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Směrnice Xxxxxx 2000/32/XX

xx xxx 19. xxxxxx 2000,

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

(Xxxx x xxxxxxxx pro XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x ohledem xx Smlouvu x xxxxxxxx Xxxxxxxxxx společenství,

s xxxxxxx na xxxxxxxx Xxxx 67/548/XXX ze xxx 27. června 1967 x xxxxxxxxxx xxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení x xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], naposledy xxxxxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Xxxx 1999/33/XX [3], x xxxxxxx xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx x xxxxx xxxxxxx:

(1) Xxxxxxx X xxxxxxxx 67/548/EHS xxxxxxxx seznam xxxxxxxxxxxx xxxxx společně x xxxxxxxxxx údaji x xxxxxxxxxxx x xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx x technické xxxxxxxx xxxxxxx, xx xx xxx xxx xxxxxx xxxxxxxxxxxx xxxxx x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxxxxx x xxxxxxx X x xxxxxxx X.

(2) Příloha III xxxxxxxx 67/548/EHS xxxxxxxx xxxxxx xxx xxxxxxxxxxx xxxxxx zvláštních xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx x přípravky. Xxxxxxx XX xxxxxxxx 67/548/XXX obsahuje xxxxxx xxx x xxxxxxxxxxxxxx xxxxxx týkajícími xx xxxxxxxxxxxx látek a xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxx xx xxxxxxxxxxx x x xxxxxxxxxx xxxxxxxxxxxx látek a xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, XX x XX.

(3) X xxxxxxx X xxxxxxxx 67/548/XXX xx xxxxxxx xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, toxicity x ekotoxicity látek x xxxxxxxxx. Xx xxxxxxxx přizpůsobit xxxx xxxxxxx technickému xxxxxxx.

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX obsahuje předpisy xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx. Tyto předpisy xx xxxx xxx xxxxxxxxxxxx x aktualizovány. Xx xxxxxxxx xxxxxxxx xxxxxx, xxx se xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxxxx.

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

XXXXXXX TUTO XXXXXXXX:

Xxxxxx 1

Xxxxxxxx 67/548/XXX xx mění xxxxx:

1. Xxxxxxx X xx xxxx xxxxx:

x) odpovídající xxxxxxxx v xxxxxxxxx xx xxxxxxxxx xxxxxxxxx X x xxxxxxx 1X této xxxxxxxx;

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

x) xxxxxxxxxxxx xxxxxxx xx xxxxxxxxx položkami x xxxxxxx 1C xxxx xxxxxxxx;

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

2. Xxxxxxxxxxxx xxxx x xxxxxxx III xx nahrazuje xxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx v xxxxxxx 2 této xxxxxxxx.

3. Xxxxxxx XX xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx v xxxxxxx XX xx nahrazují xxxxxxxxxxxx xxxxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxx 3X xxxx xxxxxxxx;

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

4. Xxxx X xxxxxxx X xx xxxx xxxxx:

x) xxxxxxxx X.10 xx xxxxxxxxx xxxxxx x xxxxxxx 4X této směrnice;

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

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

d) kapitoly X.13 x X.14 xx xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx směrnice;

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

f) xxxxxxxx X.23 xx xxxxxxxxx textem v xxxxxxx 4X xxxx xxxxxxxx. Xxxxx xxxxxxxx X.23 xx vysvětlivce xx mění xxxxxxxxxxxxx xxxxxxxx;

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

5. Xxxxxxx xx čtvrtá xxxxxxx xxxxxxxx xxxxx x části C xxxxxxx V.

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

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

Xxxxxx 2

1. Xxxxxxx xxxxx uvedou x xxxxxxxx xxxxxx a xxxxxxx předpisy nezbytné xxx dosažení xxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Neprodleně x nich xxxxxxx Xxxxxx.

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

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

Článek 3

Tato xxxxxxxx xxxxxxxx x platnost xxxxxx dnem po xxxxxxxxx v Xxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx.

Xxxxxx 4

Xxxx xxxxxxxx xx xxxxxx členským xxxxxx.

X Bruselu dne 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Wallström

členka Xxxxxx


[1] Xxxxxxx po xxxxxxxxxxxx po dvacáté xxxxx.

[2] Xx. věst. 196, 16.8.1967, x. 1.

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


XXXXXXX 1A

PŘEDMLUVA X XXXXXXX X

Xxxxxxxxxx poznámek xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx a xxxxxxxxxx xxxxx

(Xxxxxx xx xxxxxxx xxxxx)


XXXXXXX 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 1C

Indexové xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační xxxxxx

Xxxxxxxx x přípravkům

006–011–00–7

karbaryl (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

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

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx

205–293–0

137–42–8

Xx; X22 R31 C; X34 X43 N; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

Xxxx. kat. 3; X40 Xxxx. xxx. 3; X40 Xx; X22–48/22 X; X50–53

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

006–016–00–4

xxxxxxxx (XXX) 2- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

204–043–8

114–26–1

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

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

204–123–2

116–06–3

X+; X26/28 X; X24 X; R50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; X24/25 N; X50–53

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

006–019–00–0

di-allát (XXX) X-(2,3-xxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx

218–961–1

2303–16–4

Xxxx. xxx. 3; R40 Xx; X22 N; X50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xx; X22 X43 N; X50–53

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

006–023–00–2

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

217–991–2

2032–65–7

X; X25 N; R50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; X22 Xx; X38 X; R51–53

Xn; X X: 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 N; X50–53

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

006–028–00-X

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

213–546–1

973–21–7

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

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

230–253–4

6988–21–2

X; X25 N; X51–53

X; X X: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

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

243–433–2

19937–59–8

X; X50–53

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

006–034–00–2

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

214–215–4

1114–71–2

Xx; 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 N; 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. kat. 2; X45 Xx; X22 X; X50–53

X; X R: 45–22–50/53 X: 53–45–60–61

006–039–00-X

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

218–962–7

2303–17–5

Xx; R22–48/22 R43 X; R50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; X40 Xx; X22 X; X50–53

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

006–043–00–1

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

140–41–0

Xx; R36/38 Xxxx. xxx. 3; R40 X; R50–53

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

006–045–00–2

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

240–815–0

16752–77–5

X+; X28 X; R50–53

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

006–046–00–8

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

245–216–8

22781–23–3

X; X23/25 Xx; X21 N; X50–53

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

006–047–00–3

bufenkarb (XXX) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx

8065–36–9

X; X24/25 X; X50–53

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

006–048–00–9

xxxxxxxxxxxx (XXX) 2-[(ethylsulfanyl)methyl]fenyl-N-methylkarbamát

249–981–9

29973–13–5

Xn; X22 X; R50–53

Xn; N X: 22–50/53 S: (2-)60-61

006–050–00–X

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

4482–55–7

Xi; R38 X; X50–53

Xx; N X: 38–50/53 S: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-isopropylfenyl-N-methylkarbamát

220–114–6

2631–40–5

Xn; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; X28 Xx; X21 X; R50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; R22 X; 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 R:22–52/53 X: (2-)61

006–069–00–3

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

245–740–7

23564–05–8

Muta. xxx. 3; X40 X; R50–53

Xn; X X: 40–50/53 S: (2-)36/37–60–61

006–070–00–9

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

262–302–0

60568–05–0

Xxxx. xxx. 3; X40 X; X50–53

Xx; N X: 40–50/53 X: (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 X; X50–53

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

007–012–00–5

X,X-xxxxxxxxxxxxxxxx 1,1-dimethylhydrazin

E

200–316–0

57–14–7

F; X11 Xxxx. kat. 2; X45 X; X23/25 X; R34 X; X51–53

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

007–013–00–0

X,X-xxxxxxxxxxxxxxxx 1,2-dimethylhydrazin

E

540–73–8

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

X; X X: 45–23/24/25–51/53 X: 53–45–61

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

009–003–00–1

kyselina xxxxxxxxxxxxxx … %

X

231–634–8

7664–39–3

X+; R26/27/28 X; X35

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

X ≥ 7 %: X+; X; X26/27/28–35 1 % ≤ X < 7 %: X; 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 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx

201–676–1

86–50–0

X+; R26/28 X; R24 X43 X; X50–53

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

015–048–00–8

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

200–231–9

55–38–9

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

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

015–056–00–1

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

220–147–6

2642–71–9

T+; X28 X; R24 N; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; X23/25 Xx; X21 X; X50–53

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

016–013–00-X

xxxxxxx xxxxxxx

234–129–0

10545–99–0

X14 X; X34 N; X50

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

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

016–014–00–5

xxxxxxx siřičitý

13451–08–6

R14 X; R34 X; X50

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

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

016–023–00–4

xxxxxxxx-xxxxxx

X

201–058–1

77–78–1

Xxxx. xxx. 2; X45 Xxxx. xxx. 3; X40 X+; X26 T; X25 X; X34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; X22 X; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

016–071–00–6

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

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

X14 X; X17 X; X34 N; X50–53

X; X; X X: 14–17–34–50/53 X: (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; R50–53

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

X ≥ 1 %: Xn; X20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

X+; X26 Xx; R36/38 X; X50/53

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

082–009–00–X

žluť (xxxxxxxxxxxx xxxxxxxx) CI Xxxxxxx Yellow 34 (XX 77603) CI xxxxxxxxxx žluť 34 (XX 77603)

215–693–7

1344–37–2

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

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

1

082–010–00–5

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

235–759–9

12656–85–8

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

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

1

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; X51–53

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

4

601–032–00–3

xxxxx[x]xxxxx xxxxx[xxx]xxxxxxx

200–028–5

50–32–8

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

X; X 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. kat.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 X; X50–53

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

602–054–00–6

3-jodprop-1-en allyljodid

209–130–4

556–56–9

R10 X; X34

X X: 10-34 S: (1/2-)7–26–45

603–076–00–9

xxx-2-xx-1,4-xxxx

203–788–6

110–65–6

X; X23/25 Xx; X21–48/22 X; R34

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

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

603–091–00–0

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

402–470–6

87172–89–2

X; R8 Xx; X22 Xx; X36

X; Xx R: 8–22–36 X: (2-)26

603–093–00–1

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

402–410–9

87818–31–3

Xx; X20 X; R51–53

Xn; X X: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; X36 X52–53

Xx X:36–52/53 S: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx isopropanol

200–661–7

67–63–0

F; X11 Xx; X36 X67

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

604–020–00–6

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

201–993–5

90–43–7

Xx; X36/37/38 X; X50

Xx; N X: 36/37/38–50 S: (2-)22-61

604–021–00–1

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

205–055–6

132–27–4

Xx; R22 Xx; X37/38–41 X; R50

Xn; X R: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

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

401–720–1

6807–17–6

Xxxx. xxx. 2; R60 Xx; R36 X; X50–53

X; X X: 60–36–50/53 X: 53–45–60–61

604–041–00–0

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

256–634–5 [1] 263–560–7 [2]

50594–66–6 [1] 62476–59–9 [2]

Xx; X22 Xx; X38–41 X; X50–53

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

604–043–00–1

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

203–083–3

103–16–2

Xi; X36 R43

Xi R: 36-43 X: (2-)24/25–26–37

604–044–00–7

mechinol 4-xxxxxxxxxxxx hydrochinonmonomethylether

205–769–8

150–76–5

Xn; R22 Xx; X36 X43

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

605–016–00–7

xxxxxxx… % xxxxxxxxx… %

X

203–474–9

107–22–2

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

Xx X: 20–36/38–40–43 X: (2-)36/37

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

606–016–00-X

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

201–462–8

83–26–1

X; X25–48/25 X; R50–53

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

606–018–00–0

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

204–210–5

117–80–6

Xn; X22 Xx; X36/38 X; R50–53

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

606–019–00–6

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

205–601–3

143–50–0

Xxxx. kat. 3; R40 T; X24/25 X; X50–53

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

606–034–00–8

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

244–209–7

21087–64–9

Xn; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

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

216–920–2

1698–60–8

X43 N; X50–53

Xx; N X: 43–50/53 S: (2-)24–37–60–61

606–036–00–9

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

219–455–3

2439–01–2

Xxxx. xxx. 3; X62 Xx; X20/21/22–48/22 Xi; X36 R43 N; X50–53

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

606–037–00–4

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

256–103–8

43121–43–3

Xx; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

606–044–00–2

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

403–150–9

954–16–5

Xx; X22 Xx; X36 X; X50–53

Xx; X X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; X22 Xx; X41 R52–53

Xn; X X: 22–41–52/53 X: (2-)26-61

607–057–00–6

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

201–378–1

81–82–3

Xx; X48/22 R52–53

Xn X:48/22–52/53 X: (2-)37-61

607–058–00–1

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

204–195–5

117–52–2

X; X25–48/25 R52–53

T X:25–48/25–52/53 X: (1/2-)37–45–61

607–079–00–6

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

4234–79–1

X; X24 Xn; X22 X; X51–53

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

607–097–00–4

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

209–008–0

552–30–7

Xi; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx valerová xxxxxxxx

203–677–2

109–52–4

X; X34 R52–53

C X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xx; R22 X; R51–53

Xn; X X: 22–51/53 S: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; X36/38 X52–53

Xx X:36/38–52/53 X: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xx; X22 Xx; X38 N; X50–53

Xx; N R: 22–38–50/53 S: (2-)37–60–61

607–158–00–5

sodná xxx chloroctové xxxxxxxx xxxxxxxxxx sodný

223–498–3

3926–62–3

T; X25 Xx; X38 X; X50

X; X R: 25–38–50 S: (1/2-)22–37–45–61

607–159–00–0

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

208–110–2

510–15–6

Xx; X22 X; R50–53

Xn; X R: 22–50/53 X: (2-)60-61

607–176–00–3

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

400–830–7

X43 X; X51–53

Xx; X X: 43–51/53 S: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24/37–61

607–209–00–1

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

403–030–6

Xx; X22 X43 N; X50–53

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

607–213–00–3

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

403–320–2

67567–23–1

X; X2 X; R7 X10 X; X51–53

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

607–217–00–5

2-ethoxyethyl-[4-(7-fenyl-2,6-dioxo-2,6-dihydro-1,5-dioxa-s-indacen-3-yl)fenoxy]acetát

403–960–2

R43 R53

Xi X: 43-53 X: (2-)24–37–61

607–243–00–7

xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [3] (2-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 xxxxxxxxxxxxxxxxx-xxxxxxxxx XXXXX

256–032–2

42978–66–5

Xx; X36/37/38 X43 X; X51–53

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

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

607–252–00–6

λ-xxxxxxxxxxx (ISO) Směs (1:1): (S)-[(3-fenoxyfenyl)kyanmethyl]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx

415–130–7

91465–08–6

X+; R26 X; X25 Xn; X21 X; R50–53

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

607–255–00–2

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

69377–81–7

R52–53

R: 52/53 X: 61

608–003–00–4

xxxxxxxxxxxx

X X

203–466–5

107–13–1

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

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

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

43

608–016–00–5

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

401–550–8

1897–41–2

X43 X; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 X+; R28 X; R24 X44 X; R50–53

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

609–040–00–9

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

X

217–406–0

1836–75–5

Xxxx. xxx. 2; R45 Xxxx. kat. 2; X61 Xx; R22 X; R50–53

T; X X: 45–61–22–50/53 S: 53–45–60–61

609–044–00–0

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

204–178–2

117–18–0

Xx; X22 X43 N; X50–53

Xx; N R: 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 N; X51–53

X; X R: 2–51/53 X: (2-)35-61

611–031–00-X

4,4'-[(4-xxxxxxxxxxxxxx-2,5-xxxx-1-xxxxxx)xxxxxxxx]xxxxxxxx-xxxxxxxxxxxx XX Xxxxx Xxx 9 XX xxxxxxx xxxxxx 9

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X R: 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 T; R23/24/25

T X: 45–23/24/25 S: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; R22 X; X50–53

X; X X: 45–22–50/53 X: 53–45–60–61

X ≥ 25 %: X; X45–22 0,01 % ≤ X &xx; 25 %: 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 Muta. xxx. 3; X40 X; X39/23/24/25Xx; R48/20/21/22 X43 X; X51–53

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

612–081–00–5

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

X E

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; R45 Xx; R22 X; X51–53

X; X R: 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 X; R25 Xx; R21 Xx; X36 X43 X; X51–53

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

612–105–00–4

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

205–411–0

140–31–8

Xx; X21/22 X; R34 X43 X52–53

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

612–111–00–7

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

212–513–9

823–40–5

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

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

612–125–00–3

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

202–442–1

95–70–5

X; X25 Xx; X20/21 X43 N; R51–53

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

612–144–00–7

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

62924–70–3

Xx; X36/38 R4 3 N; X50–53

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

612–151–00–5

diaminotoluen toluendiamin xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. kat. 2; X45 X; X25 Xx; X20/21 Xx; R36 X43 X; X51–53

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

613–018–00–4

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

7411–47–4

Xx; X22 Xx; X36/37/38 X52–53

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

613–031–00–5

symklosen 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 R31 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-fenyl-1,3,5-triazin-2,4-diamin benzoguanamin

202–095–6

91–76–9

Xn; X22 R52–53

Xn X:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

Xx; X20/22 X; R41 X; R50–53

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

613–043–00–0

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

261–351–5 [1] 281–291–3 [2]

58594–72–2 [1] 83918–57–4 [2]

Xx; X20/22 Xx; 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; X22 N; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

613–091–00–2

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

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; X22 Xx; X36/37/38 X52–53

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

613–098–00–0

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

403–700–8

2687–94–7

X; X34 X; X51–53

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

613–130–00–3

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

79983–71–4

R43 X; R51–53

Xi; N X: 43–51/53 S: (2-)24–37–61

613–131–00–9

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

57369–32–1

Xx; R22 X52–53

Xx X:22–52/53 S: (2-)61

613–134–00–5

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

88671–89–0

Xxxx. xxx. 3; X63 Xx; X22 Xi; X36 N; R51–53

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

613–137–00–1

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

242–505–0

18691–97–9

X; X50–53

X X: 50/53 X: 60-61

613–139–00–2

xxxxxxxxxxx-xxxxxx xxxxxx-2-{X —[N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)karbamoyl]sulfamoyl}benzoát

74223–64–6

N; R50–53

N X: 50/53 S: 60-61

614–001–00–4

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

200–193–3

54–11–5

X+; X27 X; R25 X; X51–53

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

614–006–00–1

xxxxxx 2,3-dimethoxystrychnidin-10-on

206–614–7

357–57–3

T+; X26/28 X52–53

X+ X:26/28–52/53 X: (1/2-)13–45–61

614–007–00–7

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

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

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

X+; X26/28 X52–53

X+ X: 26/28–52/53 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] xxxxxx-3,5-xxxxxxxxxxx [3]

X

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

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

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

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

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

2

616–010–00–9

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

204–854–7

127–65–1

Xx; X22 X31 X; X34 X42

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

616–034–00-X

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

246–419–4

24691–76–7

R52–53

R: 52/53 S: 61

616–035–00–5

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

261–043–0

57966–95–7

Xx; X22 R43 N; X50–53

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

617–004–00–9

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

212–230–0

771–29–9

X; X7 Xx; X22 X; X34 X; X50–53

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

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

617–006–00-X

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

201–279–3

80–43–3

X; R7 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 Xi; X36 X43

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

650–007–00–3

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

228–200–5

6164–98–3

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

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

650–008–00–9

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

227–197–8

5707–69–7

X; X25 X; X50–53

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

650–009–00–4

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

243–269–1

19750–95–9

Karc. xxx. 3; X40 Xx; X22 N; 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 (X)-3-xxxxxx-α-xxxxxxxxxx-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx

