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Xxxxxxxx Xxxxxx 2000/32/XX

xx xxx 19. května 2000,

xxxxxx se xx xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxx Xxxx 67/548/EHS x xxxxxxxxxx právních x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxx [1]

(Xxxx x xxxxxxxx pro XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x ohledem xx Xxxxxxx x xxxxxxxx Evropského xxxxxxxxxxxx,

x xxxxxxx xx směrnici Xxxx 67/548/XXX ze xxx 27. xxxxxx 1967 x sbližování xxxxxxxx a xxxxxxxxx xxxxxxxx týkajících xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx nebezpečných xxxxx [2], xxxxxxxxx xxxxxxxxxx xxxxxxxx Evropského parlamentu x Xxxx 1999/33/XX [3], x xxxxxxx xx xxxxxx 28 xxxxxxx směrnice,

vzhledem k xxxxx důvodům:

(1) Příloha X směrnice 67/548/EHS xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxx společně s xxxxxxxxxx xxxxx x xxxxxxxxxxx a xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxx, xx xx měl xxx xxxxxx xxxxxxxxxxxx xxxxx x xxxxxxx příloze xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxxxxx a xxxxxxx X x xxxxxxx X.

(2) Xxxxxxx III xxxxxxxx 67/548/XXX obsahuje xxxxxx xxx udávajících xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx x xxxxxxxxx. Xxxxxxx IV xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx s xxxxxxxxxxxxxx xxxxxx týkajícími se xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX obsahuje xxxxx xx xxxxxxxxxxx x x označování xxxxxxxxxxxx látek x xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx určitých xxxxxx xxxxxx XXX, IV x VI.

(3) X xxxxxxx X xxxxxxxx 67/548/XXX xx xxxxxxx xxxxxx xxx stanovení xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, xxxxxxxx x xxxxxxxxxxx látek x xxxxxxxxx. Xx xxxxxxxx xxxxxxxxxxx tuto xxxxxxx technickému xxxxxxx.

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx xx uzávěrů xxxxxxxx proti xxxxxxxx xxxxx. Xxxx xxxxxxxx xx měly být xxxxxxxxxxxx x aktualizovány. Xx nezbytné xxxxxxxx xxxxxx, xxx xx xxxxxxx odolné xxxxx xxxxxxxx dětmi používají.

(5) Xxxxxxxx xxxx xxxxxxxx xxxx x xxxxxxx xx stanoviskem Xxxxxx xxx přizpůsobení xxxxxxxxxxx xxxxxxx xxxxxxx xxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xx xxxxx xxxxxxxxxxxx xxxxx x xxxxxxxxx,

XXXXXXX XXXX XXXXXXXX:

Xxxxxx 1

Směrnice 67/548/EHS xx mění xxxxx:

1. Xxxxxxx X xx xxxx xxxxx:

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

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

x) xxxxxxxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxx x příloze 1X xxxx směrnice;

d) xxxxxxxx xx položky v xxxxxxx 1X xxxx xxxxxxxx.

2. Odpovídající xxxx x xxxxxxx III xx xxxxxxxxx standardní xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxx 2 xxxx xxxxxxxx.

3. Xxxxxxx IV se xxxx xxxxx:

x) odpovídající xxxxxx v příloze XX xx xxxxxxxxx xxxxxxxxxxxx pokyny pro xxxxxxxx xxxxxxxxx x xxxxxxx 3X xxxx xxxxxxxx;

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

4. Část X xxxxxxx X xx xxxx xxxxx:

x) xxxxxxxx X.10 se nahrazuje xxxxxx v příloze 4X xxxx xxxxxxxx;

x) xxxxxxxx X.11 xx xxxxxxxxx xxxxxx v xxxxxxx 4X této xxxxxxxx;

x) kapitola B.12 xx xxxxxxxxx textem x příloze 4C xxxx xxxxxxxx;

x) xxxxxxxx X.13 a X.14 xx xxxxxxxxx xxxxxx x příloze 4X xxxx xxxxxxxx;

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

x) xxxxxxxx B.23 xx xxxxxxxxx textem x xxxxxxx 4F xxxx xxxxxxxx. Xxxxx xxxxxxxx X.23 xx vysvětlivce xx xxxx xxxxxxxxxxxxx xxxxxxxx;

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

5. Xxxxxxx xx xxxxxx xxxxxxx obecného xxxxx x části X xxxxxxx X.

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

7. Xxxxxxx XX xx xxxx způsobem xxxxxxxx x xxxxxxx 6 xxxx xxxxxxxx.

Článek 2

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

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx státy musí xxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxx xxxx xxxxxx xxxxx xxx xxxxxx xxx xxxxxx úředním vyhlášení. Xxxxxx odkazu si xxxxxxx xxxxxxx xxxxx.

2. Xxxxxxx státy xxxxx Xxxxxx xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx přijmou x oblasti xxxxxxxxxx xxxx xxxxxxxx, a xxxxxxxxxx tabulku xxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.

Článek 3

Tato směrnice xxxxxxxx x xxxxxxxx xxxxxx xxxx po xxxxxxxxx x Xxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx.

Xxxxxx 4

Xxxx xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.

X Bruselu xxx 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Xxxxxx

[1] Xxxxxxx po xxxxxxxxxxxx xx dvacáté xxxxx.

[2] Úř. věst. 196, 16.8.1967, x. 1.

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

PŘÍLOHA 1A

PŘEDMLUVA K XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx se českého xxxxx)

PŘÍLOHA 1X

"XXXXXXX X

X

Xxxxxx

XX

18

Xx

Xxxxx

Αργό

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"

