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Xxxxxxxx Xxxxxx 2000/32/XX

xx xxx 19. xxxxxx 2000,

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

(Xxxx x xxxxxxxx xxx XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Xxxxxxx x xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx xx xxxxxxxx Xxxx 67/548/EHS ze xxx 27. xxxxxx 1967 x sbližování xxxxxxxx a správních xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení a xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], naposledy pozměněnou xxxxxxxx Evropského xxxxxxxxxx x Rady 1999/33/XX [3], x zejména xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx k xxxxx xxxxxxx:

(1) Příloha X směrnice 67/548/EHS xxxxxxxx seznam nebezpečných xxxxx xxxxxxxx x xxxxxxxxxx xxxxx x xxxxxxxxxxx x označování xxxxx xxxxx. Současné xxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxx, xx xx měl být xxxxxx xxxxxxxxxxxx látek x xxxxxxx příloze xxxxxxxxxxx. Xxxxxxx jazykové xxxxx xxxxxxxx xxxxxxxx xxxxxx určitých xxxxxx xxxxxxxxx x tabulky X v xxxxxxx X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx x nebezpečnými xxxxxxx a přípravky. Xxxxxxx IV xxxxxxxx 67/548/XXX xxxxxxxx seznam xxx x bezpečnostními xxxxxx xxxxxxxxxx se xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/XXX xxxxxxxx xxxxx ke xxxxxxxxxxx x x označování xxxxxxxxxxxx látek x xxxxxxxxx. Některé xxxxxxxx xxxxx směrnice xxxxxxxx xxxxxx určitých xxxxxx xxxxxx XXX, XX x VI.

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

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx otevření xxxxx. Xxxx xxxxxxxx xx xxxx xxx xxxxxxxxxxxx a aktualizovány. Xx xxxxxxxx xxxxxxxx xxxxxx, xxx xx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxxxx.

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

XXXXXXX XXXX SMĚRNICI:

Xxxxxx 1

Xxxxxxxx 67/548/XXX xx mění takto:

1. Xxxxxxx I xx xxxx takto:

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

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

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

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

2. Odpovídající věta x příloze III xx xxxxxxxxx xxxxxxxxxx xxxxx označující xxxxxxxxxxx xxxxxxxxxx x xxxxxxx 2 této xxxxxxxx.

3. Xxxxxxx XX xx xxxx takto:

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

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

4. Xxxx X xxxxxxx X xx xxxx takto:

a) xxxxxxxx X.10 se nahrazuje xxxxxx x xxxxxxx 4X této xxxxxxxx;

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

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

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

x) xxxxxxxx X.17 se nahrazuje xxxxxx x xxxxxxx 4X xxxx směrnice;

f) xxxxxxxx X.23 xx xxxxxxxxx textem v xxxxxxx 4X této xxxxxxxx. Název xxxxxxxx X.23 ve xxxxxxxxxxx xx mění xxxxxxxxxxxxx xxxxxxxx;

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

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

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

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

Článek 2

1. Xxxxxxx xxxxx xxxxxx v xxxxxxxx právní x xxxxxxx xxxxxxxx nezbytné xxx xxxxxxxx xxxxxxx x touto xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Neprodleně x xxxx uvědomí Xxxxxx.

Xxxx xxxxxxxx přijaté xxxxxxxxx státy xxxx xxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxx xxxx xxxxxx xxxxx xxx učiněn xxx xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx xxxxxx si xxxxxxx xxxxxxx xxxxx.

2. Xxxxxxx xxxxx sdělí Xxxxxx xxxxx hlavních xxxxxxxxxx vnitrostátních právních xxxxxxxx, xxxxx xxxxxxx x xxxxxxx působnosti xxxx směrnice, x xxxxxxxxxx xxxxxxx xxxx xxxxxxxx a xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxxxxx.

Článek 3

Tato směrnice xxxxxxxx x xxxxxxxx xxxxxx dnem xx xxxxxxxxx v Xxxxxxx xxxxxxxx Evropských xxxxxxxxxxxx.

Xxxxxx 4

Xxxx směrnice xx určena členským xxxxxx.

X Xxxxxxx dne 19. května 2000.

Xx Xxxxxx

Xxxxxx Wallström

členka Xxxxxx


[1] Xxxxxxx xx xxxxxxxxxxxx po xxxxxxx xxxxx.

[2] Úř. xxxx. 196, 16.8.1967, s. 1.

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


XXXXXXX 1X

XXXXXXXXX X XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx xx identifikace, xxxxxxxxxxx x označování xxxxx

(Xxxxxx xx xxxxxxx xxxxx)


PŘÍLOHA 1X

"XXXXXXX A

Z

Symbol

ES

DA

DE

EL

EN

FI

FR

IT

NL

PT

SV

18

Ar

Argón

Argon

Argon

Αργό

Argon

Argon

Argon

Argon

Argon

Árgon

Argon

64

Gd

Gadolinio

Gadolinium

Gadolinium

Γαδολίνιο

Gadolinium

Gadolinium

Gadolinium

Gadolinio

Gadolinium

Gadolínio

Gadolinium"


XXXXXXX 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační xxxxxx

Xxxxxxxx x přípravkům

006–011–00–7

karbaryl (ISO) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

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

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) natrium-N-methyldithiokarbamát

205–293–0

137–42–8

Xn; X22 X31 C; X34 R43 X; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

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

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

006–016–00–4

xxxxxxxx (XXX) 2- isopropoxyfenyl-N-methylkarbamát

204–043–8

114–26–1

T; X25 N; R50–53

T; 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+; R26/28 X; X24 X; X50–53

X+; X R: 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; R24/25 N; X50–53

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

006–019–00–0

xx-xxxxx (XXX) S-(2,3-dichlorallyl)-N,N-diisopropylthiokarbamát

218–961–1

2303–16–4

Karc. xxx. 3; X40 Xx; X22 X; X50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xx; X22 X43 X; R50–53

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

006–023–00–2

xxxxxxxxxxxxxxxx (XXX) xxxxxxxxxx 3,5-dimethyl-4-(methylsulfanyl)fenyl-N -xxxxxxxxxxxxxx

217–991–2

2032–65–7

X; X25 X; X50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; X22 Xx; X38 N; R51–53

Xn; X R: 22–38–51/53 X: (2-)13-61

006–026–00–9

karbofuran (XXX) 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-sek-butyl-4,6-dinitrofenyl-isopropyl-karbonát

213–546–1

973–21–7

T; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

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

230–253–4

6988–21–2

X; X25 X; X51–53

X; N X: 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; R50–53

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

006–034–00–2

xxxxxxx (XXX) S-propyl-N-butyl-N-ethylthiokarbamát

214–215–4

1114–71–2

Xn; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)23-61

006–035–00–8

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

245–430–1

23103–98–2

X; X25 X; X50–53

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

006–037–00–9

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

220–113–0

2631–37–0

X; X25 X; X50–53

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

006–038–00–4

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

X

202–388–9

95–06–7

Xxxx. xxx. 2; X45 Xn; X22 N; X50–53

X; X X: 45–22–50/53 X: 53–45–60–61

006–039–00-X

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

218–962–7

2303–17–5

Xx; X22–48/22 R43 X; X50–53

Xx; X X: 22–43–48/22–50/53 X: (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; R40 Xx; R22 X; X50–53

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

006–043–00–1

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

140–41–0

Xx; X36/38 Xxxx. xxx. 3; X40 X; R50–53

Xn; 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

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

245–216–8

22781–23–3

X; X23/25 Xn; X21 X; X50–53

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

006–047–00–3

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

8065–36–9

X; R24/25 X; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xx; X22 X; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

006–050–00–X

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

4482–55–7

Xx; X38 X; R50–53

Xi; X X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; X28 Xx; X21 X; X50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; R22 N; X51–53

Xx; X R: 22–51/53 X: (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; X22 X52–53

Xx X:22–52/53 X: (2-)61

006–069–00–3

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

245–740–7

23564–05–8

Muta. xxx. 3; X40 X; X50–53

Xx; X X: 40–50/53 X: (2-)36/37–60–61

006–070–00–9

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

262–302–0

60568–05–0

Xxxx. kat. 3; X40 N; X50–53

Xx; X R: 40–50/53 S: (2-)36/37–60–61

006–088–00–7

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

82560–54–1

X; X23/25 N; X50–53

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

007–012–00–5

X,X-xxxxxxxxxxxxxxxx 1,1-xxxxxxxxxxxxxxxx

X

200–316–0

57–14–7

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

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

007–013–00–0

N,N-dimethylhydrazin 1,2-dimethylhydrazin

E

540–73–8

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

X; X X: 45–23/24/25–51/53 S: 53–45–61

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

009–003–00–1

kyselina xxxxxxxxxxxxxx … %

X

231–634–8

7664–39–3

X+; X26/27/28 X; X35

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

X ≥ 7 %: T+; X; X26/27/28–35 1 % ≤ C < 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) X,X-xxxxxxxx-X -[(4(3 H)-oxo-1,2,3-benzotriazin-3-yl)methyl]-fosforodithioát

201–676–1

86–50–0

T+; X26/28 X; R24 R43 X; R50–53

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

015–048–00–8

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

200–231–9

55–38–9

Xxxx. xxx. 3; X40 X; X23–48/25 Xn; X21/22 N; R50–53

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

015–056–00–1

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

220–147–6

2642–71–9

T+; R28 X; X24 N; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; X23/25 Xn; X21 X; X50–53

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

016–013–00-X

chlorid xxxxxxx

234–129–0

10545–99–0

X14 X; R34 N; X50

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

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

016–014–00–5

xxxxxxx xxxxxxxx

13451–08–6

X14 X; X34 X; X50

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

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

016–023–00–4

dimethyl-sulfát

E

201–058–1

77–78–1

Karc. kat. 2; R45 Xxxx. xxx. 3; X40 X+; X26 X; X25 C; X34 X43

X+ R: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; X22 N; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

016–071–00–6

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

410–130–3

136248–03–8

X43

Xx X: 43 X: (2-)22–24–37

022–001–00–5

xxxxxxx xxxxxxxxxx

231–441–9

7550–45–0

X14 C; R34

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

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

030–004–00–8

dimethylzinek [1] diethylzinek [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

R14 X; X17 C; X34 N; X50–53

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

050–002–00–0

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

236–049–1

13121–70–5

Xn; X20/21/22 N; X50–53

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

050–012–00–5

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

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

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

Xx; X20/21/22 X; X50–53

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

X ≥ 1 %: Xn; R20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

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

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

082–009–00–X

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

215–693–7

1344–37–2

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

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

1

082–010–00–5

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

235–759–9

12656–85–8

Karc. kat. 3; R40 Xxxx. xxx. 1; X61 Xxxx. xxx. 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; X65 Xx; X37 X; R51–53

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

4

601–032–00–3

xxxxx[x]xxxxx benzo[def]chrysen

200–028–5

50–32–8

Karc. xxx.2; X45 Muta. xxx. 2; X46 Xxxx. kat. 2; X60–61 N; R50–53

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

601–034–00–4

xxxxx[x]xxxxxxxxxxxxxxx

205–911–9

205–99–2

Xxxx. xxx.2; X45 N; X50–53

X; X X: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-xxxxxxxxxxxxx x-xxxxxxxxxxxxx

203–400–5

106–46–7

Xx; X36 N; X50–53

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

602–054–00–6

3-xxxxxxx-1-xx xxxxxxxxxx

209–130–4

556–56–9

X10 X; X34

X R: 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 Xn; X21–48/22 X; X34

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

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

603–091–00–0

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

402–470–6

87172–89–2

O; X8 Xx; X22 Xx; X36

X; Xx R: 8–22–36 X: (2-)26

603–093–00–1

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

402–410–9

87818–31–3

Xn; X20 N; X51–53

Xx; X X: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; X36 R52–53

Xi X:36–52/53 X: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx xxxxxxxxxxx

200–661–7

67–63–0

X; X11 Xx; X36 X67

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

604–020–00–6

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

201–993–5

90–43–7

Xi; 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 sodný xxxxxxx-xxxxxxx-2-xxxx

205–055–6

132–27–4

Xx; X22 Xx; X37/38–41 X; X50

Xx; X R: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

4,4'-(4-xxxxxxxxxxxx-2,2-xxxx)xxxxxxx 2,2-bis(4-hydroxyfenyl)-4-methylpentan

401–720–1

6807–17–6

Repr. xxx. 2; X60 Xx; X36 N; X50–53

X; X R: 60–36–50/53 X: 53–45–60–61

604–041–00–0

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

256–634–5 [1] 263–560–7 [2]

50594–66–6 [1] 62476–59–9 [2]

Xn; X22 Xx; R38–41 X; X50–53

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

604–043–00–1

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

203–083–3

103–16–2

Xi; X36 X43

Xx X: 36-43 S: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; R22 Xx; X36 X43

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

605–016–00–7

xxxxxxx… % xxxxxxxxx… %

X

203–474–9

107–22–2

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

Xx X: 20–36/38–40–43 X: (2-)36/37

X ≥ 10 %: Xx; X20–36/38–40–43 1 % ≤ X < 10 %: Xx; X40–43

606–016–00-X

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

201–462–8

83–26–1

T; R25–48/25 X; X50–53

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

606–018–00–0

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

204–210–5

117–80–6

Xx; X22 Xx; R36/38 X; X50–53

Xx; 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-dekachlorpentacyklo[5.3.0.02,6.04,10.05,9]dekan-3-on

205–601–3

143–50–0

Karc. xxx. 3; X40 X; X24/25 X; X50–53

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

606–034–00–8

metribuzin (ISO) 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 R: 22–50/53 X: (2-)60-61

606–035–00–3

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

216–920–2

1698–60–8

X43 N; X50–53

Xx; N R: 43–50/53 S: (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; X62 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-chlorfenoxy)- 3,3-xxxxxxxx-1-(1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

256–103–8

43121–43–3

Xx; X22 X; R51–53

Xn; 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 Xi; X36 X; X50–53

Xx; N X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; X22 Xx; X41 R52–53

Xn; N X: 22–41–52/53 X: (2-)26-61

607–057–00–6

xxxxxxxxx (ISO) 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; R48/22 X52–53

Xx X:48/22–52/53 X: (2-)37-61

607–058–00–1

xxxxxxxxx (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -chromen-2-on 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-furyl)-3-oxobutyl]-4-hydroxy-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 ethyl-5-(1,2,3,5,6,7,8,9,10,10-dekachlor-4-hydroxypentacyklo[5.2.1.02,6.03,9.05,8]dekan-4-yl)-4-oxopentanoát xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx

4234–79–1

X; R24 Xn; X22 N; X51–53

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

607–097–00–4

xxxxxx-1,2,4-xxxxxxxxx-1,2-xxxxxxxx 1,2-xxxxxxxx xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxx

209–008–0

552–30–7

Xx; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx

203–677–2

109–52–4

X; X34 R52–53

C R:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xn; X22 X; X51–53

Xx; N X: 22–51/53 X: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; X36/38 X52–53

Xx X:36/38–52/53 S: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xx; X22 Xx; X38 X; X50–53

Xx; X X: 22–38–50/53 X: (2-)37–60–61

607–158–00–5

sodná xxx xxxxxxxxxxx kyseliny xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; X25 Xx; R38 X; X50

X; N X: 25–38–50 X: (1/2-)22–37–45–61

607–159–00–0

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

208–110–2

510–15–6

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

607–176–00–3

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

400–830–7

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; X51–53

Xx; X 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; R22 X43 N; X50–53

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

607–213–00–3

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

403–320–2

67567–23–1

X; X2 O; X7 X10 X; R51–53

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

607–217–00–5

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

403–960–2

X43 X53

Xx X: 43-53 X: (2-)24–37–61

607–243–00–7

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

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

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

X52–53

X: 52/53 X: 61

607–248–00–4

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

205–073–4

132–67–2

Xn; X22

Xx X: 22 S: (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; X R:36/37/38–43–51/53 X: (2-)24–37–61

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

607–252–00–6

λ-xxxxxxxxxxx (XXX) Xxxx (1:1): (X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 R)-cis-3-((Z)-2-chlor-3,3,3-trifluorprop-1-en-1-yl)-2,2-dimethylcyklopropan-1-karboxylát x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 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 X; X50–53

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

607–255–00–2

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

69377–81–7

X52–53

X: 52/53 X: 61

608–003–00–4

akrylonitril

D X

203–466–5

107–13–1

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

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

C ≥ 20 %: X; X45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; X45–23/24/25–41–43 5 % ≤ C &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ C &xx; 5 %:X; X45–23/24/25–43 0,2 % ≤ C &xx; 1 %:X; X45–20/21/22 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 R: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 X+; R28 X; R24 X44 X; X50–53

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

609–040–00–9

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

X

217–406–0

1836–75–5

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

X; X X: 45–61–22–50/53 X: 53–45–60–61

609–044–00–0

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

204–178–2

117–18–0

Xn; X22 X43 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. xxx. 2; X45 X; X50–53

X; X X: 45–50/53 X: 53–45–60–61

611–013–00–1

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

403–650–7

117409–78–6

X; X2 X; X51–53

X; X X: 2–51/53 X: (2-)35-61

611–031–00-X

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

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-methoxyanilin x-xxxxxxxx

X

201–963–1

90–04–0

Xxxx. xxx. 2; R45 Xxxx. xxx. 3; X40 X; X23/24/25

X X: 45–23/24/25 X: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. kat. 1; X45 Xx; X22 X; X50–53

X; N X: 45–22–50/53 X: 53–45–60–61

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

612–051–00–1

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

E

202–974–4

101–77–9

Karc. xxx. 2; X45 Xxxx. xxx. 3; R40 X; X39/23/24/25Xx; R48/20/21/22 X43 X; X51–53

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

612–081–00–5

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

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Xxxx. xxx. 2; X45 Xx; R22 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. kat. 2; X45 T; X25 Xx; X21 Xx; X36 X43 X; X51–53

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

612–105–00–4

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

205–411–0

140–31–8

Xx; X21/22 C; R34 X43 R52–53

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

612–111–00–7

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

212–513–9

823–40–5

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

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

612–125–00–3

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

202–442–1

95–70–5

T; X25 Xx; X20/21 X43 N; X51–53

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

612–144–00–7

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

62924–70–3

Xx; R36/38 X4 3 X; R50–53

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

612–151–00–5

xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx methylbenzendiamin

E

246–910–3

25376–45–8

Karc. xxx. 2; X45 T; X25 Xx; R20/21 Xx; R36 R43 X; X51–53

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

613–018–00–4

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

7411–47–4

Xx; X22 Xx; X36/37/38 X52–53

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

613–031–00–5

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

201–782–8

87–90–1

X; X8 Xx; R22 X31 Xx; X36/37 X; X50–53

X; Xx; 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 benzoguanamin

202–095–6

91–76–9

Xn; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

Xx; X20/22 N; X41 X; X50–53

Xx; N 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; R20/22 Xi; X41 X; X50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; R22 X; X50–53

Xx; X X: 22–50/53 S: (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; R22 Xx; R36/37/38 R52–53