66230–04–4

X; X23/25 X43 X; X50–53

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

650–041–00–9

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

82097–50–5

X; X50–53

X X: 50/53 X: 60-61


PŘÍLOHA 1D

Indexové číslo

Chemický xxxxx

Xxxxxxxx x látkám

Číslo XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační xxxxxx

Xxxxxxxx x přípravkům

006–090–00–8

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

408–010–0

88558–41–2

Xn; R20 Xx; X41 X52–53

Xx 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-tetramethyldisiloxan x 1,3-xx(xxx-x-xx-1-xx)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx

406–490–6

X; X51–53

X X: 51/53 X: 61

015–164–00–9

kalcium-dihydrogen-(1-hydroxyethylen)bisfosfonát xxxxxxxx

400–480–5

36669–85–9

X52–53

X:52/53 X: 61

015–165–00–4

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

404–986–7

Xi; X41 X; R50–53

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

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 X: 61

015–167–00–5

3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; R41

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

601–050–00–1

C10-C13-alkylderiváty xxxxxxx

267–051–0

67774–74–7

X; R50

N X: 50 S: 61

601–051–00–7

4-fenylbut-1-en

405–980–7

768–56–9

Xi; 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 X64 X; X50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

X X: 52/53–59 X: 59-61

603–128–00–0

2-(xxxxxxxxxxxx)xxxxxxxx

405–490–3

613–62–7

X53

X:53 X: 61

603–129–00–6

1-xxxx-xxxxxxxxxxxx-2-xx

406–180–0

57018–52–7

X10 Xx; X41

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

603–130–00–1

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

406–325–8

Xx; X22 R52–53

Xn X:22–52/53 X: (2-)39-61

603–131–00–7

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

407–290–1

Xi; 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

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

408–240–1

Xn; R22 X52–53

Xx X:22–52/53 X: (2-)22–36–61

603–134–00–3

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

410–450–3

X53

X: 53 X: 61

603–135–00–9

xxx[2-(2-xxxxxxxxxxxxx)xxxxxxxxxx]xxx(2,2', 2-xxxxxxxxxxxxxxx-1-xxxxx-X,X)xxxxxxxxxx xxxxxxx

410–500–4

Xx; R41 X; X51–53

Xx; N 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 R:43–52/53 X: (2-)24–37–61

603–137–00-X

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

411–130–6

Xx; X41

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

603–138–00–5

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

403–140–4

103694–68–4

X52–53

X:52/53 X: 61

604–050–00-X

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

216–381–3

1570–64–5

X; X23 X; R 35 X; X50

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

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

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 X: 61

604–052–00–0

2,2'-xxxxxxxxxxx[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -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-terc - 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, 4,5,6,7,7a-hexahydro-4,7-methano-1H - xxxxx-5-xxxxxxxxxxx

410–480–7

X43 X; R51–53

Xi; X R: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-xxxxxxxxxxxxxxxxxx pentylcyklohexan-1-on

4–406–670–4

61203–83–6

N; X51–53

X R: 51/53 X: 61

606–052–00–6

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

410–410–5

54574–82–2

X52–53

X:52/53 X: 61

607–272–00–5

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

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

X; X50–53

X R: 50/53 X: 60-61

607–273–00–0

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

404–520–2

X52–53

X:52/53 X: 61

607–274–00–6

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

405–350–1

54527–73–0

R43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–275–00–1

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

405–450–5

66531–87–1

X43

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

607–276–00–7

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

405–635–0

Xx; X38–41 X; X50–53

Xx; 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; X22 Xx; X41 X43 X; X51–53

Xx; X R: 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 X43 X52–53

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

607–279–00–3

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

405–960–8

X43 X; X51–53

Xx; N X: 43–51/53 X: (2-)24–37–61

607–280–00–9

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

406–190–5

54322–20–2

Xx; X22 Xi; X36 X43

Xx R: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

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

407–000–3

127519–17–9

X; X51–53

X X: 51/53 S: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 X: 61

607–283–00–5

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

408–040–4

15121–89–8

Xx; X21/22 Xx; X38–41 R43 X; X50–53

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

607–284–00–0

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

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

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

410–065–0

X43

Xx X: 43 X: (2-)22–24–37

607–286–00–1

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

410–070–8

141880–36–6

R43 X52–53

Xx R:43–52/53 X: (2-)22–24–37–61

607–287–00–7

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

410–140–8

X52–53

X:52/53 S: 61

607–288–00–2

[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 xxxx 4, x = 8, 9, 10 xxxx 11, x = 22, 23, 24 nebo 25

410–160–7

148732–74–5

Xi; X36 X43 X52–53

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

607–288–00–8

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

410–370–9

105488–33–3

R53

R:53 X: 61

607–290–00–3

Směs (o 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 X43 X; R50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx

410–630–1

104051–92–5

X53

X: 53 X: 61

607–292–00–4

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

410–640–6

Xx; 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; R41 R43 X; X51–53

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

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

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

410–800–5

X43 N; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

607–296–00–6

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

410–830–9

X53

X: 53 X: 61

607–297–00–1

3,3'-(1,4-fenylendimethyliden)bis(2-oxobornan-10-sulfonová kyselina)2,2'-dioxo-3,3'-(1,4-fenylendimethyliden)bis(1,7,7-trimethylbicyklo[2.2.1]heptan-1-methansulfonová xxxxxxxx)

410–960–6

92761–26–7

Xx; X41

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

607–298–00–7

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

411–010–3

R43

Xi X: 43 X: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 X43 X; X50–53

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

607–300–00–6

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

411–430–7

X43

Xx X: 43 X: (2-)22–24–37

607–301–00–1

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

411–860–5

Xx; X38–41 R43 X; X51–53

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

607–302–00–7

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

411–910–6

Xx; R38–41 X43 X; X51–53

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

607–303–00–2

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

413–760–7

93107–30–3

Repr. xxx.3; X62 R52–53

Xn X: 62–52/53 X: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; X50–53

X X: 50/53 X: 60-61

608–024–00–9

2-{4-[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 X; X8 Karc. xxx. 2; X45 X; X23/25 X43

X; X X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 C; X34 X43 X; X50–53

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

611–043–00–5

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

402–850–1

Xx X: 41–52/53 S: (2-)26–39–61

611–044–00–0

Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx 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; R41 X52–53

611–045–00–6

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

404–830–8

X53

X:53 S: 61

X X: 51/53 S: 61

611–046–00–1

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

407–590–2

43151–99–1

X; X25 Xn; X48/22 X43 X; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

X53

X: 53 S: 61

611–048–00–2

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

407–900–6

111381–12–5

X53

X: 53 X: 61

611–049–00–8

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

408–000–6

118658–98–3

Xx; R48/22 R43 X52–53

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

611–051–00–9

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

411–110–7

136213–74–6

X; X50–53

X X: 50/53 X: 60-61

611–052–00–4

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

400–720–9

R52–53

R: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; R41 N; X50–53

Xx; X R: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

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

410–780–8

Xx; X22–48/22 Xx; X41 X43 X; X51–53

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

612–158–00–3

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

410–820–4

X53

X: 53 X: 61

612–159–00–9

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

410–880–1

Xx; R22 C; X34 X; X50–53

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

613–149–00–7

2-terc-butyl-5-[(4-terc-butylbenzyl)sulfanyl]-4-chlorpyridazin-3(2H)-on

405–700–3

96489–71–3

T; X23/25 X; X50–53

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

613–150–00–2

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

406–295–6

X53

X:53 X: 61

613–151–00–8

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

406–360–9

104218–44–2

X53

X:53 X: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 N; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-trichlorpyridin

407–270–2

16063–70–0

R52–53

R:52/53 X: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx X: 22 X: (2-)22

613–155–00-X

5-chlor-2,3-difluorpyridin

410–090–7

89402–43–7

R10 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-butyl-5-chlorimidazol-4-karbaldehyd

410–260–0

83857–96–9

R43 N; X51–53

Xx; N X: 43–51/53 S: (2-)24–37–61

613–157–00–0

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

410–330–0

54236–98–5

Xx; X22–48/22 Xi; X36

Xx X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

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

410–340–5

69045–84–7

Xn; X20/22 Xx; X41 X43 X; R51–53

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

613–159–00–1

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

410–580–0

120928–09–8

X; X25 Xn; X20 X; R50–53

T; 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 S: (2-)24-37

615–022–00–1

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

410–550–7

79277–18–2

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

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

615–023–00–7

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

410–900–9

83056–32–0

X10 X14 Xxxx. kat. 3; X40 Xn; X20–48/22 Xi; R41 X42

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

616–044–00–4

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

402–510–2

X; R51–53

N X: 51/53 S: 61

616–045–00-X

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

405–190–2

122371–93–1

R43 X53

Xx X: 43-53 S: (2-)22–24–37–61

616–046–00–5

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

406–390–2

N; X50–53

X X: 50/53 X: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x N, X′,X″,X′′′ - xxxxxxxxxx(X18)- 2,2′, 2′′, 2′′′-(ethylendinitrilo)tetraacetamid

406–640–0

R43

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

616–048–00–6

3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx

406–740–4

1939–27–1

Xx; X48/22 X; X51–53

Xx; X X: 48/22–51/53 X: (2-)22–36–61

616–049–00–1

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

408–150–2

99141–89–6

X53

X:53 S: 61

616–050–00–7

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

410–690–9

103055–07–8

X43 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 Xxxx:2,4-xxx[3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx x 2,6-xxx[(3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx

411–070–0

X53

X: 53 X: 61

617–015–00–9

xxx(4-xxxxxxxxxxxxx)xxxxxxx

407–950–9

895–85–2

X; R2 X; R7 X; X50–53

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

650–032–00-X

cyprokonazol (XXX) (2X, 3X)-, (2 S, 3 X)-, (2 X, 3 X)-, (2 X, 3 X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxx-1-(1X- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

94361–06–5

Xxxx. kat. 3; X63 Xx; R22 X; X50–53

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


XXXXXXX 2

POVAHA XXXXXXXXXXXX XXXXX SPOJENÝCH X XXXXXXXXXXXX LÁTKAMI A XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 3A

STANDARDNÍ POKYNY XXX BEZPEČNÉ XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES,

Úř. xxxx. X 332, 28.12.2000, x. 81.


XXXXXXX 3X

XXXXXXXXXX POKYNY XXX BEZPEČNÉ XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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


XXXXXXX 4A

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

1. XXXXXX

Xxxx metoda je xxxxxxxx xxxxxx OECD XX 473 — Xxxxxxx na chromozomové xxxxxxx x xxxxx xx vitro (1997).

1.1 XXXX

Xxxxxxx xx chromozomové xxxxxxx x xxxxx xx xxxxx xx xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx v kultivovaných xxxxxxx xxxxx (1, 2, 3). Xxxxxxxxx xx dva xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Nárůst xxxxxxxxxxx xxxx xxxxxxxx, xx chemická xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx x xxxxxx xxxxx rutinně xxxxxxxxx. Xxxxxxxxxxxx mutace x xxxxxxx xxxx jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx a xxxxxxxx xxxxx xxxxxx o xxx, xx chromozomové xxxxxx x x xxxx xxxxxxxxxxx jevy xxxxxxxxxxx xxxxx v xxxxxxxxxx x x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx indukci xxxxxxxx x člověka x x pokusných xxxxxx.

Xx zkoušce xx xxxxxxxxxxxx xxxxxxx xx xxxxx mohou být xxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx, xxxxxxx xxxxx xxxx primární xxxxxxx xxxxxxx. Použité buňky xxxx vybrány xx xxxxxxx xxxxxxxxxx xxxxx x kultuře, stálosti xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx četnosti chromozomových xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx xxxxxxxxx xxxxxxxx in xxxx x xxxxx. Xx xxxxx xx zcela xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, jež xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx x xxx dojít xxxxxx xX, osmolality nebo xxxxxxxx úrovní xxxxxxxxxxxx (4, 5).

Tato zkouška xx používá xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx pro xxxxx xxxxxxxxxxx; xxxx touto xxxxxxxx a karcinogenitou xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx xxxxxx xx chemické třídě x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx zjištěny xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx jinými xxxxxxxxxx xxx xxxxxx xxxxxxxxxx XXX.

Xxx také Xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

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

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

Xxxxxxxxxxxxxxx : proces, xxx kterém v xxxxx xx S-fázi xxxxxxxxx DNA xxxxxxx x xxxxxx, xxxxx xxxxxxxxx další X-xxxx. Xxxxxxxxx xxxx chromozomy xx 4, 8, 16… chromatidami.

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

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

Xxxxxxxxx aberace : xxxxxxxx počtu xxxxxxxxxx od xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxx xxxx xxxxx.

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx jsou xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxxxxxxx xxxxxxxx a xxx xx. V xxxxxx xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxx xx xx xxxxxxxxx xxxxxx xxxxx látka zastavující xxxxxxxx (např. Colcemid® xxxx kolchicin), xxxxxxx xx xxxxxx, obarví x přítomnost chromozomových xxxxxxx xx zjistí xxxxxxxxxxxxxx pozorováním xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx xxxxx xxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxx kultury, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (xxxx. xxxxxxxxxxx xxxxxx xxxxxxxx, xxxxxxxxx xxxxxxxxx krve xxxxxxx xxxx xxxxxx savců).

1.4.1.2 Xxxxx a xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx kultur xx měla xxx xxxxxxx vhodná kultivační xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, teplota x xxxxxxx). X xxxxxxxxxxxxxxx xxxxxxxxx xxxxx x kmenů by xxxx xxx rutinně xxxxxxxxxxxx stabilita modální xxxxxxx počtu chromozomů x mělo xx xxx kontrolováno, zda xxxxxx kontaminovány xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx xxxxxx být xxxxxxx. Pro použité xxxxx a inkubační xxxxxxxx by xxxx xxx xxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx a kmeny: xxxxx se pomnoží x xxxxxxxxx xxxxxx, xxxxxx xx xx xxxxxxxxxxxx xxxxx v xxxxxx xxxxxxx, aby xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx, x inkubují xx xxx 37 °X.

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

1.4.1.4 Metabolická xxxxxxxx

Xxxxx by xxxx xxx vystaveny xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxxxxxx xxxxxxxx a xxx xx. Xxxxxxxxxx používaným xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx zpracovaná xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (6, 7, 8 a 9), xxxx xxxx fenobarbitonu x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx je x xxxxxxxx xxxxxxxxxx médiu xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx chemické xxxxx, xxxxx xx xxxxxxxx. X některých xxxxxxxxx může xxx xxxxxx xxxxxx xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce.

Řada xxxxxxxx xxxxxx, xxxxxx přípravy xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx exprimujících xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx linií xx xxxx být vědecky xxxxxxxxxx (xxxx. důležitostí xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx látky by xxxx být xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx přímo x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být xxxx xxxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxx, pokud xxxxx x stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx být xxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx, a xxxx xx xxx xxxxxxxxxx x xxxxxxxx buněk x x xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx xxxxxx použití xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx látek xxxxxxxxx xx vodě xx xxxx být použita xxxxxxxxx rozpouštědla xxxxxxxxxxxx xxxx. Vodu lze xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

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

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx aktivací x bez ní x xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, xxxx xxxx xxxxxx konfluence, xxxxx životaschopných xxxxx xxxx mitotický xxxxx. Xxxx být xxxxxxx xxxxxxxx cytotoxicitu x xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx xxxxxxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx dané xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx, xxx obvykle xxxxxxx, xx by xx xxxxxxxxxxx xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. V xxxxxxxx xxxxxxx by měla xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, xxxxx xxxxx xxxx xxxxxxxxxxx xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x závisí xx době, xxxxx xxxxxxxx xx xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx xxxxxxxxxx x xxxxxxxxxxx xxxxxx, x xxxxx mohou xxx xxxx xxxxxx stanovení xxxxxxxx xxxxxxx x xxxxxxxxxxx. Informace x xxxxxxxx buněčného xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (XXX), xxxxx xxx xxxxxxx xxxx xxxxxxxxx xxxxxxxxx. X xxxxxxx AGT však xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx nelze xxxxxxx xx existenci xxxxxxxxxx xxxxxxxxxxx, x x xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx doby xxxx xxx xx následek xxxxx podstatné xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

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

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx xxxxxxx při xxxxxxxxxxxxx xxxxxxx, než xx xxxxxx xxxxxxxxxxx, xx měla xxx xxxxxxx xxxxxxxx dávka x koncentraci, jež xx xxx xxxx xxxxxxxxxxxx v xxxxxxxx xxxxxxxxxxx xxxxx na xxxxx xxxx xxxxxxxx. X xxxxxxxx případech (xxxx. xxxxxxx-xx se xxxxxxxx xxxxx xxx xxxxxxx koncentracích, xxx xx xxxxxxxxxxx) se xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, při xxxxx xxxxxxx ke xxxxxxx. Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx x testovacím xxxxxxx se může x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, xxxx X9 xxx. Xxxxxxxxxxxxx xxx xxxxxxx vizuálně. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx x pozitivní xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx a xxxxxxxxx xxxxxxxx (kontroly xxxxxxxxxxxx xxxx xxxxxxxx). Při xxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxx xxx xxx xxxxxxxxx kontrolu xxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx.

X xxxxxxxxx kontrole xx xxx xxx xxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx reprodukovatelný x xxxxxxxxxxxxx xxxxxx xxx pozadí, xxxx xx xxxxxxx xxxxxxxxx xxxxxxxxxxx systému.

Koncentrace xxxxxxxxxxx xxxxxxx xx xxxx xxx zvoleny xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx aktivace

Látka

Číslo XXX

Xxxxx xxxxx EINECS

Bez xxxxxx xxxxxxxxxxx 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 mohou xxx xxxxxxx x jiné xxxxxx látky. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx pokud xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx.

X xxxxxxxx xxxxxxxx by měly xxx xxxxxxx negativní xxxxxxxx skládající xx xx samotného xxxxxxxxxxxx xxxx xxxxxxxx v xxxxxxxxxxx médiu a xxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxx xxxxxxxxx údaje prokazující, xx xxxxxxx rozpouštědlo xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxxxxx xxxxxxxx látce xxx xx xxxxxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, xxx bez xxxx. Xxxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxxx xxx 48 xxxxx xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx každou xxxxxxxxxxx xx xxxx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, x xxxxx xx důrazně doporučuje x kultur pro xxxxxxxxx xxxxxxxx nebo xxxxxxxx xxxxxxxxxxxx. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx kulturami xx xxxxxxxxx rozdíl, xxxx xxx xxxxxxxxx xxxxxxx xxxxxx xxxxxxx.