XXXXXXX 1X

Xxxxxxxx xxxxx	Xxxxxxxx xxxxx	Xxxxxxxx x xxxxxx	Xxxxx XX	Xxxxx CAS	Klasifikace	Označení	Koncentrační limity	Poznámky x xxxxxxxxxx
006–011–00–7	xxxxxxxx (ISO) 1-xxxxxx-X-xxxxxxxxxxxxxx		200–555–0	63–25–2	Xxxx. xxx. 3; X40 Xx; R22 X; R50	Xn; X X: 22–40–50 X: (2-)22–24–36/37–46–61
006–013–00–8	xxxxxx-xxxxxxx (XXX) natrium-N-methyldithiokarbamát		205–293–0	137–42–8	Xn; X22 X31 X; X34 X43 X; X50–53	X; N X: 22–31–34–43–50/53 X: (1/2-)26–36/37/39–45–60–61
006–015–00–9	xxxxxx (XXX) 3-(3,4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx	206–354–4	330–54–1	Xxxx. kat. 3; R40 Xxxx. xxx. 3; R40 Xx; X22–48/22 N; X50–53		Xx; X X: 22–40–48/22–50/53 X: (2-)13–22–23–37–46–60–61
006–016–00–4	xxxxxxxx (XXX) 2- isopropoxyfenyl-N-methylkarbamát		204–043–8	114–26–1	T; X25 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; X50–53	X+; 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; R24/25 X; X50–53	X; N X: 24/25–50/53 S: (1/2-)28–36/37–45–60–61
006–019–00–0	xx-xxxxx (XXX) X-(2,3-xxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx		218–961–1	2303–16–4	Xxxx. kat. 3; X40 Xx; X22 X; X50–53	Xx; X R: 22–40–50/53 X: (2-)25–36/37–60–61
006–020–00–6	barban (ISO) 4-xxxxxxxx-2-xx-1-xx-X -(3-chlorfenyl)karbamát		202–930–4	101–27–9	Xn; X22 X43 X; X50–53	Xx; X R: 22–43–50/53 X: (2-)24–36/37–60–61
006–023–00–2	merkaptodimethur (ISO) xxxxxxxxxx 3,5-xxxxxxxx-4-(xxxxxxxxxxxxxx)xxxxx-X -methylkarbamát		217–991–2	2032–65–7	T; X25 X; X50–53	X; X X: 25–50/53 X: (1/2-)22–37–45–60–61
006–024–00–8	xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx		205–443–5	140–93–2	Xx; X22 Xx; X38 X; R51–53	Xn; X R: 22–38–51/53 X: (2-)13-61
006–026–00–9	xxxxxxxxxx (ISO) 2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx-X-xxxxxxxxxxxxxx		216–353–0	1563–66–2	X+; R26/28 N; X50–53	X+; X X: 26/28–50/53 S: (1/2-)36/37–45–60–61
006–028–00-X	xxxxxxxxx (XXX) 2-(1-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 R: 25–50/53 X: (1/2-)37–45–60–61
006–029–00–5	dioxakarb (XXX) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx		230–253–4	6988–21–2	X; R25 X; X51–53	X; X X: 25–51/53 X: (1/2-)37–45–61
006–033–00–7	xxxxxxxxx (XXX) 3-(3-xxxxx-4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx		243–433–2	19937–59–8	X; 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 R: 22–51/53 X: (2-)23-61
006–035–00–8	pirimikarb (ISO) 2-(xxxxxxxxxxxxx)- 5,6-dimethyl 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	promekarb (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		220–113–0	2631–37–0	X; X25 X; X50–53	X; N X: 25–50/53 X: (1/2-)24–37–45–60–61
006–038–00–4	xxxxxxxxx (XXX) 2-chlorallyl-N,N-dimethyldithiokarbamát	E	202–388–9	95–06–7	Karc. kat. 2; X45 Xn; X22 X; R50–53	T; 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; X22–48/22 X43 X; R50–53	Xn; X X: 22–43–48/22–50/53 X: (2-)24–37–60–61
006–042–00–6	xxxxxxx (XXX) 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx		205–766–1	150–68–5	Xxxx. xxx. 3; R40 Xx; X22 X; X50–53	Xx; X R: 22–40–50/53 X: (2-)36/37–60–61
006–043–00–1	monuron-TCA 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx		—	140–41–0	Xx; R36/38 Karc. xxx. 3; R40 X; R50–53	Xn; X X: 36/38–40–50/53 X: (2-)36/37–60–61
006–045–00–2	xxxxxxxx (XXX) methyl-N-[(N-methylkarbamoyl)oxy]thioacetimidát		240–815–0	16752–77–5	T+; X28 X; X50–53	X+; X X: 28–50/53 X: (1/2-)22–36/37–45–60–61
006–046–00–8	xxxxxxxxxx (XXX) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx		245–216–8	22781–23–3	X; R23/25 Xn; X21 X; X50–53	X; X R: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61
006–047–00–3	bufenkarb (ISO) xxxx: 3-(1-methylbutyl)fenyl-N-methylkarbamátu x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx		—	8065–36–9	X; X24/25 X; X50–53	X; X X: 24/25–50/53 X: (1/2-)28–36/37–45–60–61
006–048–00–9	xxxxxxxxxxxx (XXX) 2-[(xxxxxxxxxxxxx)xxxxxx]xxxxx-X-xxxxxxxxxxxxxx		249–981–9	29973–13–5	Xx; X22 X; X50–53	Xx; X X: 22–50/53 X: (2-)60-61
006–050–00–X	xxxxxxx-XXX 3-xxxxx-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx		—	4482–55–7	Xx; X38 X; X50–53	Xx; X X: 38–50/53 X: (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 (ISO) 4-(xxxxxxxxxxxxx)-3,5-xxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		206–249–3	315–18–4	X+; R28 Xx; X21 N; X50–53	X+; X X: 21–28–50/53 X: (1/2-)36/37–45–60–61
