxxxxxxx rozpouštědla).

Plynné nebo xxxxxx xxxxx xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, např. x xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Xxxxxxxxx přežití, xxxxxxxxxxxxxxxx a četnosti xxxxxx

Xx xxxxx expoziční xxxx se buňky xxxxxxx x xxxxxxxxx xx xxxxxx stanovení xxxxxxx x za xxxxxx xxxxxxxx exprese xxxxxxxx xxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx relativní xxxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxx xxxxxxx po xxxxxxxxx xxxx.

Xxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, xxx xxxxxxx xxxxxxxxx optimální xxxxxxxxxxx xxxxxxx nově indukovaných xxxxxxx (XXXX a XXXX xxxxxxxx xxxxxxx 6 xx 8 xxx, XX alespoň xxx dny). Buňky xxxx kultivovány v xxxxx xx selekčním xxxxxxxx (xxxxxxxxxx xxxxxxx) x bez xxxx (xxx xxxx) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx x klonovací xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx xxxxxxxx xxxxxxx) xx započne xx xxxxx doby exprese xxxxxxxxx xx misku xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx xxxxx pozitivní xx xxxxxxx X5178X XX+/-, xxxx xx xxx provedeno alespoň xx xxxxx xx xxxxxxxxxx xxxxxx (s xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x na xxxxxxxxxxx x pozitivních xxxxxxxxxx xxxxxxxxx xxxxxxx podle xxxxxxxxx xxxxxxx. Je-li xxxxxxxx xxxxx xx xxxxxxx L5178Y XX+/- xxxxxxxxx, mělo xx xxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxxxxx na xxxxxxxxxxx x pozitivních xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx XX6 TK+/- xxxx být xxxx xxxxxxxxx xxxxxxxxx kultury xxxxx xxxxxxxxx xxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xx xxxx xxxxxxxxx xxxxxxxxx cytotoxicity a xxxxxxxxxxxxxxxx, xxxxx kolonií x četnosti mutantů xxx xxxxxxxxxx a xxxxxxxxx kultury. X xxxxxxx xxxxxxxxx xxxxxxxx xx zkoušku X5178X XX+/- xx kolonie xxxxxxxxx xxxxxxx x xxxxx xxxxxxxxxxx zkoušené xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) a x xxxxxxxxx a xxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx malá xxxxxxx — xxxxx xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxx kolonie, xxx xxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Xx xxxxxxx XX+/- xxxx xxxxxxx xxxxxxxxxxx za xxxxxxx xxxxxxxx kolonie s xxxxxxxxx růstem (xxxxx) x xxxxxxx x xxxxxxx xxxxxx (malá) (25). U mutantních xxxxx, které xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx xxxx xxxxxxxx, a xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx xx xxxxx xxxxxx xxxx až xx xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Indukce xxxxxxx xxxxxxxxx xxxx xxxxxxx xx spojuje x xxxxxxxxxx xxxxxxx, xxxxx xxxxxxxx silné xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx xxxxxxxxx xxxxx mutantů xxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxx buňky a xxxxx xxxxx xxxxxxx.

Xxxx xx xxx udáno xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx růst. Četnost xxxxxxx by xxxx xxx vyjádřena xxxx xxxxx xxxxxxx x xxxxx xxxxxxxxxx xxxxx.

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

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx být xxxxxxxxx případ od xxxxxxx. Xxx, kde xxxx xxxxxxxxx negativních xxxxxxxx xxxxxxxxxx xx xxxxx, xx xxxxx xxxxx zdůvodnění. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx podmínek by xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx xxx xxx dvojznačné xxxxxxxx, xxx xxx xxxxxxxxx xxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx mohly xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx x podmínky xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, xxxx. xxxxxx četností xxxxxxx v xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení výsledků xxxxxxx xxxxx být xxxxxxx xxxx pomocný xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx xxxxxxxxxx by xxxxxx být xxxxxxx xxxxxxxxx faktorem pro xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x ojedinělých případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx in xxxxx znamenají, xx xxxxxxxx xxxxx xxxxxxxx x použitých xxxxxxxxxxxxx xxxxxxx xxxxx genové xxxxxx. Reprodukovatelná xxxxxxxxx xxxxxxxxx odpovědi xx xxxxxxxxxxx xx velmi xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx podmínek xxxxxxx neindukuje x xxxxxxxxx kultivovaných xxxxxxx xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxx x xxxxx xxxxx,

- počet xxxxxxxxx xxxxxx,

- xxxxxxxx počet xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx mykoplasmat.

Zkušební xxxxxxxx:

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

- xxxxxxx xxxxx, případně koncentrace XX2,

- koncentrace zkoušené xxxxx,

- xxxxx xxxxxxxx x přidané xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx doba,

- délka xxxxxxxx,

- případně xxxxxxx xxxxx během xxxxxxxx,

- xxx x xxxxxxx xxxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxxxxxx,

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

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

- xxxxxxxx xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx nebo dvojznačnou,

- xxxxxx použité x xxxxxxxx životaschopných x xxxxxxxxxx buněk,

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

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

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

- xxxxxxxx xxxxxxx, byla-li xxxxxxxxxxx, xxxxxxx xxx negativní x pozitivní xxxxxxxx,

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

- podle xxxxxxxx xxxxxxxxx odpovědi xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

- xxxxxxx xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. M., XxXxxxxx, X. X., XxXxxxxx, X. J., Tindal, X. X. (eds.) (1987), Banbury Xxxxxx 28; Xxxxxxxxx Cell Xxxxxxxxxxx, Cold Xxxxxx Xxxxxx Laboratory, Xxx Xxxx.