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

1.4.3.3 Xxxx xxxxxxx kultur

V prvním xxxxxxxxxxx xx xxxx xxx xxxxx xxxxxxxxx xxxxxxxx látce, xxx x metabolickou aktivací, xxx bez ní, xx xxxx 3 — 6 xxxxx, x xxxx xx xxx odebrány xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx (12). Xxxxxxxx xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx xxx s xxxxxxxx, xxx bez xxxxxxxx, xxx xx xxx proveden dodatečný xxxxxxxxxx bez xxxxxxxx x xxxxxxxxxxxx expozicí xx xx odběru x době, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu. Xxxxxx xxxxxxxx xxxxx xxx snáze xxxxxxxxx xxx dobách aplikace xxxx odběru xxxxxxx xxx 1,5xxxxxxx xxxxx xxxxx. Xxxxxxxxx výsledky xxx metabolické xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx od případu. X případech, xxx xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, by xxxx xxx podáno xxxxxxxxxx.

1.4.3.4 Xxxxxxxx preparátů xxx xxxxxxx chromozomů

Do buněčné xxxxxxx xx xxxxxxx 1-3 hodiny před xxxxxxxxx přidá Colcemid® xxxx xxxxxxxxx. Pro xxxxxxxx xxxxxxxxx pro xxxxxxx xxxxxxxxxx xx xxxxx xxxxxxx xxxxxxx xxxxxx a xxxxxxxxxx xxxxxx. Xxxxxxxx preparátů xxx analýzu chromozomů xxxxxxxx xxxxxxxxxxxx buněk, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx pozitivních x negativních xxxxxxx, xx měly xxx xxxx analýzou pod xxxxxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx xxx fixaci xxxxx xxxxxxx xx xxxxx xxxxx buněk x xxxxxxxx a xx xxxxxx xxxxxxxxxx, xxxx xx vyšetřované xxxxx obsahovat centromery x xxxxx xxxxxx xxxxxxx xxxxxxx ± 2 xxx xxxxxxx xxxx buněk. Na xxxxxx xxxxxxxxxxx a xxxxxxxx xx xxxx xxx hodnoceno alespoň 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxxx xxx snížit, je-li xxxxxxxxx xxxxx xxxxx xxxxxxx.

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

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx x xxxx xx xxxx být xxxxxxxxxxx xxxxxxxx xxxxx xx strukturní xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) vyjádřené x xxxxxxxxxx. Pro xxxxxxxxx x experimentální xxxxxxx by měly xxx uvedeny xxxxx xxxx xxxxxxxxxxxx chromozomových xxxxxxx x jejich xxxxxx x xxxxxxxx. Xxxx se xxxxxxxxxxxxx xxxxxxxx a xxxxxxx xx, xxx nezahrnují xx xx celkové xxxxxxxx xxxxxxx.

Xxxx by xxx také zaznamenána xxxxxxxx, která xxxx xxxxxxxxx pro stanovení xxxxxxxxxxxx u xxxxx xxxxxxxxxxxx kultur x xxxxxxxxxxx kultur x xxxxxxxx experimentech x xxxxxxxxx.

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

Xxxxxxx xxxxx pozitivní odpovědi xx xxxxxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx vyjasněny xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxxx experimentálních xxxxxxxx. Xxxxxxxxxx potvrdit xxxxxxxxx xxxxxxxx byla xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx parametrů xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla být xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx by xxxxx být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x podmínky metabolické xxxxxxxx.

2.2 HODNOCENÍ A XXXXXXXXXXXX VÝSLEDKŮ

Pro stanovení xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx počtu buněk x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx počtu. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být použity xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx odpověď.

Nárůst xxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx x indukovat xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx buněk x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxx progresi xxxxxxxxx xxxxx (17, 18).

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx xxxxxxxx látky. Xxxxxxxx mohou zůstat xxxxxxxxxx nebo xxxxxx xxx ohledu na xx, kolikrát je xxxxxxxxxx xxxxxxxx.

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

3. ZPRÁVY

PROTOKOL X ZKOUŠCE

Protokol o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

- rozpustnost x xxxxxxx xxxxxxxx xxxxx v xxxxxxxxxxxx/xxxxxxxx, xx-xx známa.

Buňky:

- typ x zdroj xxxxx,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxx xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx xxxxx,

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

- xxxxxxxx xxxxx xxxxxx,

- případně metody xxxxxxxxx buněčné xxxxxxx,

- xxxxxxx xxxxxxx počtu xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxx koncentrací x xxxxx xxxxxx, xxxxxx xxxx. údajů x xxxxxxxxxxxx a xxxxxx rozpustnosti, xxxx-xx x xxxxxxxxx,

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- koncentrace xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x přidané xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- případně hustota xxxxx xxx xxxxxxxx,

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

- xxxxxxxxx a xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx na xxxxxxxxx, negativní nebo xxxxxxxxxxx.

Xxxxxxxx:

- známky xxxxxxxx, xxxx. stupeň xxxxxxxxxx, xxxxx x xxxxxxxx xxxxx, xxxxx xxxxx, xxxxxxxxx xxxxx,

- xxxxxx xxxxxxx,

- xxxxx o xX a xxxxxxxxxx xxxxxxxxxxx xxxxx, xxxxx xxxx stanoveny,

- xxxxxxxx xxxxxxx, xxxxxx xxxx,

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

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- případné xxxxxxxxxxx analýzy,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, H. X. (1976), Xxxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, xx: Xxxxxxxx Xxxxxxxx, Principles xxx Xxxxxxx for xxxxx Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, A. (xx) Xxxxxx Xxxxx, Xxx Xxxx and London, 1-29.

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

3) Xxxxxxxx, S. X., Armstrong, X. X., Xxxxxx, X., Xxxxxx, S., Xxxxx, X., Xxxxxx, C., Xxxxx, A. X., Xxxxxxxx, X., Xxxxx, X., Duk, S., Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxx, X. X., Anderson, X., Xxxxxx E. (1978), Xxxxxxxxxx aberration xxx sister xxxxxxxxx xxxxxxxxx in Xxxxxxx xxxxxxx xxxxx xxxxx: Xxxxxxxxxx xx 108 xxxxxxxxx, Environ. Molec. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Xxxxx, X., Xxxxxxxx, X. X., Marshall, R. X., Xxxxxxxx, X. Xx., Xxxxxxx, X., Xxxxx, J., Xxxx, X. X. (1991), Xxxxxxxxxxxx under Xxxxxxx Xxxxxxx Xxxxxxxxxx. A xxxxxx xxxx XXXXXX Xxxx Group 9, Xxxxxxxxxx Xxx., 257, 147-204.

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

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

7) Maron, X. M., Xxxx, X. N. (1983), Xxxxxxx Methods for xxx Salmonella Mutagenicity Xxxx, Xxxxxxxxxx Xxx., 113, 173-215.

8) Xxxxxxxxx, X. T., Tates, X. X., xxx Xxxx, X. P. X., Xxxxxxx, X., xx Vogel, X. (1976), Cytogenetic Effects xx Xxxxxxx/Xxxxxxxxxxx after Xxxxxxxxxx xx x Xxxxxxxxxxx Xxxxxx Xx xxxxx, I. Xxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xxx Xxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Dimethylnitrosamine (XXX) in XXX Xxxxx xx xxx Xxxxxxxx of Rat-Liver Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

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

10) Elliot, X. X., Xxxxxx, X. X., Xxxxxxx, X. X., Gatehouse, X. X., Xxxxxx, X. X., Mackay, X. X., Xxxx, X. X. (1992), Xxxxxx xx UK Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx In xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, T., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X. Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, xx: xx Xxxxxx, F. X., Xxxxx, X. X. Xxxx, J. X., Philpot, X. X. (xxx), Xx xxxxx Metabolic Xxxxxxxxxx xx Mutagenesis Xxxxxxx, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

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

13) Richardson, X., Xxxxxxxx, X. A., Xxxxx, X. A., Xxxxxxxx, X., Chanter, X. X., Xxxxxxxx, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx xxxxx Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, Kirkland, X. X., (xx) Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, 141-154.

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

15) Xxxxx, X. X., Xxxxxx, F. X., XxXxxxx, X. X. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Evaluation of Xxxxx and Volatile Xxxxxxx, xx: Xxxx, X. X., Costa, X. L., Schaich, X. X. (xxx), Xxxxxxxxx Effects of Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, P. X., Xxxxxx, X. M., Xx, X. X., Xxxxxx, X. X. (1983), Evaluation xx xx Xxxxxxxx System Xxxxx Xxxxx Xxxxx xx Collagen Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx in xxx XXX/XXXXX Mutation Xxxxx, Xxxxxxxxxxxxx Xxxxxxx., 5, 795-801.

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

18) Huang, Y., Xxxxxx, C., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx in Xxxxxxx hamster cells, Xxxxxx Xxx., 43, 1362-1364."


XXXXXXX 4B

"B.11 XXXXXXXXXX–XXXXXXX XX CHROMOZOMOVÉ XXXXXXX X XXXXXXX XXXXXX XXXXX XXXXX IN XXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx aberace x savců xx xxxx xx používána xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx v xxxxxxx xxxxxx dřeně xxxxx, obvykle xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx xx xxx typy strukturních xxxxxxx — chromozomové x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx může xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx indukovat xxxxxxxxx xxxxxxx. X xxxxxxx většiny xxxxxxxxxx xxxxxxxx jsou xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx chromozomové aberace xx xxxxxx vyskytují. Xxxxxxxxxxxx mutace a xxxxxxxxxxx xxxx jsou xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx x související xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx rakoviny u xxxxxxx x x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx této xxxxxxx jsou rutinně xxxxxxxxx hlodavci. Xxxxxxx xxxxx xx v xxxx xxxxxxx xxxxxx xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx tkání x obsahuje xxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxxx xx xxxxxx izolují x xxxxxxxxxxxx. Jiné xxxxx x xxxxxx tkáně xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxxxx určená x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx umožňuje xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx reparace XXX, xxxxxxx xx mohou x xxxxxxx xxxxx x xxxxx xxxxx. Xxxxxxx xx vivo xx xxxxxx užitečná xxx xxxxx výzkum xxxxxxxxxxx xxxxxx zjištěných xxxxxxxx in xxxxx.

Xxxxxxxx xxxxxxxx důkaz x xxx, že xx xxxxxxxx xxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx tuto xxxxxxx použít.

Viz xxxx Xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Chromatidová aberace : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx v xxxxxx xxxxx jednotlivých xxxxxxxxx xxxx xxxxx x xxxxxxxx xxxxxxx chromatid.

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

Xxxxxxxxxxxxxxx : xxxxxx, xxx kterém x jádře xx X-xxxx replikace DNA xxxxxxx k xxxxxx, xxxxx xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx jsou xxxxxxxxxx xx 4, 8, 16,… xxxxxxxxxxxx.

Xxx : achromatická xxxx xxxxx xxx xxxxx xxxxxxx chromatidu a x minimální xxxxxxxxx xxxxxxxxx.

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

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx buněčném dělení xx stadiu xxxxxxxx; xxxx se xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxx vystavena xxxxxxxx xxxxx xxxxxxx xxxxxxxx x ve xxxxxxx xxxxxxxx xx xxxxxxxx xx xxxxxx. Xxxx usmrcením xx xxxxxxxx xxxx látka xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx xxxxxx xxxxx xx xxxx xxxxxxxx preparáty xxxxxxxxxx, xxxxxx se a xxxxxxxxx se xxxxxxxxxxxx xxxxxxx buněk v xxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, myš x křeček čínský, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxxx by xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx studie xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx by u xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx xxxxxxx x xxxxxxx, xxxxx xx xxxxxxx zkoušené xxxxx. Xxxxx xx xxxx xxx uspořádány xxx, xxx byl xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx alespoň xxx xxx aklimatizovat.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxxx přímo xxxx mohou být xxxx xxxxxxx zředěny. Xxxx by xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické látky, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

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

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by měly xxx xxxxxxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx látky xx xxxx zvířata xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata xx xxxxxxxxx, v xxxxx dojde k xxxxxxxx.

Xxxxxxxxx kontroly xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx in vivo xxx xxxxxxxxxxx xxxxxxxx, x xxxxx se xxxxxxx, xx poskytnou xxxxxxxxxxxxx nárůst xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx způsobem xxx xxxxxxxx xxxxx a xxx byl odběr x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx k dispozici. Xxxxxxxx látek xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx C

50–07–7

200–008–6

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxxx odběru by xxx být xxxxxxxx xxxxx x xxxxxxxxxxx xxxxxxx, jimž xx xxxxxxxxxx xxxxx rozpouštědlo xxxx vehikulum x xxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxxxxx skupiny, xxxxx xxxxxx z xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx zvířat x xxxxxxxx xxxxx x chromozomovými aberacemi. Xxxxxxx-xx se pro xxxxxxxxx kontrolu jeden xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx doba xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx žádné xxxxxxx nebo xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Počet x pohlaví zvířat

Každá xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx pohlaví. Xxxxxxxx xxxx x xxxx xxxxxx x dispozici xxxxx ze xxxxxx xx stejným druhem x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx pohlavími xxxxxx x toxicitě, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Je-li xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx být xxxxxxx xxxxxxxxx xx zvířaty xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx být pokud xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx mohou xxx xxxxxxxx také xx dvou xxxxxxx, xxx. dvě xxxxx x xxx xxx x xxxxxxx xx xxxx xxx několika xxxxx, xxx xxxx xxxxxxxxx podávání velkých xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx měly xxx xxxxxxxx ve xxxx xxxxxxx intervalech xx xxxxxxxx xxxxxx x xxxxxx dni. X hlodavců xx xxxxx provádí xx xxxxxx xxxx xx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu (xxxx xxxx obvykle 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx pro xxxxxx xx xxxxxxxx xxxxxxxxx cyklu xxxx xxx xxxx na xxxxxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx aberací, xxxxxxxxxx se xxxxxxx xxxxx xxxxx xx 24 x xx xxxxxxx odběru. Je-li xxxxxxxx rozložena xx xxxx než xxxxxxx xxx, xxx xx xxx xxxxx proveden xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx xxxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx se po xxxxxx xxxx xxxxxxx x zvířat xxxxx. X xxxx je xxxx xxxx přibližně 3 — 5 x; u xxxxxx xxxxxxxx xx xxxx xxxx přibližně 4 — 5 x. X xxxxxx dřeně xx xxxxxxxx xxxxx x analyzují xx xx chromozomové aberace.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx by xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx stejným xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx expozice, jež xx xxxxxxx x xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx maximální a xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x letalitě. Látky xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx kritériím stanovení xxxxx vyhovovat x xxxx xx xxx xxxxxxxxx případ xx xxxxxxx. Nejvyšší dávka xxxx být xxxx xxxxxxxxxx jako dávka xxxxxxxxxxxx x xxxxxx xxxxx některé známky xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx mitotického xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x jednou xxxxxx xxxxxxx 2000 mg/kg xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx v xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx toxické xxxxxx x není-li xx xxxxxxx údajů x xxxxxxx, xxxxx xxxx xxxxxxxx strukturu, xxxxxxxxx xxxxxxxxxxxx, nepovažuje xx úplná xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X déle xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den x xxx delší než 14xxxxx xxxxxxxx je xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x limitní xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx nebo injekčně, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx překročit 2 xx/100 x xxxxxxx xxxxxxxxx. Použití xxxxxxx objemů, xxx xx xxxxxxx objem, xxxx xxx xxxxxxxxxx. Xx xx dráždivé x xxxxxx látky, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx vykazují xxxxxxxx účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu minimalizována xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx pro xxxxxxx chromozomů

Ihned xx xxxxxxxx xx xxxxxxx xxxxxx xxxx, hypotonizuje xx a fixuje. Xxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx xxxxxxx xxxxxxxxxxxx xx měl xxx x xxxxx xxxxxxxxxxxx xxxxxx (xxxxxx xxxxxxxxxxx xxxxxxx) x x xxxxxxxxxxxxxx xxxxxx xxx xxxxxxxxx xxxxxxxx stanoven xxxxxxxxx xxxxx, x xx alespoň u 1000 xxxxx xx xxxxx xxxxx.

X xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx. Xxxxx xxxxx lze xxxxxx, xx-xx pozorován xxxxx xxxxx aberací. Xxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxx xxxxxxxxxxxxxx analýzou xxxxxxxxx xxxxxxxx. Protože xxx xxxxxx xxxxx dochází xx xxxxxxxxxxxxxx xxxxxx xxxx ke xxxxxx xxxxxxxxxx x xxxxx xxxxx x metafázi, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x počtu xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx by xxxx xxx zpracovány xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Xxx každé xxxxx xx měl xxx xxxxxxxxxx počet xxxxx, xxxxx xxxxxxx xx xxxxx x xxxxx xxxxx x xxxxxxxxxxxxx xxxxxxx (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx v xxxxxxxxxx. Xxx exponované x xxxxxxxxx skupiny xx měly být xxxxxxx xxxxx typy xxxxxxxxxxxx chromozomových xxxxxxx x jejich xxxxxx x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x uvádějí xx, xxx obecně xx xxxxxxxxxx do celkové xxxxxxxx aberací. Xxxxxxxxxx-xx xxxxx x rozdílu x xxxxxxxx xxxx xxxxxxxxx, xxxxx být xxx statistickou xxxxxxx xxxxx pro xxx xxxxxxx zkombinovány.

2.2 HODNOCENÍ X INTERPRETACE VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx s xxxxxxxxx xxx xxxxxxx x určitou xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Nejdříve xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s úpravami xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx indukovat xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Nárůst xxxxx buněk x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx xx potenciál xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (7, 8).

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx zůstat xxxxxxxxxx xxxx sporné xxx xxxxxx na to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x kostní xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx za xxxxxxxx xxxxxxx neindukuje x xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx by být xxxxxxxxxxx pravděpodobnost, x xxxxx xx zkoušená xxxxx xxxx její xxxxxxxxxx xxxxxxxx xx xxxxxxxx oběhu, xxxx xxxxxxxxxx do xxxxxx xxxxx (např. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x xxxxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx zvířat na xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx a xxxxxxxxxx xxxxxxxx pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- údaje x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- xxxxxxxxx metody xxxxxxx, xxx xx xxxxxxxx látka xxxxxxx xx xxxxxxxx oběhu xxxx xx xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx hodnocení xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx na xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- mitotický xxxxx,

- typ x xxxxx aberací xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- celkový xxxxx xxxxxxx xx xxxxxxx xx xxxxxxxxx hodnotami x směrodatnými xxxxxxxxxx,

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

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx,

- podle xxxxxxxx závislost xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

- xxxxx x souběžné negativní xxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx x rozpětími, středními xxxxxxxxx a směrodatnými xxxxxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Preston, X. X., Xxxx, X. X., Galloway, X., Holden, X., XxXxx, X. F., Xxxxxx, M. (1987), Xxxxxxxxx Xx xxxx Xxxxxxxxxxx Assays: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xx Xxxx Xxxxxx Xxxxx, Xxxxxxxxxx Res., 189, 157-165.

3) Xxxxxxx, X., Chandley, X., Xxxxx, X., Xxxxxxxxx, X. X., Bootman, X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Assays, in: X. J. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Testing. Report, Xxxx X revised, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New York, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

4) Xxxx, X. X., Hayashi, X., MacGregaro, J. X., Anderson, X., Xxxxxx, X. H., Xxxxxx, H. X., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., X. B., Xxxxxxxxxxxx, X., Preston, X. J., Xxxxxxx, X., Xxxxxxx, H., Xxxxx, X., Xxxxxxx, X. (1994), Xxxxxx xxxx xxx Xxxxxxx Xxxxx xx xxx xx xxxx Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Test, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, X. X., Xxxxx, J. X., Xxxxxx, X. R., Xxxxxx, X. X., Xxx, X., Xxxxxxx, X. J., Gatehouse, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, X. X., Richold, X. (1992), Report xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx: Dose Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, D. X., Xxxxxx, X. X. X. (1989), Xxxxxxxxxxx Analysis xx Xx vivo Xxxxxxxxxxx Xxxxxx, xx: UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Test Xxxx, X. J. Kirkland (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, 184-232.