006–057–00–8	nitrapyrin (XXX) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx		217–682–2	1929–82–4	Xx; R22 X; X51–53	Xx; N X: 22–51/53 S: (2-)24-61
006–060–00–4	oxykarboxin (XXX) 2-xxxxxx-4,4-xxxxx-5,6-xxxxxxx-4λ4-1,4-xxxxxxxx-3-xxxxxxxxxxxx		226–066–2	5259–88–1	Xx; R22 X52–53	Xx R:22–52/53 X: (2-)61
006–069–00–3	xxxxxxxxx-xxxxxx (ISO) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx		245–740–7	23564–05–8	Xxxx. xxx. 3; X40 X; X50–53	Xx; X X: 40–50/53 S: (2-)36/37–60–61
006–070–00–9	xxxxxxxxxxx X-xxxxxxxxxx-X-xxxxxxx-2,5-xxxxxxxx-3-xxxxxxx		262–302–0	60568–05–0	Xxxx. kat. 3; R40 N; X50–53	Xx; X R: 40–50/53 S: (2-)36/37–60–61
006–088–00–7	xxxxxxxxxxx (XXX) xxxxx-X -[({[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]karbonyl}methylamino)sulfanyl]-N-isopropyl-β-alaninát(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)-N-({[2-(ethoxykarbonyl)ethyl]isopropylamino}sulfanyl)-N-methylkarbamát		—	82560–54–1	T; X23/25 N; X50–53	X; X R: 23/25–50/53 X: (1/2-)36/37–45–60–61
007–012–00–5	N,N-dimethylhydrazin 1,1-xxxxxxxxxxxxxxxx	X	200–316–0	57–14–7	X; X11 Karc. xxx. 2; X45 X; X23/25 C; X34 X; X51–53	X; T; X R: 45–11–23/25–34–51/53 X: 53–45–61
007–013–00–0	X,X-xxxxxxxxxxxxxxxx 1,2-dimethylhydrazin	E	—	540–73–8	Karc. xxx. 2; R45 X; X23/24/25 N; X51–53	X; N X: 45–23/24/25–51/53 S: 53–45–61	X ≥ 25 %: X; X45–23/24/25 3 % &xx; X &xx; 25 %: X; X45–20/21/22 0,01 % &xx; X &xx; 3 %: X; X45
009–003–00–1	xxxxxxxx fluorovodíková … %	X	231–634–8	7664–39–3	X+; X26/27/28 X; X35	X+; X X: 26/27/28–35 S: (1/2-)7/9–26–36/37–45	X ≥ 7 %: X+; C; X26/27/28–35 1 % ≤ X &xx; 7 %: T; X23/24/25–34 0,1 % ≤ X < 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+; X26/28 X; X24 X43 X; X50–53	X+; N X: 24–26/28–43–50/53 X: (1/2-)28–36/37–45–60–61
015–048–00–8	xxxxxxxx (XXX) X,X-xxxxxxxx-X-[3-xxxxxx-4-(xxxxxxxxxxxxxx)xxxxx]-xxxxxxxxxxxxx		200–231–9	55–38–9	Xxxx. xxx. 3; R40 X; X23–48/25 Xx; X21/22 X; X50–53	X; X X: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61
015–056–00–1	azinfos-ethyl (XXX) X,X-xxxxxxx-X-[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx		220–147–6	2642–71–9	X+; R28 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 N; X50–53	X; X R: 21–23/25–50/53 X: (1/2-)36/37–45–60–61
016–013–00-X	xxxxxxx sirnatý		234–129–0	10545–99–0	R14 X; X34 X; X50	X; X X: 14–34–50 S: (1/2-)26–36/37/39–45–61	X ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; R36/37/38
016–014–00–5	chlorid siřičitý		—	13451–08–6	R14 X; X34 X; X50	X; X R: 14–34–50 X: (1/2-)26–36/37/39–45–61	X ≥ 10 %: X; R34 5 % ≤ X &xx; 10 %: Xx; R36/37/38
016–023–00–4	dimethyl-sulfát	E	201–058–1	77–78–1	Karc. xxx. 2; X45 Xxxx. xxx. 3; X40 X+; X26 X; X25 X; X34 X43	X+ R: 45–25–26–34–43 X: 53-4 5	C ≥ 25 %: X+; R45–25–26–34–43 10 % ≤ X &xx; 25 %: X+; X45–22–26–34–43 7 % ≤ C &xx; 10 %: X+; R45–22–26–36/ 37/38–43 5 % ≤ X &xx; 7 %: X; X45–22–23–36/37/38–43 3 % ≤ X &xx; 5 %: T; X45–22–23–43 1 % ≤ X &xx; 3 %: X; X45–23–43 0,1 % ≤ X &xx; 1 %: X; R45–20 0,01 % ≤ X < 0,1 %:X; X45
016–024–00-X	xxxxxxxx (ISO) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx	X,X′-xxxxxxxx-xxxxxxxxxxx(xxxxxxxxxxx)215–993–8	1468–37–7	Xx; X22 N; X50–53	Xx; X R: 22–50/53 X: (2-)60-61
016–071–00–6	3-xxxxx-6,13-xxxxxxx-10-[(3-{[4-xxxxx-6-(2-xxxxxxxxxxxxxxxx)- 1,3,5-xxxxxxx-2-xx]xxxxx}xxxxxx)xxxxx][1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx xxxxxxxx		410–130–3	136248–03–8	X43	Xx R: 43 S: (2-)22–24–37
022–001–00–5	xxxxxxx xxxxxxxxxx		231–441–9	7550–45–0	X14 X; X34	X X: 14-34 S: (1/2-)7/8–26–36/37/39–45	X ≥ 10 %: X; R34 5 % ≤ X < 10 %: Xx; R36/37/38
030–004–00–8	dimethylzinek [1] diethylzinek [2]		208–884–1 [1] 209–161–3 [2]	544–97–8 [1] 557–20–0 [2]	X14 X; X17 X; X34 N; X50–53	X; X; X R: 14–17–34–50/53 X: (1/2-)16–43–45–60–61
050–002–00–0	xxxxxxxxx (XXX) xxxxxxxxxxxxx(xxxxxxx)xxxxxxx xxxxxxxxxxxxxxxxxxxxx-xxxxxxxx		236–049–1	13121–70–5	Xx; X20/21/22 X; X50–53	Xx; 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; R20/21/22 X; R50–53	Xn; X X: 20/21/22–50/53 X: (2-)26–28–60–61	X ≥ 1 %: Xx; X20/21/22	1
050–017–00–2	xxxxxxxxxxxxxx (XXX) 1,1,1,3,3,3-xxxxxxx(2-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxxxx		236–407–7	13356–08–6	X+; R26 Xx; R36/38 N; X50/53	X+; N X: 26–36/38–50/53 X: (1/2-)28–36/37–45–60–61