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

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

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

5) Aaron, X. X., Stankowski, Xx. X. X., (1989), Xxxxxxxxxx xx xxx AS52/XPRT xxx xxx XXX/XXXX Xxxxxx: Xxxxxxxxxx xx Xxx Xxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx. 223, 121-128.

6) Xxxxx, X. X., Xxxxxxxxxx, X., Xxxxx, X. X., Moore, X., Nishi, Y., Xxxxxxxxxx, Xx. X. X., Theiss, J., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Gene Xxxxxxxx Assays Working Xxxxx Report. Report xx xxx Xxxxxxxxxxxxx Xxxxxxxx on Xxxxxxxxxxxxxxx xx Genotoxicity Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Scott, X., Galloway, S. X., Xxxxxxxx, X. X., Ishidate, M., Xxxxxxx, X., Ashby, X., Myhr, X. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. X report xxxx ICPEMC Xxxx Xxxxx 9, Mutation Xxx. 257, 147-204.

8) Xxxxx, X., XxXxxx, X., Xxxxxxx, X. X. X., Piper, X., Xxxxxxxxx, X. X. (1983), Specific Xxxx Xxxxxxxxx in X5178X Xxxxx xx Xxxxxxx. X Report xx xxx X. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 115, 225-251.

9) Li, A. X., Xxxxx, X. X., Xxxxxxx, R. X., Xxxxxx, J. X. (1988), X Xxxxxx and Analysis xx xxx Chinese Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx System xx Determine xxx Xxxxxxxxxxxx of Chemical Xxxxxx: X Xxxxxx xx Xxxxx XXX xx the U. X. Environmental Xxxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Res., 196, 17-36.

10) Xx, X. X., Xxxxxx, J. X., Xxxx, W. X., Xxxx, X. X., Xxxxx, R. X., Loveday, X. X., O'Νeill, X. X., Riddle, X. X., Xxxxxxxxxx, L. X. Xx., Yang, X. L. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx of xxx Xxxxxxx Xxxxxxx Xxxxx Cell/Hypoxanthine-Guanine Phosphoribosyl Xxxxxxxxxxx Gene Mutation Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

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

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

13) Xxxxxx, X. T., Xxxxxx, A. G., Xxxxx, X. (1984), Xxxxxxxxx xxx xxx X5178X/XX+/--XX+/- Xxxxx Xxxxxxxx Xxxx Mutagenicity Xxxxx, xx: Xxxxxx, X. X. xx xx (xxx.) Handbook xx Xxxxxxxxxxxx Xxxx Procedures, Xxxxxxxx Science Xxxxxxxxxx, Xxx Xxxx, 239-268.

14) Xxxxxx, X. X., Xxxxx, X. X., Xxxxxx, G. X., Xxxxx, X. X. X., Xxxx, X., XxXxxxxx, X. B., Xxxxxxx S. C. (1989), Mammalian Cell Xxxx Xxxxxxxx Assays Xxxxx xxxx Xxxxxx Xxxxxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Xxxxxxxx, X. X., ed., Xxxxxxxxx University Xxxxx, 66-101.

15) Abbondandolo, A., Xxxxxxx, S., Corti, X., Xxxxxx, X., Xxxxxxxx, X., Mazzaccoro, X. (1977), Xxxxxxxxx xx 6-Thioguanine-Resistant Xxxxxxx xx V79 Xxxxxxx Xxxxxxx Xxxxx by Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Res. 46, 365-373.

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

17) Xxxxx, X., Johnson, X. O., Xxxxxxx, X. F. X., Xxxxxx A. X., Xxxxx X. X. X. (1979), Xxxxxxxxxx xxx Xxxxxxxxxxxxxxxx xx xxx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxxxx Assay Xxxxxx, Xxxxx. Res. 59, 61-108.

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

19) Xxxxxxx, B. X., Combes, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, G. X., Xxxxxx, J. X., Wolf, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-Induced X9 xx: Xx xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, X., Xxxxxxxx, X. (1976), X Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, V: Xx xxxxx Metabolic Xxxxxxxxxx in Mutagenesis Xxxxxxx, xx Xxxxxx, X. X., Xxxxx, X. X., Xxxx, X. X., Xxxxxxx, X. M. (eds), Xxxxxxxx, North-Holland, 85-88.

21) Xxxxx, D. X., Xxxxxx, X. X., XxXxxxx, K. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Evaluation xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Costa, X. X., Xxxxxxx, X. M. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, New Xxxx, Xxxxxx, 91-103.

22) Xxxxxx, X. X., Xxxxxx, J. M., Xx, A. P., Xxxxxx, A. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Gels xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx in xxx XXX/XXXXX Xxxxxxxx Xxxxx, Environ. Mutagenesis, 5, 795-801.