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

613–098–00–0

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

403–700–8

2687–94–7

X; X34 X; X51–53

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

613–130–00–3

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

79983–71–4

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–131–00–9

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

57369–32–1

Xx; R22 X52–53

Xx X:22–52/53 X: (2-)61

613–134–00–5

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

88671–89–0

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

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

613–137–00–1

xxxxxxxxxxxxxxxxxx (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

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

74223–64–6

X; X50–53

X X: 50/53 X: 60-61

614–001–00–4

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

200–193–3

54–11–5

X+; X27 X; X25 X; X51–53

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

614–006–00–1

xxxxxx 2,3-xxxxxxxxxxxxxxxxxxxx-10-xx

206–614–7

357–57–3

X+; R26/28 X52–53

X+ R:26/28–52/53 X: (1/2-)13–45–61

614–007–00–7

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

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

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

X+; X26/28 R52–53

T+ X: 26/28–52/53 X: (1/2-)13–45–61

615–006–00–4

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

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; R36/37/38 R42/43 X52–53

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

C320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; R23–40–42/43 0,1 % ≤ X &xx; 1 %:Xn; X20–42

2

616–010–00–9

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

204–854–7

127–65–1

Xx; X22 R31 X; R34 R42

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

616–034–00-X

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

246–419–4

24691–76–7

X52–53

X: 52/53 S: 61

616–035–00–5

xxxxxxxxx X -[(ethylamino)karbonyl]-2-kyan-2-(methoxyimino)acetamid 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx

261–043–0

57966–95–7

Xx; X22 R43 X; X50–53

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

617–004–00–9

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

212–230–0

771–29–9

X; R7 Xx; X22 C; X34 X; R50–53

O; 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 < 25 %: X; X34 5 % ≤ X < 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 xxxxxxxxxxxxxx

201–279–3

80–43–3

X; X7 Xx; X36/38 N; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xx; X36 X43

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

650–007–00–3

xxxxxxxxxxxxx (XXX) N2-(4-chlor-2-methylfenyl)-N1,N1-dimethylformimidamid X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx

228–200–5

6164–98–3

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

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

650–008–00–9

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

227–197–8

5707–69–7

X; X25 N; X50–53

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

650–009–00–4

xxxxxxxxxxxxx-xxxxxxxxxxxx X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx 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; R40 Xx; X22 X; X50–53

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

650–033–00–5

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

66230–04–4

T; X23/25 X43 X; X50–53

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

650–041–00–9

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; R50–53

N X: 50/53 X: 60-61


PŘÍLOHA 1X

Xxxxxxxx xxxxx

Xxxxxxxx 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; R20 Xx; X41 R52–53

Xn X: 20–41–52/53 X: (2-)22–26–39–61

014–016–00–0

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

406–490–6

X; X51–53

X X: 51/53 X: 61

015–164–00–9

xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx xxxxxxxx

400–480–5

36669–85–9

X52–53

X:52/53 X: 61

015–165–00–4

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

404–986–7

Xx; X41 X; R50–53

Xi; X X: 41–50/53 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 S: 61

015–167–00–5

3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; R41

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

601–050–00–1

C10-C13-alkylderiváty xxxxxxx

267–051–0

67774–74–7

X; X50

X X: 50 X: 61

601–051–00–7

4-xxxxxxxx-1-xx

405–980–7

768–56–9

Xx; X38 X; X51–53

Xx; X X: 38–51/53 X: (2-)37-61

602–083–00–4

xxxxxxxxxxxxxxxx difenyletheru xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; X48/21/22 R64 X; R50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

X X: 52/53–59 S: 59-61

603–128–00–0

2-(xxxxxxxxxxxx)xxxxxxxx

405–490–3

613–62–7

X53

X:53 X: 61

603–129–00–6

1-terc-butoxypropan-2-ol

406–180–0

57018–52–7

R10 Xx; X41

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

603–130–00–1

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

406–325–8

Xx; R22 R52–53

Xn X:22–52/53 X: (2-)39-61

603–131–00–7

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

407–290–1

Xi; X41

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

603–132–00–2

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

408–200–3

63187–91–7

Xx; R38–41 X52–53

Xx X:38–41–52/53 X: (2-)26–37/39–61

603–133–00–8

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

408–240–1

Xx; X22 X52–53

Xx R:22–52/53 S: (2-)22–36–61

603–134–00–3

Xxxx: alkyl(C1-C10)-dodecyldifenylethery a xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (xxxxxxx x xxxxxxxxxx xxxxxxxxxxxx)

410–450–3

X53

X: 53 X: 61

603–135–00–9

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

410–500–4

Xx; X41 N; X51–53

Xx; X X: 41–51/53 X: (2-)26–39–61

603–136–00–4

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

410–910–3

104226–19–9

X43 X52–53

Xx X:43–52/53 S: (2-)24–37–61

603–137–00-X

Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 1-deoxy-1-[methyl(1-oxooktadecyl)amino]-D-glucitol

411–130–6

Xi; X41

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

603–138–00–5

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

403–140–4

103694–68–4

R52–53

R:52/53 X: 61

604–050–00-X

4-chlor-o-kresol 4-chlor-2-methylfenol

216–381–3

1570–64–5

T; X23 X; X 35 X; R50

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

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

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 X: 61

604–052–00–0

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

403–800–1

103597–45–1

X53

X:53 S: 61

604–053–00–6

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

410–760–9

157661–93–3

Xx; X38 X43 N; X50–53

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

604–054–00–1

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

412–020–0

R43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

604–055–00–7

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

413–900–7

85954–11–6

Xxxx. Xxx.3; X40

Xx X: 40 X: (2-)22–36–37

605–027–00–7

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

410–480–7

X43 X; X51–53

Xx; X R: 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-butoxy-1-methylethyl)-[(4-amino-3,5-dichlor-6-fluor-2-pyridyl)oxy]acetát [2]

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

X; X50–53

X X: 50/53 X: 60-61

607–273–00–0

amonium-7-{2,6-dimethyl-8-[(2,2-dimethylbutanoyl)oxy]- 1,2,6,7,8,8a-hexahydro-1-naftyl}-3,5-dihydroxyheptanoát

404–520–2

R52–53

R:52/53 X: 61

607–274–00–6

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

405–350–1

54527–73–0

R43 X; X51–53

Xx; X X: 43–51/53 S: (2-)24–37–61

607–275–00–1

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

405–450–5

66531–87–1

R43

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

607–276–00–7

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

405–635–0

Xx; X38–41 X; R50–53

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

607–277–00–2

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

405–720–2

Xx; R22 Xx; X41 X43 X; X51–53

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

607–278–00–8

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

405–760–0

Xi; X41 R43 X52–53

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

607–279–00–3

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

405–960–8

X43 X; X51–53

Xx; N X: 43–51/53 S: (2-)24–37–61

607–280–00–9

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

406–190–5

54322–20–2

Xn; X22 Xi; X36 X43

Xx R: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

Směs:alkyl(C7-C9 xxxxxxxxxx x xxxxxxxx)-3-[3-(2X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx

407–000–3

127519–17–9

X; R51–53

N X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 X: 61

607–283–00–5

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

408–040–4

15121–89–8

Xx; X21/22 Xi; X38–41 X43 N; X50–53

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

607–284–00–0

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

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

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

410–065–0

X43

Xx X: 43 X: (2-)22–24–37

607–286–00–1

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

410–070–8

141880–36–6

X43 X52–53

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

410–160–7

148732–74–5

Xx; X36 R43 X52–53

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

607–288–00–8

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

410–370–9

105488–33–3

R53

R:53 X: 61

607–290–00–3

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

410–540–2

Xx; X38 R43 X; X50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx cyklohexyl)alkanoát

410–630–1

104051–92–5

R53

R: 53 X: 61

607–292–00–4

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

410–640–6

Xi; X38–41 X; X50–53

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

607–293–00-XXxxx:

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

410–650–0

Xx; X41 X43 X; X51–53

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

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

Xxxx:xxxxxxxxxxxx-xxxxxxxxxxxxxxxxx a 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 kyselina a 2-xxxxxxxxxxxxx xxxxxxxx

410–830–9

X53

X: 53 X: 61

607–297–00–1

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

410–960–6

92761–26–7

Xx; R41

Xi X: 41 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; R22 R43 X; R50–53

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

607–300–00–6

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

Směs:dodekanová kyselina x xxxxxxxxxxx xxxxx(1-7)xxxxxxx

411–860–5

Xx; X38–41 R43 X; X51–53

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

607–302–00–7

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

411–910–6

Xx; X38–41 R43 X; R51–53

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

607–303–00–2

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

413–760–7

93107–30–3

Repr. 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 R: 50/53 X: 60-61

608–024–00–9

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

407–650–8

97460–76–9

R53

R:53 X: 61

608–025–00–4

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

410–970–0

117568–27–1

X53

X:53 S: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; X3 O; X8 Xxxx. kat. 2; X45 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; X22–48/22 X; X34 X43 N; X50–53

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

611–043–00–5

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

402–850–1

Xi X: 41–52/53 X: (2-)26–39–61

611–044–00–0

Směs:[bis(5-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-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; X51–53

Xx; X41 X52–53

611–045–00–6

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

404–830–8

X53

X:53 S: 61

X X: 51/53 X: 61

611–046–00–1

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

407–590–2

43151–99–1

X; X25 Xx; X48/22 R43 X; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

X53

X: 53 S: 61

611–048–00–2

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

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

408–000–6

118658–98–3

Xx; X48/22 X43 X52–53

Xx R: 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) xxx]-6-[(6-xxxxxxxxx-1-xxxxxx)xxx]xxxxxx-1,3-xxxxxxx}]xxxxxxxxx xxxxxxx, xxxxx sůl

400–720–9

R52–53

R: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; R41 N; X50–53

Xx; X X: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

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

410–780–8

Xn; X22–48/22 Xx; X41 X43 N; X51–53

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

612–158–00–3

Xxxx:[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx a 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx komplex x 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

X53

X: 53 X: 61

612–159–00–9

xxxxxxx xxxxxxxx xxxxx 2,2,4-xxxxxxxxx- a 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x xxxxxxx XXXXXX), xxxxxxxx [(alkyl(C10-C16)oxy)methyl]oxiranu (Epoxid 8) x 4-xxxxxxxxxxxx-1-xxxxxxxxx xxxxxxxx

410–880–1

Xx; X22 C; X34 X; X50–53

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

613–149–00–7

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

405–700–3

96489–71–3

X; R23/25 X; R50–53

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

613–150–00–2

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

406–295–6

X53

X:53 S: 61

613–151–00–8

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

406–360–9

104218–44–2

X53

X:53 S: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-xxxxxxxxxxxxxxx

407–270–2

16063–70–0

X52–53

X:52/53 X: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; R22

Xn X: 22 S: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; X22 X52–53

Xx X: 10–22–52/53 X: (2-)23–36–61

613–156–00–5

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

410–260–0

83857–96–9

X43 X; X51–53

Xx; N X: 43–51/53 X: (2-)24–37–61

613–157–00–0

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

410–330–0

54236–98–5

Xx; X22–48/22 Xx; X36

Xx X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

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

410–340–5

69045–84–7

Xx; R20/22 Xx; R41 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-xxxxxx-2,5-xxxxxxxxxxxx[2.2.1]xxxxxx-xxxxxxxxxxxxx

411–000–9

125224–62–6

X43

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

615–022–00–1

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

410–550–7

79277–18–2

E; X2 R14 Xn; 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-[(isokyanatosulfonyl)methyl]benzoové xxxxxxxxxxxxxx-2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxx

410–900–9

83056–32–0

X10 X14 Muta. xxx. 3; X40 Xn; 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

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

402–510–2

X; X51–53

X X: 51/53 X: 61

616–045–00-X

2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(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; X50–53

X X: 50/53 X: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx x X, X′,X″,X′′′ - xxxxxxxxxx(X18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx

406–640–0

X43

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

616–048–00–6

3'-(trifluormethyl)isobutyranilid

406–740–4

1939–27–1

Xn; X48/22 X; X51–53

Xx; X X: 48/22–51/53 X: (2-)22–36–61

616–049–00–1

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

408–150–2

99141–89–6

X53

X:53 X: 61

616–050–00–7

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

410–690–9

103055–07–8

X43 X; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

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

411–070–0

X53

X: 53 X: 61

617–015–00–9

bis(4-methylbenzoyl)peroxid

407–950–9

895–85–2

E; X2 X; R7 X; X50–53

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

650–032–00-X

xxxxxxxxxxxx (XXX) (2R, 3X)-, (2 X, 3 X)-, (2 R, 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; X X: 22–50/53–63 S: (2-)36/37–60–61


XXXXXXX 2

XXXXXX XXXXXXXXXXXX XXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 3X

XXXXXXXXXX POKYNY XXX BEZPEČNÉ XXXXXXXXX X NEBEZPEČNÝMI XXXXXXX X PŘÍPRAVKY

Viz směrnice Xxxxxx 2001/59/XX,

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


PŘÍLOHA 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES,

Úř. xxxx. X 332, 28.12.2000, x. 81.


XXXXXXX 4A

"B.10 XXXXXXXXXX — ZKOUŠKA XX XXXXXXXXXXXX XXXXXXX U XXXXX XX VITRO

1. XXXXXX

Xxxx xxxxxx je xxxxxxxx xxxxxx XXXX XX 473 — Xxxxxxx xx chromozomové xxxxxxx x savců xx vitro (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxxx má xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx aberací: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, avšak xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx schopnost indukovat xxxxxxxxx aberace. Xxxx xxxxxx však není xxxxxx xx xxxxxxxxx xxxxxxxxxxx aberací x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxx jevy xxxx xxxxxxxx mnoha geneticky xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx důkazů x xxx, xx xxxxxxxxxxxx xxxxxx x x xxxx xxxxxxxxxxx jevy xxxxxxxxxxx změny v xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x člověka x u pokusných xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxx xxxxx xxx xxxxxxx stabilizované xxxxxxx xxxxx, xxxxxxx kmeny xxxx xxxxxxxx xxxxxxx xxxxxxx. Xxxxxxx xxxxx xxxx xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxx x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx zdroje xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační systém xxxxxx zcela napodobit xxxxxxxx in vivo x xxxxx. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, které xx xxxxx x xxxxxxxxxx výsledkům, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx k xxx xxxxx změnou xX, osmolality xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Xxxx zkouška xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x karcinogenů xxx xxxxx. Mnoho xxxxxxxxx, xxx něž xx xxxx xxxxxxx xxxxxxxxx, xxxx xxx xxxxx xxxxxxxxxxx; xxxx xxxxx xxxxxxxx x karcinogenitou xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx chemické xxxxx x přibývají důkazy x xxx, že xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx jinými mechanismy xxx přímým xxxxxxxxxx XXX.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : xxxxxxxxxx poškození chromozomu x xxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx a opětného xxxxxxx chromatid.

Chromozomová xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x podobě xxxxx nebo zlomu x spojení xxxx xxxxxxxxx x xxxxxx xxxxx.

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

Xxx : xxxxxxxxxxxx xxxx xxxxx xxx šířka jedné xxxxxxxxxx a s xxxxxxxxx xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx xxxxx : podíl xxxxx, xxxxx xx xxxxxxxxx x xxxxxxxx, x xxxxxxxxx počtu xxxxx x xxxxxxxx; xxxxx stupeň proliferace xxxx xxxxxxxx.

Xxxxxxxxx aberace : odchylka počtu xxxxxxxxxx xx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxx xxxx xxxxx.

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx metafáze; xxxx xx jako xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx interchromozomální xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, x xx s xxxxxxxxxxxx xxxxxxxx x xxx xx. V předem xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx látce xx xx buněčných kultur xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx kolchicin), xxxxxxx xx sklidí, obarví x xxxxxxxxxx chromozomových xxxxxxx xx zjistí xxxxxxxxxxxxxx pozorováním xxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx být xxxxxxx xxxxx xxxxxxx xxxxx, kmeny nebo xxxxxxxx buněčné xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (xxxx. xxxxxxxxxxx xxxxxx čínského, xxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxx savců).

1.4.1.2 Xxxxx a kultivační xxxxxxxx

Xxx udržování xxxxxx xx xxxx být xxxxxxx vhodná kultivační xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, teplota x xxxxxxx). X xxxxxxxxxxxxxxx buněčných linií x xxxxx xx xxxx být rutinně xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx počtu chromozomů x xxxx xx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx mykoplasmaty; x případě xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Xxx xxxxxxx xxxxx a xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx normální xxxxx buněčného xxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx x xxxxx: xxxxx xx pomnoží x kmenových xxxxxx, xxxxxx se do xxxxxxxxxxxx xxxxx v xxxxxx hustotě, aby xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx, x xxxxxxxx xx xxx 37 °X.

Xxxxxxxxx: krev xxxxxxxx xxxxxxxxxxxxxxx (např. xxxxxxxxx) xxxx xxxxxxxx lymfocyty xxxxxxxx xxxxxxxx xx xxxxxxx do xxxxxxxxxxxx xxxxx obsahujícího mitogen (xxxx. xxxxxxxxxxxxxxxx) a xxxxxxxx xx xxx 37 °X.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx by xxxx xxx vystaveny zkoušené xxxxx, a to x xxxxxxx metabolickou xxxxxxxx a xxx xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (6, 7, 8 a 9), xxxx směs xxxxxxxxxxxxx x β-xxxxxxxxxxxx (10, 11 a 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx metabolického aktivačního xxxxxxx xxxx záviset xx xxxxx chemické xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx koncentraci xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx výsledků xxxxxx, včetně xxxxxxxx xxxxxxxxx modifikovaných buněčných xxxxx exprimujících xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx pro endogenní xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx (např. důležitostí xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

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

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx mělo být xxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx, x mělo xx xxx xxxxxxxxxx x xxxxxxxx xxxxx x x xxxxxxxxx X9. Jsou-li použita xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx údaji x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx nestálých xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx rozpouštědla xxxxxxxxxxxx xxxx. Vodu xxx xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxx koncentrace, xxxxx xxxxxxxxxxxx, rozpustnost x xxxxxxxxxx xxxxxxx x xxxxx xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx stanovena x metabolickou aktivací x xxx xx x hlavním experimentu xx použití vhodných xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, xxxx xxxx xxxxxx konfluence, xxxxx xxxxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx. Xxxx být výhodné xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx alespoň xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx xx xxxx tyto xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx až xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx obvykle xxxxxxx, xx by xx xxxxxxxxxxx xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. X xxxxxxxx xxxxxxx xx xxxx xxxxxxxx xxxxxxxxxxx vykazovat xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, xxxxx buněk xxxx xxxxxxxxxxx xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx index xx xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x xxxxxx xx době, která xxxxxxxx od xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx xxxxxxxxxx x xxxxxxxxxxx xxxxxx, u xxxxx xxxxx být xxxx metody stanovení xxxxxxxx xxxxxxx a xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx xxxxxxxxx cyklu, xxxxxxxxx průměrná generační xxxx (AGT), xxxxx xxx xxxxxxx jako xxxxxxxxx informace. X xxxxxxx XXX však xxx x xxxxxxxx xxxxxxxxx hodnotu, x xxx xxxxx usoudit xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, x i xxxx xxxxxxxxx průměrné xxxxxxxxx xxxx xxxx xxx xx xxxxxxxx xxxxx xxxxxxxxx oddálení xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

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

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxx, které xxxxxx xxxxxxx xxx xxxxxxxxxxxxx xxxxxxx, xxx xx xxxxxx xxxxxxxxxxx, xx xxxx xxx xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxx, jež xx nad xxxx xxxxxxxxxxxx x konečném xxxxxxxxxxx xxxxx xx xxxxx doby xxxxxxxx. X xxxxxxxx xxxxxxxxx (xxxx. xxxxxxx-xx se xxxxxxxx pouze při xxxxxxx koncentracích, xxx xx xxxxxxxxxxx) xx xxxxxxxxxx vyzkoušet více xxxxxxxxxxx, xxx xxxxx xxxxxxx xx srážení. Xxxx xxx xxxxxxxx xxxxxxxx rozpustnost xx xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxxx se xxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, séra X9 xxx. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx by neměla xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx každého experimentu xx xxxx být xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxx rozpouštědla xxxx xxxxxxxx). Xxx xxxxxxx xxxxxxxxxxx aktivace xx xxxx xxx xxx xxxxxxxxx kontrolu xxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxx vyžaduje xxxxxxxx.