082–009–00–X	xxxx (xxxxxxxxxxxx xxxxxxxx) XX Xxxxxxx Xxxxxx 34 (XX 77603) CI xxxxxxxxxx xxxx 34 (XX 77603)		215–693–7	1344–37–2	Xxxx. xxx. 3; R40 Xxxx. xxx. 1; R61 Xxxx. kat. 3; X62 X33 N; X50–53	X; X R: 61–33–40–50/53–62 X: 53–45–60–61		1
082–010–00–5	červeň (xxxxxxx-xxxxxxxxxx-xxxxx xxxxxxxx) XX Xxxxxxx Xxx 104 (XX 77605) CI xxxxxxxxxx xxxxxx 104 (XX 77605)		235–759–9	12656–85–8	Karc. xxx. 3; X40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 X; X50–53	X; X X: 61–33–40–50/53–62 X: 53–45–60–61		1
601–024–00-X	kumen [1] xxxxxxxxxxxx [2]		202–704–5 [1] 203–132–9 [2]	98–82–8 [1] 103–65–1 [2]	X10 Xx; X65 Xx; X37 X; X51–53	Xx; X R: 10–37–51/53–65 X: (2-)24–37–61–62		4
601–032–00–3	xxxxx[x]xxxxx benzo[def]chrysen		200–028–5	50–32–8	Karc. xxx.2; R45 Muta. xxx. 2; R46 Xxxx. kat. 2; X60–61 X; X50–53	X; X R: 45–46–60–61–50/53 X: 53–45–60–61
601–034–00–4	xxxxx[x]xxxxxxxxxxxxxxx		205–911–9	205–99–2	Xxxx. xxx.2; X45 N; R50–53	T; 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-xxxxxxx-1-xx xxxxxxxxxx		209–130–4	556–56–9	X10 X; R34	C 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; R21–48/22 X; R34	T X: 21–23/25–34–48/22 X: (1/2-)26–36/37/39–45	X ≥ 50 %: X; R21–23/25–34–48/22 25 % ≤ C &xx; 50 %: X; X21–23/25–36/38–48/22 10 % ≤ C &xx; 25 %: Xx; R20/22–48/22 3 % ≤ C &xx; 10 %: Xx; R20/22
603–091–00–0	exo-4-isopropyl-1-methyl-7-oxabicyklo[2.2.1]heptan-2-ol		402–470–6	87172–89–2	O; R8 Xx; X22 Xx; X36	X; Xn R: 8–22–36 S: (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; X51–53	Xx; X X: 20–51/53 X: (2-)23-61
603–097–00–3	1,1', 1′′-nitrilotripropan-2-ol xxxxxxxxxxxxxxxxxx		204–528–4	122–20–3	Xx; R36 R52–53	Xi X:36–52/53 X: (2-)26-61
603–117–00–0	xxxxxx-2-xx xxxxxxxxxxxxxxxx xxxxxxxxxxx		200–661–7	67–63–0	X; X11 Xx; X36 R67	F; Xx X: 11–36–67 X: (2-)7–16–24/25–26
604–020–00–6	xxxxxxx-2-xx 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (XXX)		201–993–5	90–43–7	Xx; R36/37/38 X; X50	Xx; X X: 36/37/38–50 S: (2-)22-61
604–021–00–1	2-xxxxxxxxxx, sodná xxx xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx sodný xxxxxxx-xxxxxxx-2-xxxx		205–055–6	132–27–4	Xx; X22 Xx; X37/38–41 X; R50	Xn; X X: 37/38–41–50 X: (2-)22–26–61
604–024–00–8	4,4'-(4-xxxxxxxxxxxx-2,2-xxxx)xxxxxxx 2,2-bis(4-hydroxyfenyl)-4-methylpentan		401–720–1	6807–17–6	Repr. xxx. 2; X60 Xx; X36 N; X50–53	X; X X: 60–36–50/53 X: 53–45–60–61
604–041–00–0	xxxxxxxxxxx [1] xxxxxxxxxxx-xxxxxxx [2] 5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxxx xxxxxxxx [1] xxxxxxx-5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxx [2]		256–634–5 [1] 263–560–7 [2]	50594–66–6 [1] 62476–59–9 [2]	Xx; X22 Xx; R38–41 N; X50–53	Xx; X X: 22–38–41–50/53 X: (2-)24–39–60–61
604–043–00–1	monobenzonbenzyl (4-xxxxxxxxxxxx)xxxxx hydrochinonmonobenzylether 4-(benzyloxy)fenol		203–083–3	103–16–2	Xi; X36 X43	Xx X: 36-43 X: (2-)24/25–26–37
604–044–00–7	mechinol 4-xxxxxxxxxxxx hydrochinonmonomethylether		205–769–8	150–76–5	Xn; X22 Xx; X36 X43	Xx X: 22–36–43 X: (2-)24/25–26–37/39–46
605–016–00–7	xxxxxxx… % ethandial… %	X	203–474–9	107–22–2	Xxxx. kat. 3; X40 Xx; R20 Xx; X36/38 X43	Xx X: 20–36/38–40–43 X: (2-)36/37	X ≥ 10 %: Xn; X20–36/38–40–43 1 % ≤ X &xx; 10 %: Xx; X40–43
606–016–00-X	xxxxxx (XXX) 2-(xxxxxxxxxxxxxxx)xxxxx-1,3-xxxx		201–462–8	83–26–1	X; X25–48/25 X; X50–53	X; X X: 25–48/25–50/53 X: (1/2-)37–45–60–61
606–018–00–0	xxxxxxx (XXX) 2,3-dichlor-1,4-naftochinon		204–210–5	117–80–6	Xn; X22 Xx; X36/38 X; R50–53	Xn; N X: 22–36/38–50/53 X: (2-)26–60–61
606–019–00–6	xxxxxxxxxx (XXX) perchlorpentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-on xxxxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx 1,2,4,5,6,7,8,8,9,10-xxxxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx		205–601–3	143–50–0	Xxxx. xxx. 3; R40 X; X24/25 N; R50–53	T; X R: 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-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-4,5-xxxxxxx-1,2,4-xxxxxxx-5-xx		244–209–7	21087–64–9	Xx; X22 N; X50–53	Xx; X X: 22–50/53 X: (2-)60-61
606–035–00–3	chloridazon (ISO) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx xxxxxxx		216–920–2	1698–60–8	X43 X; X50–53	Xx; X X: 43–50/53 X: (2-)24–37–60–61
606–036–00–9	xxxxxxxxxxxxxx (XXX) 6-methyl-2 X-[1,3]xxxxxxxx[4,5-x]xxxxxxxxxx-2-xx		219–455–3	2439–01–2	Xxxx. xxx. 3; X62 Xx; X20/21/22–48/22 Xx; X36 R43 N; X50–53	Xx; X X: 20/21/22–36–43–48/22–50/53–62 S: (2-)24–37–60–61