23) Xxxxxxxxx, X. L., Xxxxx, X. M., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxx, J. X. (1990), Xxxxxxxxx Xxxxxxxxxx xx Mutations xx the Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Xxxxx xx Xxxxx Xxxxxxxx Xxxxx, Xxxx. Natl. Xxxx. Sci. U. X. X, 87, 51-55.

24) Xxxxx, M. X., Clive, X., Xxxxxx, J. C., Xxxxxx, X. E., Xxxxxx, X. G., Xxxxxx, N. X., Xxxxxx, X. (1985), Xxxxxxxx of Trifluorothymidine, Xxxxxxxxx (XXX+) Mutants xx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx. 151, 161-174.

25) Xxxxxxx, X. X., Xxxxx, X. P., Little, X. X. (1990), Xxxxxxxxx Xxxxxxx Analysis xx Recessive Xxxxxxxxx xx a Xxxxxxxxxxxx Xxxxxxxxx Xxxxx xx Xxxxx Xxxxx, Mutatation Xxx. 229, 89-102.

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


XXXXXXX 4X

"X.23 ZKOUŠKA XX XXXXXXXXXXXX XXXXXXX XX SPERMATOGONIÍCH SAVCŮ

1. XXXXXX

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

1.1 XXXX

Xxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx ve xxxxxxxxxxxxxxx xxxxx xx xxxx xx identifikovat xxxxxx xxxxx, xxxxx způsobují xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx savců (1, 2, 3, 4, 5). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx aberací: xxxxxxxxxxxx x chromatidové. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Xxxx xxxxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a není x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx xx xxxxxxxxxxxxxxx x předpokládá xx xxxx, že xxxx xxxxxxx xxxxxxxx xxxxxxxxx indukce dědičných xxxxxx x xxxxxxxxxxxx xxxxxxx.

X této xxxxxxx xxxx rutinně xxxxxxxxx xxxxxxxx. Xxxxx cytogenetickou xxxxxxxx in vivo xx detekují chromozomové xxxxxxx xxx xxxxxx xxxxxxxxxxxxx. Jiné xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx xxxxxxxxxxxxxx typu xx spermatogoniích by xxxx být — xxxxx xxx dojde xx ztrátě léze — vyšetřeno první xxxxxxxxx xxxxxxx xxxxxx, xxxxx následuje po xxxxxxxx. Další xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx x xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxxxx, xxx xxxx xxxxxxxx somatických xxxxx xxxxxxx také x germinálních xxxxxxx. Xxxxx xx tato xxxxxxx xx spermatogoniemi xxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX.

Xx xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx spermatogonií x xxxxxx citlivostí xx xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxxxx xxxxxxx tedy xxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x převládajícími xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X závislosti xx xxx xxxxxx xx varlatech, xxxxx xxxx xxxxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx celkovému xxxxxxxx xxxxx x důsledku xxxxxxxxx x fyziologické xxxxxxx Sertoliho xxxxx x xxxxxxx xxxx xxxxxxx xxxxxx x xxxxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx látka xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx do cílové xxxxx, není xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx chromozomu x podobě xxxxx xxxx xxxxx a xxxxxxx obou xxxxxxxxx x tomtéž xxxxx.

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

Xxxxxxxxx aberace : xxxxxxxx xxxxx chromozomů xx xxxxxxxx hodnoty x xxxxxxxxx buněk.

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx pozorovatelné xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx xxx xxxxxxxxxxx, xxxx xx xxxx xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx změny.

1.3 PODSTATA XXXXXXXX METODY

Zvířata jsou xxxxxxx způsobem xxxxxxxxxx xxxxxxxx xxxxx x xx vhodné xxxx xx xxxxxxxx xxxxxxxx. Xxxx usmrcením xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx xxxx Colcemid®). X xxxxxxxxxxxx xxxxx xx poté xxxxxxxx xxxxxxxxx chromozomů, xxxxxx xx a xxxxxxxxx xx xxxxxxxxxxxx aberace xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx a xxxx; xxx xxxx xxxxxx xxxxx xxxxxxxxxx xxxxxx vhodného xxxxx xxxxx. Měly xx xxx xxxxxxx xxxxx xxxxxxx laboratorní xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx překročit ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx xxxxx xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx skupinu x skupinu, která xx xxxxxxxx. Klece xx xxxx být xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx jednoznačně identifikují. Xxxx započetím xxxxxx xx xxxxxxx v xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx dní aklimatizovat.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x popřípadě zředěny. Xxxxxxx zkoušené xxxxx xxxxx xxx podávány xxxxx xxxx xxxxx xxx xxxx podáním xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, pokud xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx mít xxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx by xxx xxxxxxxxx podezření, xx xxxxxxx se xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx než známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by xxxx být xxxxxxxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by xxxx xxxxxxx kontrolní skupiny xxxxxxxxxx identický xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

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

Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx zvoleny xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola podávána xxxxx xxxxxxxx než xxxxxxxx xxxxx x xxx byl xxxxx x jejím xxxxxxx xxxxxxxx jen jednou. Xxx xxxxxxxxx xxxxxxxx xxxx být xxxxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx látek xxx pozitivní xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx podle Xxxxxx