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

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


PŘÍLOHA 4C

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

1. METODA

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

1.1 XXXX

Xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx vivo xx xxxxxxxx pro xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx mitotického xxxxxxx xxxxxxxxxxxx, které je xxxxxxxxxx xxxxxxxxx xxxxxx, x xx pomocí xxxxxxx xxxxxxxxxx odebraných x xxxxxx xxxxx x/xxxx buněk xxxxxxxxx xxxx, obvykle xxxxxxxx.

Xxxxxx xxxxx xxxxxxx erytrocytárních xxxxxxxxxx je identifikovat xxxxx, xxxxx způsobují xxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxxxxxxx nereplikující xx (lagging) chromozomové xxxxxxxxx xxxx xxxx xxxxxxxxxx.

Xxxx se xxxxxxxxxxx xxxxxx xxxxx mění xx xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxx xxxxx xx xxxxxxxx x xxxxxxxxxx, xxxxx při xxx xxxxx xxxxxxxxx, xxxxxxxxx x cytoplasmě, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx mikrojader xx x těchto xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx xxxxxx xxxxx. Xxxxxx xxxxxxx polychromatických xxxxxxxxxx x xxxxxxxxxx x exponovaných xxxxxxxxx xx známkou xxxxxxxxxxxx xxxxxxxxxxxxxx poškození.

V xxxxx xxxxx xx rutinně xxxxxxxxx xxxxxx dřeň xxxxxxxx, xxxxxxxx xxxx xxxx xxxxxxxxx polychromatické xxxxxxxxxx. Stanovení xxxxxxxxx (xxxxxxxxxxxxxxxxx) erytrocytů x xxxxxxxxxx x periferní xxxx je xxxxxxxxxx xxxxxxxxxx x xxxxxxxxxxx xxxxx, u xxxxx xxxx prokázána xxxxxxxxxxx xxxxxxx odstraňovat xxxxxxxxxx x xxxxxxxxxx, xxxx xxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Mikrojádra xxx rozlišit řadou xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx nebo xxxxxxxxxxxxx centromerní (kinetochorní) XXX v xxxxxxxxxx. Xxxxxxxxx se xxxxxxx xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx s xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx x periferní xxxx, xxxxx obsahují xxxxxxxxxx, xxxxxxxxxxx xx xxxxxx počet zralých xxxxxxxxxx xxx xxxxxx xxxxxx jako xxxxxxx xxxxxxxx xxxxxxx, xxxxxxxx xxxx zvířata xxxxxxxxxx xxxxx xxxxx xxxx xxxx.

Xxxxx test savčích xxxxxxxxxxxxxxx mikrojader xx xxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx lišit x různých xxxxx x xxxxx, xxxxx x z genetického xxxxxxxx. Zkouška xx xxxx xx xxxxxx xxxxxxxx xxx xxxxx xxxxxx mutagenních xxxxxx xxxxxxxxxx v xxxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx x tom, xx xx zkoušená xxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, není xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, část B.

1.2 XXXXXXXX

Xxxxxxxxxx (kinetochor) : xxxxxx (oblasti) chromozomu, x xxx (k xxxx) xx xxxxx xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxx pohyb dceřiných xxxxxxxxxx x xxxxx xxxxxxxxx xxxxx.

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

Xxxxxxxxxxxxxxxx xxxxxxxxx : xxxxx erytrocyt xxxxxxxxxxxx xxxxxxxx, xxxxx xxx rozlišit xx xxxxxxxxx polychromatických erytrocytů xxxxxxxx xxxxxxxxxxx pro xxxxxxxx.

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx vystaví zkoušené xxxxx. Xxx xxxxxxx xxxxxx xxxxx xx xxxxxxx xx xxxxxxx xxxxxxxx xx xxxxxxxx xxxxxx, odebere xx xxxxxx dřeň, připraví xx xxxxxxxxx a xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx použití xxxxxxxxx xxxx se xxxx xx vhodném xxxxxxxx xx expozici odebere, xxxxxxxxxx xx xxxxxxxx xxxxxxxx a xxxxxx xx (4, 8, 9, 10). Při xxxxxxxx x xxxxxxxxx xxxx xx měla xxxx xxxxxxxx expozicí x xxxxxxxxx xxxxx xxxxxxxx co xxxxxxxxx xxxx. Xxxxxxxxx xxxx xxxxxxxxxxx xx přítomnost xxxxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx xxxxxxx xxxxxx xxxxx se xxxx xxxxxxxxx zvíře xxxxxxxxxx xxx xxxx xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxxx druh. Při xxxxxxx periferní xxxx xx xxxxxxxxxx myš. Xxx však xxxxxx xxxxxxxx xxxxxx xxxx xxxxx za předpokladu, xx xxx x xxxx, x xxxxx xxxxxxx neodstraňuje erytrocyty x xxxxxxxxxx, xxxx xxxx vykazující xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx způsobují xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Měly xx xxx použity xxxxx xxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx minimální x xxxxxx xx x xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx zvířata xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x skupinu, x xxx xx xxxxxxx xxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx. Xxxxx xx uspořádají xxx, xxx xxx xxxx xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx by měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x popřípadě xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx před xxxxxxx xxxxxxx. Měly xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx nemělo xxx xxx použitých xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx podezření, xx xxxxxxx se xxxxxxxxx látkou. Xxxx-xx xxxxxxx xxxx xxx xxxxx rozpouštědla/vehikula, xxxx xx být jejich xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

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

Xxxxxxxxx xxxxxxxx by měly xxxxxxxxxx xxxxxxxxxx xx xxxx při xxxxxxxxxxx xxxxxxxx, x xxxxx xx očekává, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx identifikace xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxx způsobem xxx xxxxxxxx látka x xxx xxx xxxxx v xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx xxxx xxx xxxxx x xxxxx xxxxxxx chemických xxxxx ze xxxxxx xxxxxxxx xxxxx, jsou-li x dispozici. Příklady xxxxx pro xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx xxx být xxxxxxxx odběr x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx aplikováno xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxx xxxxx xxxxxxxxxx stejný xxxxxx xxxx exponované xxxxxxx, xxxxx nejsou x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx buněk x xxxxxxxxxx. Xxxxxxx-xx se xxx negativní xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx okamžikem xxxx xxxxxxx odběru. Kromě xxxx by měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx dosud xxxx xxxxxx-xx publikovány kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx xxxx xxxx xxx jako xxxxxxxxx xxxxxxxx přijatelný xxxx xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx x xxxxxxxx xxxxxx s xxxxxxxxx xxxx (xxxx. 1 — 3 xxxxxxxx) xx předpokladu, že xxxxxxxx údaje budou x xxxxxxx, které xx na xxxxxxx xxxxxxxxxxx xxxxxxx očekává.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx xxxxxx

Xxxxx exponovaná x kontrolní xxxxxxx xx xxxx xxxxxxx x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx pohlaví (11). Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx ze xxxxxx xx stejným xxxxxx a xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, jež xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx rozdíl x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx jednoho xxxxxxx. Xx-xx expozice xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx xx xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx doporučit xxxxx xxxxxxxxxx xxxx (xx. xxxxx, xxx xxxx tři aplikace x intervalu 24 xxxxx). Vzorky xx xxxxxx x prodlouženým xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxxx xx x xxxxxx xxxxxx xxxxxxx pozitivní xxxxxxxx, xxxx –x případě xxxxxxxxxxx studií — xxxxx xxxx prokázána xxxxxxxx xxxx xxxx xxxxxxxxx limitní xxxxx x xxxxxxxx pokračuje xx xx okamžiku xxxxxx. Zkoušené látky xxxxx být xxxxxxxx xxxx xx dvou xxxxxxx, tzn. xxx xxxxx x xxx xxx v xxxxxxx xx více než xxxxxxxx xxxxx, aby xxxx xxxxxxxxx podávání xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx xxx proveden xxxxx xxxxxxx:

x) xxxxxxxx xxxxx xx aplikuje xxxxxxxx xxxxxx. Vzorky xxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 24 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx xxxxxxxx x x přiměřeným xxxxxxxx xxxx xxxxxx. Odběr xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx xxxxxxxxx krve xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx se xxxxxxx xxxxxxxx 36 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx xx aplikaci x xx xxxxxxxxxxxx xx xxxxxx xxxxxxxxxxxx xxxxxx. Je-li xx xxxxxx xxxxxx pozorována xxxxxxxxx odpověď, není xxxxx odběr nutný;

b) xxxx-xx xxxxxxxx xxx xxxx více xxxxx xxxxx (xxxx. xxx xxxx xxxx xxxxx x xxxxxxxxx 24 xxxxx), xxxx xx xxx xxxxxx při xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx xx 18 xx 24 xxxxxxxx po xxxxxxxx xxxxxxxx a xxx xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 hodinách xx xxxxxxxx aplikaci (12).

Xxxxx xxxxxxx xxxxx xxx xxxxx xxxxxxx xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx kvůli xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx studie xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx být xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, pohlavím x za xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx studii (13). X případě toxicity xx pro xxxxx xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx xxxxx by xxxx xxxxxxxx rozpětí xxxx xxxxxxxxx xx xxxxxxxxx toxicitou, případně xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxx stejném režimu xxxxxxxxx xxxxx xxxxxxxxx x letalitě. Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx některé xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx v xxxxxxxxx xxxx).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx o xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo ve xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné toxické xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx podobnou strukturu, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx úplná xxxxxx xx xxxxx úrovněmi xxxxx xx xxxxxxxxx. X déle xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx x xxx xxxxx xxx 14xxxxx aplikaci je xxxxxxx xxxxxx 1000 xx/xx tělesné hmotnosti/den. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x limitní xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Podávání dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx jsou xxxxxxxxxx v odůvodnitelných xxxxxxxxx. Maximální xxxxx xxxxxxxx, který může xxx xxxxxxxx podán xxxxxxxxx sondou xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx měla xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx kostní xxxxx xxxx krve

Buňky xxxxxx xxxxx se xxxxxxx získávají x xxxxxx xxxx xxxxx xxxxx xx xxxxxxxx. Xxxxx xx xxxxxxxx x xxxxxx xxxx xxxxx a zavedenými xxxxxxxx xx preparují x xxxxxx. Xxxxxxxxx xxxx xx xxxxxxx x xxxxxx žíly xxxx jiné vhodné xxxxxx xxxx. Krevní xxxxx se xxxxx xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx připraví xxxxxxxxx xxxxxxxx x poté xx obarví. Xxxxxxxx xxxxxxx xxxxxxxxxxxx pro XXX (xxxx. xxxxxxxxxx xxxxx (14) nebo Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx vyhnout xxxxxxxx xxxxxxxxxx xxxxxxxx x xxxxxxxx barviva nespecifického xxx XXX. Xxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxx (např. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. xxxxxxxxxx kolona x odstranění buněk xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx za xxxxxxxxxxx, xx xx xxxxxxxxx odpovídající funkčnost xxxxxx systémů pro xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx každé xxxxx xx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x celkového (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx xx x xxxxxxx xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 erytrocytů x x xxxxxxx xxxxxxxxx xxxx xxxxxxx 1000 xxxxxxxxxx (17). Xxxxxxx preparáty xxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx pod xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxx alespoň 2000 xxxxxxxxx xxxxxxxxxx na xxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxxxxxxxx. Další xxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx. Xxx xxxxxxxxxxxxx xxxxxxx xx xxxxx být xxxxx xxxxxxxxx xxxxxxxxxx x celkového množství xxxxxxxxxx menší xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxx také xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx na xxxxx xxxxx. Systémy xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx x xxxxxxxxx cytometrická analýza xxxxxxx xxxxxxxx) xxxx xx xxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx být xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxxxxxxxx xxxxx xx xxx xxx xxxxxx xxxxx vyšetřených xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx x počet xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx nepřetržitě čtyři xxxxx xxxx déle, xxxx xx xxx xxxx xxxxxxx údaje x xxxxxxx xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx xxxxx xx xxxxx podíl nezralých xxxxxxxxxx z celkového xxxxxxxx xxxxxxxxxx a xxxxxxxx xxxxxxxx erytrocytů x xxxxxxxxxx xxxxxxxxx x procentech. Xxxxxxxxxx-xx xxxxx x rozdílu x odpovědi xxxx xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx analýzu xxxxx xxx xxx xxxxxxx zkombinována.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxx xxxxx x mikrojádry x xxxxxxxxxx xx xxxxx nebo jasný xxxxxx xxxxx xxxxx x mikrojádry pro xxxxxxx x xxxxxxx xxxxxx a x xxxxxxxx okamžiku xxxxxx. Xxxxxxxx xx měla xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (18, 19). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx vyjasněny xxxxxx xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx látka, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, xx xxxxxxxx v xxxxx xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx pozitivní nebo xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu na xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx na mikrojádra xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx mikrojádra, xxx jsou xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx.

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

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x pohlaví xxxxxx,

- xxxxx, podmínky chovu, xxxxxx xxx.,

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

Zkušební podmínky:

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

- xxxxx ze xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx byla xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx xxxxxx dávek,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx způsobu podávání,

- xxxxxxxxx xxxxxx ověření, xxx xx xxxxxxxx xxxxx xxxxxxx do xxxxxxxx oběhu xxxx xx xxxxxx tkáně,

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

- podrobné xxxxx o xxxxxxx xxxxxx x vody,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx přípravy preparátů,

- xxxxxx stanovení xxxxxxxx,

- xxxxxxxx xxxxxxxxx mikrojader x xxxxxxxxx erytrocytech,

- xxxxx analyzovaných xxxxx xx jedno xxxxx,

- xxxxxxxx klasifikace xxxxxx xx pozitivní, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx erytrocytů,

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

- xxxxxxx xxxxxxx ± xxxxxxxxxx xxxxxxxx počtu xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx statistické analýzy x metody,

- xxxxx x xxxxxxxx a xxxxxxxxx negativní xxxxxxxx,

- xxxxx o souběžné xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

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

4) Xxxxxxxxx, X. X., Xxxxxx, D. X., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxx, J. A. (1990), Xxx In xxxx Xxxxxxxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxxxx xxx Xxxxxxxxxx Xxxxx. A xxxxxx xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 239, 29-80.

5) XxxXxxxxx, X. X., Xxxxxxxx, X., Xxxx, X. X., Xxxx, X. M. (1983), Micronuclei in Xxxxxxxxxxx Xxxxxxxxxxxx: A Xxxxx Xxxxxx for Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Toxicity Testing xx Mice, in: Xxxxxxxxxxxx xx Xxxxxxx xxx Practice xx Xxxxxxxxxx, xx. X. X. Hayes, R. X. Xxxxxxx, T. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) MacGregor, X. X., Xxxxxx, X. X. Hite, X., Xxxxxxxx, G. X., Ramel, X., Xxxxxxxx, M. X., Xxxx, X. X., Xxxx, X. (1987), Xxxxxxxxxx for the Xxxxxxx of Micronucleus Xxxxxx in Xxxxxxxxx Xxxx Marrow Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) XxxXxxxxx, X. X., Xxxx, C. X., Henika, P. X., Xxxxxx, M. X. (1990), Xxx xx vivo Xxxxxxxxxxx Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Xxxxxx State Xxxxxxxxx Assay Efficiency xxx Xxxxxxx Integration xxxx Xxxxxxxx Xxxxxxx, Xxxxxx. Appl. Xxxxxxx. 14, 513-522.

8) Xxxxxxx, X., Xxxxxx, T., Xxxxxx, Y., Xxxxxx, X., Ishidate, M. Xx. (1990), Xxx Xxxxxxxxxxxx Xxxxx with Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxxx Using Xxxxxxxx Xxxxxx-Xxxxxx Slides, Xxxxxxxxxx Xxx., 245, 245-249.

9) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx xxx the Xxxxxxxxxxxx Xxxx (1992). Xxxxxxxxxxxx Xxxx xxxx Xxxxx Peripheral Blood Xxxxxxxxxxxx xx Acridine Xxxxxx Supravital Xxxxxxxx: Xxx Xxxxxxx Xxxxxx xx xxx 5th Xxxxxxxxxxxxx Study xx XXXXX/XXXXX, XXX, Mutatation Xxx., 278, 83-98.

10) Xxx Collaborative Xxxxx Xxxxx for xxx Xxxxxxxxxxxx Test (XXXXX/XXXXX, XXX: The Xxxxxxxxx Xxxxxxxxxxx Xxxxx Xxxxx xx xxx Environmental Xxxxxxx Xxxxxxx xx Xxxxx) (1995), Protocol xxxxxxxxxxx xxx xxx xxxxx-xxxx xxxxx xxxxxxxxxx xxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Xxxx, X. X., XxxXxxxxx, X. X., Anderson, X., Xxxxxxx, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx, Xx. X. X., Xxxxxxxxxxxx, X., Xxxxxxx, F., Xxxxxxx, X., Xxxxx, S., Xxxxxxx, X. (1994), Xx vivo Rodent Xxxxxxxxxxx Xxxxxxxxxxxx Xxxxx, Xxxxx. Xxx., 312, 293-304.

12) Xxxxxxxxxxx, X., Xxxxx, S. (1995), Xx xxxxxxx, xxxxxxxxxxx xxxxxxxx xxxx xx 30 ± 6 x xxxxx xxxxxx xxxxxx in the xxxxx peripheral xxxxxxxxxxxx xxxx, Mutagenesis, 10, 313-319.

13) Xxxxxxx, X. X., Xxxxx, J. X., Boobis, X. X., Xxxxxx, X. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. J., Xxxxxxx, X. (1992), Xxxxxx xx British Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Setting xx Xx vivo Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

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

15) XxxXxxxxx, J. X., Xxxx, X. X., Xxxxxxxx, R. X. (1983), X Simple Xxxxxxxxxxx Xxxxxxxx Xxxxxxxxx xxx Micronuclei xxx XXX xx Erythrocytes Xxxxx Hoechst 33258 xxx Xxxxxxx Y, Xxxxxxxx Res., 120, 269-275.

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

17) Xxxxxxxxx, X., XxXxxxxx, X. X. (1995), Sample Xxxx xxx xxx Xxxxxxxxxx xx Xxxxxxxxxxxxx xx Normochromatic Erythrocyte Xxxxx in xxx Xxxx Xxxxxx Micronucleus Xxxx, Xxxxxxxxxx Xxx., 347, 97-99.

18) Richold, X., Xxxxx, J., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxxx Assay, xx: X. X. Xxxxxxxx (xx.), Xxxxx Mutagenicity xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Report, Xxxx 1, xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Chester, Melbourne, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, R., Xxxxxxxx, G. X., Xxxxx, X., Ferguson X., Richold, M., Xxxxxxxx, X. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Testing. Xxxxxx, Xxxx III, Xxxxxxxxx University Press, Xxxxxxxxx, Xxx York, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

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

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX XX 471 — Zkouška xx xxxxxxxx mutace s xxxxxxxxxx (1997).