606–037–00–4	xxxxxxxxxxx (XXX) 1-(4-xxxxxxxxxxx)- 3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-on		256–103–8	43121–43–3	Xn; X22 X; R51–53	Xn; X X: 22–51/53 X: (2-)61
606–044–00–2	2,4,6-xxxxxxxxxxxxxxxxxxx fenyl(2,4,6-trimethylfenyl)methanon		403–150–9	954–16–5	Xn; X22 Xx; R36 X; X50–53	Xx; N X: 22–36–50/53 S: (2-)26–60–61
607–043–00-X	xxxxxxx (XXX) 3,6-dichlor-2-methoxybenzoová xxxxxxxx		217–635–6	1918–00–9	Xx; X22 Xx; X41 X52–53	Xx; X X: 22–41–52/53 X: (2-)26-61
607–057–00–6	xxxxxxxxx (ISO) 3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X-xxxxxxx-2-xx		201–378–1	81–82–3	Xx; X48/22 R52–53	Xn X:48/22–52/53 S: (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 H -xxxxxxx-2-xx		204–195–5	117–52–2	X; R25–48/25 X52–53	X X:25–48/25–52/53 X: (1/2-)37–45–61
607–079–00–6	xxxxxxx (XXX) ethyl-4-oxo-5-(perchlor-5-hydroxypentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-yl)pentanoát xxxxx-5-(1,2,3,5,6,7,8,9,10,10-xxxxxxxxx-4-xxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx)-4-xxxxxxxxxxxx xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx		—	4234–79–1	X; R24 Xx; X22 X; X51–53	X; X R: 22–24–51/53 X: (1/2-)36/37–45–61
607–097–00–4	benzen-1,2,4-trikarbox-1,2-anhydrid 1,2-xxxxxxxx xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxx		209–008–0	552–30–7	Xx; X37–41 X42/43	Xx R: 37–41–42/43 X: (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-XXX (XXX) 2,3,6-xxxxxxxxxxxxxxxx kyselina		200–026–4	50–31–7	Xn; R22 X; X51–53	Xx; X X: 22–51/53 S: (2-)61
607–153–00–8	xxxxxxxxx (XXX) (4-chlor-2-oxo-2,3-dihydro-1,3-benzothiazol-3-yl)octová xxxxxxxx		223–297–0	3813–05–6	Xx; R36/38 X52–53	Xx X:36/38–52/53 X: (2-)22-61
607–156–00–4	xxxxxxxxxxx (XXX) 4-chlorfenyl-4-chlorbenzen-1-sulfonát		201–270–4	80–33–1	Xn; X22 Xx; X38 N; X50–53	Xx; X X: 22–38–50/53 X: (2-)37–60–61
607–158–00–5	sodná xxx chloroctové kyseliny xxxxxxxxxx xxxxx		223–498–3	3926–62–3	X; R25 Xx; X38 X; X50	X; X X: 25–38–50 S: (1/2-)22–37–45–61
607–159–00–0	chlorobenzilát (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 X: 22–50/53 X: (2-)60-61
607–176–00–3	Xxxx: α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-xxxxxxxxxxx(xxxxxxxxxx);α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-({3-[3-(2 H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propionyl}oxy)poly(oxyethylen)		400–830–7	—	R43 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: O,O′-diisopropyl-trisulfanbis(karbothioát); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx)		403–030–6	—	Xx; R22 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 O; X7 X10 N; X51–53	X; X X: 2–7–10–51/53 X: (2-)3/7–14–33–36/37/39–61
607–217–00–5	2-xxxxxxxxxxx-[4-(7-xxxxx-2,6-xxxxx-2,6-xxxxxxx-1,5-xxxxx-x-xxxxxxx-3-xx)xxxxxx]xxxxxx		403–960–2	—	X43 X53	Xx X: 43-53 S: (2-)24–37–61
607–243–00–7	xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-hydroxyethyl)amonium-3,6-dichlor-2-methoxybenzoát [3] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [3]		217–846–3 [1] 246–590–5 [2] 258–527–9 [3]	1982–69–0 [1] 25059–78–3 [2] 53404–28–7 [3]	X52–53	X: 52/53 S: 61
607–248–00–4	Xxxxxxxx-xxxxxxx Xxxxxxx-X-(1-xxxxxx)xxxxxxxx		205–073–4	132–67–2	Xx; R22	Xn X: 22 X: (2)
607–249–00-X	(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx xxxxxxxxxxxxxxxxx-xxxxxxxxx XXXXX		256–032–2	42978–66–5	Xx; X36/37/38 R43 X; X51–53	Xx; X R:36/37/38–43–51/53 X: (2-)24–37–61	X ≥ 10 %: Xx; X36/37/38–43 1 % ≤ X &xx; 10 %: Xx; X43
607–252–00–6	λ-xxxxxxxxxxx (XXX) 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 S)-cis-3-((Z)-2-chlor-3,3,3-trifluorprop-1-en-1-yl)-2,2-dimethylcyklopropan-1-karboxylát		415–130–7	91465–08–6	T+; R26 X; X25 Xx; X21 X; X50–53	X+; X X: 21–25–26–50/53 X: (1/2-)28–36/37/39–38–45–60–61
607–255–00–2	xxxxxxxxxx (XXX) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx xxxxxxxx		—	69377–81–7	X52–53	X: 52/53 X: 61
608–003–00–4	akrylonitril	D X	203–466–5	107–13–1	X; Xxx Xxxx. xxx. 2; X45 T; X23/24/25 Xi; X37/38–41 X43 N; X51–53	X; X; X X: 45–11–23-/24/25–37/38–41–43–51/53 X: 9–16–53–45–61	C ≥ 20 %: X; X45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; X45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ X &xx; 5 %:T; X45–23/24/25–43 0,2 % ≤ C &xx; 1 %:T; X45–20/21/22 0,1 % ≤ X &xx; 0,2 %: T; X45	43