X xxxxxxxxx xxxxxxxx xx xxx xxx xxxxxx xxxxx xxxxxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx, které xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x xxxxxxxxxxxxx nárůst xxx xxxxxx, xxxx xx prokáže xxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx pozitivních xxxxxxx by měly xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx EINECS

Bez xxxxxx metabolické aktivace

methyl-methansulfonát

66–27–3

200–625–0

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

mitomycin X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X xxxxxx xxxxxxxxxxxx xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

Xxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx x xxxx xxxxxx xxxxx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx xxxxx xxxxx x xxxxx použití xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx třídy.

V okamžiku xxxxxxxx xx xxxx xxx xxxxxxx negativní xxxxxxxx skládající se xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx x xxxxxxxxxxx xxxxx x xxxxxxxxxx stejným způsobem xxxx xxxxxxx. Kromě xxxx by xxxx xxx neexponované xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud žádné xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx mutagenní účinky.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx zkoušené xxxxx

Xxxxxxxxxxxxx xxxxx se xxxxxxx zkoušené xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému, xxx xxx něho. Xxxxxxxx lymfocytů xx xxxx xxx xxxxxxxx xxx 48 xxxxx xx mitogenní xxxxxxxxx.

1.4.3.2 Xxx xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxx duplicitní xxxxxxx, x totéž xx xxxxxxx xxxxxxxxxx x xxxxxx pro xxxxxxxxx kontrolu xxxx xxxxxxxx xxxxxxxxxxxx. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx údajů xxxxxxxx (13, 14), xx xxxx duplicitními kulturami xx xxxxxxxxx xxxxxx, xxxx být přípustné xxxxxxx xxxxxx xxxxxxx.

Xxxxxx xxxx těkavé xxxxx xx xxxx xxx xxxxxxxx xxxxxxxx metodami, xxxx. x xxxxx xxxxxxxxxx kultivačních nádobách (15, 16).

1.4.3.3 Doba xxxxxxx kultur

V prvním xxxxxxxxxxx by xxxx xxx xxxxx vystaveny xxxxxxxx xxxxx, xxx x xxxxxxxxxxxx xxxxxxxx, xxx bez ní, xx xxxx 3 — 6 hodin, x xxxx xx xxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx normální xxxxx xxxxxxxxx xxxxx (12). Jestliže xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx xxx x xxxxxxxx, xxx xxx xxxxxxxx, měl xx xxx xxxxxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx x nepřetržitou xxxxxxxx xx do odběru x xxxx, která xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx xxxxx xxx xxxxx xxxxxxxxx xxx xxxxxx aplikace xxxx xxxxxx delších xxx 1,5xxxxxxx xxxxx xxxxx. Negativní výsledky xxx metabolické xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. X xxxxxxxxx, xxx xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx výsledků za xxxxxxxx, by xxxx xxx xxxxxx xxxxxxxxxx.

1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

Xx xxxxxxx xxxxxxx xx xxxxxxx 1-3 hodiny xxxx xxxxxxxxx xxxxx Xxxxxxxx® xxxx kolchicin. Pro xxxxxxxx preparátů pro xxxxxxx xxxxxxxxxx xx xxxxx buněčná xxxxxxx xxxxxx x xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx analýzu xxxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx analýzou xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxx xxxxx xxxxx x xxxxxxxx x xx ztrátě xxxxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x xxxxx rovném xxxxxxx xxxxxxx ± 2 xxx xxxxxxx xxxx xxxxx. Xx xxxxxx xxxxxxxxxxx a xxxxxxxx xx xxxx xxx hodnoceno xxxxxxx 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, případně xxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxxx xxx xxxxxx, je-li xxxxxxxxx xxxxx počet xxxxxxx.

Xxxxxx xx xxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx, xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx x endoreduplikace, jsou-li xxxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx a xxxx xx xxxx xxx xxxxxxxxxxx množství xxxxx xx xxxxxxxxxx chromozomovou xxxxxxx (xxxxxxxxx) vyjádřené x procentech. Xxx xxxxxxxxx a xxxxxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x četností. Xxxx xx zaznamenávají xxxxxxxx a xxxxxxx xx, xxx xxxxxxxxxx xx xx xxxxxxx xxxxxxxx aberací.

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

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

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx nepožaduje. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe x xxxxxxxx xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxxx potvrdit negativní xxxxxxxx xxxx diskutována x xxxx 1.4.3.3. Xxxxx xxxxxxxxx studie x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx x následných xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx být změněny, xxxxx xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, např. xxxxxx počtu xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x závislosti na xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx počtu. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Statistická xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

Xxxxxxxx látka, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, xx x xxxxx systému xxxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx xxxx xxxxxx xxx ohledu na xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx výsledky xx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x kultivovaných somatických xxxxxxx savců xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx savců xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx vehikula,

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

Xxxxx:

- typ x zdroj xxxxx,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxx xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx cyklu,

- xxxxxxx xxxxx krve, xxx xxxx xxxxxxx xxxx krev xxxx xxxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- případně xxxxxx xxxxxxxxx buněčné kultury,

- xxxxxxx xxxxxxx počtu xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

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

- složení xxxxx, xxxxxxxx koncentrace XX2,

- xxxxxxxxxxx zkoušené xxxxx,

- objem vehikula x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxx xxxxxxxx,

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

- pozitivní x xxxxxxxxx kontroly,

- xxxxxx xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx aberací,

- počet xxxxxxxxxxxxx metafází,

- metody xxxxxxxxx xxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- známky xxxxxxx,

- údaje o xX x xxxxxxxxxx xxxxxxxxxxx xxxxx, xxxxx xxxx stanoveny,

- definice xxxxxxx, včetně xxxx,

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

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. J. (1976), Cytological Xxxxxxx xxx Detecting Xxxxxxxx Xxxxxxxx, xx: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx xxx Xxxxxxx for xxxxx Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, X. (ed) Xxxxxx Xxxxx, Xxx Xxxx xxx Xxxxxx, 1-29.

2) Xxxxxxxx, M. Xx., Xxxxxx, T. (1985), Xxx Xx xxxxx Xxxxxxxxxxx Aberration Xxxx Xxxxx Xxxxxxx Xxxxxxx Lung (XXX) Xxxxxxxxxx Cells xx Xxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxx Research, Xxx. 5, Ashby, X. xx xx., (xxx) Elsevier Science Xxxxxxxxxx, Amsterdam-New Xxxx-Xxxxxx, 427-432.

3) Xxxxxxxx, X. X., Armstrong, M. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxx, A. X., Xxxxxxxx, X., Xxxxx, X., Duk, X., Xxxxx, J., Xxxxxxxx, X. X., Xxxxxxx, X. A., Xxxxxxxx, X., Zeiger E. (1978), Xxxxxxxxxx aberration xxx xxxxxx xxxxxxxxx xxxxxxxxx xx Xxxxxxx xxxxxxx ovary xxxxx: Xxxxxxxxxx xx 108 xxxxxxxxx, Environ. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Xxxxx, X., Xxxxxxxx, X. X., Marshall, X. X., Ishidate, M. Xx., Xxxxxxx, D., Xxxxx, X., Xxxx, X. C. (1991), Xxxxxxxxxxxx under Xxxxxxx Xxxxxxx Xxxxxxxxxx. X xxxxxx from ICPEMC Xxxx Xxxxx 9, Xxxxxxxxxx Res., 257, 147-204.

5) Morita, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxx, X., (1992), Clastogenicity xx xxx pH xx Xxxxxxx Xxxxxxxx Xxxxxxxxx Xxxxx, Mutatation Xxx., 268, 297-305.

6) Xxxx, X. N., McCann, X., Xxxxxxxx, X. (1975), Methods xxx Xxxxxxxxx Carcinogens and Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Mutagenicity Xxxx, Xxxxxxxx Res., 31, 347-364.

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

8) Natarajan, X. X., Xxxxx, X. X., van Xxxx, X. X. X., Xxxxxxx, X., xx Vogel, N. (1976), Xxxxxxxxxxx Xxxxxxx xx Mutagen/Carcinogens xxxxx Xxxxxxxxxx xx a Xxxxxxxxxxx System In xxxxx, X. Induction xx Xxxxxxxxxx Aberrations xxx Xxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Dimethylnitrosamine (XXX) xx CHO Xxxxx in xxx Xxxxxxxx of Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

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

10) Xxxxxx, X. X., Xxxxxx, X. X., Elcombe, X. X., Gatehouse, X. X., Gibson, X. G., Mackay, X. X., Wolf, X. X. (1992), Xxxxxx xx UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx In xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X. Xxxx Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, in: xx Serres, X. X., Fouts, X. X. Xxxx, J. X., Philpot, X. X. (xxx), In xxxxx Metabolic Activation xx Xxxxxxxxxxx Testing, Xxxxxxxx, North-Holland, 85-88.

12) Xxxxxxxx, S. X., Xxxxxxx, X. X., Xxxxxxxx, X. Jr., Xxxxx, X. L., Xxxxxxxx, D. J., Xxxxxx, X., Xxxxxxx, X., Sofumi, X. (1994), Report from Xxxxxxx Xxxxx on Xx vitro Tests xxx Chromozomal Xxxxxxxxxxx, Xxxxxxxxxx Res., 312, 241-261.

13) Richardson, X., Xxxxxxxx, D. X., Xxxxx, X. X., Xxxxxxxx, G., Xxxxxxx, X. X., Xxxxxxxx, X. (1989), Analysis xx Xxxx from Xx xxxxx Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, Kirkland, X. X., (ed) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 141-154.

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

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

16) Xxxxxx, X. X., Xxxxxx, X. M., Xx, X. X., Xxxxxx, X. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Gels xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxxxxxxxx Mutagen., 5, 795-801.

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

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


XXXXXXX 4X

"X.11 XXXXXXXXXX–XXXXXXX XX CHROMOZOMOVÉ XXXXXXX X BUŇKÁCH XXXXXX XXXXX SAVCŮ XX XXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX TG 475 — Xxxxxxx na xxxxxxxxxxxx xxxxxxx v xxxxxxx xxxxxx xxxxx xxxxx (1997).

1.1 ÚVOD

Zkouška xx xxxxxxxxxxxx aberace x xxxxx in xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx indukovaných xxxxxxxxx xxxxxx x xxxxxxx xxxxxx xxxxx xxxxx, xxxxxxx hlodavců (1, 2, 3, 4). Rozlišují xx xxx xxxx strukturních xxxxxxx — chromozomové x chromatidové. Nárůst xxxxxxxxxxx xxxx xxxxxxxx, xx chemická látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx aberace. V xxxxxxx většiny chemických xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx typu, xxxxx chromozomové xxxxxxx xx xxxxxx vyskytují. Xxxxxxxxxxxx mutace a xxxxxxxxxxx jevy jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx a xxxxxxxx xxxxx xxxxxx o xxx, xx xxxxxxxxxxxx xxxxxx x související xxxx způsobující xxxxx x xxxxxxxxxx a x xxxxxx somatických xxxxx xxxxxxxxx nádory, xxxx xxxxx xx xxxxxxx rakoviny x xxxxxxx a x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx jsou rutinně xxxxxxxxx xxxxxxxx. Xxxxxxx xxxxx xx x xxxx zkoušce xxxxxx xxxx, xxxxxxxx je xxxxxx xxxxxxxxxxxxxxxx xxxxx x obsahuje xxxxxxxx xxxxx x xxxxxxx xxxxxx, které xx xxxxxx xxxxxxx a xxxxxxxxxxxx. Xxxx druhy x cílové xxxxx xxxxxx předmětem xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx DNA, xxxxxxx se mohou x xxxxxxx xxxxx x xxxxx xxxxx. Xxxxxxx xx vivo xx xxxxxx xxxxxxxx xxx další výzkum xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx in xxxxx.

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

Xxx xxxx Xxxxxx úvod, část X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx x xxxxxxx xxxx xxxxxxxxx x xxxxxx místě.

Endoreduplikace : xxxxxx, xxx kterém x xxxxx po X-xxxx replikace XXX xxxxxxx k mitóze, xxxxx xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx jsou xxxxxxxxxx se 4, 8, 16,… xxxxxxxxxxxx.

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

Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx xxxxxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx u použitých xxxxx.

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

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

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxxxx jsou xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxx a ve xxxxxxx xxxxxxxx po xxxxxxxx xx xxxxxx. Xxxx xxxxxxxxx se xxxxxxxx xxxx xxxxx xxxxxxxxxxx metafázi (xxxx. xxxxxxxxx nebo Xxxxxxxx®). X xxxxx kostní xxxxx xx poté xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx a xxxxxxxxx se xxxxxxxxxxxx xxxxxxx buněk x xxxxxxxx.

1.4 POPIS ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx je xxxxxxxx potkan, myš x xxxxxx čínský, xxxxxx xxx xxxxxx xxxxxxxx vhodný xxxxx xxxx. Měly xx xxx použity běžně xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx x xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx xxxxxxx se xxxxxxxx výběrem xxxxxxx xx kontrolní xxxxxxx x skupinu, xxxxx xx vystaví zkoušené xxxxx. Xxxxx xx xxxx být uspořádány xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata se xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x laboratorních xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx vehikulech a xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx xxxx mohou xxx xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých xxxxxxxx xxxxx toxické xxxxxx a xxxx xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by být xxxxxx xxxxxxxx podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx nejdříve xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx aplikace xxxxxxxx látky xx xxxx zvířata xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx jako xxxxxxx xx xxxxxxxxx, x xxxxx dojde x xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx poskytovat xxxxxxxxxx xxxxxxx in xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx se xxxxxxx, xx poskytnou xxxxxxxxxxxxx nárůst xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx měly xxx zvoleny xxx, xxx xxx účinek xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx byla xxxxxxxxx xxxxxxxx podávána xxxxx xxxxxxxx xxx xxxxxxxx xxxxx a xxx byl odběr x jejím případě xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx kontrolu xxxxx být xxxxxxx xxxxxxxx xxxxx xx xxxxxx xxxxxxxx třídy, xxxx-xx x dispozici. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx EINECS

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

mitomycin C

50–07–7

200–008–6

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X okamžiku xxxxxxx odběru xx xxx xxx xxxxxxxx xxxxx x xxxxxxxxxxx xxxxxxx, jimž je xxxxxxxxxx pouze rozpouštědlo xxxx vehikulum x xxx jinak xxxxxxxxxx xxxxxx proces jako xxxxxxxxxx skupiny, pokud xxxxxx x dosavadních xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x četnosti xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx jeden xxxxx, xx nejvhodnějším xxxxxxxxx xxxx prvního xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx tehdy, xxxxxxxxxx-xx xxxxx kontrolní údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Každá xxxxxxxxxx x kontrolní xxxxxxx se xxxxxx x alespoň pěti xxxxxxxxxxxxxxxx xxxxxx pro xxxxx xxxxxxx. Xxxxxxxx xxxx v době xxxxxx x dispozici xxxxx ze studií xx stejným xxxxxx x za xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx pohlavími xxxxxx x toxicitě, xxxx postačující xxxxxxxx xxxxxxx xxxxxxx. Je-li xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx u některých xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx xx zvířaty xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xx xxxx xxx xxxxx xxxxx xxxxxxxx jednorázově. Xxxxxxxx xxxxx xxxxx xxx podávány také xx xxxx dávkách, xxx. xxx dávky x xxx xxx x rozmezí xx xxxx xxx několika xxxxx, xxx xxxx xxxxxxxxx podávání xxxxxxx xxxxxx materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx měly xxx xxxxxxxx xx xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxxx x xxxxxx dni. X xxxxxxxx xx xxxxx xxxxxxx xx xxxxxx xxxx od xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx cyklu (xxxx xxxx obvykle 12 — 18 x). Xxxxxxxx doba xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx pro xxxxxx na xxxxxxxx xxxxxxxxx cyklu xxxx xxx xxxx xx xxxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx aberací, xxxxxxxxxx xx provést xxxxx xxxxx po 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx do xxxx xxx jednoho xxx, xxx xx xxx xxxxx xxxxxxxx xx xxxxxx době xx xxxxxxxx aplikace, xxxxx odpovídá 1,5násobku xxxxxxxx délky xxxxxxxxx xxxxx.

Xxxx xxxxxxxxx se xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. X xxxx xx xxxx doba přibližně 3 — 5 x; x xxxxxx xxxxxxxx xx tato xxxx xxxxxxxxx 4 — 5 x. X xxxxxx dřeně xx xxxxxxxx xxxxx x analyzují xx xx xxxxxxxxxxxx aberace.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se kvůli xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx dávek, xxxx by xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, pohlavím x xx xxxxxxxx xxxxxx xxxxxxxx, jež xx použijí x xxxxxx xxxxxx (5). X případě xxxxxxxx xx pro xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru stačí, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx je xxxxxxxxxx jako dávka xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx podle očekávání x xxxxxxxx. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx a mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx být xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx jako dávka xxxxxxxxxxxx x xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx mitotického indexu).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx dávkou xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx xxxx xx xxxx xxxxxxx v xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx základě xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx za xxxxxxxxx. X xxxx trvajících xxxxxx xx xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx a xxx delší xxx 14xxxxx xxxxxxxx xx xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx se obvykle xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx nebo vhodnou xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx xxxxxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx xxxx injekčně, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl překročit 2 xx/100 g xxxxxxx xxxxxxxxx. Použití xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx být xxxxxxxxxx. Xx xx dráždivé x xxxxxx xxxxx, xxxxx xxxxxxx při xxxxxxx koncentracích xxxxxxxx xxxxxxxx účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx zajišťující xxxxxxxxxx objem při xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx se odebere xxxxxx dřeň, xxxxxxxxxxxx xx x xxxxxx. Xxxxx xx xxxxxxx xx podložní xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

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

X každého xxxxxxx xx xxxx xxx analyzováno alespoň 100 buněk. Xxxxx xxxxx xxx snížit, xx-xx pozorován xxxxx xxxxx aberací. Všechny xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx xx xxxx xxx před xxxxxxxxxxxxxx analýzou nezávisle xxxxxxxx. Xxxxxxx xxx xxxxxx často xxxxxxx xx chromozomálním xxxxxx xxxx xx ztrátě xxxxxxxxxx x části xxxxx x metafázi, xxxx xx vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x počtu xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx zvířata by xxxx být xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Pro každé xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx, počet xxxxxxx xx buňku x xxxxx xxxxx x xxxxxxxxxxxxx xxxxxxx (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Pro exponované x kontrolní xxxxxxx xx měly xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx se, xxx xxxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx. Xxxxxxxxxx-xx xxxxx o xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, mohou být xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx zkombinovány.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx xx dávce xxxx jasný xxxxxx xxxxx xxxxx s xxxxxxxxx xxx xxxxxxx x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x úpravami xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx má xxxxxxxxx indukovat numerické xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx chromozomy xxxx xxxxxxxx, xx zkoušená xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (7, 8).

Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, xx xxxxxxxx x xxxxx systému xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx poskytne xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx xxxx xxxxxx xxx xxxxxx na to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxxxxxxxx xxxxxxx xx xxxx xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx x xxxxxx xxxxx testovacího xxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx látka xx xxxxxxxx xxxxxxx neindukuje x kostní xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx xx být xxxxxxxxxxx pravděpodobnost, x xxxxx xx zkoušená xxxxx xxxx její xxxxxxxxxx dostanou xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx do cílové xxxxx (např. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- xxxxx, xxxxx x pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

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

Zkušební xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- xxxxx xx xxxxxx xxx xxxxxxxx rozsahu, pokud xxxx provedena,

- xxxxxxxxxx xxxxxxxxx xxxxxx dávek,

- xxxxx o přípravě xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxxx xxxx (xxx) xx xxxxxxxxxxxx dávku (xx/xx xxxxxxx hmotnosti/den),

- xxxxxxxx xxxxx o xxxxxxx krmiva a xxxx,

- xxxxxxxx popis xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx hodnocení xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx na jedno xxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx pozitivní, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxx x xxxxx xxxxxxx uvedený xxxxxxxxxx xxx každé xxxxx,

- celkový xxxxx xxxxxxx ve xxxxxxx xx středními xxxxxxxxx x směrodatnými xxxxxxxxxx,

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

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx odpovědi xx dávce,

- případné xxxxxxxxxxx analýzy,

- údaje x xxxxxxxx negativní xxxxxxxx,

- dosavadní xxxxx x xxxxxxxxx kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- údaje x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. D. (1984), Xxxxxxxxxxx Xxxxx in Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: a Xxxxxxxxx Xxxxxxxx, S. Venitt, X. X. Xxxxx (xxx), IRL Xxxxx, Xxxxxx, Xxxxxxxxxx X. X., 275-306.

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

3) Richold, X., Chandley, X., Xxxxx, X., Gatehouse, X. G., Xxxxxxx, X., Henderson, X. (1990), In xxxx Xxxxxxxxxxx Assays, xx: X. X. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx Xxxxx, XXXXX Recommended Xxxxxxxxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx X xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

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

5) Xxxxxxx, R. X., Xxxxx, X. A., Xxxxxx, X. R., Xxxxxx, P. X., Xxx, X., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Hodson-Walker, X., Xxxxxx, X. X., Xxxxxxxx, D. X., Xxxxxxx, X. (1992), Xxxxxx of Xxxxxxx Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Society Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx In xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Richold, X., Papworth, D. X., Savage, J. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx of Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Test Data, X. X. Xxxxxxxx (xx.) Cambridge University Xxxxx, Xxxxxxxxx, 184-232.

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

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


XXXXXXX 4C

"B.12 MUTAGENITA–TEST XXXXXXX ERYTROCYTÁRNÍCH XXXXXXXXXX XX VIVO

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx OECD XX 474 — Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx (1997).

1.1 XXXX

Xxxx savčích erytrocytárních xxxxxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxx xxxxxxxxx chromozomů xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx látkou, x to xxxxxx xxxxxxx erytrocytů xxxxxxxxxx x kostní dřeně x/xxxx buněk periferní xxxx, xxxxxxx xxxxxxxx.

Xxxxxx xxxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxx je xxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxx xxxxxxxxx xxxx celé xxxxxxxxxx.

Xxxx se erytroblast xxxxxx xxxxx xxxx xx xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxx xxxxx je xxxxxxxx a mikrojádra, xxxxx při xxx xxxxx xxxxxxxxx, xxxxxxxxx x cytoplasmě, která xxxxx xxxxx neobsahuje. Xxxxxxxxxxxx mikrojader xx x těchto xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx xxxxxx jádro. Xxxxxx xxxxxxx polychromatických xxxxxxxxxx s xxxxxxxxxx x exponovaných xxxxxxxxx xx xxxxxxx indukovaného xxxxxxxxxxxxxx poškození.

V xxxxx xxxxx xx xxxxxxx xxxxxxxxx kostní xxxx xxxxxxxx, xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Stanovení nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx v xxxxxxxxx xxxx xx rovnocenně xxxxxxxxxx u xxxxxxxxxxx xxxxx, x xxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx odstraňovat xxxxxxxxxx x xxxxxxxxxx, nebo xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxxxxxxxx xxx xxxxxxxx řadou xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx přítomnosti xxxx xxxxxxxxxxxxx centromerní (kinetochorní) XXX v mikrojádře. Xxxxxxxxx se zejména xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx s xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx v xxxxxxxxx xxxx, xxxxx xxxxxxxx xxxxxxxxxx, připadající xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx lze rovněž xxxxxx xxxx konečný xxxxxxxx zkoušky, xxxxxxxx xxxx zvířata xxxxxxxxxx xxxxx týdny nebo xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx je xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx zohlednit faktory xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx DNA, třebaže xx xxxxx lišit x xxxxxxx xxxxx x xxxxx, xxxxx x z xxxxxxxxxxx xxxxxxxx. Zkouška xx xxxx xx xxxxxx xxxxxxxx pro xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx x systémech xx vitro.

Jestliže existuje xxxxx o tom, xx se xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx nedostanou do xxxxxx xxxxx, není xxxxxx tuto xxxxxxx xxxxxx.

Xxx xxxx Obecný xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) chromozomu, x xxx (x xxxx) se xxxxx xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxx pohyb xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxx buněk.

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

Xxxxxxxxxxxxxxxx xxxxxxxxx : xxxxx erytrocyt xxxxxxxxxxxx xxxxxxxx, xxxxx xxx rozlišit xx xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

Xxxxxxxxxxxxxxx erytrocyt : xxxxxxx xxxxxxxxx ve xxxxxxxxx xxxxxxxxxx, který xxxxx xxxxxxxx xxxxxxxx, x může být xxxx rozlišen xx xxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx se vhodným xxxxxxxx vystaví zkoušené xxxxx. Při xxxxxxx xxxxxx dřeně se xxxxxxx ve vhodném xxxxxxxx xx xxxxxxxx xxxxxx, xxxxxxx xx xxxxxx dřeň, xxxxxxxx xx xxxxxxxxx a xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx periferní xxxx xx xxxx xx vhodném xxxxxxxx xx xxxxxxxx odebere, xxxxxxxxxx se xxxxxxxx xxxxxxxx x obarví xx (4, 8, 9, 10). Xxx xxxxxxxx x periferní xxxx by měla xxxx xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxx xxxxxxxx xx xxxxxxxxx xxxx. Preparáty xxxx xxxxxxxxxxx na xxxxxxxxxx xxxxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Přípravky

1.4.1.1 Výběr xxxxx zvířete

Při použití xxxxxx dřeně se xxxx testovací zvíře xxxxxxxxxx myš xxxx xxxxxx, xxxxxx xxx xxxxxx jakýkoli vhodný xxxxx xxxx. Xxx xxxxxxx xxxxxxxxx xxxx xx doporučuje myš. Xxx však použít xxxxxxxx xxxxxx xxxx xxxxx xx xxxxxxxxxxx, xx jde x xxxx, x xxxxx xxxxxxx neodstraňuje erytrocyty x xxxxxxxxxx, nebo xxxx vykazující xxxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx x xxxxxx xx u xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx výběrem rozdělí xx kontrolní skupinu x skupinu, x xxx xx xxxxxxx xxxxxxxx. Xxxxxxx se xxxxxxxxxxx identifikují. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx. Klece xx xxxxxxxxxx xxx, xxx byl xxxx xxxxxx xxxxxx minimalizován.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx měly xxx před xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx před podáním xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxxxx xxx xxx použitých xxxxxxxx xxxxx xxxxxxx xxxxxx x mělo by xxx xxxxxxxxx podezření, xx reaguje se xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se pokud xxxxx xxxxxxxx zvážit xxxxxxx vodných rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx xxx pohlaví. S xxxxxxxx aplikace zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx identický xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x expozici.

Pozitivní xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xx xxxx při xxxxxxxxxxx xxxxxxxx, x nichž xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx pozadí. Xxxxx xxxxxxxxx kontroly xx xxxx xxx xxxxxxx xxx, aby xxx xxxxxx xxxxxxxx, ale xxx při xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx přijatelné, aby xxxxxxxxx kontrola xxxx xxxxxxxx jiným způsobem xxx xxxxxxxx xxxxx x xxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx navíc může xxx vzato x xxxxx xxxxxxx chemických xxxxx ze xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx pozitivní xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx odběru xx xxx být xxxxxxxx odběr x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx je aplikováno xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x která xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx exponované xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxx. Xxxxxxx-xx se xxx negativní xxxxxxxx xxxxx odběr, je xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Kromě xxxx xx měly xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx publikovány xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.

Xxx použití xxxxxxxxx krve xxxx xxx jako xxxxxxxxx xxxxxxxx xxxxxxxxxx také xxxxxx xxxx odebraný xxxx xxxxxxxx, xxxxx xxxx x xxxxxxxx xxxxxx x xxxxxxxxx xxxx (xxxx. 1 — 3 xxxxxxxx) xx předpokladu, xx xxxxxxxx xxxxx xxxxx x xxxxxxx, xxxxx xx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Počet a xxxxxxx zvířat

Každá exponovaná x xxxxxxxxx xxxxxxx xx xxxx xxxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx (11). Xxxxxxxx xxxx v xxxx xxxxxx x xxxxxxxxx xxxxx ze xxxxxx se stejným xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx xxxxxxxxx, xx neexistuje xxxx xxxxxxxxx rozdíl v xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx jednoho pohlaví. Xx-xx expozice xxxxxxx xxxxxxxxxx pro xxxxxx xxxxxxx, xxxx xx xxxx například x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx být xxxxxxx provedena xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx doporučit xxxxx xxxxxxxxxx xxxx (xx. jednu, xxx xxxx tři xxxxxxxx x xxxxxxxxx 24 xxxxx). Vzorky xx xxxxxx s prodlouženým xxxxxxx xxxxxxxx jsou xxxxxxxxxx, pokud se x xxxxxx xxxxxx xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –x případě xxxxxxxxxxx studií — xxxxx byla xxxxxxxxx xxxxxxxx xxxx byla xxxxxxxxx limitní xxxxx x podávání xxxxxxxxx xx do okamžiku xxxxxx. Xxxxxxxx xxxxx xxxxx xxx podávány xxxx ve xxxx xxxxxxx, xxx. dvě xxxxx x xxx xxx x xxxxxxx xx více než xxxxxxxx hodin, aby xxxx xxxxxxxxx podávání xxxxxxx objemů xxxxxxxxx.

Xxxx xxxx být proveden xxxxx xxxxxxx:

x) xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx xxxxxx. Xxxxxx xxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx nejdříve 24 xxxxx po xxxxxxxx x poslední xxxxxxxxxx 48 xxxxx xx xxxxxxxx x x přiměřeným xxxxxxxx xxxx xxxxxx. Xxxxx xxxxx xxx 24 xxxxx xx aplikaci xxxx xxx xxxxxxxxx. Xxxxxx periferní krve xx xxxxxxxx xxxxxxx xxxxxxx, přičemž xxxxx xxxxx se provede xxxxxxxx 36 xxxxx xx xxxxxxxx a xxxxxxxx xxxxxxxxxx 72 xxxxx xx xxxxxxxx x xx prvnímodběru xx dodrží odpovídající xxxxxx. Xx-xx po xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx odběr nutný;

b) xxxx-xx podávány xxx xxxx více xxxxx xxxxx (např. dvě xxxx xxxx xxxxx x intervalu 24 xxxxx), měly xx xxx xxxxxx xxx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx po 18 xx 24 xxxxxxxx po poslední xxxxxxxx x xxx xxxxxxx periferní xxxx xxxxxx po 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 xxx xxxxxxxx rozsahu xxxxx, xxxx xx být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, pohlavím x xx stejného xxxxxx xxxxxxxx, jež xx použijí v xxxxxx xxxxxx (13). X xxxxxxx toxicity xx xxx xxxxx xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx pokrývat rozpětí xxxx maximální xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že vyšší xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x xxxxxxxx. Xxxxx xx specifickou biologickou xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx xxxxxxxxx stanovení xxxxx vyhovovat a xxxx by xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx dávka xxxx xxx xxxx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx známky xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx v kostní xxxxx xxxx x xxxxxxxxx krvi).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx dávkou o xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx xxxx ve xxxx dávkách x xxxxxx xxx nevykazuje xxxxx pozorovatelné xxxxxxx xxxxxx x není-li xx xxxxxxx údajů x látkách, xxxxx xxxx podobnou strukturu, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx úplná studie xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx pro 14denní xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den a xxx xxxxx než 14xxxxx aplikaci je xxxxxxx xxxxxx 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx člověka xxxx znamenat xxxxxxx xxxxxx x limitní xxxxxxx vyšší úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx kanylou, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx podávání jsou xxxxxxxxxx v odůvodnitelných xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx najednou podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x tělesné hmotnosti. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx xxxxxxxxx z xxxxxx xxxx xxxxx xxxxx xx xxxxxxxx. Xxxxx xx xxxxxxxx x xxxxxx xxxx xxxxx x zavedenými xxxxxxxx xx xxxxxxxxx x xxxxxx. Xxxxxxxxx xxxx xx xxxxxxx x xxxxxx žíly xxxx xxxx vhodné xxxxxx xxxx. Xxxxxx xxxxx se xxxxx xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx připraví xxxxxxxxx xxxxxxxx x xxxx xx xxxxxx. Xxxxxxxx xxxxxxx specifického xxx XXX (např. xxxxxxxxxx xxxxx (14) nebo Xxxxxxx 33258 x xxxxxxx-X (15)) se xxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx s xxxxxxxx xxxxxxx nespecifického xxx DNA. Tato xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Přídavné xxxxxxx (xxxx. celulosová xxxxxx x xxxxxxxxxx buněk xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, xx se xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx se xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx (xxxxxxx + zralé) xxxxxxxx xxxxxxxxxx, přičemž se x případě xxxxxx xxxxx použije xxxxxxx xxxxxxx 200 erytrocytů x x případě xxxxxxxxx xxxx xxxxxxx 1000 xxxxxxxxxx (17). Xxxxxxx preparáty včetně xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by xxxx být xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx se xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx být získány xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx mikrojader. Xxx xxxxxxxxxxxxx analýze xx xxxxx být xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx týdny xxxx xxxx, xxx xxxx xxxxxxxx xx výskyt xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx xx xxxxx xxxxx. Systémy xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx x xxxxxxxxx cytometrická analýza xxxxxxx suspenze) jsou xx xxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxx přijatelnými xxxxxxxxxxxxx manuálního xxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx být xxxxxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx analyzované xxxxx xx xxx xxx xxxxxx počet xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx a xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxxx xx xxx xxxx xxxxxxx xxxxx x xxxxxxx erytrocytech, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx xxxxx xx xxxxx xxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxx x mikrojádry vyjádřené x xxxxxxxxxx. Neexistuje-li xxxxx x xxxxxxx x odpovědi xxxx xxxxxxxxx, xxxxx xxx xxx statistickou xxxxxxx xxxxx pro obě xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxx x xxxxxxxxxx xx xxxxx nebo xxxxx xxxxxx xxxxx xxxxx x mikrojádry pro xxxxxxx x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím faktorem xxx pozitivní xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, nejlépe x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx látka, jejíž xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx xxxxxxxx x tomto xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok o xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx je xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxxxxx mitotického xxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxxx mikrojádra v xxxxxxxxx xxxxxxxxxxxx testovacího xxxxx.

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

3. ZPRÁVY

PROTOKOL O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, stáří x xxxxxxx zvířat,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

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

Xxxxxxxx podmínky:

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

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

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx zkoušené xxxxx,

- xxxxxxxxxx způsobu podávání,

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

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

- xxxxxxxx xxxxx x kvalitě xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx stanovení toxicity,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x nezralých xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx buněk xx xxxxx xxxxx,

- xxxxxxxx klasifikace xxxxxx xx pozitivní, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx erytrocytů,

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

- xxxxxxx hodnota ± xxxxxxxxxx odchylka xxxxx xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx ve xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x metody,

- údaje x souběžné x xxxxxxxxx xxxxxxxxx kontrole,

- xxxxx x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Heddle, J. X. (1973), A Xxxxx In xxxx Xxxx xxx Xxxxxxxxxxx Xxxxxx, Xxxxxxxxxx Res., 18, 187-190.

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

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

4) Xxxxxxxxx, K. X., Xxxxxx, X. X., Xxxxxx, X. C., Xxxxxxxx, X. X., Xxxxxx, J. X. (1990), Xxx In xxxx Xxxxxxxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxxxx and Xxxxxxxxxx Xxxxx. X xxxxxx xx the U. X. Xxxxxxxxxxxxx Protection Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Xxx., 239, 29-80.

5) MacGregor, X. X., Xxxxxxxx, R., Xxxx, W. N., Xxxx, X. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Screen for Xxxxxxxxxxx Damage Xxxxxx Xxxxxxx Xxxxxxxx Xxxxxxx xx Mice, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx xx Xxxxxxxxxx, xx. X. X. Xxxxx, X. X. Xxxxxxx, X. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. T., Xxxxxx, X. X. Hite, X., Xxxxxxxx, G. X., Ramel, X., Xxxxxxxx, M. F., Xxxx, X. X., Xxxx, X. (1987), Xxxxxxxxxx xxx the Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx xx Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

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

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

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

10) Xxx Collaborative Xxxxx Xxxxx xxx the Xxxxxxxxxxxx Test (XXXXX/XXXXX, XXX: Xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxx Group xx xxx Environmental Xxxxxxx Xxxxxxx xx Xxxxx) (1995), Protocol xxxxxxxxxxx xxx xxx xxxxx-xxxx mouse peripheral xxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, M., Xxxx, X. X., MacGregor, X. T., Xxxxxxxx, X., Blackey, X. X., Xxxxxx-Xxxxxxx, X., Xxxxxx, Xx. X. X., Xxxxxxxxxxxx, F., Xxxxxxx, F., Xxxxxxx, X., Sutou, S., Xxxxxxx, X. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Micronucleus Xxxxx, Xxxxx. Xxx., 312, 293-304.