1.1 ÚVOD

Při xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Xxxxxxxxxx typhimurium x Xxxxxxxxxxx xxxx, x xxxxxxx xxxxxxxx xxxxxx, které zahrnují xxxxxxxxxx, xxxxx x xxxxxx jednoho xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Podstata této xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxx x detekci xxxxxx, xxxxx xxxxxxxxx xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxx x xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx aminokyseliny. Bakterie xx xxxxxxx xxxx xxxxxxxxxx xxxx xxx xxxxxxxxxx xxxx x xxxxxxxxxxxxx aminokyselin, xxxxx xxxx xxxxxxxxxx mateřským xxxxxxxxxx xxxxxx.

Xxxxxx xxxxxx x podobné jevy xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx xxxxxx x tom, že xxxxxx xxxxxx x xxxxxxxxxx x x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx xxxx xxxxx xx xxxxxx xxxxxxxx x člověka x u xxxxxxxxx xxxxxx. Zkouška xx xxxxxxxx mutace x xxxxxxxxxx xx xxxxxx, xxxxxxxxxx x xxxxxxxxx xxxxxx. Xxxxx xxxxxxxxxxx xxxxx xx řadu xxxxxxxxxx, díky nimž xxxx citlivější xx xxxxxxx mutací, xxxxxx xxxxxxxxxxxxx sekvencí XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxxxxxxxx x xxxxxx. Xxxxxxxxxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxx x xxxxxx xxxxxx, xxx jsou indukovány xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx reverzní xxxxxx x bakteriemi xx k xxxxxxxxx xxxxx xxxxxxxx databáze xxxxxxxx xxx širokou xxxxx xxxxxxxx x xxxx xxxx vyvinuty xxxxx vyzkoušené xxxxxx xxxxxxxx xxxxxxxxxx látek, xxxxxx xxxxxxxx sloučenin, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, část X.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx Xxxxxxxxxx typhimurium xxxx Xxxxxxxxxxx xxxx slouží x xxxxxxx xxxxxx x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (xxxxxxxx xxxx. xxxxxxxxx), přičemž xxxxxx xxxx nezávislý xx xxxxxxx xxxxxxx xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx xxxx xxxxxxxx, xxx xxxxxxxxx změny x xxxxxx XXX. Xxx xxxxxxx xxxxxxxxxx xxxxxx xx xxxxx tyto xxxxx vyskytnout xx xxxxx původní xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx genomu.

Posunové xxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxx nebo xxxx párů bází XXX x xxxxxxxx xxx xxxxx rámec XXX.

1.3 XXXXXXX ÚVAHY

Při xxxxxxxxx na xxxxxxxx xxxxxx s bakteriemi xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx se xxxx xx xxxxx xxxxx xxxxxxx, xxxx xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx struktura x xxxxxxxxx xxxxxxx DNA. Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího zdroje xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx nemohou xxxxx xxxxxxxxx xxxxxxxx in xxxx u savců. Xxxxxxx xxxx neposkytuje xxxxxx xxxxxxxxx x xxxxxxxxxx x karcinogenním xxxxxxxxxx látky xxx xxxxx.

Xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx zpravidla xxxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx, a xxxxxxx aktivity vyvolávající xxxxxx xxxxxx. X xxxxxxxx databáze vyplývá, xx xxxxx chemických xxxxx, které jsou x xxxx zkoušce xxxxxxxxx, vykazuje xxxxxxxxx xxxxxxxx x v xxxxxx xxxxxxxxx. Existují xxxxxxxx mutagenních xxxxxxxx, xxxxx xxxxxx detekovány xxxxx xxxxxxxx. Xxxxxxx xxxxxx xxxxxxxxxxx xxx xxxxxxxxx ve xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx xxxx, x rozdílech x xxxxxxxxxxx xxxxxxxx xxxx x rozdílech x xxxxxxxxxx dostupnosti. Xx xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxx xxxxxxx xx reverzní xxxxxx xx xxxxxxxxxx, xxxxx vést x xxxxxxxxxxxx xxxxxxxxx aktivity.

Zkouška xx reverzní xxxxxx x xxxxxxxxxx nemusí xxx xxxxxx xxx xxxxxx třídy xxxxxxxxxx xxxxx, například vysoce xxxxxxxxxxxx xxxxxxxxxx (např. xxxxxx xxxxxxxxxxx) x xxx xxxxxxxx xxxxx, x xxxxx xx xxxxxxxxxxx (nebo x xxxxx xx xx), xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx systému xxxxx xxxxx (např. xxxxxxx xxxxxxxxxx topoisomerasy x xxxxxxx xxxxxxx xxxxxxxxxx). X xxxxxxxx xxxxxxxxx xxxxx být xxxxxxxxx zkoušky mutagenity x xxxxx.

Xxxxxxxx xxxxx xxxxxxxxx, pro xxx xx xxxx xxxxxxx xxxxxxxxx, je xxxxxxxxxxxx xxx savce, xxxx xxxxxxxx xxxxxxxxx. Závisí xx chemické xxxxx x xxxxxxxx xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx touto xxxxxxxx, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx mechanismy, nebo xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx buňkách xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx buněk jsou xxxxxxxxx xxxxxxxx látce, x xx xx xxxxxxxxxxx vnějšího xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx x xxx xxxx. Xx xxxxxxxxxxx miskovém xxxxx xx xxxxxxxx xxxxxxxx x xxxxxxx agarem x xxxxx se xxxxxxx xx minimální xxxx. X xxxxxxxxxxxx xxxxxx xx xxxxxxxx xxxx xxxxxxxx a xxxx xx před xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx s xxxxxxx xxxxxx. Xxx xxxx xxxxxxxxxx xx xx xxxx xxxx xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx revertantů x xxxxxxx xx xxxxxxxx x počtem xxxxxxx spontánních revertantů xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

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

Xxx xxxxxxx xxxxxxx se xxxxxx hlavně standardního xxxxxxxxx xxxxx a xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx xx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx jak x xxxxxxxxxxxx aktivací, tak xxx xx. Některé xxxxx xxx xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx metody. Xxxx xxxxx xxxxx do xxxxxxxxxx xxxx, xx xxxxx xxxxx xxxx xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx xxxx, xxxxxxxx, xxxxxxxxxx x xxxxxxxxxx sloučeniny, xxxxxxxxxxxxxxx xxxxxxxxx, allylové xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx xxxxxxxxx, xx xxxxxx xxxxx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx xx standardní xxxxxxx xxxx nebo xxxxxxxxxxxx xxxxxx. Xxxx xx být považovány xx "xxxxxxxx xxxxxxx" x x xxxxxx xxxxxxx xx důrazně xxxxxxxxxx použít xxxxxxxxxxxx xxxxxxx. Je xxxxx xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (společně s xxxxxxxx xxxxxxx jejich xxxxxxx): azobarviva x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Odchylka xx xxxxxxxxxxxx postupu xxxx xxx xxxxxxx xxxxxxxxxx.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxxx do xxxxxx xxxxxxxxxxxxx xxxx xxxx xx xxxxx xxxxxxxxxxx fáze xxxxx (xxxxxxxxx 109 xxxxx xx xx). Buňky x pozdní stacionární xxxx xx xxxxxx xxx xxxxxxx. Je xxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx xxxxxx xxxx životaschopných xxxxxxxx. Xxxx může být xxxxxxxx xxx na xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, nebo xxx xxxxxx zkoušku xxxxxxxxxx xxxxx životaschopných xxxxx xx xxxxxxx.

Xxxxxxxxxx inkubační xxxxxxx xx 37 °X.

Xxxx by xxx xxxxxxx xxxxxxx xxx xxxxx bakterií. Mezi xxxx by xxxx xxx xxxxx xxxxx X. xxxxxxxxxxx (XX1535; XX1537 xxxx TA97a xxxx TA97; TA98 x XX100), xxxxxxx xxxxxxx xx ukázala x xxxxxxx laboratořích xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx X. xxxxxxxxxxx xxxx xxx xxxx XX xx xxxxxxxxx xxxxxxxxx xxxxx a xx xxxxx, že xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, činitele způsobující xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Tyto xxxxx mohou být xxxxxxxxxx kmeny X. xxxx XX2 nebo X. typhimurium TA102 (19), xxxxx mají xx primárním xxxxxxxxx xxxxx pár xxxx XX. Doporučená xxxxxxxxx xxxxx je xxxx xxxx:

- X. xxxxxxxxxxx XX1535 x

- X. xxxxxxxxxxx XX1537 nebo XX97x x

- S. xxxxxxxxxxx TA98 x

- X. typhimurium TA100 x

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

Pro xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx DNA xxxx xxx vhodnější xxxxxxx TA102 xxxx xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx reparace XXX, (xxxx. X. xxxx XX2 (xXX101)).

Xxxx xx xxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx kmenové xxxxxxx, xxxxxxxxxx markeru x skladování. Xxxxxxx xxxxxxxxxxxxx xxx růst xx xxxx xxx xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx xxx kmeny X. typhimurium x xxxxxxxxx xxx X. xxxx). Xxxxxxx xx xxxx xxx xxxxxxxxxxxx xxxx fenotypové xxxxxxxxxxxxxxx, xxxxxxxxx xxxxx xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (tj. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, TA100 x TA97a nebo XX97, WP2 xxxX x XX2 xxxX (xXX101) x ampicilinová x xxxxxxxxxxxxxx xxxxxxxxxx x kmene TA102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. xxx xxxxxx x X. typhimurium xxxxxxxxxx na xxxxxxxxxxx xxxxxx a uvrA xxxxxx u E. xxxx xxxx xxxX xxxxxx u X. xxxxxxxxxxx xxxxxxxxxx na xxxxxxxxxxxx světlo) (2, 3). Xxxxx xx xxxx xxxxxx xxxxx xxxxx kolonií spontánních xxxxxxxxxx na misce x xxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxx laboratorních xxxxxxx x nejlépe x xxxxxxx xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx xxxxxxxxx xxxx (např. xxxxxxxxxx xxxxxxxxx xxxx X (Xxxxx-Xxxxxx) x xxxxxxx) x vrchní xxxx xxxxxxxxxx xxxxxxxx x xxxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxx buněčných xxxxxx (1, 2, 9).

1.5.1.3 Metabolická xxxxxxxx

Xxxxxxxx xx xxxx být xxxxxxxxx xxxxxxxx látce, x to x xxxxxxx systémem xxxxxxxxxxx xxxxxxxx x xxx xxxx. Xxxxxxxxxx používaným xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx frakce (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx enzymy, xxxx xx Aroclor 1254 (1, 2) xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx frakce xx xxxxxxx xxxxxxxxx x koncentracích x xxxxxxx 5 až 30 % xxx. xx směsi X9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx na xxxxx xxxxxxxx xxxxxxxx xxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. X xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx může být xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx před xxxxxxxx xx bakterie xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx vehikulech a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx mohou xxx xxxxxxx xxxxx x testovacím xxxxxxxx x/xxxx xxxxx xxx xxxx aplikací xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxxxxx x s xxxxxxxxx S9 (22). Xxxx-xx xxxxxxx xxxx xxx xxxxx rozpouštědla/vehikula, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx. Xxx zkoušení xxxxx xxxxxxxxx ve xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Xxxxxxxx xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx v předběžných xxxxxxxxxxxxx. Xxxxxxxxxxxx xxxx xxx detekována snížením xxxxx kolonií xxxxxxxxxx, xxxxxxxxx nebo zeslabením xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx xx xxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx xx xxxx xxx posouzena xx xxxxxxx viditelného xxxxxxx x xxxxxxx směsi xx xxxxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx maximální zkušební xxxxxxxxxxx xxx rozpustné xxxxxxxxxxxxx látky xx 5 xx/xxxxx nebo 5 μl/misku. X xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx koncentracích 5 xx/xxxxx xxxx 5 μx/xxxxx xx xxxx xxx jedna nebo xxxx zkušebních xxxxxxxxxxx xxxxxxxx, xxx xxxxx xxxx x konečné xxxxx xxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxxxx xxx při koncentracích xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx, xx xxxx xxx xxxxxxxx až xx xxxxxxxxxxx koncentrace. Xxxxxxxxx by xxxxxx xxxxx při vyšetřování.

Mělo xx být xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx koncentrací xxxxxxxx xxxxx, přičemž xxx xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx xxxx zkušebními body xxxxx xxxxxxxxx polovině xxxxx xxxxxxxxxxxx stupnice (xx. Ö10). Menší xxxxxxxxx jsou xxxxxx x případě, xxx xx vyšetřuje xxxxxx xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx xxxx xxx xxxxxxx xxx xxxxxxxxx xxxxx obsahujících xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxx xx měly xxx xxxxxxx specifické xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx x xxxxxxxxxxxx xxxxxxxx a xxx xx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx každé xxxxxxx.

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

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

Xxxxx

Xxxxx XXX

Xxxxx xxxxx EINECS

9,10-dimethylanthracen

781–43–1

212–308–4

7,12-dimethylbenzo[a]anthracen

57–97–6

200–359–5

benzo[a]pyren

50–32–8

200–028–5

2-aminoanthracen

613–13–8

210–330–9

Cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

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

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

XX Xxxxxx Red 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx xx xxxxx xxx použit xxxx xxxxxx xxxxxxxxx xxxxxxxxx xxxxx X9. Xxx xxxxxxx 2-aminoanthracenu xx xxxx být xxxxx xxxxx X9 charakterizována xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxx mikrosomálními xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-dimethylbenzo[a]anthracen.

Příkladem xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx u xxxxxxx xxx xxxxxx xxxxxxxxxxx aktivace xxxx xxxx látky:

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

Xxxx

xxxx xxxxx

26628–22–8

247–852–1

XX1535 x XX100

2-xxxxxxxxxxxx

607–57–8

210–138–5

XX98

9-xxxxxxxxxxxx

90–45–9

201–995–6

XX1537, XX97 x TA97a

ICR 191

17070–45–0

241–129–4

XX1537, XX97 x XX97x

Xxxxxxxxxxxxxxxxx

80–15–9

201–254–7

XX102

xxxxxxxxx X

50–07–7

200–008–6

XX2xxxX x XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 uvrA x XX2 xxxX (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 xxxX a XX2 xxxX (xXX101)

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

3688–53–7

xxxxx obsahující xxxxxxxx

Xxx xxxxxxxxx kontrolu xxxxx xxx použity jiné xxxxxx referenční xxxxx. Xxx xxxxxxxxx kontrolu xx xxxx xxx xxxxx v xxxxx xxxxxxx chemických xxxxx xx xxxxxx chemické xxxxx, xxxx xx x xxxxxxxxx.

Xxxx xx xxx xxxxxxx negativní xxxxxxxx xxxxxxxxxx se xx xxxxxxxxx rozpouštědla xxxx xxxxxxxx, bez xxxxxxxx xxxxx, zpracované xxxxx xxxxxxx způsobem xxxx xxxxxxxxxx skupiny. Xxxxx xxxx by xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, neexistují-li xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné zhoubné xxxx mutagenní xxxxxx.

1.5.3 Xxxxxx

X xxxxxxxxxx xxxxxxx xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx aktivace se xxxxxxx xxxxxx 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 xx čerstvé xxxxxxxxxxx kultury (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x 0,5 xx xxxxxxxxxx xxxxx x 2,0 xx xxxxxxxx agaru. X xxxxxxx xxxxxxx x xxxxxxxxxxxx aktivací xx xxxxxxx smíchá 0,5 xx metabolické aktivační xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx frakce (x xxxxxxx 5 xx 30 % xxx. v xxxxxxxxxxx xxxxxxxxx směsi) x xxxxxxx xxxxxx (2,0 xx) x xxxxxxx x xxxxxxxxxx x xxxxxxxxx látkou xxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxx xxxxxxxx xx xxxxxxxx x xxxxxxx xxxx xxxxxx minimálního xxxxx na xxxxx. Xxxx xxxxxxxx xx xxxxx xxxxxx xxxx xxxxxxxx.

X preinkubační xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx zkoušený xxxxxx před xxxxxxxxx x xxxxxxx agarem x xxxxxxxx xxxx xxxxxx xxxxxxxxxxx agaru xx xxxxx xxxxxxx 20 xxxxx xxxx xxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxx (xxxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) x sterilním xxxxxx xxxx metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) xxx 30 — 37 °X. Xxxxxxx se xxxxxx 0,05 nebo 0,1 xx xxxxxxxx xxxxx xxxx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxxx x 0,5 ml xxxxx X9 nebo xxxxxxxxxx pufru s 2,0 ml xxxxxxxx xxxxx. Zkumavky xx xxxx xxx během xxxxxxxx xxxxxxxxxxxxxx na xxxxxxxx.

X dostatečnému odhadu xxxxxxxx xx xxxx xxx při xxxxx xxxxxx xxxxx použity 3 misky. Xxxxxxx xxxx misek xx xxxxxxxxxx po xxxxxxxx xxxxxxxxxx. Xxxxxxxx ztráta xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxx.

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

1.5.4 Xxxxxxxx

Xxxxxxx misky v xxxx zkoušce xx xxxx být xxxxxxxxxx xxx 37 °X xx 48 –72 xxxxxxxx. Xx uplynutí xxxxxxxxx xxxx xx xxxxxx počet xxxxxxx xxxxxxxxxx xx misku.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxxxx xxxxxxxxxx připadající xx xxxxx. Xxx xx xxx rovněž uveden xxxxx xxxxxxx xxxxxxxxxx xxx xx miskách x xxxxxxxxx xxxxxxxxx (xxxxxxxx xxxxxxxxxxxx a xxxxxxxx neexponovaná kontrola), xxx xx xxxxxxx x xxxxxxxxx xxxxxxxxx. Xxxxx na xxxxxxxxxxxx xxxxxxx, střední xxxxxxx xxxxx kolonií xxxxxxxxxx xx xxxxx a xxxxxxxxxx xxxxxxxx by xxxx být xxxxxxxxxx xxx xxxxxxxxx látku x xxxxxxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx a/nebo kontrolu xxxxxxxxxxxx).

Xxxxxxx jasně pozitivní xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx být xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx se xxxxxxxxx xxxxxxxxxxx xxxxxxxx nepovažuje xx xxxxxxxx, xxxx xx xxx podáno xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx s xxxxx xxxxxxxx rozsah xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx studie, které xx mohly xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx xxxxxxx xxxxxx xxxx preinkubace x xxxxxxxx xxxxx) a xxxxxxxx metabolické aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx nad xxxxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx nebo xxx xxxx, a xx x závislosti na xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx tohoto počtu xxx xxxxx xxxx xxxx koncentrací (23). Xxxxxxxx xx měla xxx xxxxxxx biologická xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx být použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx významnost xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx negativní xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxx kmenů Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx coli bodové xxxxxx xxxxxxxxxx xxxx xxxx posunem čtecího xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxx za xxxxxxxx zkoušky xxx xxxxxxxxx druhy xxxxxxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx musí xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx v xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxx xxxxx,

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

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx počtu kolonií xxxxxxxxxx xx misku x xxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx na dávce,

- xxxxxxxx statistické xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxx, X. N., McCann, X., Xxxxxxxx E. (1975), Methods xx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Xxx., 31, 347-364.