608–016–00–5	2,3,5,6-xxxxxxxxxx-1,4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxx		401–550–8	1897–41–2	X43 X; R50–53	Xi; 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; X24 X44 X; X50–53	X+; X X: 61–24–28–44–50/53 X: 53–45–60–61
609–040–00–9	xxxxxxxx (XXX) (2,4-dichlorfenyl)(4-nitrofenyl)ether	E	217–406–0	1836–75–5	Karc. xxx. 2; X45 Xxxx. xxx. 2; X61 Xx; R22 X; X50–53	X; X X: 45–61–22–50/53 X: 53–45–60–61
609–044–00–0	xxxxxxxx (ISO) 1,2,4,5-xxxxxxxxxx-3-xxxxxxxxxxx		204–178–2	117–18–0	Xx; X22 R43 X; X50–53	Xx; X R: 22–43–50/53 X: (2-)24–37–60–61
611–008–00–4	4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx		200–453–6	60–09–3	Xxxx. kat. 2; X45 N; X50–53	X; X X: 45–50/53 X: 53–45–60–61
611–013–00–1	4-hydroxy-3-{4-[2-methoxy-4-(3-sulfonatofenylazo)fenylazo]-3-methylfenylazo}-6-(3-sulfonatoanilino)naftalen-2-sulfonát xxxxxxxxx		403–650–7	117409–78–6	X; X2 N; X51–53	X; X X: 2–51/53 X: (2-)35-61
611–031–00-X	4,4'-[(4-iminocyklohexa-2,5-dien-1-yliden)methylen]dianilin-hydrochlorid CI Xxxxx Xxx 9 XX xxxxxxx xxxxxx 9		209–321–2	569–61–9	Xxxx. xxx. 2; X45	X X: 45 X: 53-45
612–035–00–4	2-xxxxxxxxxxxxx x-xxxxxxxx	X	201–963–1	90–04–0	Xxxx. xxx. 2; X45 Xxxx. kat. 3; X40 X; X23/24/25	X X: 45–23/24/25 X: 53-45
612–042–00–2	xxxxxxxx xxxxxxx-4,4'-xxxxxx 4,4'-xxxxxxxxxxxxxx xxxxxxx-4,4'-xxxxxxxxxx	X	202–199–1	92–87–5	Xxxx. kat. 1; X45 Xn; R22 X; R50–53	T; X X: 45–22–50/53 X: 53–45–60–61	X ≥ 25 %: X; X45–22 0,01 % ≤ X < 25 %: X; 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; R40 X; R39/23/24/25Xn; R48/20/21/22 X43 X; X51–53	X; X X: 45–39/23/24/25–43–48/20/21/22–51/53 X:53–45–61
612–081–00–5	3,3'-xxxxxxxxxxxxxxxx, soli x-xxxxxxx, xxxx	X X	210–322–5 265–294–7 277–985–0	612–82–8 64969–36–4 74753–18–7	Xxxx. xxx. 2; R45 Xx; X22 X; X51–53	X; X R: 45–22–51/53 X: 53–45–61
612–099–00–3	4-xxxxxx-x-xxxxxxxxxxxxx4-xxxxxx-1,3-xxxxxxxxxxxxx4-xxxxxxxxxxxx-1,3-xxxxxx 2,4-xxxxxxxxxxxx	X	202–453–1	95–80–7	Xxxx. xxx. 2; X45 T; X25 Xx; X21 Xx; X36 X43 N; X51–53	X; X X: 45–21–25–36–43–51/53 X: 53–45–61
612–105–00–4	2-(piperazin-1-yl)ethylamin2-(piperazin-1-yl)ethan-1-amin		205–411–0	140–31–8	Xn; X21/22 X; R34 X43 X52–53	X X: 21/22–34–43–52/53 X: (1/2-)26–36/37/39–45–61
612–111–00–7	2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,3-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,3-xxxxxx 2,6-xxxxxxxxxxxx		212–513–9	823–40–5	Xxxx. xxx. 3; X40 Xn; X21/22 X43 N; X51–53	Xx; X R: 21/22–40–43–51/53 X: (2-)24–36/37–61
612–125–00–3	2-methyl-p-fenylendiamin2-methyl-1,4-fenylendiamin2-methylbenzen-1,4-diamin 2,5-toluendiamin		202–442–1	95–70–5	T; X25 Xx; X20/21 X43 X; R51–53	T; X X: 20/21–25–43–51/53 X: (1/2-)24–37–45–61
612–144–00–7	xxxxxxxxxxx (XXX) X-(2-xxxxx-6-xxxxxxxxxxx)-X-xxxxx-2,6-xxxxxxx-4-(xxxxxxxxxxxxxx)xxxxxx		—	62924–70–3	Xx; R36/38 R4 3 X; X50–53	Xx; X X: 36/38–43–50/53 X: (2-)36/37–60–61
612–151–00–5	xxxxxxxxxxxxx toluendiamin xxxxxxxxxxxxxxxxxxx methylbenzendiamin	E	246–910–3	25376–45–8	Karc. xxx. 2; X45 X; X25 Xx; R20/21 Xx; X36 X43 X; R51–53	T; X X: 45–20/21–25–36–43–51/53 X: 53–45–61
613–018–00–4	xxxxxxxxxx (XXX) 1,1'-bis[(3,5-dimethylmorfolin-4-karbonyl)methyl]-4,4'-bipyridin-1,1'-diium		—	7411–47–4	Xn; X22 Xi; X36/37/38 X52–53	Xx R: 22–36/37/38–52/53 X: (2-)22–36–61
613–031–00–5	xxxxxxxxx xxxxxxxxxxxxxxxxxxxx xxxxxxxx xxxxxxxx-1,3,5-xxxxxxxxxxxx 1,3,5-trichlor-1,3,5-triazin-2(1H), 4(3X), 6(5H)-trion		201–782–8	87–90–1	O; X8 Xx; X22 X31 Xx; X36/37 X; X50–53	X; Xn; N X: 8–22–31–36/37–50/53 X: (2-)8–26–41–60–61
613–038–00–3	6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxx xxxxxxxxxxxxx		202–095–6	91–76–9	Xx; X22 R52–53	Xn X:22–52/53 X: (2-)61
613–042–00–5	imazalil (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1 H-imidazol		252–615–0	35554–44–0	Xn; X20/22 X; X41 X; R50–53	Xn; X X: 20/22–41–50/53 X: (2-)26–39–60–61
613–043–00–0	xxxxxxxx-xxxxxx (ISO) 1-[2-(allyloxy)-2-(2,4-dichlorfenyl)ethyl]- 1X -imidazol-1-ium-hydrogensulfát [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx		261–351–5 [1] 281–291–3 [2]	58594–72–2 [1] 83918–57–4 [2]	Xx; R20/22 Xx; X41 X; R50–53	Xn; X X: 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 X; X50–53	Xx; N R: 22–50/53 X: (2-)60-61