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxx (xxxxxxx)

79–06–1

201–173–7

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

51–18–3

200–083–5

X xxxxxxxx každého xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxx xxxxx podstupuje stejný xxxxxx xxxx exponované xxxxxxx, xxxxx nejsou x dosavadních kontrolních xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx a xxxxxxxx buněk x xxxxxxxxxxxxxx aberacemi. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx rozpouštědlo/vehikulum nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx zvířat

Každá exponovaná x xxxxxxxxx skupina xxxx xxxxxxxxx xxxxxxx xxx xxxxxxxxxxxxxxxx samců.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx být xxxxx možno xxxxxxxx xxxxxxxxxxx xxxx nadvakrát (xx. xxx xxxxx xxxxxxxx xxxx xxxx xxxxxxxxxx). Xxxxxxxx xxxxx xxxxx xxx podávány xxxx xx xxxx xxxxxxx, tzn. xxx xxxxx v xxx xxx x xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx usnadněno xxxxxxxx xxxxxxx xxxxxx materiálu. Xxxx režimy xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xx skupině x xxxxxxxx dávkou xx měly být xx expozici xxxxxxxxx xxx xxxxxx. Poněvadž xxxxxxxx xxxxxxxxx xxxxx xxxx xxx zkoušenou xxxxxx ovlivněna, xxxxxxx xx jeden xxxxx xxxxx x xxxxx xxxxxxxx xxxxx xxxxxxxxx 24 x 48 xxxxx xx xxxxxxxx. X xxxxxxx jiné xxx xxxxxxxx xxxxx xx xxx xxx xxxxx proveden xx 24 hodin xxxx xx takové xxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx není xxxxx xxxx xxxxxxxxx xxxx xxx xxxxxxx xxxxxx (6).

Navíc xxxxx xxx xxxxxx xxxxxxxxx xxxx v xxxx xxxx. Xxxxxxxxx x xxxxxxx chemických xxxxx, xxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (lagging) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx S-nezávislé účinky, xxxx xxx vhodnější xxxxxxxx xxxxx (1).

Xxxxxxxx xxxxx xxxxxxxxx expozice xxxx být určena xxxxxx xx xxxxxxx. X xxxxxxx plánu x xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx xxxxx xxxxx) xx poslední xxxxxxxx. Xxxxx xxxxxxx xxxxx být xxxxxxxxx xxxxx odběry x xxxx xxxx.

Xxxx usmrcením xx xxxxxxxx intraperitoneálně xxxx xxxxxx xxxxx xxxxx zastavující metafázi (xxxx. Colcemid® xxxx xxxxxxxxx). Xxxx se xx xxxxxx xxxx xxxxxxx x zvířat xxxxx. X myši xx tato doba xxxxxxxxx 3 — 5 hodin; x xxxxxx čínského je xxxx xxxx přibližně 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx údajů xxxxxx xxx zjištění rozsahu, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx x xxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxxxx xx xxxxxxx v xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí tři xxxxxx xxxxx. Tyto xxxxxx xxxxx by xxxx pokrývat xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx stačí, xxxx bude xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka je xxxxxxxxxx jako xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx by xxxxx dávky xxxxx xxx stejném xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x letalitě.

Látky xx xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx xx případu. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xx spermatogoniích některé xxxxxx toxicity (xxxx. xxxxxxx počtu xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxxx xxxxxxxx; xxxx xxxxxxx by xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x jednou xxxxxx alespoň 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx se úplná xxxxxx xx xxxxx xxxxxxxx xxxxx za xxxxxxxxx. Očekávaná xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx podává xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx způsoby xxxxxxxx xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx najednou podán xxxxxxxxx sondou xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx 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 se nanese xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx mělo xxx xxxxxxxxxxx xxxxxxx 100 xxxxx x xxxxx xxxxxxxxxxxx xxxxxxxx (tj. xxxxxxxxx 500 metafází xx xxxxxxx). Tento xxxxx xxx snížit, xx-xx pozorován velký xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx včetně xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx měly xxx xxxx xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx dochází ke xxxxxxxxxxxxxx zlomům nebo xxxxxx chromozomů u xxxxx metafází, xxxx xx vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx by měly xxx xxxxxxxxxx ve xxxxx tabulky. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxx xx měl xxx xxxxxxxxxx počet xxxxx xx strukturními xxxxxxxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx exponované x kontrolní skupiny xx xxxx být xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x uvádějí xx, xxx obecně xx xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, měl by xxx pro xxxxxxxxx xxxxxxx cytotoxických xxxxxx xxxx xxxx cytotoxicity xxxxxxxx u xxxxx xxxxxxxxxxxx xxxxxx x xxxxxx sloužících jako xxxxxxxxx xxxxxxxx poměr xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxxx xxxxxxxx, x to x xxxxxxxx xxxxxx 100 xxxxxxxx xx xxxxx xx jedno xxxxx. Xxxxx je xxxxxxxxx xxxxx mitosa, 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, např. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx xx xxxxx xxxx jasný xxxxxx xxxxx xxxxx x xxxxxxxxx pro xxxxxxx x určitou dávkou x k xxxxxxxx xxxxxxxx xxxxxx. Nejdříve xx xxxx být xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (8). Statistická xxxxxxxxxx by neměla xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx nesplňují xxxx uvedená kritéria, xx v tomto xxxxxxx xxxxxxxx xx xxxxxxxxxxx.