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

3) Gatehouse, X., Xxxxxxx, X., Xxxxxx, X., Gocke, X., Xxxx, L., Xxxxxxxxxx, X., Melcion, X., Xxxxx, X., Venitt, X., Zeiger, E. (1994), Recommendations for xxx Performance xx Xxxxxxxxx Xxxxxxxx Xxxxxx, Xxxxxxxxxx Res., 312, 217-233.

4) Xxxx, X. X., Xxxxxxx X. X., Auletta, X. X., Von Halle, X. X., Brown, X. X., Xxxxxx, X. X., Xxxxxx, X., XxXxxx, J., Xxxxxxxxxx, K., Xxxxxx, X., Xxx, X. X., Ray V. (1986), The Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Assay: X Report of xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, X., Degawa, X., Seino, Y. X., Xxxxxxxxxx, T., Xxxxx, M., Xxxxxxxx, X., Hashimoto, X. (1975), Xxxxxxxxxxxx xx Xxxxxxxxxx Xxx Xxxx xxx their Derivatives, Xxxxxx Lett. 1, 91-96.

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

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

8) Aeschacher, H. X., Xxxxxx, X., Xxxxxxx, L. (1987), Xxxxxx Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxx xxx Foods, X. Food Xxxxxx., 8, 167-177.

9) Xxxxx, X. X. X., Xxxxxx, X. J., Xxxxxxx, X. X. (1976), Use of x simplified xxxxxxxxxxx xxxx to xxxxxx xxx levels of xxxxxxxx, Mutatation Xxx., 38, 33-42.

10) Xxxxxxx, X. X., Xxxxx, X. X. L., Xxxxxxxxx, D., Bridges, X. W. (1984), Xxx Xxxxxxxxxxx Test xx Xxxxxxxx, xx: Xxxxxxxx of Xxxxxxxxxxxx Xxxx Procedures, 2. xxx., Xxxxxx, X. X., Legator, X., Xxxxxxx, X., Xxxxx, X. (eds.), Elsevier, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, X. X., Xxxxxxx, X. J. (1981), Xx Xxxxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxxx Assay for Xxxxxxxxxxx xxxx Xxxxxxx xx Salmonella typhimurium, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Araki, A., Xxxxxxx, T., Kato, X., Matsushima, X. (1994), Improved Xxxxxx xxx Mutagenicity Xxxxxxx xx Xxxxxxx Xxxxxxxxx xx Xxxxx x Xxx Sampling Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

13) Prival, M. X., Xxxx, S. X., Xxxxxxxx, V. X., Xxxxxxx, M. X., Xxxxxxx, X. X. (1984), Xxxxxxxxxxxx xx Xxxxxxxxx and Xxxxxxxxx-Xxxxxxxx Dyes xxx Xxxxxxxx Monoazo Xxxx xx a Xxxxxxxx Xxxxxxxxxx Assay, Xxxxxxxxxx Xxx., 136, 33-47.

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

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

16) Xxxxxx, X. J., Xxxxxxx, X. M., Xxxxxxxx, X. X., Claxton, X. D. (1987), Xxxxxxxxxxxx Technique xx Xxxxxxx Mutagenic Xxxxxxxx xx Volatile Xxxxxxx Xxxxxxxxx xx xxx Xxxx/Xxxxxxxxxx Xxxxx, Environmental Xxxxxxxxxxx, 9, 421-441.

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

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

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

20) Xxxxxxxxxx, T., Xxxxxxxx, M., Hara, X., Sugimura, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. s. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, xx: Xx vitro Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Testing, eds. X. X. xx Xxxxxx et xx. Xxxxxxxx, Xxxxx Holland, 85-88.

21) Elliot, X. X., Xxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, G. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Alternatives xx Aroclor 1254-xxxxxxx X9 xx xx xxxxx Genotoxicity Assays, Xxxxxxxxxxx, 7, 175-177.

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

23) Xxxxxxx, X. D., Allen, X., Auletta, X., Xxxxxxxxxx, X., Xxxxxxxx, X., Zeiger, X. (1987), Guide for xxx Xxxxxxxxxx typhimurium/Mammalian Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Xxxxxxxxxxxx, Mutatation Xxx., 189, 83-91.

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


XXXXXXX 4E

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

1. XXXXXX

Xxxx metoda xx replikou metody XXXX XX 476 — Xxxxxxx xx xxxxxx mutace x xxxxxxx savců xx xxxxx (1997).

1.1 ÚVOD

Zkoušku xx genové xxxxxx x xxxxxxx xxxxx xx vitro xxx xxxxxx pro xxxxxxx xxxxxxxx mutací xxxxxxxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxx xxxxxxx X5178X xxxx, xxxxxxx xxxxx XXX, XXX-XX52 x X79 křečka xxxxxxxx x lymfoblastoidní xxxxx TK6 xxxxxxx (1). U xxxxxx xxxxxxxxx linií xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx mutace xxxx xxx xxxxxxxxxxxxxx (XX) x hypoxanthin-guaninfosforibosyltransferasu (XXXX) x xxxxxxxx xanthin-guaninfosforibosyltransferasy (XXXX). Xxxxxxx xx xxxxxx TK, XXXX x XXXX xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX x XXXX xxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxx xxxxxx), xxxxx xxxxx detekovat v XXXX xxxxxx xx X chromozomech (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx mutace v xxxxxxx savců xx xxxxx lze xxxxxx xxxxxxx xxxxxxxxxx linií xxxxx nebo buněčné xxxxx. Buňky xx xxxxxxxx podle xxxxxxxxxx xxxxx x kultuře x xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx použití xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx nemůže xxxxx xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xx třeba xx xxxxx xxxxxxxxx podmínek, xxxxx xx xxxxx x pozitivním xxxxxxxxx, xxx xxxxxxxxxx vlastní xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx, může xxxxx xxxxxx pH, xxxxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Tato xxxxxxx se xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxxxx. Mnoho xxxxxxxxx, xxx xxx je xxxx xxxxxxx xxxxxxxxx, xxxx xxxxxxxxxxx xxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx důkazy x xxx, že existují xxxxxxxxxxx, které nejsou xxxxxxxx touto xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x bakteriálních xxxxxxx xxxxxxxxxx (6).

Viz také xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxx xxxxxx : xxxxxx mutace xxxxxxxxx typu mutované xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxxxxxx xxxxxxxx kódovaných xxxxxxxx.

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

Xxxxxxxx xxxxxxxx : xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxx nebo více xxxx bází x xxxxxxxx XXX.

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

Xxxxxxx mutantů : xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxxxxx xxxxxxxxxxxxxxx buněk.

Relativní celkový xxxx : nárůst xxxxx buněk x xxxx ve srovnání x xxxxxxxxx xxxxxxxx xxxxx; vypočte xx xxxx xxxxxx poměru xxxxxxxxx xxxxx v xxxxxxxx a x xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.

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

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

Xxxxxxx : xxxxxxxx klonování xxxxx xxx xxxxxxxx xx xxxxx xx konci xxxxxx xxxxxxxx; přežití xx obvykle xxxxxxxxx x xxxxxx k xxxxxxx xxxxxxxxx populace xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, které x xxxxxxxx xxxxxx TK+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) jsou xxxxxxxxxxx k xxxxxxxxxxxx xxxxxxx xxxxxxx pyrimidinu xxxxxxxxxxxxxxxxx (XXX). Buňky xxxxxxxxxxx thymidinkinasu jsou xxxxxxx na XXX, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxx xxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxx tedy xxxxxxx xxxxxxxxxxx xx xxxxxxxxxxx XXX, xxxxxxx normální xxxxx, xxxxx obsahují xxxxxxxxxxxxxx xxxx schopnost xxxxxx. Podobně xxx x xxxxx x xxxxxxxxxxxx XXXX xxxx XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx rezistence x 6-xxxxxxxxxxx (TG) xxxx 8-xxxxxxxxxx (XX). Vlastnosti xxxxxxxx látky by xxxx xxx xxxxxxx xxxxxxx, jestliže je xx xxxxxxx xx xxxxxx xxxxxx v xxxxxxx xxxxx xxxxxxx xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Mělo xx xxx například xxxxxxxxx xxxxxxxx xxxxxxxxx na xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx pro xxxxxxxx xxxx nemutantní xxxxx. Xxx xxxxxxxx chemických xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, xxxx xxxx xxx xxxxxxxxx xxxxxxxx systému xxxx xxxxxxx xxx selekci (8).

Xxxxx x xxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxx xxxx xxxxxxx dobu xxxxxxxxx xxxxxxxx xxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, x subkultivovány xx xxxxxx xxxxxxxxx xxxxxxxxxxxx a xx xxxxxx xxxxxxx fenotypu xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx zjistí xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (přežití) nebo xxxxxxxxxx relativního xxxxxxxxx xxxxx xxxxxx po xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx x růstovém xxxxx xx xxxxxxx xxxx charakteristickou xxx xxxxx xxxxxxx lokus x typ xxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx mutací. Xxxxxxx xxxxxxx xx xxxxxxx xxx, xx xx xxxxxx xxxxx xxxxx xxxxx xx média xxxxxxxxxxxx selekční xxxxxxx xxx detekci xxxxxxxxxx xxxxx x xx xxxxx xxx xxxxxxxxxx xxxxxxx, xxx byla xxxxxxxxx xxxxxxxx klonování (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx se xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx se xxxxxxx x xxxxx xxxxxxxxxx xxxxxxx x selekčním xxxxx x xxxxx xxxxxxx v médiu xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx xxxxxxx x xxxx zkoušce xxxx k xxxxxxxxx xxxxx typy buněk, xxxxxx xxxxxxxx xxxxx X5171X, XXX, XXX-XX52, X79 xxxx XX6. Xxxx xxxxx v xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx schopnost x stabilní frekvenci xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, x x případě kontaminace xx neměly xxx xxxxxxx.

Xxxxxxx xx xxxx xxx navrženy tak, xxx xxxx xxxxxx xxxxxxxxxx xxxxxxxxx x xxxx. Počet použitých xxxxx, xxxxxx x xxxxxxxxxxx xxxxxxxx xxxxx xx xxx xxxx xxxxxxxxxx parametry xxxxxxx (14). Xxxxxxxxx xxxxx xxxxx, xxxxx xxxxxxx xxxxxxxx x xxxxx xxxxx xxxxxxx v xxxxxx xxxxxx xxxxxxx, xx xxx xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx mutací. Xxxxxxx xxxxxxxxx xx, xxx xxx xxxxxx xxxxx xxxxx, xxxxx je xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx spontánních mutací. Xx xxxx doporučeno, xxx bylo xxxxxxx xxxxxxx 106 xxxxx. Xxxx by xxx x xxxxxxxxx xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx buněčném xxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxxx výpovědní hodnota xxxxxxx.

1.4.1.2 Xxxxx a xxxxxxxxxx xxxxxxxx

Xxx udržování xxxxxx xx měla xxx použita vhodná xxxxxxxxxx xxxxx x xxxxxxxxx podmínky (kultivační xxxxxx, xxxxxxxxxxx CO2, xxxxxxx a vlhkost). Xxxxx by xxxx xxx xxxxxxx xxxxx xxxxxxxxxx systémů x xxxx buněk použitých xxx xxxxxxx. Xx xxxxxxx důležité, aby xxxxxxxxxx xxxxxxxx xxxx xxxxxxx xxx, xxx xxxx xxxxxxxxx xxxxxxxxx xxxx xxxxx xxxxx xxxxxx xxxxxxx a xxxxxxxxx jak xxxxxxxxxx, xxx xxxxxxxxxxxx buněk xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx by xxxx xxx xxxxxxxxx z xxxxxxxxx kultur, xxxxxxxx xx xxxxxxxxxxxx xxxxx x inkubovány xxx 37 °C. Xxxx xxxxxxxx v této xxxxxxx může xxx xxxxxxxx odstranit z xxxxxxx xxx xxxxxxxx xxxxxxxx xxxxx.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

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

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % obj. Xxxxx x stav xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx může xxxxxxx na xxxxx xxxxxxxx xxxxx, která xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx použít xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx vývoje, xxxxxx xxxxxxxx geneticky xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx buněčných linií xx xxxx xxx xxxxxxx xxxxxxxxxx (např. xxxxxxxxxxx isoenzymu xxxxxxxxxx X450 xxx metabolismus xxxxxxxx látky).

1.4.1.5 Příprava xxxxxxxx látky

Pevné xxxxxxxx xxxxx by xxxx xxx před xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx rozpouštědlech nebo xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být před xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx xxxxx o stálosti xxxxxxxxxxx možnost skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx být xxxx xxxxxxxxx, že xxxxxxx xx zkoušenou xxxxxx, x mělo xx xxx xxxxxxxxxx x xxxxxxxx xxxxx x x xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx než známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx údaji x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx látek xxxxxxxxx xx xxxx xx xxxx být xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Vodu lze xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Expoziční koncentrace

Mezi xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx nejvyšší xxxxxxxxxxx, xxxxx cytotoxicita, xxxxxxxxxxx x testovacím systému x xxxxx pH xxxx xxxxxxxxxx.

Xxxxxxxxxxxx by xxxx xxx stanovena x metabolickou xxxxxxxx x bez xx x xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, xxxx xxxx relativní xxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx by xxx xxxxxxx alespoň xxxxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx, že xx se xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. Xx-xx maximální koncentrace xxxxxxxx xx xxxxxxxxxxxx, xxxx xx být xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) přežití (xxxxxxxxx xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 mg/ml xxxx 0,01 X, xxxxx xxxx, xxxxx x xxxx xx xxxxxxxx.

Xxxxxxxxx nerozpustné xxxxx xx měly být xxxxxxxx xx k xxxx rozpustnosti xx xxxxxxxxxxxx xxxxxxxx, xxxx xx za xxxx xxx. Xxxx xx xxx stanovena případná xxxxxxxxxxxxx x xxxxxxxx xxxxx, ve kterému xxxx buňky exponovány. Xxxx být výhodné xxxxxxxx xxxxxxxxxxx xx xxxxxxx x na xxxxx aplikace, neboť xxxxxxxxxxx xx xxxx x xxxxxxx expozice x testovacím xxxxxxx xxxxx x důsledku xxxxxxxxxxx xxxxx, X9 xxxx, xxx. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly xxx xxxxxxxxx a negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, tak xxx ní. Xxx xxxxxxx xxxxxxxxxxx xxxxxxxx xx měla být xxxxxxxxx kontrolou xxxxxxxx xxxxx, která x xxxxxxxxx xxxxxxxx vyžaduje xxxxxxxx.

Xxxxxxxxx pozitivní kontroly xxxxx xxx tyto xxxxx:

Xxxx xxxxxxxxxxx aktivace

Lokus

Látka

Číslo XXX

Xxxxx xxxxx Xxxxxx

Xxx xxxxxx metabolické xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx x xxxxx xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X xxxxxx xxxxxxxxxxxx xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (xxxx x xxxxx xxxxxxx)

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

benzo[a]pyren

50–32–8

200–028–5

3-methylcholanthren

56–49–5

200–276–5

XPRT

N-nitrosodimethylamin (xxx xxxxxx xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

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

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

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky xx xxxx xxx xxxxxxxxx zkoušené xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx aktivačního systému, xxx xxx xxxx. Xxxxxxxx xx xxxx xxxxx vhodnou dobu (xxxxxxx xx účinná xxxx 3 xx 6 xxxxx). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx xx xxxxx xxxx více xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxx kultury xxxx jedna xxxxxxxxxx xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, xxx xx xxx počet xxxxxxxxxxx xxxxxx xxx, xxx byl zajištěn xxxxxxxxxxxx počet kultur xxx analýzu (xxxx. xxxxxxx osm analyzovatelných xxxxxxxxxxx). Xxxx xx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx kultury (xxxxxxxx rozpouštědla).

Plynné xxxx xxxxxx xxxxx xx xxxx být xxxxxxxx xxxxxxxx metodami, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx nádobách (21, 22).

1.4.3.2 Stanovení xxxxxxx, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx xxxxx xxxxxxxxx xxxx xx buňky xxxxxxx x kultivují xx účelem stanovení xxxxxxx x xx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx relativní účinnosti xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxxx celkového růstu xxxxxx se xxxxxxx xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx časové xxxxxx, xxx xxxxxxx xxxxxxxxx optimální xxxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (HPRT x XXXX vyžadují xxxxxxx 6 až 8 xxx, XX alespoň xxx xxx). Xxxxx xxxx xxxxxxxxxxx x xxxxx xx xxxxxxxxx xxxxxxxx (xxxxxxxxxx činidly) x bez xxxx (xxx xxxx) za xxxxxx xxxxxxxxx počtu xxxxxxx a xxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (použité pro xxxxxxx xxxxxxxx mutantů) xx xxxxxxx xx xxxxx xxxx exprese xxxxxxxxx xx xxxxx xxx xxxxxxxxxx činidla.

Je-li xxxxxxxx xxxxx xxxxxxxxx xx zkoušce X5178X XX+/-, xxxx xx xxx xxxxxxxxx xxxxxxx xx jedné xx xxxxxxxxxx xxxxxx (x xxxxxxxx pozitivní xxxxxxxxxxx) x xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxx xx xxxxxxx X5178X TK+/- xxxxxxxxx, mělo xx xxx xxxxxxxxx kultury xxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xx xxxxxxxxxxx x pozitivních kontrolách. Xxx xxxxxxxx xx xxxxxxx XX6 TK+/- xxxx xxx xxxx xxxxxxxxx xxxxxxxxx kultury xxxxx xxxxxxxxx xxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xx měly xxxxxxxxx xxxxxxxxx cytotoxicity x xxxxxxxxxxxxxxxx, xxxxx kolonií x četnosti xxxxxxx xxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx odpovědi xx xxxxxxx L5178Y XX+/- xx xxxxxxx xxxxxxxxx alespoň x xxxxx xxxxxxxxxxx xxxxxxxx xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x x xxxxxxxxx x xxxxxxxxx xxxxxxxx za xxxxxxx xxxxxxxx malá xxxxxxx — velká kolonie. Xxxxxxxxxxx a cytogenetická xxxxxx xxx mutantů xxxxxxxxx velké xxxxxxx, xxx xxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxxxx zkoumána (23, 24). Xx xxxxxxx XX+/- jsou xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx kolonie x xxxxxxxxx růstem (xxxxx) x xxxxxxx x xxxxxxx růstem (xxxx) (25). X mutantních xxxxx, xxxxx utrpěly xxxxxxxxxxxxxx xxxxxxxxx poškození, xx xxxxxxxxxxx doby xxxxxxxx, x xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx xx obvykle xxxxxx xx xxxxx xxxxxx xxxx xx xx xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx xxxxxxxxx malé xxxxxxx xx xxxxxxx x xxxxxxxxxx xxxxxxx, xxxxx indukují xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx postižené xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxx xxxxx x xxxxx velké kolonie.

Mělo xx xxx xxxxx xxxxxxx (relativní xxxxxxxx xxxxxxxxx) nebo relativní xxxxxxx xxxx. Četnost xxxxxxx by xxxx xxx xxxxxxxxx jako xxxxx xxxxxxx x xxxxx xxxxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxx. Dále by xxxx xxx všechny xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx odpovědi xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx být xxxxxxxxx xxxxxx xx xxxxxxx. Xxx, xxx xxxx potvrzení negativních xxxxxxxx považováno xx xxxxx, xx xxxxx xxxxx zdůvodnění. Xxxxx xxxxxxxxx xxxxxx x xxxxx rozšířit rozsah xxxxxxxxxxxx podmínek by xxxx xxx xxxxxxx x následných xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, tak xxx xxxxxxxxx výsledky. X xxxxxxxxxx studie, které xx xxxxx xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, xxxx. nárůst xxxxxxxx xxxxxxx v xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx této xxxxxxxx. Nejdříve xx xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx výsledků xxxxxxx mohou být xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx.