613–091–00–2	xxxxxxxxxx-xxxxxxxxx [1] xxxxxxxxxx-xxxxxx [2] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx-xxxxxxxxx [1] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxx-xxxxxxxx [2]		225–062–8 [1]	4636–83–3 [1] 29873–36–7 [2]	Xx; X22 Xx; X36/37/38 X52–53	Xx; X: 22–36/37/38–52/53 S: (2-)22–36–61
613–098–00–0	1-xxxxxxxxxxxxxxx-2-xx 1-xxxxx-2-xxxxxxxxxx		403–700–8	2687–94–7	X; X34 X; R51–53	C; 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; X X: 43–51/53 X: (2-)24–37–61
613–131–00–9	xxxxxxxxxx (ISO) 1,2,5,6-tetrahydro-4 X-xxxxxxx[3,2,1-xx]xxxxxxxx-4-xx		—	57369–32–1	Xx; X22 X52–53	Xx X:22–52/53 X: (2-)61
613–134–00–5	xxxxxxxxxxxx (XXX) 2-(4-chlorfenyl)-2-[(1 X-1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx		—	88671–89–0	Xxxx. xxx. 3; X63 Xx; X22 Xx; X36 X; X51–53	Xx; X X: 22–36–51/53–63 X: (2-)36/37–46–61
613–137–00–1	xxxxxxxxxxxxxxxxxx (XXX) 1-(1,3-xxxxxxxxxxxx-2-xx)-1,3-xxxxxxxxxxxxxxxx		242–505–0	18691–97–9	X; X50–53	X R: 50/53 X: 60-61
613–139–00–2	metsulfuron-methyl xxxxxx-2-{X —[X-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxxx]xxxxxxxxx}xxxxxxx		—	74223–64–6	X; X50–53	X X: 50/53 S: 60-61
614–001–00–4	xxxxxxx (XXX) 3-(1-methylpyrrolidin-2-yl)pyridin		200–193–3	54–11–5	T+; X27 X; R25 X; R51–53	T+; X X: 25–27–51/53 X: (1/2-)36/37–45–61
614–006–00–1	xxxxxx 2,3-xxxxxxxxxxxxxxxxxxxx-10-xx		206–614–7	357–57–3	X+; R26/28 X52–53	X+ X:26/28–52/53 S: (1/2-)13–45–61
614–007–00–7	xxxxxx-xxxxxx [1] xxxxxx-xxxxxx [2] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [3] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [4]		225–432–9 [1] 227–317–9 [2] 269–439–5 [3] 269–710–8 [4]	4845–99–2 [1] 5786–97–0 [2] 68239–26–9 [3] 68310–42–9 [4]	X+; X26/28 R52–53	T+ X: 26/28–52/53 S: (1/2-)13–45–61
615–006–00–4	2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-methyl-1,3-fenylendiisokyanát [1] 4-xxxxxx-x-xxxxxxxxxxxxxxxxxx [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] m-tolylidendiisokyanát [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [2] xxxxxx-3,5-xxxxxxxxxxx [3]	C	202–039–0 [1] 209–544–5 [2] 247–722–4 [3]	91–08–7 [1] 584–84–9 [2] 26471–62–5 [3]	Xxxx. xxx. 3; X40 X+; X26 Xx; X36/37/38 R42/43 X52–53	X+ X: 26–36/37/38–40–42/43–52/53 X: (1/2-)23–36/37–45–61	C320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; R23–40–42/43 0,1 % ≤ X &xx; 1 %:Xn; X20–42	2
616–010–00–9	xxxxxxx-xxxxxxxxxxxxxx X-xxxxx-4-xxxxxxxxxxxx-1-xxxxxxxxxx, xxxxx xxx		204–854–7	127–65–1	Xx; X22 R31 X; R34 X42	X X: 22–31–34–42 X: (1/2-)7–22–26–36/37/39–45
616–034–00-X	xxxxxxxxxxxx (XXX) 6-methyl-3,4-dihydro-2H-pyran-5-karboxanilid		246–419–4	24691–76–7	R52–53	R: 52/53 S: 61
616–035–00–5	cymoxanil X -[(xxxxxxxxxx)xxxxxxxx]-2-xxxx-2-(xxxxxxxxxxxx)xxxxxxxx 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx		261–043–0	57966–95–7	Xx; X22 R43 X; X50–53	Xx; N X: 22–43–50/53 S: (2-)36/37–60–61
617–004–00–9	(1,2,3,4-xxxxxxxxxx-1-xxxxxx)xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxx	212–230–0	771–29–9	X; X7 Xx; X22 X; R34 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 % ≤ X &xx; 25 %: X; X34 5 % ≤ X &xx; 10 %: Xx; X36/37/38
617–006–00-X	xxx(α, α-xxxxxxxxxxxxxx)xxxxxxx bis(2-fenylpropan-2-yl)peroxid xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx xxxxxxxxxxxxxx		201–279–3	80–43–3	X; X7 Xx; X36/38 N; X51–53	X; Xx; X X: 7–36/38–51/53 S: (2-)3/7–14–36/37/39–61
617–008–00–0	xxxxxxxxxxxxxxxx		202–327–6	94–36–0	X; X2 Xx; X36 X43	X; Xi; X: 2–36–43 S: (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; X50–53	Xx; X X: 21/22–40–50/53 S: (2-)22–36/37–60–61
650–008–00–9	xxxxxxxxxx (XXX) 4-[(2-xxxxxxxxxx)xxxxxxxxx]-3-xxxxxxxxxxxxxx-5(4 X)-xx		227–197–8	5707–69–7	X; X25 N; X50–53	X; N X: 25–50/53 S: (1/2-)22–24–36/37–45–60–61
650–009–00–4	xxxxxxxxxxxxx-xxxxxxxxxxxx X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx N2-(4-chlor-2-methylfenyl)-N1,N1-dimethylformimidamid-hydrochlorid X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx		243–269–1	19750–95–9	Xxxx. xxx. 3; X40 Xx; X22 X; X50–53	Xx; N X: 22–40–50/53 X: (2-)22–36/37–60–61
650–033–00–5	esfenvalerát (XXX) [(S)-(3-fenoxyfenyl)kyanmethyl]-(S)-2-(4-chlorfenyl)-3-methylbutanoát (S)-3-fenoxy-α-kyanbenzyl-(S)-2-(4-chlorfenyl)-3-methylbutanoát		—	66230–04–4	T; X23/25 X43 X; X50–53	X; N X: 23/25–43–50/53 S: (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; R50–53	N X: 50/53 S: 60-61