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné nebo xxxxxx bez xxxxxx xx xx, kolikrát xx experiment opakován.

Pozitivní xxxxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx savců xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx znamenají, xx xxxxxxxx látka xx xxxxxxxx xxxxxxx xxxxxxxxxx x germinálních xxxxxxx xxxxxxxxxxx xxxxx chromozomové xxxxxxx.

Xxxx by xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx zkoušená xxxxx xxxx její xxxxxxxxxx dostanou xx xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Testovací xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx x xxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx atd.,

- individuální xxxxxxxx zvířat xx xxxxxxx xxxxxxx, včetně xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx hodnoty x xxxxxxxxxx xxxxxxxx pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxx usmrcení,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx rozvrhu expozice x odběru,

- xxxxxx xxxxxxxxx toxicity,

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

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx buněk xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky toxicity,

- xxxxxxxxx index,

- xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x první x xxxxx xxxxxxxx xxxxxx,

- xxx a xxxxx aberací xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx ve xxxxxxx,

- xxxxx xxxxx x xxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxx x souběžné pozitivní xxxxxxxx,

- změny xxxxxxx, xxxxx xxxx pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Adler, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Xxxxxxxxxxxxx xx Xxxxxxxx Mutagens Xxxxxxx xx their Cell-Cycle Xxxxxxxxxxxxxx, xx: Genetic Xxxxxxxxxx of Environmental Xxxxxxxxx, Part B: Xxxxxxx Xxxxxxx and Xxxxxxx Xxxxxxxxxxx, Ramel, X., Lambert, X., Xxxxxxxxx, X. (xxx) Xxxx, Xxx Xxxx, 477-484.

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

3) Xxxxx, E. P., Xxxxxxx, X., Xxxx, X. X. (1964), Xx Air-drying Xxxxxx xxx Xxxxxxx Xxxxxxxxxxxx xxxx Mammalian Xxxxxx, Xxxxxxxxxxxx Cell Genetics, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, J., Xxxxxxxx, X., Gatehouse, X. G., Xxxxxxxxx, X. (1990), Xx xxxx Cytogenetic Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx on Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Part I xxxxxxx, Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, I. X., Xxxxxx X. X., Xxxxxxx, J., Xxxxx, X., Xxxxxxxx, W., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx N. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx of Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Xxxxxx of xxx Xxxxxxx Group xx Xxxxxxxxx Xxxx Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.

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

8) Xxxxxx, X. X., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx of Xx vivo Cytogenetic Xxxxxx, in: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Port Xxxxxxx, Xxxxxxxxx, Sydney, 184-232."


XXXXXXX 4X

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

1. XXXXXX

Xxxx xxxxxx je xxxxxxxx xxxxxx XXXX TG 486 — Xxxxxxx xx xxxxxxxxxxxx syntézu XXX (XXX) x xxxxxxxxx xxxxxxx savců xx vivo (1997).

1.1 XXXX

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

Xxxx xxxxxxx in xxxx xxxxxxxxx metodu vyšetření xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx v játrech. Xxxxxxxxxxx xxx je xxxxxxxxxx xxxxxxxxx DNA x xxxxxxxx xxxxxxxx x jaterních xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx xxxxxx, kde xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Xxxx xxxx xxxxxxx xxxxxx pro xxxxxxxxx xxxx poškození XXX xx xxxx.

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

Xxxxxx neplánované xxxxxxx XXX (XXX) xx zhodnotí xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx xxxxx, které xxxxxxxx plánovanou xxxxxxxx XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx xx autoradiografické xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx zkoušky na XXX in vivo xx xxxxxxxxxx xxxxxxxxx xxxxx potkana. Jiné xxxxx než xxxxx xxxxx xxx rovněž xxxxxxx, xxxxxx však xxxxxxxxx xxxx metody.

Detekce xxxxxxxx XXX xxxxxx xx xxxxx bází XXX xxxxxxxxxxx x xxxxxxxxxxx x xxxxx xxxxxxxxx. Xxxxxxx na XXX xx tedy xxxxxx xxxxxxx xxx xxxxxxx dlouhých xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 xxxx) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("short-patch xxxxxx") (xxxxx až tři xxxx) jsou xxxxxxx xxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxx. Xxxxx může důsledkem xxxxxxxxxxxxx reparace, chybné xxxxxxxx xxxx xxxxxx xxxxxxxxx xxxx DNA xxxxx k mutagenním xxxxxxxxx. Rozsah odpovědi XXX neposkytuje xxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, xx xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX není opraveno xxxxxxxxxxx reparací. Nedostatek xxxxxxxxxxxx informací, které xxxx xxxxxxx poskytuje x xxxxxxxxx xxxxxxxx, xx xxxxxxx potenciální xxxxxxxxxx xxxxxx xxxx, xxxxx xx xxxxxxxxxx x celém xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Opravované xxxxx : čistý xxxxx xxx odpovídajících xxxxxxxx xxxxxx (NNG), xxxxx xxx předvolená xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx zkoušku.