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

13) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, X. X., Xxx, X., Xxxxxxx, D. J., Xxxxxxxxx, D. G., Xxxxxx-Xxxxxx, X., Morton, X. X., Xxxxxxxx, X. J., Rochold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Working Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Mutagenesis, 7, 313-319.

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

15) XxxXxxxxx, J. X., Xxxx, X. X., Xxxxxxxx, X. X. (1983), A Xxxxxx Xxxxxxxxxxx Staining Xxxxxxxxx xxx Xxxxxxxxxxx xxx XXX xx Xxxxxxxxxxxx Xxxxx Hoechst 33258 xxx Xxxxxxx X, Xxxxxxxx Res., 120, 269-275.

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

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

18) Richold, X., Xxxxx, X., Xxxxxxx, X., Xxxxxxxx, X., Gatehouse, X. X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxxx Assay, xx: X. J. Xxxxxxxx (xx.), Basic Mutagenicity xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx 1, xxxxxxx, Xxxxxxxxx University Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, R., Xxxxxxxx, X. X., Xxxxx, G., Ferguson X., Richold, X., Xxxxxxxx, X. X., Xxxxxx, X. X. X. (1989), Staticical Xxxxxxxx xx In xxxx Xxxxxxxxxxx Assays, xx: X. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx III, Xxxxxxxxx University Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

"X.13/14 XXXXXXXXXX — ZKOUŠKA NA XXXXXXXX XXXXXX S XXXXXXXXXX

1. METODA

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

1.1 XXXX

Xxx xxxxxxx na reverzní xxxxxx x xxxxxxxxxx xx používají bakteriální xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Xxxxxxxxxx typhimurium x Xxxxxxxxxxx coli, x xxxxxxx bodových xxxxxx, které xxxxxxxx xxxxxxxxxx, xxxxx a xxxxxx xxxxxxx xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Xxxxxxxx této xxxxxxx na reverzní xxxxxx s bakteriemi xxxxxxx x xxxxxxx xxxxxx, které xxxxxxxxx xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxx a xxxxxxxx xxx xxxxxxx xxxxxxxxx bakterií xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx díky své xxxxxxxxxx xxxx v xxxxxxxxxxxxx xxxxxxxxxxxx, které xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx kmenem.

Bodové mutace x podobné xxxx xxxx příčinou xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x člověka x xxxxxxxx xxxxx důkazů x tom, že xxxxxx mutace x xxxxxxxxxx x x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx xxxx xxxxx na xxxxxx xxxxxxxx x xxxxxxx x u xxxxxxxxx xxxxxx. Xxxxxxx na xxxxxxxx mutace x xxxxxxxxxx xx xxxxxx, xxxxxxxxxx x relativně xxxxxx. Mnoho xxxxxxxxxxx xxxxx má xxxx xxxxxxxxxx, díky xxxx xxxx xxxxxxxxxx xx xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx xxxxx xxx velké molekuly x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX nebo xxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxxxxxxxx x xxxxxx. Specifičnost xxxxxxxxxxx xxxxx xxxx poskytnout xxxxxxx užitečné xxxxxxxxx x typech mutací, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx činiteli. Pro xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx x dispozici xxxxx rozsáhlá xxxxxxxx xxxxxxxx xxx xxxxxxx xxxxx xxxxxxxx x xxxx xxxx xxxxxxxx xxxxx vyzkoušené xxxxxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx fyzikálně-chemickými xxxxxxxxxxx.

Xxx také xxxxxx xxxx, část X.

1.2 XXXXXXXX

Xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx nebo Xxxxxxxxxxx xxxx xxxxxx x detekci xxxxxx x kmeni vyžadujícím xxxxxxxxxxxxx (xxxxxxxx resp. xxxxxxxxx), xxxxxxx xxxxxx xxxx nezávislý na xxxxxxx přísunu xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx bází xxxx xxxxxxxx, jež xxxxxxxxx xxxxx x xxxxxx XXX. Xxx xxxxxxx reverzních mutací xx xxxxx xxxx xxxxx vyskytnout xx xxxxx xxxxxxx xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx genomu.

Posunové xxxxxxxx xxxx xxxxxxxx, jež xxxxxxxxx adici xxxx xxxxxx jednoho nebo xxxx párů bází XXX a xxxxxxxx xxx xxxxx rámec XXX.

1.3 VÝCHOZÍ ÚVAHY

Při xxxxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xx xxxxxxxxx prokaryotické xxxxx, xxxxx xx xxxx xx buněk xxxxx xxxxxxx, jako xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx struktura x xxxxxxxxx xxxxxxx DNA. Xxxxxxx xxxxxxxxx in xxxxx obecně vyžadují xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx aktivace. Metabolické xxxxxxxxx xxxxxxx in xxxxx nemohou xxxxx xxxxxxxxx xxxxxxxx in xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx x karcinogenním xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx zpravidla využívána xxx počáteční vyšetření xxxxxxxxxxx xxxxxxxx, x xxxxxxx aktivity xxxxxxxxxxxx xxxxxx mutace. X xxxxxxxx databáze xxxxxxx, xx xxxxx xxxxxxxxxx xxxxx, xxxxx xxxx x této xxxxxxx xxxxxxxxx, xxxxxxxx mutagenní xxxxxxxx i v xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx. Příčiny xxxxxx skutečností lze xxxxxxxxx ve specifické xxxxxx detekovanéhokonečného jevu, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx xxxx x xxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx straně faktory, xxxxx xxxxxxx xxxxxxxxx xxxxxxx na xxxxxxxx xxxxxx xx xxxxxxxxxx, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx aktivity.

Zkouška xx reverzní xxxxxx x bakteriemi nemusí xxx xxxxxx xxx xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (např. xxxxxx antibiotika) x xxx chemické xxxxx, x xxxxx xx xxxxxxxxxxx (xxxx x xxxxx se xx), xx xxxxxxxxxx zasahují xx xxxxxxxxxxxx xxxxxxx xxxxx savců (např. xxxxxxx inhibitory xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). X xxxxxxxx xxxxxxxxx mohou xxx xxxxxxxxx xxxxxxx mutagenity x xxxxx.

Xxxxxxxx mnoho xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xx xxxxxxxxxxxx xxx savce, není xxxxxxxx xxxxxxxxx. Závisí xx xxxxxxxx xxxxx x xxxxxxxx xxxxx xxxxxxxxxxx, xxx nejsou xxxxxxxxxx touto xxxxxxxx, xxxxx xxxxxx jinými, xxxxxxxxxxxxxxx xxxxxxxxxx, nebo xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx buňkách neexistují.

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx látce, x xx xx xxxxxxxxxxx xxxxxxxx metabolického xxxxxxxxxxx systému x xxx něho. Xx xxxxxxxxxxx miskovém xxxxx xx xxxxxxxx xxxxxxxx x xxxxxxx xxxxxx x ihned xx xxxxxxx na minimální xxxx. V xxxxxxxxxxxx xxxxxx se xxxxxxxx xxxx xxxxxxxx a xxxx xx před xxxxxxxxx na minimální xxxx xxxxxx x xxxxxxx agarem. Xxx xxxx xxxxxxxxxx xx xx xxxx xxxx xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxx se xxxxxxxx x počtem xxxxxxx spontánních xxxxxxxxxx xx xxxxxxxxx misce x rozpouštědlem.

Je xxxxxxx xxxxxxx xxxxxxx xxxxxxxxx xxxxxxx na xxxxxxxx xxxxxx s bakteriemi. Xxxx běžně xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxx xxxx (1, 2, 3, 4), preinkubační xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx test (9, 10) x xxxxxxxxx xxxxxx (11). Xxxxxx pro zkoušení xxxxx x xxx xxxx popsány (12).

Zde xxxxxxx xxxxxxx xx xxxxxx hlavně xxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxxxxxxxx metod. Každá x xxxx xx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx ní. Xxxxxxx xxxxx lze xxxxxxxx xxxxxxxxx za použití xxxxxxxxxxxx xxxxxx. Tyto xxxxx xxxxx xx xxxxxxxxxx xxxx, xx xxxxx xxxxx xxxx xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, dvojvazné xxxx, xxxxxxxx, xxxxxxxxxx a xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx připouští, xx xxxxxx xxxxx xxxxxxxx nelze vždy xxxxxxxxx xxxxxxxxxxxx postupy, xxxx xx xxxxxxxxxx xxxxxxx xxxx nebo xxxxxxxxxxxx xxxxxx. Xxxx xx xxx xxxxxxxxxx xx "xxxxxxxx případy" x x jejich xxxxxxx xx xxxxxxx xxxxxxxxxx použít xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "zvláštní xxxxxxx" (společně x xxxxxxxx xxxxxxx jejich xxxxxxx): xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx látky (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxx xxx xxxxxxx zdůvodněna.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx měly xxx kultivovány xx xxxxxx xxxxxxxxxxxxx fáze xxxx xx časné xxxxxxxxxxx xxxx růstu (xxxxxxxxx 109 xxxxx xx ml). Xxxxx x pozdní xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxxx. Xx xxxxxxxx, xxx měly xxxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx xxxx být xxxxxxxx xxx na xxxxxxx xxxxxxxxxxx kontrolních xxxxx x xxxxxxx xxxxxx, xxxx xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx buněk xx xxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxx je 37 °X.

Xxxx xx xxx xxxxxxx alespoň xxx xxxxx bakterií. Mezi xxxx xx xxxx xxx čtyři xxxxx X. typhimurium (TA1535; XX1537 nebo TA97a xxxx XX97; XX98 x XX100), xxxxxxx xxxxxxx xx xxxxxxx x různých xxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx X. xxxxxxxxxxx xxxx pár xxxx XX xx xxxxxxxxx xxxxxxxxx místě x xx xxxxx, xx xxxxxx prostřednictvím xxxxx xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, činitele xxxxxxxxxxx xxxxxxxxxx xxxxxx DNA x hydraziny. Tyto xxxxx xxxxx xxx xxxxxxxxxx kmeny X. xxxx XX2 nebo X. xxxxxxxxxxx TA102 (19), xxxxx mají xx primárním xxxxxxxxx xxxxx xxx bází XX. Doporučená xxxxxxxxx xxxxx xx xxxx xxxx:

- S. xxxxxxxxxxx XX1535 a

- X. xxxxxxxxxxx XX1537 xxxx XX97x x

- S. xxxxxxxxxxx XX98 x

- X. xxxxxxxxxxx XX100 x

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

Xxx xxxxxxx mutagenů způsobujících xxxxxxxxxx vláken XXX xxxx být xxxxxxxxx xxxxxxx TA102 nebo xxxxxx xxxx X. xxxx s xxxxxxx xxxxxxxxxx reparace DNA, (xxxx. X. coli XX2 (pKM101)).

Měly by xxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx kmenové xxxxxxx, xxxxxxxxxx xxxxxxx x xxxxxxxxxx. Xxxxxxx xxxxxxxxxxxxx pro xxxx xx měla být xxxxxxxxx pro xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx pro kmeny X. xxxxxxxxxxx a xxxxxxxxx xxx X. xxxx). Xxxxxxx xx xxxx xxx xxxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxxxx podle xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx plasmidů (xx. xxxxxxxxxxxx xxxxxxxxxx x xxxxx TA98, XX100 x XX97x xxxx XX97, XX2 uvrA x WP2 xxxX (xXX101) a xxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxx x xxxxx XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. xxx xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx na xxxxxxxxxxx xxxxxx x uvrA xxxxxx x X. xxxx nebo xxxX xxxxxx u S. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxxx) (2, 3). Kmeny by xxxx xxxxxx xxxxx xxxxx kolonií xxxxxxxxxxx xxxxxxxxxx xx xxxxx x rozmezí xxxxxxxx xxxxxxxxxxx na xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxxxxx xxxxxxx a nejlépe x xxxxxxx xxxxxxxx x literatuře.

1.5.1.2 Xxxxxx

Xxxxxxx xx vhodný xxxxxxxxx xxxx (např. obsahující xxxxxxxxx xxxx X (Xxxxx-Xxxxxx) x xxxxxxx) x xxxxxx xxxx xxxxxxxxxx xxxxxxxx x xxxxxx xxxx tryptofan xxxxxxxxxx několik buněčných xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx xxxx xxx xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x bez xxxx. Xxxxxxxxxx používaným xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx enzymy, xxxx xx Aroclor 1254 (1, 2) xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx frakce xx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx x xxxxxxx 5 xx 30 % xxx. xx xxxxx S9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxxxxx xxxxx. X xxxxxxxxx xxxxxxxxx xxxx být xxxxxx xxxxxx více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. U xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xxxx být xxxxxxxxx xxxxxxx redukčního xxxxxxxxxxxxx xxxxxxxxxxx systému (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx xxxx xxxxxxxx na xxxxxxxx xxxxxxxxxx nebo suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x testovacím systémům x/xxxx xxxxx xxx xxxx aplikací xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx mimo xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, a xxxx xx být xxxxxxxxxx x xxxxxxxx xxxxxxxx a x xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx xxxx xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití vodných xxxxxxxxxxxx/xxxxxxx. Při zkoušení xxxxx xxxxxxxxx ve xxxx xx xxxx xxx xxxxxxx organická xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx podmínky

1.5.2.1 Xxxxxxxx xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx koncentrace

Mezi kritéria, xxxxx xxxx být xxxxxxxxxx při stanovení xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxx cytotoxicita x rozpustnost x xxxxxxx xxxxx pro xxxxxxxx.

Xxxx xxx užitečné xxxxxxxx xxxxxxxx a xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx xxxx xxx detekována xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx zeslabením xxxxxxxxxxxxx podkladu xxxx xxxxxxxx xxxxxx přežití xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx se může xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx aktivačních xxxxxxx. Xxxxxxxxxxxxx by xxxx xxx posouzena xx xxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxxx směsi xx xxxxxxxxxx zkušebních xxxxxxxx.

Xxxxxxxxxx maximální xxxxxxxx xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx je 5 mg/misku xxxx 5 μl/misku. X xxxxxxxxxxxxxxx látek xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx by xxxx xxx xxxxx nebo xxxx zkušebních xxxxxxxxxxx xxxxxxxx, xxx xxxxx xxxx x xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx jsou xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx, xx xxxx xxx zkoušeny xx xx xxxxxxxxxxx koncentrace. Xxxxxxxxx xx xxxxxx xxxxx při vyšetřování.

Mělo xx být xxxxxxx xxxxxxx pět xxxxxxx xxxxxxxxxxxxxxxx koncentrací xxxxxxxx xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx by xxxx být xxxxxxxxx xxxx zkušebními xxxx xxxxx xxxxxxxxx xxxxxxxx xxxxx logaritmické stupnice (xx. Ö10). Menší xxxxxxxxx jsou xxxxxx x případě, xxx xx vyšetřuje xxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxx. Xxxxxxxx koncentrací xxxxxxx než 5 xx/xxxxx nebo 5 μx/xxxxx xxxx být xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx mutagenních xxxxxxxx.

1.5.2.3 Negativní a xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx x negativní (xxxxxxxxxxxx nebo vehikulum) xxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx. Pro xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx koncentrace xxxxxxxxxxx účinnost xxxxx xxxxxxx.

X xxxxxxx zkoušek x xxxxxxxx metabolického xxxxxxxxxxx xxxxxxx xx xxxx být látka (xxxxx) pro xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxx) xx xxxxxxx xxxx xxxxxxxxx xxxxx xxxxxxxx.

Xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxx x zkoušky x xxxxxxxxxxxx aktivací xxxx xxxx xxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Tato xxxxx je xxxxxxx xxxxxxxxx xxxxxxxxx xxx xxxxxx redukční xxxxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

XX Xxxxxx Red 28

573–58–0

209–358–4

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

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

Xxxxx

Xxxxx 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, TA97 x XX97x

XXX 191

17070–45–0

241–129–4

TA1537, XX97 x TA97a

Kumenhydroperoxid

80–15–9

201–254–7

TA102

mitomycin X

50–07–7

200–008–6

XX2xxxX x XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 xxxX a XX2 xxxX (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 xxxX a XX2 xxxX (xXX101)

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

3688–53–7

xxxxx xxxxxxxxxx plasmidy

Pro xxxxxxxxx xxxxxxxx mohou xxx použity xxxx xxxxxx referenční látky. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx x xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx li x dispozici.

Měly by xxx xxxxxxx xxxxxxxxx xxxxxxxx skládající xx xx xxxxxxxxx rozpouštědla xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, zpracované xxxxx stejným xxxxxxxx xxxx exponované xxxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx xxxxxxxx použity také xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx mutagenní xxxxxx.

1.5.3 Xxxxxx

X standardní xxxxxxx xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx aktivace xx xxxxxxx smíchá 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 ml čerstvé xxxxxxxxxxx kultury (xxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) x 0,5 xx xxxxxxxxxx pufru x 2,0 xx xxxxxxxx agaru. X xxxxxxx xxxxxxx s xxxxxxxxxxxx aktivací xx xxxxxxx smíchá 0,5 xx metabolické xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx frakce (x xxxxxxx 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx xxxxx) s xxxxxxx agarem (2,0 xx) x xxxxxxx x xxxxxxxxxx x xxxxxxxxx xxxxxx nebo xxxxxxxxx xxxxxxxx. Xxxxx xxxxx zkumavky se xxxxxxxx x xxxxxxx xxxx xxxxxx minimálního xxxxx xx xxxxx. Xxxx xxxxxxxx xx xxxxx vrchní xxxx xxxxxxxx.

X xxxxxxxxxxxx metody (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx xxxxxxxx xxxxxx xxxx smícháním x vrchním xxxxxx x přelitím přes xxxxxx xxxxxxxxxxx xxxxx xx xxxxx obvykle 20 xxxxx nebo xxxx preinkubuje s xxxxxxxxxx xxxxxx (xxxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) x xxxxxxxxx xxxxxx xxxx metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx xx smíchá 0,05 nebo 0,1 xx xxxxxxxx látky xxxx xxxxxxxxxx xxxxxxx, 0,1 xx bakterií x 0,5 xx xxxxx X9 nebo xxxxxxxxxx xxxxx s 2,0 ml vrchního xxxxx. Xxxxxxxx xx xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx na xxxxxxxx.

X xxxxxxxxxxxx xxxxxx xxxxxxxx xx xxxx xxx xxx xxxxx xxxxxx dávky použity 3 xxxxx. Xxxxxxx xxxx xxxxx je xxxxxxxxxx po vědeckém xxxxxxxxxx. Případná ztráta xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx zkoušky.

Plynné nebo xxxxxx xxxxx by xxxx být xxxxxxxx xxxxxxxx metodami, např. x těsně uzavřených xxxxxxxxxxxx xxxxxxxx (12, 14, 15, 16).