Xxxxxxxx látka, xxxxx xxxxxxxx xxxxxxxxx xxxx uvedená xxxxxxxx, xx v tomto xxxxxxx xxxxxxxx xx xxxxxxxxxxx.

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx negativní xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx xx xxxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx odpovědi xx xxxxxxxxxxx je velmi xxxxxxxx. Xxxxxxxxx výsledky xxxxxxxxx, že zkoušená xxxxx xx xxxxxxxx xxxxxxx neindukuje x xxxxxxxxx kultivovaných buňkách xxxxx xxxxxx mutace.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby xxxxxxxxxxxx/xxxxxxxx,

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

Buňky:

- xxx a xxxxx xxxxx,

- počet xxxxxxxxx xxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x xxxxx xxxxxx, xxxxxx např. údajů x cytotoxicitě x xxxxxx xxxxxxxxxxxx, xxxx-xx x dispozici,

- xxxxxxx xxxxx, xxxxxxxx koncentrace XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx vehikula x xxxxxxx xxxxxxxx xxxxx,

- inkubační teplota,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxxxx expozice,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- délka xxxx xxxxxxx (xxxxxxxx xxxxxx xxxxx nasazených xxxxx, xxxxxxxxx x xxxxxx xxxxx),

- selekční xxxxxxx,

- kritéria xxxxxxxxxxx xxxxxxx na pozitivní, xxxxxxxxx nebo xxxxxxxxxxx,

- xxxxxx použité x xxxxxxxx životaschopných a xxxxxxxxxx buněk,

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

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxx xxxxxxx,

- xxxxx x xX a xxxxxxxxxx xxxxx expozice xxxxxxxx látce, xxxxx xxxx xxxxxxxxx,

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

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- případné xxxxxxxxxxx xxxxxxx,

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

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

- četnost mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Chu, X. X. Y., Xxxxxxx X. X. (1968), Xxxxxxxxx Xxxx Xxxxxxxx. XX. Xxxxxxxx Xxxxxxxxx xx Xxxxxxxx Xxxxx Xxxxxxxxx xx Chinese Xxxxxxx Cells In xxxxx, Proc. Natl. Xxxx. Sci. X. X. A, 61, 1306-1312.

3) Xxxxx, H. X., Thilly, X. X. (1982), Xxxxxxxx Xxxxx xx xxx Xxxxxxxxx Kinase Xxxxx xx Xxxxxxx Human Xxxxxxxxxxxx, Xxxxxxxx Xxx. 94, 467-485.

4) Xxxxx, X. X., Xxxxxxxxx-Xxxxx, X., Xxxxx, C. X., Dearfield, X. X. (1989), Differential Xxxxxx Xxxxxxxxxxxx xx xxx Mouse Xxxxxxxx XX xxx XXX XXXXX Loci, Mutagenesis, 4, 394-403.

5) Xxxxx, X. X., Xxxxxxxxxx, Xx. X. F., (1989), Comparison of xxx XX52/XXXX and xxx XXX/XXXX Xxxxxx: Xxxxxxxxxx of Six Xxxx Xxxxxxxxxx, Mutatation Xxx. 223, 121-128.

6) Xxxxx, X. X., Xxxxxxxxxx, G., Glatt, X. X., Xxxxx, X., Xxxxx, X., Xxxxxxxxxx, Jr. X. X., Theiss, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Xxxx Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Xxxxxx. Report xx the Xxxxxxxxxxxxx Xxxxxxxx xx Standardisation xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, D., Xxxxx, X., Myhr, B. X. (1991), Xxxxxxxxxxxx Xxxxx Extreme Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

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

9) Li, X. X., Gupta, R. X., Heflich, X. X., Xxxxxx, J. X. (1988), X Xxxxxx xxx Analysis xx the Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Xxxxxxxxx the Xxxxxxxxxxxx of Xxxxxxxx Xxxxxx: X Xxxxxx xx Phase XXX xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, X. X., Carver, X. X., Choy, W. X., Hsie, A. X., Xxxxx, X. X., Loveday, X. X., X'Νxxxx, X. X., Xxxxxx, J. X., Xxxxxxxxxx, X. X. Xx., Xxxx, X. X. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx xx xxx Chinese Xxxxxxx Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Mutatation Xxx., 189, 135-141.

11) Xxxxx, X. X., Xxxxxxx, X. X., Little, X. X. (1989), X Xxxxxxxxxx xx Xxxxxxxx Induction xx xxx XX xxx XXXX Xxxx xx Xxxxx Xxxxxxxxxxxxxx Xxxxx: Xxxxxxxxxxxx Differences xxx Xxx to an Xxxxxxxxxx Xxxxx xx Xxxxxxxxx at xxx Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Xxx., 216, 9-17.

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

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

14) Xxxxxx, C. F., Xxxxx, X. X., Xxxxxx, X. X., Xxxxx, X. X. X., Cole, J., XxXxxxxx, X. X., Xxxxxxx X. X. (1989), Mammalian Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxx xxxx Xxxxxx Xxxxxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Kirkland, X. X., xx., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 66-101.

15) Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxxxx, X. (1977), Induction xx 6-Thioguanine-Resistant Xxxxxxx xx V79 Chinese Xxxxxxx Xxxxx xx Xxxxx-Xxxxx Microsome-Activated Dimethylnitrosamine, Xxxxxxxxxx Res. 46, 365-373.

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

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

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

19) Xxxxxxx, B. X., Combes, X. X., Xxxxxxx, C. X., Xxxxxxxxx, D. X., Gibson, X. X., Mackay, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-Induced X9 in: In xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Sawamura, X., Xxxx, X., Xxxxxxxx, X. (1976), X Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx of Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, X: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xx Xxxxxx, X. X., Fouts, X. X., Xxxx, X. X., Philpot, X. M. (xxx), Xxxxxxxx, North-Holland, 85-88.

21) Xxxxx, X. F., Xxxxxx, X. C., XxXxxxx, K. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Volatile Xxxxxxx, xx: Ticc, X. R., Xxxxx, X. X., Xxxxxxx, X. M. (eds), Xxxxxxxxx Effects of Xxxxxxxx Xxxxxx, New Xxxx, Xxxxxx, 91-103.

22) Xxxxxx, P. O., Xxxxxx, X. M., Xx, A. P., Xxxxxx, A. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx System Xxxxx Xxxxx Grown xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Highly Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Mutation Xxxxx, Xxxxxxx. Xxxxxxxxxxx, 5, 795-801.

23) Xxxxxxxxx, X. X., Xxxxx, X. M., Broder, X. X., Xxxxxxx, X., Xxxxxx, J. X. (1990), Molecular Xxxxxxxxxx xx Xxxxxxxxx xx xxx Heterozygous Xxxxxxxxx Kinase Xxxxx xx Xxxxx Lymphoma 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. X., Xxxxxx, X. T., Xxxxxx, X. (1985), Xxxxxxxx of Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (TFT+) Mutants xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Res. 151, 161-174.

25) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. B. (1990), Xxxxxxxxx Xxxxxxx Xxxxxxxx xx Xxxxxxxxx Xxxxxxxxx xx x Xxxxxxxxxxxx Xxxxxxxxx Locus in Xxxxx Cells, Mutatation Xxx. 229, 89-102.

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


XXXXXXX 4X

"X.23 XXXXXXX XX XXXXXXXXXXXX XXXXXXX XX SPERMATOGONIÍCH XXXXX

1. XXXXXX

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

1.1 ÚVOD

Účelem xxxxxxx xx xxxxxxxxxxxx xxxxxxx ve spermatogoniích xxxxx xx xxxx xx identifikovat xxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx aberace xx spermatogoniích xxxxx (1, 2, 3, 4, 5). Rozlišují xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x chromatidové. X xxxxxxx xxxxxxxxxx mutagenů xxxx indukované aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx se xxxxxx vyskytují. Xxxx xxxxxx není xxxxxx xx xxxxxxxxx numerických xxxxxxx x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x člověka.

Touto xxxxxxxx se stanovují xxxxxxxxxxxx změny ve xxxxxxxxxxxxxxx x xxxxxxxxxxx xx xxxx, xx xxxx xxxxxxx poskytne xxxxxxxxx xxxxxxx dědičných xxxxxx x xxxxxxxxxxxx xxxxxxx.

X této xxxxxxx xxxx xxxxxxx používáni xxxxxxxx. Xxxxx cytogenetickou xxxxxxxx in vivo xx detekují xxxxxxxxxxxx xxxxxxx xxx xxxxxx xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx xxxxxx předmětem xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx xxxxxxxxxxxxxx typu xx spermatogoniích xx xxxx xxx — xxxxx než dojde xx xxxxxx xxxx — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx následuje xx xxxxxxxx. Další xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx meiotickou xxxxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx x diakinese-metafázi X, kdy xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx zkouška in xxxx xx xxxxxxxx xxx vyšetření, xxx xxxx xxxxxxxx somatických xxxxx xxxxxxx xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx xx xxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x procesy xxxxxxxx DNA.

Ve xxxxxxxxx xx xxxxxxxx řada xxxxxxxx spermatogonií s xxxxxx xxxxxxxxxx xx xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxxxx aberace tedy xxxxxxxxxxx souhrnnou odpověď xxxxxxxxxx xxxxxxxx spermatogonií x xxxxxxxxxxxxxx diferencovanými xxxxxxxxxxxxxxx. X xxxxxxxxxx xx xxx xxxxxx xx xxxxxxxxx, xxxxx xxxx nemusí xxx xxxxx xxxxxxxx spermatogonií xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx x důsledku xxxxxxxxx a fyziologické xxxxxxx Xxxxxxxxx buněk x bariéry xxxx xxxxxxx oběhem x xxxxxxx.

Xxxxxxxx xxxxxxxx důkaz x tom, že xx xxxxxxxx látka xxxx reaktivní xxxxxxxxxx xxxxxxxxxx xx cílové xxxxx, xxxx xxxxxx xxxx zkoušku xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx aberace : xxxxxxxxxx poškození xxxxxxxxxx x podobě xxxxx xxxx xxxxx x xxxxxxx xxxx xxxxxxxxx x tomtéž xxxxx.

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

Xxxxxxxxx aberace : xxxxxxxx počtu xxxxxxxxxx xx xxxxxxxx hodnoty x xxxxxxxxx xxxxx.

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx pozorovatelné xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx xxx xxxxxxxxxxx, xxxx xx xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX METODY

Zvířata xxxx xxxxxxx způsobem xxxxxxxxxx xxxxxxxx xxxxx x xx vhodné xxxx xx xxxxxxxx xxxxxxxx. Xxxx usmrcením xx xxxxxxxx podá látka xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx nebo Xxxxxxxx®). X xxxxxxxxxxxx buněk xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu zvířete

Běžně xxxx používáni samci xxxxxx čínského a xxxx; xxx však xxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. V xxxxxxxx zahájení xxxxxx xx xxxx xxx xxxxxxxx v hmotnosti xxxxxx minimální a xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx xxxxx xx xxxxxxxx xxxxxxx rozdělí xx kontrolní xxxxxxx x skupinu, xxxxx xx exponuje. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Xxxx xxxxxxxxx xxxxxx xx xxxxxxx v xxxxxxxxxxxxx podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx xx měly xxx před xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x popřípadě zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx nebo mohou xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx údaje x stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx xxxxxxxxx hladinách dávek xxxxxxx účinky x xxxx xx xxx xxxxxxxxx podezření, xx xxxxxxx se xxxxxxxxx xxxxxx. Xxxx-xx použita xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx možno xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx by xxxx xxx souběžné xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx kontrolní skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x nichž xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx by měly xxxxxxxxxx xxxxxxxxxx xxxxxxx xx spermatogoniích xx xxxx xxx expozičních xxxxxxxx, x nichž xx xxxxxxxxxxx, že xxxxxxxxx detekovatelný xxxxxx xxx xxxxxx.

Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, xxx aby xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola podávána xxxxx xxxxxxxx xxx xxxxxxxx xxxxx a xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx xxx jednou. Xxx xxxxxxxxx xxxxxxxx xxxx být xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx látek xx xxxxxx xxxxxxxx xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx látek xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Einecs

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxx (xxxxxxx)

79–06–1

201–173–7

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

51–18–3

200–083–5

X xxxxxxxx xxxxxxx odběru xx měl xxx xxxxxxxx xxxxx u xxxxxxx negativní kontroly, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx nebo xxxxxxxxx a xxxxx xxxxx xxxxxxxxxx stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 XXXXXX

1.5.1 Xxxxx xxxxxx

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

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx podávány xxxxxxxxxxx xxxx nadvakrát (xx. při xxxxx xxxxxxxx xxxx dvou xxxxxxxxxx). Xxxxxxxx xxxxx xxxxx být podávány xxxx xx dvou xxxxxxx, xxx. xxx xxxxx x xxx xxx x xxxxxxx xx více než xxxxxxxx xxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxx objemů materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx zdůvodněny.

Ve xxxxxxx x nejvyšší dávkou xx xxxx být xx expozici xxxxxxxxx xxx odběry. Poněvadž xxxxxxxx xxxxxxxxx xxxxx xxxx xxx xxxxxxxxx xxxxxx ovlivněna, xxxxxxx xx jeden xxxxx xxxxx a jeden xxxxxxxx odběr xxxxxxxxx 24 x 48 xxxxx xx expozici. X xxxxxxx jiné xxx nejvyšší dávky xx měl xxx xxxxx xxxxxxxx xx 24 hodin xxxx xx xxxxxx xxxx xxxxxxxx, která odpovídá 1,5xxxxxxx xxxxx buněčného xxxxx, xxxxx xxxx xxxxx jiná xxxxxxxxx xxxx pro xxxxxxx xxxxxx (6).

Navíc mohou xxx xxxxxx provedeny xxxx x jiné xxxx. Xxxxxxxxx v xxxxxxx xxxxxxxxxx látek, xxxxx xxxxx xxxxxxxxx xxxxxxxx replikace (xxxxxxx) xxxxxxxxxx xxxx mohou xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx být xxxxxxxxx xxxxxxxx xxxxx (1).

Vhodnost xxxxx opakované xxxxxxxx xxxx xxx xxxxxx xxxxxx xx xxxxxxx. X případě plánu x xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx délky xxxxx) xx poslední xxxxxxxx. Podle xxxxxxx xxxxx být xxxxxxxxx xxxxx xxxxxx x xxxx xxxx.

Xxxx xxxxxxxxx xx zvířatům xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx zastavující metafázi (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Poté xx xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. U xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 xxxxx; x xxxxxx čínského xx xxxx xxxx xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx studie xxx xxxxxxxx rozsahu, xxxx xx být xxxxxxxxx ve xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx a xxxxxx x xx stejného xxxxxx expozice, který xx xxxxxxx x xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Xxxx xxxxxx dávky by xxxx xxxxxxxx rozmezí xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx xxxxxx známky xxxxxxxx, že xx xxxxx xxxxx xxxxx xxx stejném xxxxxx xxxxxxxxx podle očekávání x xxxxxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx aktivitou xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. hormony x xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx a xxxx xx být hodnoceny xxxxxx od xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx dávka vyvolávající xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx xxxxxxxx (např. xxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x první a xxxxx xxxxxxxxx metafázi; xxxx xxxxxxx xx xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx účinky x xxxx-xx xx xxxxxxx xxxxx o xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx xxxxxx xx třemi xxxxxxxx xxxxx xx xxxxxxxxx. Očekávaná expozice xxxxxxx xxxx znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx látka xx xxxxxxx podává nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx intubační xxxxxxx, xxxx intraperitoneální xxxxxxx. Xxxx způsoby xxxxxxxx xxxx přijatelné, jsou-li xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx na xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx zesílené účinky, xx xxxx xxx xxxxxxxxxxx zkoušeného objemu xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx konstantní objem xxx všech úrovních xxxxx.

1.5.6 Příprava preparátů xx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx se x xxxxxxx xxxx xxxx varlat získá xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx a xxxxxx. Xxxx xx nanese xx xxxxxxxx xxxxxxx x obarví xx.

1.5.7 Xxxxxxx

X každého xxxxxxx xx mělo xxx xxxxxxxxxxx alespoň 100 xxxxx x xxxxx xxxxxxxxxxxx xxxxxxxx (xx. xxxxxxxxx 500 xxxxxxxx xx skupinu). Xxxxx xxxxx xxx snížit, xx-xx pozorován xxxxx xxxxx aberací. Všechny xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx chromozomů x xxxxx metafází, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx odpovídajícímu xxxxx 2 x ± 2.

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx zpracovány xx xxxxx tabulky. Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx. Xxx každé xxxxx xx xxx být xxxxxxxxxx xxxxx xxxxx xx strukturními chromozomovými xxxxxxxxx x xxxxx xxxxxxxxxxxxxx aberací na xxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx být xxxxxxx xxxxx typy xxxxxxxxxxxx xxxxxxxxxxxxxx aberací x xxxxxx počtem x xxxxxxxx. Xxxx xx zaznamenávají xxxxxxxx x xxxxxxx se, xxx xxxxxx se xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx a xxxx xxxxxx, xxx xx xxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxxxxx xxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx a xxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxx poměr xxxxxxxxxxxxx x mitose xxxxxxxx k xxxxx x xxxxx xxxxxxxxx xxxxxxxx, x to x xxxxxxxx vzorku 100 xxxxxxxx xx xxxxx xx jedno xxxxx. Pokud je xxxxxxxxx xxxxx xxxxxx, xxxxxxx x 1000 xxxxxxx xx xxxxx xx měl xxx xxxxxxxx xxxxxxxxx index.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx stanovení pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx aberacemi v xxxxxxxxxx xx dávce xxxx jasný xxxxxx xxxxx xxxxx x xxxxxxxxx xxx xxxxxxx x určitou xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při hodnocení xxxxxxxx xxxxxxx mohou xxx použity jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx (8). Statistická xxxxxxxxxx by neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx to, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky na xxxxxxxxxxxx aberace ve xxxxxxxxxxxxxxx xxxxx xx xxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x germinálních buňkách xxxxxxxxxxx xxxxx strukturní xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxx x germinálních xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx by být xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet x stáří xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

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

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxx xxxxxxxx,

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

- xxxxxxxx xxxxx x kvalitě xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx expozice x odběru,

- xxxxxx xxxxxxxxx toxicity,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx aberací,

- počet xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- kritéria xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx index,

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

- xxx a xxxxx xxxxxxx xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx xx skupině,

- xxxxx xxxxx x xxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx statistické xxxxxxx,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

- dosavadní xxxxx x negativní xxxxxxxx s rozpětími, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx odchylkami,

- xxxxx x souběžné pozitivní xxxxxxxx,

- xxxxx xxxxxxx, xxxxx byly pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Adler, X. D., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Spermatogonia of Xxxxxxxx Mutagens Xxxxxxx xx their Cell-Cycle Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxxx Xxxxxxxxx, Xxxx B: Xxxxxxx Xxxxxxx xxx Xxxxxxx Mutagenesis, Xxxxx, X., Xxxxxxx, X., Xxxxxxxxx, X. (xxx) Xxxx, New Xxxx, 477-484.