Čistý počet xxx odpovídajících buněčným xxxxxx (XXX) : xxxxxxxxxxxxx xxxx UDS xxxxxxxx buněk v xxxxxxxxxxxxxxxxx zkoušce xx XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (XX) xxxxxxxxxxxxxx jádrům xx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx jádrům (XX): XXX = XX — CG. Xxxxxxx XXX se xxxxxxx pro xxxxxxxxxx xxxxx, xxxx společně xxx buňky x xxxxxxx, v paralelních xxxxxxxxx xxx.

Xxxxxxxxxxx xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx DNA xx xxxxxxxxx x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx XXX x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx region x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx založena xx xxxxxxxxxxx 3H-TdR xx XXX xxxxxxxxx xxxxx, xxx xx xxxx xxxxxxx xxxxx x X-xxxx xxxxxxxxx xxxxx. Inkorporace 3X-XxX xx obvykle xxxxxxxxx xxxxxxxxxxxxxxx, jelikož xxxx xxxxxxxx není tak xxxxxxx na vliv X-xxxx xxxxx xxxx xxxx. xxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 POPIS METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxxxxx lze xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x xxxxxxxxx zvířat xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx xxx xxx xxxxxxx.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

Xxxxx xxxxxx xxxxxxxx podle xxxxxxxx xxxxx k xxxxx X, xxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxx vzduchu 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx se xxxxxxxx výběrem xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, která xx xxxxxxxx. Klece xx xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx jednoznačně xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx se nechají x xxxxxxxxxxxxx podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx zkoušené xxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx xxxx xxxxxxxx zvířatům xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx mohou xxx podávány xxxxx xxxx xxxxx být xxxx podáním zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx neprokazují možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx xxxxxxxxx xxxxxxxx dávek toxické xxxxxx a mělo xx být vyloučeno xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx rozpouštědla/vehikula, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje se xxxxxxxx xxxxxx xxxxxxx xxxxx možno xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx. S xxxxxxxx xxxxxxxx zkoušené látky xx xxxx xxxxxxx xxxxxxxxx skupiny podstoupit xxxxxx proces jako xxxxxxx ve skupinách, x xxxxx dojde x xxxxxxxx.

Xxxxxxxxxxx xxxxxxxxxx xx xxxx xxx xxxxx, x nichž xx xxxxx, xx xxxxxx podávání x xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx k xxxxxxx XXX detekovatelnému nad xxxxxxx. Xxxxxxxxx kontroly xxxxxxxxxx metabolickou aktivaci xx xxxx xxx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxxxx odpověď (4). Dávky mohou xxx zvoleny xxx, xxx xxx účinek xxxxxxxx, ale aby xxx xxxxxx nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx odběru

Látka

Číslo CAS

Číslo xxxxx Einecs

Časné xxxx xxxxxx (2 až 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx xxxx xxxxxx (12 až 16 x)

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

53–96–3

200–188–6

Xxxxx xxx xxxxxxx také xxxx xxxxx pro xxxxxxxxx xxxxxxxx. Xx xxxxxxxxx, aby byla xxxxxxxxx xxxxxxxxx látka xxxxxxxx xxxxx xxxxxxxx, xxx xxxxxxxx látka.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Měl by xxx použit dostatečný xxxxx xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxx odpovědi xx xxxxxxx. Xxxxx xxxxxxx xx xx xxxx xxxxxxx xxxxxxx xx tří xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx jsou xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx xxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx skupiny nezbytné xxxxx xxxxx až xxx xxxxxxx.

Xxxxxxxx xxxx x xxxx studie x xxxxxxxxx údaje xx studií se xxxxxxx xxxxxx a xx použití xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx neexistuje xxxx pohlavími xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, jako xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx xx být xxxxxxx provedena se xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx expozice

Zkoušené látky xxxx zpravidla xxxxxxxx xxxxxxxxxxx.

1.5.3 Dávkování

Za xxxxxxxxxx xxxxxxxx xx používají xxxxxxx xxx úrovně xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx toxicity, xx xxxxx xxxxx by xxxxx xxxxx očekávání xxx xxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx by xxxx xxx zpravidla 50 % xx 25 % xxxxx xxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx aktivitou xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. hormony a xxxxxxxx) nemusí xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx by xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx údajů xxxxxx xxx xxxxxxxx xxxxxxx, xxxx xx xxx provedena ve xxxxxx laboratoři, se xxxxxxx xxxxxx, kmenem, xxxxxxxx x xx xxxxxxxx režimu xxxxxxxx, xxx xx xxxxxxx x hlavní xxxxxx.