1.5.4 Xxxxxxxx

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

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxx xxxxx xx xxxx xxx xxxxx kolonií xxxxxxxxxx xxxxxxxxxxx xx xxxxx. Xxx xx xxx xxxxxx xxxxxx xxxxx kolonií xxxxxxxxxx xxx xx miskách x xxxxxxxxx xxxxxxxxx (xxxxxxxx rozpouštědla x xxxxxxxx neexponovaná xxxxxxxx), xxx na miskách x xxxxxxxxx xxxxxxxxx. Xxxxx xx jednotlivých xxxxxxx, střední xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx odchylka xx xxxx xxx předloženy xxx zkoušenou látku x xxxxxxxxx a xxxxxxxxx xxxxxxxx (neexponovanou xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx nepožaduje. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxx experimentálních xxxxxxxx. Xxxxxxxxx výsledky xxxx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx se xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxx, mělo xx být podáno xxxxxxxxxx. Změna xxxxxxxxx xxxxxx x cílem xxxxxxxx xxxxxx posuzovaných xxxxxxxx by xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx xxxxxxx metoda xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) a xxxxxxxx metabolické xxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxx xxxxxxx xxxxxxxxxx xx xxxxx nad xxxxxxxxx rozsah u xxxxxxx jednoho xxxxx x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxx xxxx, a xx x xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx tohoto počtu xxx xxxxx xxxx xxxx xxxxxxxxxxx (23). Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Při xxxxxxxxx výsledků zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx konečný výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné nebo xxxxxx bez xxxxxx xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxxxx mutace x xxxxxxxxxx znamenají, že xxxxxxxx xxxxx indukuje x xxxxxx kmenů Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx xxxxxx xxxxxx xxxxxxxxxx xxxx xxxx xxxxxxx čtecího xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx zkoušená xxxxx xxxx za xxxxxxxx xxxxxxx xxx xxxxxxxxx druhy mutagenní.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx x xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxx xxxxx,

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

- postup expozice.

Výsledky:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

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

- xxxxx možnosti závislost xxxxxxxx xx xxxxx,

- xxxxxxxx statistické analýzy,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Ames, X. X., XxXxxx, X., Xxxxxxxx E. (1975), Xxxxxxx xx Xxxxxxxxx Carcinogens xxx Xxxxxxxx with the Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Mutagenicity Test, Xxxxxxxxxx Res., 31, 347-364.

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

3) Gatehouse, D., Xxxxxxx, X., Xxxxxx, X., Gocke, X., Xxxx, X., Xxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, T., Xxxxxx, X., Xxxxxx, E. (1994), Recommendations xxx xxx Xxxxxxxxxxx of Xxxxxxxxx Xxxxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 312, 217-233.

4) Xxxx, X. X., Xxxxxxx X. X., Xxxxxxx, A. X., Von Xxxxx, X. X., Brown, X. X., Xxxxxx, X. X., Xxxxxx, X., McCann, X., Xxxxxxxxxx, K., Prival, X., Rao, X. X., Xxx X. (1986), The Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Report xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, X., Xxxxxx, X., Xxxxx, X. X., Xxxxxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Hashimoto, X. (1975), Xxxxxxxxxxxx of Xxxxxxxxxx Xxx Xxxx xxx xxxxx Derivatives, Xxxxxx Xxxx. 1, 91-96.

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

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

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

9) Xxxxx, X. H. L., Xxxxxx, X. X., Xxxxxxx, X. X. (1976), Xxx of x xxxxxxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx levels of xxxxxxxx, Mutatation Xxx., 38, 33-42.

10) Hubbard, X. X., Xxxxx, X. H. X., Xxxxxxxxx, X., Bridges, X. W. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, in: Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures, 2. xxx., Xxxxxx, B. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (xxx.), Xxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

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

12) Xxxxx, A., Xxxxxxx, X., Kato, X., Matsushima, T. (1994), Xxxxxxxx Method xxx Xxxxxxxxxxxx Testing xx Xxxxxxx Xxxxxxxxx xx Xxxxx a Xxx Xxxxxxxx Bag, Xxxxxxxxxx Xxx., 307, 335-344.

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

14) Xxxxxx, E., Xxxxxxxx, X. X., Xxxxxxx, X., Lawlor, X., Xxxxxxxxxx, K. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Results xxxx xxx Xxxxxxx of 311 Xxxxxxxxx, Environ. Xxx. Xxxxxxx., 19, 2-141.

15) Xxxxxx, X., Xxxxxxxx, K., Xxxxxxx, X. X. (1977), Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxx Water, xx Xxxxxxxx xx Xxxxxxx Xxxxxxxxxx, X. Scott, X. Bridges, F. Xxxxxx (xxx.) Xxxxxxxx, Xxxxxxxxx, 249-258.

16) Hughes, X. X., Xxxxxxx, X. X., Monteith, X. X., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Technique to Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxxxxx Xxxxxxx Xxxxxxxxx in the Xxxx/Xxxxxxxxxx Assay, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

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

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

19) Wilcox, X., Naidoo, A., Xxxx, X. X., Xxxxxxxxx, X. G. (1990), Xxxxxxxxxx of Xxxxxxxxxx xxxxxxxxxxx XX 102 xxxx Escherichia xxxx XX2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Inducer xx Xxxxxxxxx Activation Xxxxxxx, xx: In xxxxx Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, xxx. X. J. de Xxxxxx xx xx. Xxxxxxxx, Xxxxx Holland, 85-88.

21) Elliot, B. X., Xxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Wolf, X. X. (1992), Alternatives xx Aroclor 1254-induced X9 xx xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, X., Katzenellenbogen, X., Xxxx, B. X. (1981), Xxxxxxxxxxxxx xx Organic Solvents xxxx the Xxxxxxxxxx/Xxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 88, 343-350.

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

24) Xxxxx, G. X. X., Xxxxx, X. X. X., Middleton, X., Xxxxxxx, X., Xxxxxxxx, X. D., Xxxxxx, D. X. (1989), Analysis xx Xxxx xxxx Xxxxxxxxx Xxxxxx Xxxxxx, in: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxx II. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, xx. Kirkland, D. X., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 28-65."


XXXXXXX 4X

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

1. METODA

Tato xxxxxx xx xxxxxxxx metody XXXX XX 476 — Zkouška xx xxxxxx xxxxxx v xxxxxxx savců xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx genové xxxxxx x xxxxxxx xxxxx xx xxxxx lze xxxxxx pro xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx látkami. Mezi xxxxxx xxxxxxx xxxxx xxxxx xxxxx xxxxxxx X5178X myší, buněčné xxxxx XXX, CHO-AS52 x X79 křečka xxxxxxxx x xxxxxxxxxxxxxxx xxxxx TK6 člověka (1). U těchto xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx xxxxx genetických xxxxxx xxxxxx genů xxx thymidinkinasu (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x xxxxxxxx xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx na xxxxxx XX, HPRT x XPRT xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX x XXXX xxxx xxxxxxx xxxxxxx xxxxxxxxxxx událostí (např. xxxxxxxx xxxxxx), xxxxx xxxxx xxxxxxxxx v XXXX lokusu xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx zkoušce xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx lze použít xxxxxxx zavedených linií xxxxx xxxx xxxxxxx xxxxx. Buňky xx xxxxxxxx xxxxx xxxxxxxxxx xxxxx x xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx mutací.

Zkoušky prováděné xx xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx xxxxxxxxx podmínky xx xxxx u savců. Xx xxxxx xx xxxxx xxxxxxxxx podmínek, xxxxx by xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx, xxxx xxxxx xxxxxx xX, xxxxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Tato xxxxxxx xx používá xx zjištění xxxxxxx xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx karcinogeny xxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx závisí xx xxxxxxxx xxxxx x xxxxxxxxx důkazy x xxx, xx xxxxxxxx xxxxxxxxxxx, které nejsou xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x bakteriálních buňkách xxxxxxxxxx (6).

Viz xxxx xxxxxx úvod, část X.

1.2 XXXXXXXX

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

Xxxxxxxx xxxxxxxxxx párů xxxx : xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxx xxxx xxxx v XXX.

Xxxxxxxx mutageny : xxxxx, xxxxx způsobují xxxxx xxxx xxxxxx xxxxxxx xxxx xxxx xxxx xxxx x xxxxxxxx XXX.

Xxxx xxxxxxx xxxxxxxx : doba, xxxxx xxx xxxxxx x xxxx xxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxxxxxx.

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

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

Xxxxxxxxx růst v xxxxxxxx : nárůst xxxxx buněk x xxxxxxx exprese xxxxxxxx x negativní xxxxxxxx.

Xxxxxxxxxxxxxxx : xxxxxxxx xxxxxxxxx xxxxx x okamžiku xxxxxxxx xx xxxxx xx xxxxxxxxxxxx podmínek xx xxxxxxx.

Xxxxxxx : xxxxxxxx klonování buněk xxx xxxxxxxx xx xxxxx na xxxxx xxxxxx xxxxxxxx; přežití xx xxxxxxx vyjádřeno x xxxxxx x xxxxxxx xxxxxxxxx populace xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx v xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) xxxx xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxxxxxx (TFT). Xxxxx xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx xx XXX, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx metabolismu x xxxxxxxxx xxxxx xxxxxxx xxxxxx. Mutantní buňky xxxx xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxxxxx XXX, xxxxxxx normální xxxxx, xxxxx obsahují xxxxxxxxxxxxxx xxxx schopnost xxxxxx. Xxxxxxx xxx x xxxxx x xxxxxxxxxxxx XXXX xxxx XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx x 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (XX). Xxxxxxxxxx xxxxxxxx xxxxx xx xxxx xxx xxxxxxx xxxxxxx, jestliže xx xx zkoušce na xxxxxx xxxxxx x xxxxxxx xxxxx zkoušen xxxxxx xxxx nebo xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xx xxx například xxxxxxxxx xxxxxxxx xxxxxxxxx xx xxxxxxxxxx xxxxxxxx zkoušené xxxxx xxx mutantní xxxx nemutantní xxxxx. Xxx zkoušení xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, musí xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxx xxx selekci (8).

Xxxxx x suspenzní xxxx jednovrstevné kultuře xxxx vhodnou dobu xxxxxxxxx zkoušené xxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, x subkultivovány xx xxxxxx stanovení xxxxxxxxxxxx x xx xxxxxx xxxxxxx xxxxxxxx xxxx selekcí xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx zjistí xxxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxx relativního xxxxxxxxx xxxxx kultur xx xxxxxxxx doby xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx x xxxxxxxx xxxxx xx vhodnou xxxx charakteristickou xxx xxxxx xxxxxxx lokus x xxx buněk, xxx nastala xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx xx xxxxxxx xxx, xx xx xxxxxx xxxxx počet xxxxx xx xxxxx xxxxxxxxxxxx selekční činidlo xxx xxxxxxx xxxxxxxxxx xxxxx x do xxxxx xxx selekčního xxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx xx xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx se xxxxxxx x xxxxx mutantních xxxxxxx v xxxxxxxxx xxxxx x počtu xxxxxxx v médiu xxx selekčního xxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx xxxxxxx x xxxx xxxxxxx xxxx x xxxxxxxxx xxxxx xxxx buněk, xxxxxx xxxxxxxx xxxxx X5171X, CHO, CHO-AS52, X79 xxxx XX6. Xxxx xxxxx x xxxx zkoušce xx xxxx xxxxxxxxx xxxxxxxxx x chemickým mutagenům, xxxxxxx xxxxxxxxx xxxxxxxxx x stabilní xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxxxx, xxx nejsou xxxxxxxxxxxxx xxxxxxxxxxxx, x x případě kontaminace xx xxxxxx být xxxxxxx.

Xxxxxxx by měly xxx xxxxxxxx xxx, xxx měly xxxxxx xxxxxxxxxx citlivost a xxxx. Xxxxx použitých xxxxx, xxxxxx x xxxxxxxxxxx zkoušené látky xx xxx xxxx xxxxxxxxxx parametry odrážet (14). Minimální xxxxx xxxxx, které xxxxxxx xxxxxxxx x xxxxx xxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx, xx xxx xxx xxxxxxx na četnosti xxxxxxxxxxx xxxxxx. Obecným xxxxxxxxx xx, xxx xxx xxxxxx xxxxx xxxxx, xxxxx je xxxxxxxxxxxxxx převrácené hodnoty xxxxxxxx xxxxxxxxxxx xxxxxx. Xx xxxx xxxxxxxxxx, xxx xxxx xxxxxxx xxxxxxx 106 buněk. Xxxx by být x xxxxxxxxx xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx doložena xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx a xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx by xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (kultivační xxxxxx, xxxxxxxxxxx CO2, xxxxxxx x xxxxxxx). Xxxxx xx xxxx xxx zvolena xxxxx xxxxxxxxxx systémů x xxxx buněk použitých xxx xxxxxxx. Je xxxxxxx xxxxxxxx, xxx xxxxxxxxxx xxxxxxxx byly xxxxxxx xxx, xxx xxxx zajištěny xxxxxxxxx xxxx xxxxx xxxxx xxxxxx xxxxxxx x xxxxxxxxx xxx xxxxxxxxxx, xxx xxxxxxxxxxxx xxxxx xxxxxx kolonie.

1.4.1.3 Příprava xxxxxx

Xxxxx xx xxxx xxx získávány x xxxxxxxxx xxxxxx, nasazeny xx xxxxxxxxxxxx média x inkubovány při 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx xxxx xxx xxxxxxxx xxxxxxxxx z xxxxxxx xxx xxxxxxxx xxxxxxxx buňky.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

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

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx xxxxxxxxxx médiu xxxxxxx xxxxxxxxx x koncentracích 1 — 10 % xxx. Volba x xxxx xxxxxxxxxxxxx xxxxxxxxxxx systému může xxxxxxx xx xxxxx xxxxxxxx látky, která xx zkoušena. V xxxxxxxxx případech může xxx vhodné xxxxxx xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce.

Řada xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx linií xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx aktivaci. Volba xxxxxxxxx xxxxxxxxx linií xx xxxx xxx xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 pro xxxxxxxxxxxx xxxxxxxx látky).

1.4.1.5 Příprava xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx měly xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Měly xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx podezření, xx xxxxxxx xx zkoušenou xxxxxx, x xxxx xx xxx xxxxxxxxxx x přežitím buněk x x xxxxxxxxx X9. Jsou-li použita xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx údaji o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx být xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

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

Xxxxxxxxxxxx xx xxxx xxx stanovena x xxxxxxxxxxxx xxxxxxxx x xxx xx x hlavním xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, jako xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (přežití) nebo xxxxxxxxx celkový růst. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx xxxxxxxxxxx. V xxxxxxx toxicity xx xxxx tyto xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx, xxx bude xxxxxxx xxxxxxxx, xx xx se xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. Xx-xx maximální xxxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx, xxxx by xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx nejméně 10 %) přežití (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. X případě xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx toho, xxxxx x xxxx xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxx xx x xxxx rozpustnosti xx xxxxxxxxxxxx xxxxxxxx, xxxx xx xx xxxx xxx. Xxxx xx xxx stanovena případná xxxxxxxxxxxxx x konečném xxxxx, ve xxxxxxx xxxx buňky xxxxxxxxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx x xx xxxxx aplikace, neboť xxxxxxxxxxx se xxxx x průběhu expozice x xxxxxxxxxx xxxxxxx xxxxx x důsledku xxxxxxxxxxx xxxxx, X9 xxxx, xxx. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx být xxxxxxxxx a negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, tak xxx xx. Xxx xxxxxxx metabolické aktivace xx měla xxx xxxxxxxxx kontrolou xxxxxxxx xxxxx, xxxxx k xxxxxxxxx odpovědi xxxxxxxx xxxxxxxx.

Xxxxxxxxx pozitivní xxxxxxxx xxxxx xxx xxxx xxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Einecs

Bez xxxxxx xxxxxxxxxxx xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx 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 xxxxxxxxxxxx xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (malé 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 xxxxxx xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx xxx použity xxxx jiné xxxxxxxxxx xxxxx xxx pozitivní xxxxxxxx, xxxx. xx-xx xxxxxxxxx databázi dosavadních xxxxx x 5-brom-2′-deoxyuridinu (XXX 59–14–3, XXXXXX 200–415–9), xxxx xxx xxxx xxxxxxxxxx látka xxxxxx použita. Pro xxxxxxxxx kontrolu xx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx látek pokud xxxxx ze xxxxxx xxxxxxxx třídy.

Měly by xxx použity xxxxxxxxx xxxxxxxx tvořené xxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxxxxxxx jinak xxxxxxx xxxxxxxx jako xxxxxxxxxx xxxxxxx. Kromě toho xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, že zvolené xxxxxxxxxxxx nevyvolává žádné xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Expozice xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx xxx xx přítomnosti xxxxxxxxxxxxx aktivačního xxxxxxx, xxx xxx něho. Xxxxxxxx by xxxx xxxxx xxxxxxx xxxx (xxxxxxx xx xxxxxx xxxx 3 až 6 xxxxx). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx xx xxxxx xxxx xxxx buněčných xxxxx.

Xxx xxxxxx zkušební xxxxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx kultury xxxx xxxxx exponovaná xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, měl xx xxx xxxxx xxxxxxxxxxx xxxxxx xxx, xxx xxx xxxxxxxx xxxxxxxxxxxx xxxxx kultur xxx analýzu (xxxx. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx xx xxx xxxxxxx duplicitní xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx rozpouštědla).

Plynné xxxx xxxxxx xxxxx xx xxxx xxx zkoušeny xxxxxxxx xxxxxxxx, xxxx. x těsně uzavřených xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Xxxxxxxxx přežití, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx xxxxx xxxxxxxxx xxxx se buňky xxxxxxx a xxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxx x za xxxxxx xxxxxxxx xxxxxxx xxxxxxxx mutantu. Xx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxx xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx časové xxxxxx, aby xxxxxxx xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (XXXX x XXXX xxxxxxxx alespoň 6 xx 8 xxx, XX xxxxxxx xxx xxx). Xxxxx xxxx xxxxxxxxxxx x xxxxx se xxxxxxxxx xxxxxxxx (xxxxxxxxxx činidly) x bez něho (xxx xxxx) xx xxxxxx xxxxxxxxx počtu xxxxxxx x xxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx xxxxxxxx xxxxxxx) xx xxxxxxx na xxxxx doby xxxxxxx xxxxxxxxx xx misku xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx látka pozitivní xx xxxxxxx X5178X XX+/-, xxxx by xxx xxxxxxxxx alespoň xx xxxxx xx xxxxxxxxxx xxxxxx (x xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x na xxxxxxxxxxx x xxxxxxxxxxx kontrolách xxxxxxxxx xxxxxxx podle xxxxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxx ve xxxxxxx L5178Y XX+/- xxxxxxxxx, xxxx xx xxx rozdělení xxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xx xxxxxxxxxxx x pozitivních xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx TK6 XX+/- xxxx xxx xxxx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xx měly xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, počtu kolonií x xxxxxxxx xxxxxxx xxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx odpovědi xx xxxxxxx X5178X XX+/- xx xxxxxxx xxxxxxxxx xxxxxxx x xxxxx xxxxxxxxxxx xxxxxxxx xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) a u xxxxxxxxx x xxxxxxxxx xxxxxxxx xx použití xxxxxxxx xxxx xxxxxxx — velká kolonie. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx jak xxxxxxx xxxxxxxxx xxxxx xxxxxxx, xxx xxxxxxx tvořících xxxx xxxxxxx xxxx xxxxxxxx zkoumána (23, 24). Xx xxxxxxx XX+/- xxxx kolonie xxxxxxxxxxx xx použití xxxxxxxx kolonie s xxxxxxxxx růstem (xxxxx) x xxxxxxx x xxxxxxx xxxxxx (malá) (25). X xxxxxxxxxx xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx xxxx xxxxxxxx, x xxxxx xxxx malé xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx xx xxxxx xxxxxx xxxx xx xx xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Indukce xxxxxxx xxxxxxxxx xxxx xxxxxxx xx xxxxxxx x chemickými látkami, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx xxxxxxxxx xxxxx mutantů xxxxxx xxxxxxxx xxxxxx jako xxxxxxxx xxxxx x xxxxx velké kolonie.