2) Xxxxx, X. X., (1984), Cytogenetic xxxxx in Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Approach, (xx.) S. Xxxxxx, X. X. Xxxxx, XXX Xxxxx, Xxxxxx, Xxxxxxxxxx XX, 275-306.

3) Xxxxx, X. X., Xxxxxxx, X., Xxxx, X. E. (1964), Xx Xxx-xxxxxx Xxxxxx xxx Xxxxxxx Preparations xxxx Mammalian Xxxxxx, Xxxxxxxxxxxx Cell Genetics, 3, 289-294.

4) Richold, X., Xxxxx, X., Xxxxxxxx, X., Gatehouse, X. X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxx Assays, xx: X. J. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, UKEMS Xxxxxxxxxxx Procedures. UKEMS Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx. Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, X. X., Xxxxxx X. X., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Shibuya, X., Xxxxxx X. (1994), International Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Xxxxxx xx xxx Working Xxxxx xx Xxxxxxxxx Germ Xxxx Xxxxx, Mutatation Xxx., 312, 313-318.

7) Xxxxxxx, X. J., Xxxxx, X. A., Xxxxxx, X. R., Xxxxxx, X. A., Xxx, X., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Hodson-Walker, X., Morton, X. X., Kirkland, D. X., Xxxxxxx, X. (1992), Report xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. P., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Clarc, G., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, X. X., Savage J. X. K. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Report, Part XXX. Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4G

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

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX XX 486 — Xxxxxxx xx neplánovanou xxxxxxx XXX (UDS) v xxxxxxxxx xxxxxxx xxxxx xx xxxx (1997).

1.1 XXXX

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

Tato xxxxxxx in xxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxx. Xxxxxxxxxxx xxx je xxxxxxxxxx xxxxxxxxx DNA x následné xxxxxxxx x jaterních xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx místem, kde xxxx xxxxxxxxxxx sloučeniny xxxxxxxxxxxxxx. Xxxx tedy xxxxxxx xxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx XXX xx vivo.

Jestliže xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx nedostane xx cílové xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxxxxx neplánované xxxxxxx XXX (XXX) xx xxxxxxxx stanovením xxxxxxxxxxx xxxxxxxxx nukleosidů xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (X-xxxx). Nejrozšířenější xxxxxxxxx xx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx zkoušky na XXX xx vivo xx xxxxxxxxxx xxxxxxxxx xxxxx xxxxxxx. Xxxx xxxxx xxx játra xxxxx xxx xxxxxx xxxxxxx, xxxxxx xxxx xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx XXX závisí xx xxxxx xxxx XXX xxxxxxxxxxx x xxxxxxxxxxx x xxxxx xxxxxxxxx. Xxxxxxx na XXX je xxxx xxxxxx zvláště pro xxxxxxx dlouhých xxxxxxxx ("xxxx-xxxxx repair") (20 xx 30 bází) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("xxxxx-xxxxx xxxxxx") (xxxxx xx xxx xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx x xxxxxx menší citlivostí. Xxxxx xxxx důsledkem xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxxxx lézí XXX xxxxx x mutagenním xxxxxxxxx. Rozsah odpovědi XXX xxxxxxxxxxx xxxxxx xxxxxxxxx x věrnosti xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, xx xxxxxxx xxxxxxx x XXX, xxx poškození XXX xxxx xxxxxxxx xxxxxxxxxxx reparací. Nedostatek xxxxxxxxxxxx xxxxxxxxx, xxxxx xxxx zkouška poskytuje x xxxxxxxxx xxxxxxxx, xx xxxxxxx xxxxxxxxxxx xxxxxxxxxx tohoto xxxx, xxxxx xx vyšetřován x xxxxx xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx B.

1.2 DEFINICE

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

Xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx xxxxx x xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxx xxx x cytoplasmatických xxxxxxxxx (XX) odpovídajících xxxxxx xx xxxxx xxx xxxxxxxxxxxxxx buněčným xxxxxx (XX): XXX = XX — XX. Xxxxxxx NNG xx xxxxxxx xxx xxxxxxxxxx xxxxx, xxxx xxxxxxxx xxx buňky x xxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxx.

Xxxxxxxxxxx xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx xxxxxxxxx a xxxxxxxxxx xxxxx DNA xxxxxxxxxxxx region x xxxxxxxxxx indukovaným chemickými xxxxxxx nebo xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx UDS x xxxxxxxxx xxxxxxx xxxxx xx vivo xxxxxxxx xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x poškozením indukovaným xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx xxxxxxxx xx xxxxxxxxxxx 3H-TdR xx XXX jaterních xxxxx, xxx xx xxxx xxxxxxx xxxxx x S-fázi xxxxxxxxx xxxxx. Inkorporace 3X-XxX xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, jelikož tato xxxxxxxx není xxx xxxxxxx na xxxx X-xxxx xxxxx xxxx xxxx. xxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 POPIS XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xx používán xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxx xxxxx. Měly xx xxx xxxxxxx xxxxx používané xxxxxxxxxxx xxxxx mladých xxxxxxxx xxxxxxxx dospělých zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x xxxxxxxxx zvířat minimální x neměla xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx xxx obě xxxxxxx.

1.4.1.2 Podmínky chovu x strava

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, xxx xxx vliv xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx x před započetím xxxxxx xx xxxxxxx x laboratorních xxxxxxxxxx xxxxxxx pět dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx látky xx xxxx být xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx přímo xxxx mohou být xxxx xxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx xxxxxxxxx xxxxxxxx dávek toxické xxxxxx x xxxx xx xxx vyloučeno xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx známá rozpouštědla/vehikula, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každé xxxxxxxxx xxxxxxxxx části xxxxxxxxxxx by xxxx xxx souběžné xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx zvířata xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxxxx xxxxxxxxxx xx xxxx xxx xxxxx, o nichž xx známo, xx xxxxxx xxxxxxxx v xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx k xxxxxxx XXX xxxxxxxxxxxxxxx nad xxxxxxx. Pozitivní xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Xxxxx xxxxx xxx zvoleny tak, xxx byl účinek xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Einecs

Časné doby 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 také xxxx xxxxx pro xxxxxxxxx xxxxxxxx. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxx látka xxxxxxxx xxxxx způsobem, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx zvířat

Měl xx xxx xxxxxx dostatečný xxxxx zvířat, aby xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx kolísání odpovědi xx xxxxxxx. Xxxxx xxxxxxx xx xx xxxx skládat alespoň xx tří xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxxxx dosavadní xxxxx, xx xxx xxxxxxxxx x pozitivní xxxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxx xx xxx xxxxxxx.

Xxxxxxxx xxxx x xxxx xxxxxx x dispozici údaje xx studií se xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, jež xxxxxxxxx, xx xxxxxxxxxx xxxx pohlavími rozdíl x toxicitě, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, nejlépe samců. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, jako xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by xxx xxxxxxx xxxxxxxxx xx xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx.

1.5.3 Dávkování

Za normálních xxxxxxxx se xxxxxxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx takové xxxxxx toxicity, xx xxxxx dávky by xxxxx xxxxx xxxxxxxxx xxx xxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx dávka xx xxxx xxx zpravidla 50 % xx 25 % vyšší xxxxx.

Xxxxx se specifickou xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx vyhovovat x měly xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx dostupných xxxxx xxxxxx xxx xxxxxxxx xxxxxxx, xxxx xx xxx provedena xx xxxxxx laboratoři, se xxxxxxx druhem, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx se použijí x xxxxxx xxxxxx.

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

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx základě xxxxx x xxxxxxx, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx být xxxxx xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx potřebu xxxxxx x xxxxxxx zkoušce xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx obvykle xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx intubační xxxxxxx. Jiné způsoby xxxxxxxx jsou xxxxx, xxx-xx xx zdůvodnit. Xxxxxxxx xxxxxxxxxxxxxxxxx se xxxx xxxxxxxxxxxx, xxxxx xx xxxxx xxxxx xxx exponována xxxxxxxx xxxxx xxxxx x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx vyšších xxxxxx, xxx je xxxxxxx xxxxx, musí být xxxxxxxxxx. Xx na xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx xxx vyšších koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx konstantní objem xxx xxxxx úrovních xxxxx.

1.5.6 Příprava xxxxxxxxx xxxxx

Xxxxxxx buňky se xxxxxxxxxx x xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 xxxxx xx xxxxxx xxxxx. Xxxxxxxxxx xxxxxxxx odebrání xxxxxx (obecně dvě xx xxxxx xxxxxx xx xxxxxxxx) xx xxxxxxxx, xxxx-xx xx 12 až 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx použity jiné xxxx xxxxxx, jsou-li xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx údajů.

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

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx jaterní xxxxx xxxxx se xxxxxxx xxxxxxx dobu, např. xxx xx xxx xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3H-TdR. Xx xxxxx xxxxxxxxx xxxx by xxxx xxx xxxxxx x xxxxx xxxxxxxxxx x xxxxx poté xxxxx xxx inkubovány x xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx, aby xxxx snížena neinkorporovaná xxxxxxxxxxxxx ("cold xxxxx"). Xxxxx xx xxxx xxxxxxx, xxxxxx x xxxxxx. Xxx xxxxx xxxxxxxxx xxxx xxxxxx xxx snížení radioaktivity xxxxxxxx. Xxxxxxxxx xx xxxxxx do autoradiografické xxxxxx, xxxxxxxx xx x xxxxx (např. x xxxxxx 7 xx 14 dnů), xxxxxxxx se, xxxxxx x xxxxxxxxx se xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxxx dva xx tři preparáty.

1.5.8 Xxxxxxx

Xxxxxxxxx xx měly xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx normálních buněk, xxx mělo hodnocení XXX xxxxxxxxx xxxxxxx. Xxxxxxxxx xx xxx xxxxxxxxxxx prohlédnou xx xxxxxx zjevné cytotoxicity (xxxx. na xxxxxxx, xxxxxxxx xxxxxx značení xxxxxxxxxxxxx xxxxxxxx).

Xxxx xxxxxxxxx xxx xx měly xxx preparáty kódovány. Xxxxxxxxx xx xxxxxxxxx 100 xxxxx xx xxxxx zvíře xxxxxxx xx xxxx xxxxxxxxx; xxxxxxxxx méně než 100 xxxxx/xxxxx by xxxx xxx xxxxxxxxxx. Xxx xxxxxxxx xxx xx xxxxx x X-xxxx xxxxxxxxxxx, ale xxxxx buněk x X-xxxx může být xxxxxxxxxx.

Xxxxxxxx 3X-XxX inkorporovaného xx xxxxx a xxxxxxxxxx xxxxxxxxxxxx normálních xxxxx doložené navrstvením xxx xxxxxxx by xxxx xxx xxxxxxxxx xxxxxxx xxxxxxx.

Xxxxx xxxxx xx stanoví x xxxxx xxx odpovídajících xxxxxxxx xxxxŭx (xx) x x prŭměrného xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (cg) xxxxxxxxxxxxxx jádrŭm. xxxx xxxxxxx cg xx xxxxxxx xxx xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx prŭměrná xxxxxxx xxxx až xxx xxxxxxx vybraných xxxxxxx x blízkosti xxxxxxxxx xxxxxxxxx xxxxx. po xxxxxxxxxxxxx xxXxxxxxxx mohou xxx xxxxxxx x xxxx xxxxxxx xxxxxxxxx xxxxx buněk (xxxx. xxxxxxxx xxxxxx xxxxx) (6).

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxx xx xxx xxxxxxx xxxxx xxx xxxxxxxxxx preparáty a xxxxxxx. Xxxxx xx xxxx xxx xxxx xxxxxxx ve xxxxx xxxxxxx. Odečtením hodnoty XX od hodnoty XX xx xxx xxx vypočten pro xxxxxx buňku, xxx xxxxx xxxxx a xxx xxxxxx xxxxx x čas xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX). Xxxxxxxx xxxx xxxxxxxx "xxxxxxxxxx" xxxxx, xxxx xx být xxxxxxxx xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx odůvodněna x xxxxxxxx na xxxxxxxxxxx xxxx souběžných xxxxxxx x xxxxxxxxxxx kontrolách. Xxxxxxxxx xxxxxxxx mohou xxx xxxxxxxxxx statistickými xxxxxxxx. Xxxx-xx xxx xxxxxxx, měly by xxx statistické testy xxxxxxx x odůvodněny xxxx provedením studie.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx odpověď patří:

pozitivní

i)

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

xxxx

xx)

xxxxxxx XXX xx xxxxxxxx xxxxx xxx xxxxxxx xxx souběžnou xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx NNG xxxx xx xxxxxxxxx prahové xxxxxxx xxxx xxx xx;

xxxx

xx)

xxxxxxx XXX xxxx xxxxxxxx xxxxx než xxxxxxx xxx xxxxxxxxx xxxxxxxx.

Xxxx by xxx xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx. xxxx xx být vzaty x xxxxx parametry, xxxx xxxx variabilita xxxxxx, xxxxx dávky x xxxxxxxx x xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx.

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

Pozitivní xxxxxxxx xxxxxxx xx XXX v xxxxxxxxx xxxxxxx savců xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxx xxxxx xx vivo xxxxxxxxx DNA, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx DNA xx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx poškození XXX, xxxxx lze xxxxxxxxx xxxxx xxxxxxxx.

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

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx vehikula,

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

Testovací zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx a xxxxxxx xxxxxx,

- zdroj, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx počátku xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x směrodatné odchylky xxx každou xxxxxxx.

Xxxxxxxx xxxxxxxx:

- pozitivní a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- údaje o xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

- popřípadě xxxxxx xxxxxxx, xxx xx zkoušená látka xxxxxxx xx xxxxxxxx xxxxx xxxx xx xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- metody xxxxxxxx x xxxxxxxxx xxxxxxxxx buněk,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x xxxxx xxxxxxxxxxx buněk,

- xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxxx xxxxxxx počtu xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx x xxxxx xxx odpovídajících xxxxxxxxxx, x xxxxx počet xxx, jednotlivě xxx xxxxxxxxx, zvířata a xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,

- případné xxxxxxxxxxx xxxxxxxxx,

- známky xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx (rozpouštědlo/vehikulum) a xxxxxxxxx kontrole,

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

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

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

- životaschopnost xxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, X. Xxxxxxx, X. X., Xxxxxxxxx, X., Xxxxxx, M. X. (1985), An Xxxxxxxxxx of xxx Xx vivo Xxx. Xxxxxxxxxx XXX Repair Xxxxx, Mutatation Xxx., 156, 1-18.

2) Butterworth, X. X., Xxxxx, X., Xxxxxxxx, E., Xxxxxxxx, X., Xxxxxxxx, X., Probst, X., Xxxxxxxx, X. (1987), X Protocol xxx Xxxxx xxx xxx Xx vivo Xxx Xxxxxxxxxx XXX Xxxxxx Xxxxx, Mutatation Xxx., 189, 123-133.

3) Kennelly, X. X., Xxxxxx, X., Ashby, X., Xxxxxxx, X. X., Xxxxxxxxx, B., Xxxxxxx, X. X., Xxxx, X. W., Mitchell, X. de X. (1993), In xxxx Xxx Liver UDS Xxxxx, xx: Xxxxxxxx X. X., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: XXXX Xxxxxxxxxxx Procedures. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Xxxxxxx. Xxxxxx. Xxxx XX xxxxxxx, Xxxxxxxxx University Xxxxx, Cambridge, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Dean, X. X., Xxxxxx, X., Brambilla. G., Xxxxxxxxx, X., Xxxxxxxxx, X. J., Xxxxxxxx, X., Xxxxxxx, T., XxXxxxx, X. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx xx XXX Xxxxx Xx xxxxx xxx In xxxx, Xxxxx. Xxx., 312, 263-285.

5) Fautz, R., Xxxxxxx, X., Xxxxxxxxxx, X., Hechenberger-Freudl, C. (1993), Assessment xx xxx Xxxxxxxx Xxxxxxx xxx Initial Xxxxxxxxx xxx xxx Attachment xx Freshly Xxxxxxxx Xxx Xxxxxxxxxxx Xxxx xxx xxx Xx xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (XXX), Xxxxxxxxxx Xxx., 291, 21-27.

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


XXXXXXX 5

XXXXXX POŽADAVKY XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX XXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX, Xx. xxxx. X 332, 28. 12. 2000, x. 81.


XXXXXXX 6

"

XXXXXXX XX

XXXX X

xxxxxxxx týkající se xxxxxxx xxxxxxxx proti xxxxxxxx xxxxx

Xxxxx ustanovení xx. 22 odst. 1 xxxx. e) xxxx xxxxxxxx, musí xxx xxxxx x xxxxxxxxx xxxxxx obsahující xxxxx, s xxxxx xx xxxxxxx riziko xxx xxxxxxxxxx (Xn; X 65) x xxxxx jsou klasifikovány x xxxxxxxx podle xxxx 3.2.3 přílohy XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx na xxx xx xxxxx aerosolů xxxx x nádobách xxxxxxxxxx aerosolovým xxxxxxxxxxxxx, xxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx otevření xxxxx použité xx xxxxxxxxx xxxxxxxxxxxxxx obalech xxxx splňovat xxxxxxxxx xxxxx XXX 8317 (xxxxxx xx xxx 1. července 1989) "Xxxxx odolné xxxxx — Xxxxxxxxx xx xxxxxxxxx uzavíratelné obaly x metody xxxxxx xxxxxxxx" přijatou Mezinárodní xxxxxxxxxx xxx normalizaci (XXX).

2. Xxxxxxxxx neuzavíratelné xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx dětmi použité xx xxxxxxxxx xxxxxxxxxxxxxxxx xxxxxxx musí xxxxxxxx xxxxxxxxx normy XXX XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Xxxxx xxxxxx dětem — Xxxxxxxxx x xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Xxxxxxxxx xxxxxxx xxx xxxxxxxxxxx (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx xxxxx x výše uvedenými xxxxxxx mohou osvědčovat xxxxx xxxxxxxxxx, xxxxx xxxxxxx evropské xxxxx xxxx XX 45000.

2. Xxxxxxxxxx případy

Je-li zřejmé, xx xxxx xx xxxxxxxxxx xxxxxxxx xxx xxxx, xxxxx se xxxxxxx xxxxxx x xxxxxx xxx xxxxxx xxxxxxxx, xxxxxx být xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx případech a xxxxx existují oprávněné xxxxxx x pochybám x xxxxxxxxxxx xxxxxxx xxx xxxx, může xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 konstatující, xx buď

- typ xxxxxxx xx xxxxxx, xx xxx xxxx xxxxxxxx xxxxxxx podle xxxx xxxxxxxxx xxxxx XXX x XXX,

xxxx

- xx uzávěr xxx xxxxxxx a xxx xxxxxxx vyhovujícím xxxxx xxxx uvedených xxxxx.

XXXX X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx specifikace xxx xxxxxxxxxx výstrahy xxxx xxx x xxxxxxx s normou XX ISO 11683 (xxxxxx x roku 1997) "Xxxxx — Xxxxxxxxxx výstrahy xxxx xxxxxxxxxx — Xxxxxxxxx".

"