Xxxxxxxx xxxxx xxxx být xxxxxxxxxx xxxx xxxx xxxxx vyvolávající známky xxxxxxxx x xxxxxxx (xxxx. xxxxxxxxxx xxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx na xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, očekávána genotoxicita, xxxxxx xxx úplná xxxxxx xxxxxxxx. Očekávaná xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční sondou xxxx xxxxxxx xxxxxxxxx xxxxxxx. Xxxx způsoby xxxxxxxx xxxx xxxxx, xxx-xx xx xxxxxxxxx. Xxxxxxxx intraperitoneálně se xxxx xxxxxxxxxxxx, neboť xx xxxxx xxxxx xxx exponována xxxxxxxx xxxxx xxxxx x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Maximální objem xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx vyšších objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx a xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx jaterních xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx x xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 xxxxx xx xxxxxx xxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (obecně xxx xx xxxxx xxxxxx xx xxxxxxxx) xx xxxxxxxx, xxxx-xx xx 12 xx 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Mohou však xxx xxxxxxx xxxx xxxx odběru, xxxx-xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx údajů.

Krátkodobé xxxxxxx xxxxxxxxx buněk xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx kolagenasou xx xxxx a xxxxxx xx, xxx xx čerstvě xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx xxxxx z xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.

1.5.7 Stanovení XXX

Xxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxx xx obvykle xxxxxxx xxxx, xxxx. xxx xx osm xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3H-TdR. Xx xxxxx xxxxxxxxx xxxx by xxxx xxx médium x xxxxx xxxxxxxxxx x xxxxx xxxx mohou xxx xxxxxxxxxx x xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx, aby xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx xx xxxx xxxxxxx, xxxxxx a xxxxxx. Xxx xxxxx xxxxxxxxx xxxx xxxxxx xxx xxxxxxx radioaktivity xxxxxxxx. Preparáty xx xxxxxx xx xxxxxxxxxxxxxxxxx xxxxxx, xxxxxxxx se x temnu (např. x xxxxxx 7 xx 14 xxx), xxxxxxxx xx, xxxxxx x xxxxxxxxx se xxxxxxxxxx xxxx xxxxxxx. X každého xxxxxxx xx připraví xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx, xxx xxxx xxxxxxxxx XXX xxxxxxxxx xxxxxxx. Xxxxxxxxx se xxx xxxxxxxxxxx prohlédnou xx xxxxxx xxxxxx xxxxxxxxxxxx (xxxx. xx xxxxxxx, xxxxxxxx úroveň xxxxxxx xxxxxxxxxxxxx izotopem).

Před počítáním xxx by měly xxx xxxxxxxxx kódovány. Xxxxxxxxx xx xxxxxxxxx 100 buněk na xxxxx xxxxx alespoň xx xxxx xxxxxxxxx; xxxxxxxxx xxxx xxx 100 xxxxx/xxxxx xx xxxx xxx xxxxxxxxxx. Xxx xxxxxxxx xxx xx xxxxx v X-xxxx nevyšetřují, xxx xxxxx buněk x X-xxxx xxxx xxx xxxxxxxxxx.

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

Xxxxx buněk xx xxxxxxx z xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (xx) x z xxŭxxxxxxx xxxxx zrn v xxxxxxxxxxxxxxxxx xxxxxxxxx (cg) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx xx se xxxxxxx xxx xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx prŭměrná hodnota xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxx x blízkosti xxxxxxxxx xxxxxxxxx xxxxx. po xxxxxxxxxxxxx xxXxxxxxxx mohou xxx použity x xxxx xxxxxxx xxxxxxxxx xxxxx buněk (xxxx. xxxxxxxx celých xxxxx) (6).

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx xx xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx a xxxxxxx. Xxxxx xx xxxx xxx xxxx xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX xx xxxxxxx XX xx xxx xxx vypočten pro xxxxxx buňku, xxx xxxxx xxxxx x xxx každou dávku x čas xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX). Xxxxxxxx xxxx počítány "xxxxxxxxxx" xxxxx, xxxx xx xxx xxxxxxxx xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx odůvodněna x xxxxxxxx na xxxxxxxxxxx xxxx souběžných údajích x xxxxxxxxxxx kontrolách. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Mají-li být xxxxxxx, xxxx xx xxx statistické testy xxxxxxx x xxxxxxxxxx xxxx provedením studie.

2.2 XXXXXXXXX A INTERPRETACE XXXXXXXX

Xxxx příklady xxxxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx patří:

pozitivní

i)

hodnota XXX xxxx xxx xxxxxxxx úrovní, xxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxx;

xxxx

xx)

xxxxxxx XXX xx xxxxxxxx xxxxx xxx xxxxxxx xxx souběžnou xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx XXX leží xx xxxxxxxxx prahové xxxxxxx xxxx xxx xx;

xxxx

xx)

xxxxxxx XXX xxxx xxxxxxxx xxxxx xxx xxxxxxx xxx souběžnou xxxxxxxx.

Xxxx xx xxx xxxxxxxxx biologická relevance xxxxx, xx. xxxx xx xxx xxxxx x xxxxx xxxxxxxxx, xxxx jsou xxxxxxxxxxx xxxxxx, vztah dávky x xxxxxxxx x xxxxxxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx však xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x aktivitě zkoušené xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx to, kolikrát xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx zkoušky na XXX x xxxxxxxxx xxxxxxx xxxxx in xxxx xxxxxxxxx, že xxxxxxxx xxxxx indukuje x xxxxxxxxx buňkách xxxxx in xxxx xxxxxxxxx DNA, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx DNA xx xxxxx. Negativní xxxxxxxx xxxxxxxxx, že zkoušená xxxxx za xxxxxxxx xxxxxxx neindukuje xxxxxxxxx XXX, které xxx xxxxxxxxx touto xxxxxxxx.