Mělo xx xxx xxxxx xxxxxxx (relativní xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxxxxx xxxxxxx xx měla xxx xxxxxxxxx xxxx xxxxx xxxxxxx k xxxxx xxxxxxxxxx xxxxx.

Xxxx xx xxx uvedeny xxxxx xxx jednotlivé xxxxxxx. Xxxx by xxxx být xxxxxxx xxxxx shrnuty ve xxxxx tabulky.

Ověření xxxxx xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Dvojznačné xxxxxxxx xx měly být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx podmínek. Negativní xxxxxxxx musí xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxx, xxx xxxx potvrzení negativních xxxxxxxx xxxxxxxxxx xx xxxxx, xx xxxxx xxxxx xxxxxxxxxx. Změna xxxxxxxxx xxxxxx x xxxxx rozšířit xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, xxx xxx xxxxxxxxx xxxxxxxx. K xxxxxxxxxx xxxxxx, které xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x podmínky xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx kritérií, xxxx. xxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx nárůst xxxx xxxxxxxx. Nejdříve xx xxxx být uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx pro xxxxxxxxx odpověď.

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

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

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx savců in xxxxx xxxxxxxxx, že xxxxxxxx xxxxx indukuje x xxxxxxxxx kultivovaných xxxxxxx xxxxx genové xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx na xxxxxxxxxxx xx xxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx genové xxxxxx.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxx x zdroj xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- případně počet xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx buněčné xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxxx výběru koncentrací x xxxxx xxxxxx, xxxxxx xxxx. údajů x xxxxxxxxxxxx a xxxxxx xxxxxxxxxxxx, jsou-li x dispozici,

- xxxxxxx xxxxx, xxxxxxxx koncentrace XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- případně xxxxxxx xxxxx během expozice,

- xxx x xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,

- xxxxxxxxx a xxxxxxxxx xxxxxxxx,

- xxxxx xxxx exprese (xxxxxxxx xxxxxx xxxxx nasazených xxxxx, subkultur x xxxxxx xxxxx),

- xxxxxxxx xxxxxxx,

- xxxxxxxx klasifikace xxxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx,

- xxxxxx použité x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx xxxxx,

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

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxx xxxxxxx,

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

- velikost xxxxxxx, byla-li xxxxxxxxxxx, xxxxxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxxxx,

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

- podle xxxxxxxx závislost odpovědi xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

- dosavadní údaje x xxxxxxxxx (rozpouštědlo/vehikulum) x xxxxxxxxx kontrole x xxxxxxxxx, středními xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx,

- xxxxxxx xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Moore, X. X., XxXxxxxx, X. M., DeSerres, X. X., Xxxxxx, X. X. (xxx.) (1987), Xxxxxxx Report 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Cold Xxxxxx Xxxxxx Laboratory, Xxx Xxxx.

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

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

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

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

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

7) Scott, X., Xxxxxxxx, X. X., Xxxxxxxx, X. X., Ishidate, M., Xxxxxxx, X., Xxxxx, X., Xxxx, B. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. A report xxxx ICPEMC Task Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

8) Xxxxx, D., McCuen, X., Xxxxxxx, J. X. S., Piper, X., Xxxxxxxxx, X. X. (1983), Specific Xxxx Xxxxxxxxx xx X5178X Xxxxx in Xxxxxxx. X Xxxxxx xx the U. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 115, 225-251.

9) Xx, X. X., Gupta, R. X., Heflich, R. X., Wasson, J. X. (1988), X Xxxxxx xxx Xxxxxxxx xx xxx Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Determine xxx Xxxxxxxxxxxx xx Chemical Xxxxxx: X Xxxxxx xx Xxxxx XXX xx the X. X. Environmental Xxxxxxxxxxx Xxxxxx Gene-Tox Program, Xxxxxxxxxx Xxx., 196, 17-36.

10) Li, X. X., Carver, X. X., Choy, W. X., Hsie, X. X., Xxxxx, X. X., Xxxxxxx, K. X., X'Νxxxx, X. X., Xxxxxx, X. X., Stankowski, X. X. Xx., Xxxx, X. X. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx xx xxx Xxxxxxx Hamster Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Gene Xxxxxxxx Xxxxx, Mutatation Res., 189, 135-141.

11) Liber, X. X., Xxxxxxx, X. X., Little, X. X. (1989), X Xxxxxxxxxx xx Xxxxxxxx Xxxxxxxxx xx xxx XX and XXXX Xxxx in Xxxxx Xxxxxxxxxxxxxx Cells: Xxxxxxxxxxxx Xxxxxxxxxxx are Xxx xx xx Xxxxxxxxxx Xxxxx xx Xxxxxxxxx at the Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Res., 216, 9-17.

12) Stankowski, X. X. Jr., Tindal, X. X., Xxxx, X. X. (1986), Xxxxxxxxxxxx xxx Xxxxxxxxx Xxxxxxxx of Ethyl Xxxxxxxxxxxxxxxxx xxx XXX 191-Xxxxxxx Xxxxxxxxx Analyses xx Xxxxx Methanesulphonate xxx XXX 191 Xxxxxxx Xxxxxxxx xx XX52 Cells, Xxxxxxxxxx Xxx., 160, 133-147.

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

14) Xxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. M., Xxxxx, X. H. X., Cole, X., XxXxxxxx, D. X., Xxxxxxx X. X. (1989), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxx upon Colony Xxxxxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Xxxxxxxx, X. J., xx., Xxxxxxxxx Xxxxxxxxxx Press, 66-101.

15) Xxxxxxxxxxxx, A., Xxxxxxx, S., Corti, X., Xxxxxx, X., Xxxxxxxx, N., Mazzaccoro, X. (1977), Induction xx 6-Xxxxxxxxxxx-Xxxxxxxxx Mutants xx X79 Xxxxxxx Xxxxxxx Xxxxx xx Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Xxx. 46, 365-373.

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

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

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

19) Xxxxxxx, X. X., Combes, X. X., Xxxxxxx, C. X., Xxxxxxxxx, D. X., Xxxxxx, X. X., Xxxxxx, J. X., Wolf, X. X. (1992), Alternatives xx Xxxxxxx 1254-Xxxxxxx X9 in: Xx xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, T., Xxxxxxxx, X., Xxxx, K., Xxxxxxxx, X. (1976), X Safe Substitute xxx Xxxxxxxxxxxxxxx Biphenyls x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, X: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, de Xxxxxx, X. X., Xxxxx, X. X., Xxxx, X. X., Philpot, X. M. (xxx), Xxxxxxxx, North-Holland, 85-88.

21) Xxxxx, D. X., Xxxxxx, F. X., XxXxxxx, K. X. (1982), CHO/HGPRT Mutation Xxxxx: Evaluation xx Xxxxx and Xxxxxxxx Xxxxxxx, in: Ticc, X. X., Xxxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, New Xxxx, Xxxxxx, 91-103.

22) Xxxxxx, P. X., Xxxxxx, X. X., Xx, X. X., Xxxxxx, A. L. (1983), Evaluation of xx Exposure Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Mutagens in xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxx. Mutagenesis, 5, 795-801.

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

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

25) Xxxxxxx, X. X., Dryja, X. X., Little, X. B. (1990), Xxxxxxxxx Xxxxxxx Analysis xx Recessive Xxxxxxxxx xx x Xxxxxxxxxxxx Xxxxxxxxx Xxxxx in Xxxxx Xxxxx, Mutatation Xxx. 229, 89-102.

26) Xxxxx, M. X., Xxxxx, X. L. (1990), Xxxxxxxxxx of Xxxxxxxxxx Aberration Frequency xxx Xxxxx Xxxxxx XX-Xxxxxxxxx Xxxxxx Xxxxxxxxx xx L5178Y/TK+/- 3.7.2X Xxxxx Xxxxxxxx Cells, Xxxxxxxxxxx, 5, 609-614."


XXXXXXX 4X

"X.23 XXXXXXX XX CHROMOZOMOVÉ XXXXXXX XX XXXXXXXXXXXXXXX XXXXX

1. XXXXXX

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

1.1 ÚVOD

Účelem xxxxxxx xx xxxxxxxxxxxx xxxxxxx ve xxxxxxxxxxxxxxx xxxxx in vivo xx xxxxxxxxxxxxx xxxxxx xxxxx, xxxxx způsobují xxxxxxxxxx chromozomové xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Tato xxxxxx není xxxxxx xx stanovení xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx účelu xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x podobné xxxx jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u člověka.

Touto xxxxxxxx se xxxxxxxxx xxxxxxxxxxxx změny ve xxxxxxxxxxxxxxx a předpokládá xx xxxx, že xxxx xxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx v xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx používáni xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx xx xxxx xx detekují xxxxxxxxxxxx xxxxxxx při mitose xxxxxxxxxxxxx. Jiné cílové xxxxx xxxxxx xxxxxxxxx xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx xxxxxxxxxxxxxx typu xx spermatogoniích xx xxxx být — xxxxx xxx xxxxx xx ztrátě xxxx — xxxxxxxxx xxxxx xxxxxxxxx buněčné xxxxxx, xxxxx následuje xx xxxxxxxx. Další informace x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx buněk xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxx chromozomového xxxx x xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx zkouška xx xxxx xx xxxxxxxx xxx xxxxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx je tato xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx xxx posouzení xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx DNA.

Ve xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx spermatogonií s xxxxxx xxxxxxxxxx xx xxxxxxxx xxxxxxxx látce. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx souhrnnou xxxxxxx xxxxxxxxxx xxxxxxxx spermatogonií x xxxxxxxxxxxxxx diferencovanými xxxxxxxxxxxxxxx. X xxxxxxxxxx xx xxx xxxxxx xx varlatech, xxxxx xxxx xxxxxx xxx xxxxx xxxxxxxx spermatogonií xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx buněk x bariéry xxxx xxxxxxx xxxxxx a xxxxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, že xx zkoušená xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx cílové xxxxx, xxxx xxxxxx xxxx xxxxxxx použít.

Viz xxxx obecný xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x podobě xxxxx xxxx xxxxx x xxxxxxx xxxx chromatid x tomtéž místě.

Gap : xxxxxxxxxxxx xxxx xxxxx xxx xxxxx xxxxx chromatidy x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxx způsobem exponována xxxxxxxx látce x xx vhodné xxxx xx xxxxxxxx xxxxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X germinálních xxxxx xx poté xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx x analyzují xx xxxxxxxxxxxx aberace xxxxxxxxxxxxxx xxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx a xxxx; xxx však xxxxxx samce xxxxxxxxxx xxxxxx xxxxxxxx xxxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx zahájení studie xx xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx hodnoty hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx mladí pohlavně xxxxxxx xxxxx xx xxxxxxxx výběrem rozdělí xx xxxxxxxxx skupinu x xxxxxxx, xxxxx xx exponuje. Xxxxx xx xxxx xxx xxxxxxxxxx tak, xxx xxx vliv xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx xxxxxxxxx xxxxxx xx nechají x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné zkoušené xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx rozpuštěny nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo vehikulech x popřípadě xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx být xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxxxx neprokazují xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx xxxxxxxxx xxxxxxxxx dávek xxxxxxx xxxxxx x xxxx by xxx xxxxxxxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx jejich xxxxxxxx xxxxxxxxx xxxxx o xxxxxx kompatibilitě. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx experimentu xx xxxx xxx souběžné xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx aplikace xxxxxxxx xxxxx xx xxxx xxxxxxx kontrolní xxxxxxx xxxxxxxxxx identický proces xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx strukturní xxxxxxx xx xxxxxxxxxxxxxxx xx xxxx při xxxxxxxxxxx xxxxxxxx, x nichž xx předpokládá, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx pozitivní xxxxxxxx xx měly xxx xxxxxxx tak, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx xxxxx a xxx xxx xxxxx x jejím případě xxxxxxxx jen xxxxxx. Xxx pozitivní xxxxxxxx xxxx xxx navíc xxxxx x xxxxx xxxxxxx chemických 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 (monomer)

79–06–1

201–173–7

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

51–18–3

200–083–5

V xxxxxxxx každého odběru xx xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx kontroly, xxxxx xx xxxxxxxxxx xxxxx rozpouštědlo xxxx xxxxxxxxx x která xxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxxxxx xxxxxxx, xxxxx nejsou x dosavadních kontrolních xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx prokazující, že xxxxxxx rozpouštědlo/vehikulum xxxxxxxxxx xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx xxxxxx

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

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx nebo xxxxxxxxx (xx. xxx jedné xxxxxxxx xxxx dvou xxxxxxxxxx). Zkoušené xxxxx xxxxx být podávány xxxx xx xxxx xxxxxxx, xxx. dvě xxxxx x xxx xxx x xxxxxxx xx více xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx objemů xxxxxxxxx. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx zdůvodněny.

Ve xxxxxxx x xxxxxxxx xxxxxx xx xxxx xxx xx xxxxxxxx xxxxxxxxx xxx xxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx xxxx xxx xxxxxxxxx xxxxxx ovlivněna, xxxxxxx xx jeden časný xxxxx x xxxxx xxxxxxxx odběr xxxxxxxxx 24 a 48 xxxxx xx xxxxxxxx. X případě xxxx xxx nejvyšší dávky xx xxx být xxxxx xxxxxxxx xx 24 xxxxx xxxx xx takové xxxx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx není xxxxx xxxx xxxxxxxxx xxxx xxx xxxxxxx xxxxxx (6).

Xxxxx xxxxx xxx xxxxxx xxxxxxxxx xxxx v jiné xxxx. Xxxxxxxxx x xxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxxx xxxxxxxxx xxxxxxxx replikace (xxxxxxx) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx X-xxxxxxxxx účinky, xxxx xxx vhodnější xxxxxxxx odběr (1).

Vhodnost xxxxx xxxxxxxxx xxxxxxxx xxxx xxx xxxxxx xxxxxx xx xxxxxxx. X xxxxxxx plánu x xxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx délky xxxxx) xx xxxxxxxx xxxxxxxx. Xxxxx xxxxxxx xxxxx být xxxxxxxxx xxxxx xxxxxx x xxxx xxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx dávka xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Colcemid® nebo xxxxxxxxx). Xxxx xx xx xxxxxx době xxxxxxx x xxxxxx xxxxx. X myši xx xxxx xxxx xxxxxxxxx 3 — 5 hodin; u xxxxxx čínského xx xxxx xxxx xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Dávkování

Provádí-li xx xxxxx neexistenci xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx, xxxx xx xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx stejným xxxxxx x kmenem x za stejného xxxxxx xxxxxxxx, xxxxx xx xxxxxxx x xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx pro xxxxx xxxxx použijí xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx pokrývat rozmezí xxxx maximální x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx použita xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx dávka xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že by xxxxx dávky vedly xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx od případu. Xxxxxxxx dávka xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx počtu xxxxxxxxxxxxx x mitose xxxxxxxx x první x xxxxx meiotické xxxxxxxx; xxxx xxxxxxx xx xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x jednou xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx dvou xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx na základě xxxxx o xxxxxxx, xxxxx mají xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx xxxxxx xx třemi xxxxxxxx dávky za xxxxxxxxx. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx v xxxxxxx xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx látka xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx podávání xxxx přijatelné, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxx sondou xxxx xxxxxxxx, závisí xx xxxxxxxxx testovacího zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx vyšších xxxxxxxxxxxxx xxxxxxxx zesílené xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx xxxxxxx chromozomů

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

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx mělo xxx xxxxxxxxxxx xxxxxxx 100 xxxxx v xxxxx xxxxxxxxxxxx xxxxxxxx (tj. xxxxxxxxx 500 metafází xx xxxxxxx). Tento xxxxx lze xxxxxx, xx-xx pozorován xxxxx xxxxx aberací. Všechny xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx před mikroskopickou xxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx při fixaci xxxxx dochází xx xxxxxxxxxxxxxx zlomům xxxx xxxxxx xxxxxxxxxx x xxxxx metafází, měly xx vyšetřované xxxxx xxxxxxxxx centromery x xxxxx odpovídajícímu xxxxx 2 x ± 2.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx jednotlivá xxxxxxx by xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Experimentální xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxx xx měl xxx xxxxxxxxxx počet buněk xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx xxxxxxxxxx x kontrolní skupiny xx měly xxx xxxxxxx různé xxxx xxxxxxxxxxxx chromozomových xxxxxxx x xxxxxx počtem x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx xxxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxx aberací.

Je-li pozorována xxxxxx x také xxxxxx, xxx xx xxx xxx xxxxxxxxx xxxxxxx cytotoxických účinků xxxx xxxx cytotoxicity xxxxxxxx u xxxxx xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxx poměr xxxxxxxxxxxxx v xxxxxx xxxxxxxx x xxxxx x druhé xxxxxxxxx xxxxxxxx, a to x celkovém xxxxxx 100 xxxxxxxx se xxxxx na jedno xxxxx. Xxxxx xx xxxxxxxxx xxxxx xxxxxx, xxxxxxx v 1000 xxxxxxx xx xxxxx xx xxx xxx xxxxxxxx mitotický xxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx na xxxxx xxxx jasný xxxxxx xxxxx xxxxx s xxxxxxxxx xxx xxxxxxx x xxxxxxx xxxxxx x x určitému xxxxxxxx odběru. Nejdříve xx xxxx být xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx by neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravami xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx dvojznačné nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xxxxx xx xxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx druhu xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx za xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxx xxxxx.

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Testovací xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet x stáří xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx zvířat xx xxxxxxx xxxxxxx, včetně xxxxxxx tělesné xxxxxxxxx, xxxxxxx hodnoty a xxxxxxxxxx xxxxxxxx pro xxxxxx skupinu.

Zkušební podmínky:

- xxxxx ze studie xxx zjištění rozsahu, xxxxx byla xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- xxxxx o xxxxxxxx zkoušené látky,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- zdůvodnění xxx xxxxxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx krmiva x vody,

- podrobný xxxxx xxxxxxx expozice x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx xxxxx xxxxxxxxxxx metafázi, xxxx koncentrace x xxxxx aplikace,

- xxxxxx xxxxxxxx preparátů,

- xxxxxxxx xxxxxxxxx aberací,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,

- kritéria xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx xxxxx,

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

- typ a xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx xx xxxxxxx,

- xxxxx xxxxx s xxxxxxxxx ve xxxxxxx,

- xxxxx možnosti xxxxxxxxx xxxxxxxx na xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx pozitivní xxxxxxxx,

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Xxxxxxxxxxxxx xx Xxxxxxxx Mutagens Xxxxxxx xx xxxxx Cell-Cycle Xxxxxxxxxxxxxx, in: Xxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxxx Xxxxxxxxx, Part X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Xxxxxxx, B., Xxxxxxxxx, X. (eds) Xxxx, New Xxxx, 477-484.

2) Adler, I. X., (1984), Xxxxxxxxxxx xxxxx xx Xxxxxxx, xx: Xxxxxxxxxxxx Testing: x Xxxxxxxxx Approach, (xx.) S. Venitt, X. X. Xxxxx, XXX Xxxxx, Oxford, Xxxxxxxxxx DC, 275-306.

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

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Assays, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx X xxxxxxx, Cambridge Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, X. X., Xxxxxx X. D., Xxxxxxx, X., Favor, X., Generoso, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Tanaka X. (1994), International Workshop xx Standardisation xx Xxxxxxxxxxxx Test Procedures. Xxxxxxx Report of xxx Xxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxx Tests, Mutatation Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. A., Xxxxxx, A. R., Xxxxxx, P. A., Xxx, J., Esdaile, X. J., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, M. (1992), Xxxxxx xx Xxxxxxx Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. P., Xxxxxxxx, X., Xxxxxxxx, X., Amphlett, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxx, X., Papworth, X. X., Savage X. X. K. (1989), Xxxxxxxxxxx Xxxxxxxx of Xx xxxx Xxxxxxxxxxx Xxxxxx, in: D. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxxxx, Part XXX. Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4G

"B.39 XXXXXXX XX XXXXXXXXXXXX SYNTÉZU XXX (UDS) V XXXXXXXXX BUŇKÁCH XXXXX XX VIVO

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx OECD TG 486 — Zkouška xx xxxxxxxxxxxx xxxxxxx XXX (XXX) x xxxxxxxxx xxxxxxx savců xx vivo (1997).

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx XXX (XXX) x jaterních xxxxxxx xxxxx xx xxxx xx identifikovat xxxxxxxx xxxxx, xxxxx xxxxxxxx reparace DNA x jaterních xxxxxxx xxxxxxxxxxxx zvířat (1, 2, 3, 4).

Xxxx xxxxxxx xx vivo xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx účinků xxxxxxxxxx xxxxx x játrech. Xxxxxxxxxxx jev xx xxxxxxxxxx xxxxxxxxx DNA x xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx místem, xxx xxxx xxxxxxxxxxx sloučeniny xxxxxxxxxxxxxx. Xxxx xxxx xxxxxxx xxxxxx pro xxxxxxxxx xxxx xxxxxxxxx XXX xx vivo.

Jestliže xxxxxxxx důkaz o xxx, že xx xxxxxxxx látka nedostane xx cílové tkáně, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx XXX (XXX) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx značených xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx plánovanou xxxxxxxx XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx tritiem (3X-XxX). Xxx zkoušky xx XXX xx xxxx xx xxxxxxxxxx používají xxxxx xxxxxxx. Xxxx xxxxx xxx játra xxxxx xxx xxxxxx xxxxxxx, nejsou xxxx xxxxxxxxx této xxxxxx.

Xxxxxxx xxxxxxxx UDS závisí xx xxxxx xxxx XXX xxxxxxxxxxx x xxxxxxxxxxx x xxxxx xxxxxxxxx. Xxxxxxx xx XXX xx xxxx xxxxxx xxxxxxx xxx xxxxxxx dlouhých reparací ("xxxx-xxxxx xxxxxx") (20 xx 30 xxxx) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("xxxxx-xxxxx repair") (xxxxx xx tři xxxx) xxxx xxxxxxx xxxx detekovány s xxxxxx xxxxx xxxxxxxxxx. Xxxxx xxxx důsledkem xxxxxxxxxxxxx xxxxxxxx, chybné xxxxxxxx nebo xxxxxx xxxxxxxxx xxxx XXX xxxxx k xxxxxxxxxx xxxxxxxxx. Xxxxxx xxxxxxxx XXX neposkytuje žádnou xxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, xx xxxxxxx reaguje x XXX, ale xxxxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx informací, xxxxx xxxx xxxxxxx poskytuje x xxxxxxxxx xxxxxxxx, xx xxxxxxx potenciální xxxxxxxxxx xxxxxx jevu, xxxxx xx xxxxxxxxxx x xxxxx genomu.

Viz xxxx obecný xxxx, xxxx B.

1.2 DEFINICE

Opravované xxxxx : xxxxx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx jádrům (NNG), xxxxx xxx předvolená xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx zkoušku.

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

Neplánovaná xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx DNA xx vyštěpení x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xx XXX x xxxxxxxxx buňkách xxxxx xx vivo xxxxxxxx xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx úseku XXX xxxxxxxxxxxx region x poškozením indukovaným xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx xxxxxxxx xx xxxxxxxxxxx 3H-TdR xx DNA xxxxxxxxx xxxxx, kde xx xxxx xxxxxxx buněk x X-xxxx xxxxxxxxx xxxxx. Inkorporace 3X-XxX xx obvykle xxxxxxxxx xxxxxxxxxxxxxxx, jelikož tato xxxxxxxx xxxx tak xxxxxxx na xxxx X-xxxx xxxxx jako xxxx. xxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr druhu xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxxxxx lze xxxxxx xxxxxxxx vhodný xxxx xxxxx. Xxxx xx xxx použity xxxxx xxxxxxxxx xxxxxxxxxxx xxxxx mladých xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X okamžiku xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % střední hodnoty xxxxxxxxx pro xxx xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx výběrem rozdělí xx xxxxxxxxx xxxxxxx x xxxxxxx, xxxxx xx exponuje. Xxxxx xx měly xxx xxxxxxxxxx xxx, xxx xxx vliv xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx xx xxxxxxx x xxxxxxxxxxxxx podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx suspendovány xx vhodných rozpouštědlech xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou xxx podávány xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

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

1.4.2.2 Kontroly

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

Pozitivními xxxxxxxxxx xx xxxx xxx xxxxx, x xxxxx xx známo, že xxxxxx podávání x xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx x nárůstu XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Xxxxxxxxx kontroly xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Dávky xxxxx xxx zvoleny xxx, xxx byl xxxxxx xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx odběru

Látka

Číslo XXX

Xxxxx xxxxx Xxxxxx

Xxxxx xxxx xxxxxx (2 až 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx doby xxxxxx (12 xx 16 x)

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

53–96–3

200–188–6

Xxxxx xxx xxxxxxx xxxx xxxx xxxxx pro xxxxxxxxx kontrolu. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx kontrolní xxxxx xxxxxxxx xxxxx způsobem, xxx xxxxxxxx látka.

1.5 XXXXXX

1.5.1 Počet a xxxxxxx xxxxxx

Xxx by xxx xxxxxx dostatečný xxxxx xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx. Každá xxxxxxx xx se xxxx xxxxxxx xxxxxxx xx xxx analyzovatelných xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx dostatečné dosavadní xxxxx, xx xxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx skupiny xxxxxxxx xxxxx jedno xx xxx zvířata.

Jestliže jsou x xxxx studie x xxxxxxxxx údaje xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx stejného xxxxxxx expozice, jež xxxxxxxxx, xx xxxxxxxxxx xxxx pohlavími xxxxxx x xxxxxxxx, bude xxxxxxxxxxx zkoušení jednoho xxxxxxx, xxxxxxx xxxxx. Xx-xx expozice člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je xxxx xxxxxxxxx x xxxxxxxxx farmaceutických xxxxx, xxxx xx xxx xxxxxxx provedena xx xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xxxx xxxxxxxxx podávány xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx xxxxxxxxxx xxxxxxxx xx používají xxxxxxx xxx xxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, že xxxxx xxxxx by xxxxx xxxxx xxxxxxxxx xxx xxxxxxx režimu xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx xx xxxx být xxxxxxxxx 50 % až 25 % xxxxx xxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx netoxických dávkách (xxxx. xxxxxxx x xxxxxxxx) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx x xxxx by xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxx-xx xx kvůli neexistenci xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx zjištění xxxxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx laboratoři, xx xxxxxxx xxxxxx, kmenem, xxxxxxxx x xx xxxxxxxx xxxxxx expozice, xxx xx xxxxxxx x hlavní xxxxxx.

Xxxxxxxx xxxxx xxxx xxx xxxxxxxxxx xxxx jako xxxxx vyvolávající xxxxxx xxxxxxxx v játrech (xxxx. xxxxxxxxxx xxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx dávkou x xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx účinky x xxxx-xx xx základě xxxxx x xxxxxxx, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx xxx úplná xxxxxx nezbytná. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx použít x limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx podává xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx xxxx xxxxx, xxx-xx je xxxxxxxxx. Xxxxxxxx xxxxxxxxxxxxxxxxx xx xxxx xxxxxxxxxxxx, neboť xx xxxxx xxxxx xxx exponována xxxxxxxx xxxxx přímo x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Maximální xxxxx xxxxxxxx, který může xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx je xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, které obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava xxxxxxxxx xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx x xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 xxxxx xx podání dávky. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (obecně dvě xx čtyři xxxxxx xx xxxxxxxx) xx xxxxxxxx, není-li xx 12 xx 16 xxxxxxxx xxxxx pozitivní xxxxxxx. Mohou xxxx xxx použity jiné xxxx odběru, jsou-li xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx údajů.

Krátkodobé xxxxxxx xxxxxxxxx xxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxx jater xxxxxxxxxxx xx situ a xxxxxx xx, xxx xx čerstvě xxxxxxxxxxx xxxxxxx buňky zachytily xx vhodném povrchu. Xxxxxxx buňky x xxxxxxxxx kontroly xx xxxx xxxxxxxxx xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx jaterní xxxxx xxxxx se xxxxxxx xxxxxxx xxxx, xxxx. xxx xx osm xxxxx, xxxxxxxx s xxxxxx xxxxxxxxxxx 3H-TdR. Xx xxxxx inkubační xxxx xx xxxx xxx xxxxxx z xxxxx odstraněno x xxxxx poté xxxxx xxx inkubovány s xxxxxx obsahujícím xxxxxxxx xxxxxxxxxxx xxxxxxxxx, xxx xxxx snížena neinkorporovaná xxxxxxxxxxxxx ("xxxx chase"). Xxxxx xx xxxx xxxxxxx, xxxxxx x xxxxxx. Xxx xxxxx xxxxxxxxx xxxx xxxxxx xxx snížení xxxxxxxxxxxxx xxxxxxxx. Preparáty xx xxxxxx xx xxxxxxxxxxxxxxxxx xxxxxx, exponují xx x xxxxx (xxxx. x chladu 7 xx 14 xxx), xxxxxxxx se, obarví x spočítají se xxxxxxxxxx zrna stříbra. X xxxxxxx zvířete xx xxxxxxxx dva xx tři xxxxxxxxx.

1.5.8 Xxxxxxx

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

Xxxx xxxxxxxxx xxx xx xxxx xxx preparáty kódovány. Xxxxxxxxx xx xxxxxxxxx 100 buněk xx xxxxx zvíře xxxxxxx xx xxxx xxxxxxxxx; xxxxxxxxx xxxx xxx 100 buněk/zvíře xx xxxx být zdůvodněno. Xxx xxxxxxxx xxx xx xxxxx x X-xxxx nevyšetřují, xxx xxxxx xxxxx v X-xxxx xxxx být xxxxxxxxxx.

Xxxxxxxx 3H-TdR inkorporovaného xx xxxxx a xxxxxxxxxx xxxxxxxxxxxx normálních xxxxx doložené navrstvením xxx stříbra xx xxxx xxx xxxxxxxxx xxxxxxx metodou.

Počet buněk xx xxxxxxx x xxxxx xxx odpovídajících xxxxxxxx xxxxŭx (xx) x x prŭměrného xxxxx zrn x xxxxxxxxxxxxxxxxx oblastech (cg) xxxxxxxxxxxxxx xxxxŭx. jako xxxxxxx cg xx xxxxxxx buď xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx xxxxxx cytoplasmy, xxxx xxŭxxxxx hodnota xxxx xx xxx xxxxxxx vybraných oblastí x blízkosti dotyčných xxxxxxxxx jader. po xxxxxxxxxxxxx xxXxxxxxxx mohou xxx xxxxxxx i xxxx xxxxxxx stanovení xxxxx buněk (xxxx. xxxxxxxx xxxxxx xxxxx) (6).

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx by xxx xxxxxxx údaje pro xxxxxxxxxx preparáty x xxxxxxx. Xxxxx xx xxxx být dále xxxxxxx xx formě xxxxxxx. Xxxxxxxxx xxxxxxx XX xx xxxxxxx XX by xxx xxx vypočten xxx xxxxxx buňku, xxx xxxxx zvíře x xxx každou xxxxx x čas čistý xxxxx xxx odpovídajících xxxxxxxx jádrům (XXX). Xxxxxxxx xxxx xxxxxxxx "xxxxxxxxxx" xxxxx, měla xx xxx kritéria xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx xxxxxxxxxx x xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx xxx xxxxxxx, měly by xxx xxxxxxxxxxx xxxxx xxxxxxx a xxxxxxxxxx xxxx xxxxxxxxxx xxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx kritérií xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx patří:

pozitivní

i)

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

xxxx

xx)

xxxxxxx XXX je xxxxxxxx vyšší než xxxxxxx xxx souběžnou xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx XXX xxxx xx dosavadní xxxxxxx xxxxxxx xxxx pod xx;

xxxx

xx)

xxxxxxx XXX xxxx xxxxxxxx xxxxx xxx xxxxxxx xxx souběžnou xxxxxxxx.

Xxxx xx být xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, tj. xxxx xx xxx vzaty x xxxxx xxxxxxxxx, xxxx jsou xxxxxxxxxxx xxxxxx, xxxxx xxxxx x xxxxxxxx a xxxxxxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx však xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx xx xx, kolikrát xx experiment opakován.

Pozitivní xxxxxxxx xxxxxxx na XXX v jaterních xxxxxxx savců xx xxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x xxxxxxxxx xxxxxxx xxxxx in xxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxx neplánovanou xxxxxxxx XXX in xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxxxx xxxxx xxxxxxxx.

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

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx druh/kmen,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx atd.,

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

Zkušební xxxxxxxx:

- pozitivní a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- údaje o xxxxxxxx zkoušené látky,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- zdůvodnění xxxxxxx podávání,

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

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

- podrobné xxxxx x xxxxxxx xxxxxx x xxxx,

- podrobný xxxxx xxxxxxx expozice x odběru,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx x kultivace xxxxxxxxx xxxxx,

- použitá xxxxxxxxxxxxxxxxx technika,

- xxxxx xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx statistické xxxxxxxxx,

- xxxxxx xxxxxxxx,

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

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

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

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

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

2) Xxxxxxxxxxx, X. E., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X., Mirsalis, X., Xxxxxx, X., Xxxxxxxx, X. (1987), X Xxxxxxxx xxx Xxxxx for xxx Xx xxxx Rat Xxxxxxxxxx XXX Xxxxxx Xxxxx, Mutatation Xxx., 189, 123-133.

3) Kennelly, X. C., Xxxxxx, X., Xxxxx, X., Xxxxxxx, X. X., Xxxxxxxxx, B., Xxxxxxx, X. J., Dean, X. W., Mitchell, X. xx X. (1993), Xx xxxx Xxx Xxxxx UDS Xxxxx, xx: Kirkland X. X., Fox X., (eds), Supplementary Xxxxxxxxxxxx Tests: XXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx. Xxxxxx. Part XX xxxxxxx, Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Sydney, 52-77.

4) Xxxxx, S., Xxxx, X. X., Xxxxxx, X., Xxxxxxxxx. X., Xxxxxxxxx, B., Doolittle, X. J., Xxxxxxxx, X., Xxxxxxx, X., XxXxxxx, C. X., Xxxx, H. (1993), Xxxxxxxxxxxxxxx xxx the Xxxxxxxxxxx xx UDS Xxxxx Xx vitro xxx Xx xxxx, Xxxxx. Xxx., 312, 263-285.

5) Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, X. (1993), Assessment xx xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxx xxx the Xxxxxxxxxx xx Freshly Xxxxxxxx Xxx Xxxxxxxxxxx Xxxx xxx xxx Xx xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (UDS), Xxxxxxxxxx Xxx., 291, 21-27.

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


PŘÍLOHA 5

OBECNÉ XXXXXXXXX XX XXXXXXXXXXX A XXXXXXXXXX XXXXXXXXXXXX LÁTEK X XXXXXXXXX

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


XXXXXXX 6

"

XXXXXXX XX

XXXX X

xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx dětmi

Kromě ustanovení xx. 22 odst. 1 xxxx. x) xxxx xxxxxxxx, musí xxx obaly o xxxxxxxxx objemu xxxxxxxxxx xxxxx, x nimiž xx spojeno xxxxxx xxx vdechování (Xx; X 65) x xxxxx xxxx klasifikovány x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx směrnice, x výjimkou xxxxx xxxxxxxxx xx xxx xx xxxxx xxxxxxxx xxxx x nádobách xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx, xxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxxxxx dětmi.

1. Xxxxxxxxx xxxxxxxxxxxx obaly

Uzávěry xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx uzavíratelných xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx XXX 8317 (xxxxxx xx xxx 1. července 1989) "Xxxxx odolné dětem — Požadavky xx xxxxxxxxx uzavíratelné obaly x xxxxxx xxxxxx xxxxxxxx" přijatou Xxxxxxxxxxx xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Xxxxxxxxx neuzavíratelné xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx použité xx opakovaně neuzavíratelných xxxxxxx musí splňovat xxxxxxxxx normy XXX XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Xxxxx xxxxxx dětem — Xxxxxxxxx x xxxxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx obaly jiných xxx farmaceutických výrobků" xxxxxxxx Xxxxxxxxx xxxxxxx xxx normalizaci (XXX).

3. Xxxxxxxx

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

2. Xxxxxxxxxx xxxxxxx

Xx-xx xxxxxx, xx xxxx xx xxxxxxxxxx xxxxxxxx xxx xxxx, neboť xx xxxxxxx dostat x xxxxxx xxx xxxxxx xxxxxxxx, nemusí xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx případech x xxxxx existují xxxxxxxxx xxxxxx x pochybám x xxxxxxxxxxx xxxxxxx xxx dítě, xxxx xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx xxxxx odpovědná xx xxxxxxx xxxxxxx xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx laboratoří xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- typ xxxxxxx xx xxxxxx, xx jej xxxx xxxxxxxx xxxxxxx xxxxx xxxx uvedených xxxxx XXX a XXX,

xxxx

- xx uzávěr xxx xxxxxxx x xxx xxxxxxx vyhovujícím podle xxxx uvedených norem.

ČÁST X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx

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

"