Xxxx xx xxx diskutována xxxxxxxxxxxxxxx, x jakou xx zkoušená látka xxxxxxx xx krevního xxxxx xxxx. do xxxxxx tkáně (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx a xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx rozpětí xxxxxxx xxxxxxxxx, střední hodnoty x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- pozitivní a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

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

- případně xxxxxxxx mezi koncentrací xxxxxxxx látky v xxxxxx xxxx xxxx (xxx) xx xxxxxxxxxxxx xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- podrobný xxxxx xxxxxxx expozice x odběru,

- metody xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx a kultivace xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx a xxxxx xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxx xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- xxxxxxxx statistické xxxxxxxxx,

- xxxxxx toxicity,

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

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

- xxxxx xxxxx "opravovaných" xxxxx, xx-xx xxxxxxxx,

- xxxxx xxxxx v X-xxxx, xx-xx stanoven,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. Xxxxxxx, X. X., Xxxxxxxxx, X., Xxxxxx, X. X. (1985), An Xxxxxxxxxx of xxx Xx xxxx Xxx. Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Res., 156, 1-18.

2) Butterworth, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, G., Xxxxxxxx, X. (1987), X Xxxxxxxx and Xxxxx for xxx Xx xxxx Xxx Xxxxxxxxxx XXX Repair Xxxxx, Xxxxxxxxxx Res., 189, 123-133.

3) Xxxxxxxx, X. X., Waters, X., Ashby, X., Xxxxxxx, P. X., Xxxxxxxxx, X., Xxxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, X. xx G. (1993), In xxxx Xxx Xxxxx XXX Xxxxx, xx: Xxxxxxxx X. J., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: XXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Part II xxxxxxx, Xxxxxxxxx University Xxxxx, Cambridge, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Dean, X. W., Xxxxxx, X., Brambilla. X., Xxxxxxxxx, B., Xxxxxxxxx, X. X., Furihata, X., Xxxxxxx, T., XxXxxxx, X. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx UDS Xxxxx Xx xxxxx xxx Xx xxxx, Xxxxx. Res., 312, 263-285.

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

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


PŘÍLOHA 5

XXXXXX XXXXXXXXX XX KLASIFIKACI X XXXXXXXXXX XXXXXXXXXXXX LÁTEK X XXXXXXXXX

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


XXXXXXX 6

"

XXXXXXX IX

ČÁST X

xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx xxxxx xxxxxxxx dětmi

Kromě xxxxxxxxxx xx. 22 xxxx. 1 písm. x) xxxx xxxxxxxx, xxxx xxx xxxxx o xxxxxxxxx objemu xxxxxxxxxx xxxxx, s xxxxx xx xxxxxxx xxxxxx xxx vdechování (Xx; X 65) x xxxxx jsou xxxxxxxxxxxxx x označeny podle xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx xx trh xx formě aerosolů xxxx x xxxxxxxx xxxxxxxxxx xxxxxxxxxxx rozprašovačem, xxxxxxxx xxxxxxx xxxxxxxx xxxxx otevření xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx splňovat požadavky xxxxx ISO 8317 (xxxxxx xx xxx 1. července 1989) "Xxxxx odolné dětem — Xxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxx xxxxxxxx" xxxxxxxx Xxxxxxxxxxx xxxxxxxxxx pro xxxxxxxxxxx (XXX).

2. Xxxxxxxxx neuzavíratelné xxxxx

Xxxxxxx odolné xxxxx xxxxxxxx xxxxx použité xx xxxxxxxxx xxxxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx CEN XX 862 (xxxxxx x března 1997) "Xxxxx — Obaly xxxxxx dětem — Xxxxxxxxx x xxxxxxxx xxxxxxx pro opakovaně xxxxxxxxxxxxxx obaly xxxxxx xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Evropským výborem xxx normalizaci (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx xxxxx x xxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxx, xxxxx xxxxxxx xxxxxxxx xxxxx xxxx EN 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx xxxxxx, xx xxxx je xxxxxxxxxx bezpečný xxx xxxx, xxxxx xx xxxxxxx xxxxxx x xxxxxx bez xxxxxx xxxxxxxx, nemusí xxx xxxxxxx xxxxxxxxx.

Xx všech xxxxxxxxx případech a xxxxx xxxxxxxx xxxxxxxxx xxxxxx x xxxxxxxx x bezpečnosti uzávěru xxx xxxx, může xxxxxxxxxxxx xxxxx požadovat, xxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx laboratoří xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx takový, xx xxx xxxx xxxxxxxx xxxxxxx podle xxxx xxxxxxxxx xxxxx XXX x XXX,

xxxx

- xx xxxxxx xxx xxxxxxx x byl xxxxxxx xxxxxxxxxxx podle xxxx uvedených xxxxx.

XXXX X

Xxxxxxxx týkající xx xxxxxxxxxxxx xxxxxxx

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

"