XXXXXXX 1D

Indexové číslo	Chemický xxxxx	Xxxxxxxx x xxxxxx	Xxxxx XX	Xxxxx XXX	Xxxxxxxxxxx	Xxxxxxxx	Xxxxxxxxxxxx xxxxxx	Xxxxxxxx x xxxxxxxxxx
006–090–00–8	2-[(3-xxxxxxx-2-xx-1-xx)xxx]xxxxx-X-xxxxxxxxxxxxx		408–010–0	88558–41–2	Xx; X20 Xx; R41 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-xxxxxxxxxxxxxxxxxxxx x 1,3-di(hex-x-en-1-yl)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx		406–490–6	—	X; X51–53	X R: 51/53 X: 61
015–164–00–9	xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx xxxxxxxx		400–480–5	36669–85–9	X52–53	X:52/53 X: 61
015–165–00–4	Xxxx: X, X, X', X''-xxxxxxxxxx-4,4'-xxxxxxxxxxxxx(xxxxxxxxxxxxxx)-xxx(xxxxxxxxxxxxxxxx) x xxxxxxx[4-(xxxxxxxxxxxxx)xxxxx]xxxxxxxxx-xxxxxxxxxxxxxxxx		404–986–7	—	Xx; X41 X; R50–53	Xi; X X: 41–50/53 X: (2-)15–26–39–60–61
015–166–00-X	3,9-xxx(2,6-xx-xxxx-xxxxx-4-xxxxxxxxxxxx)-2,4,8,10-xxxxxxxx-3,9-xxxxxxxxxxxx[5.5]xxxxxxx		410–290–4	80693–00–1	X53	X:53 S: 61
015–167–00–5	3-[hydroxy(fenyl)fosfinoyl]propanová xxxxxxxx		411–200–6	14657–64–8	Xx; X41	Xx X: 41 X: (2-)26-39
601–050–00–1	X10-X13-xxxxxxxxxxxxx xxxxxxx		267–051–0	67774–74–7	X; R50	N X: 50 X: 61
601–051–00–7	4-xxxxxxxx-1-xx		405–980–7	768–56–9	Xx; X38 N; X51–53	Xx; X X: 38–51/53 X: (2-)37-61
602–083–00–4	xxxxxxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx		251–084–2	32534–81–9	Xx; X48/21/22 X64 X; R50–53	Xn; 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 R: 52/53–59 S: 59-61
603–128–00–0	2-(xxxxxxxxxxxx)xxxxxxxx		405–490–3	613–62–7	X53	X:53 X: 61
603–129–00–6	1-xxxx-xxxxxxxxxxxx-2-xx		406–180–0	57018–52–7	X10 Xi; X41	Xx R: 10-41 X: (2-)26-39
603–130–00–1	Směs xxxxxxx: α-(xxxxxxxxxxxxxxxxx)-ω-xxxxxxxxxxx(xxxxxxxxxx)		406–325–8	—	Xx; R22 X52–53	Xx X:22–52/53 X: (2-)39-61
603–131–00–7	Xxxx (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxxx)xxxxx]-X-xxxxxxxx		407–290–1	—	Xx; X41	Xx X: 41 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 S: (2-)26–37/39–61
603–133–00–8	Xxxx:3-(4-xxxxx-2-xxxxx-5-xxxxxxxxxxxx)xxxxxx-1,2-xxxx x 3,3'-[(2-xxxxx-5-xxxxx-1,4-xxxxxxx)xxxxxxx]xx(xxxxxx-1,2-xxxx)		408–240–1	—	Xx; R22 X52–53	Xx X:22–52/53 X: (2-)22–36–61
603–134–00–3	Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx a xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (xxxxxxx a xxxxxxxxxx nerozvětvené)		410–450–3	—	R53	R: 53 X: 61
603–135–00–9	bis[2-(2-methoxyethoxy)ethanolato]bis(2,2', 2-xxxxxxxxxxxxxxx-1-xxxxx-X,X)xxxxxxxxxx xxxxxxx		410–500–4	—	Xx; X41 X; X51–53	Xx; X X: 41–51/53 X: (2-)26–39–61
603–136–00–4	3-{4-[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 R: 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; X 35 N; X50	X; X; N R: 23–35–50 S: (1/2-)26–36/37/39–45–61	X ≥ 25 %: X; X; R23–35 10 % ≤ X &xx; 25 %: X;X20–35 5 % ≤ X &xx; 10 %: X;X20–34 3 % ≤ X < 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'-methylenbis[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -benzotriazol-2-yl)- 4,4'-xxx(1,1,3,3-xxxxxxxxxxxxxxxx)- 2,2'-xxxxxxxxxxxxxxx		403–800–1	103597–45–1	X53	X:53 S: 61
604–053–00–6	4-terc - xxxxx-2-xxxxxx-6-(1-xxxxxxxxxxxxxxxx)xxxxx		410–760–9	157661–93–3	Xx; R38 X43 N; X50–53	Xx; X X: 38–43–50/53 X: (2-)24–37–60–61
604–054–00–1	Směs:2-methoxy-4-(4-methylidentetrahydropyran-2-yl)fenol a 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -pyran-2-yl)fenol		412–020–0	—	R43 R52–53	Xi X:43–52/53 X: (2-)24–37–61
604–055–00–7	4,4'-xxx[(2,3-xxxxxxxxxxx)xxx]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx		413–900–7	85954–11–6	Xxxx. Xxx.3; X40	Xx X: 40 X: (2-)22–36–37
605–027–00–7	Xxxx:3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X-xxxxx-6-xxxxxxxxxxx a 3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X - xxxxx-5-xxxxxxxxxxx		410–480–7	—	X43 X; X51–53	Xx; X R: 43–51/53 X: (2-)24–37–61
606–051–00–0	4-xxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxx-1-xx		4–406–670–4	61203–83–6	X; X51–53	X X: 51/53 X: 61
606–052–00–6	4-(X, X-xxxxxxxxxxxx)-2-xxxxxxx-2'-xxxxxxxxxxxxxxxxx 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx xxxxxxxx		410–410–5	54574–82–2	X52–53	X:52/53 S: 61
607–272–00–5	xxxxxxxxxxx-xxxxxx (XXX) [1] xxxxxxxxxx-xxxxxxxxx (XXX) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-butoxy-1-methylethyl)-[(4-amino-3,5-dichlor-6-fluor-2-pyridyl)oxy]acetát [2]		279–752–9 [1] —	81406–37–3 [1] 154486–27–8 [2]	X; X50–53	X X: 50/53 X: 60-61
607–273–00–0	amonium-7-{2,6-dimethyl-8-[(2,2-dimethylbutanoyl)oxy]- 1,2,6,7,8,8x-xxxxxxxxx-1-xxxxxx}-3,5-xxxxxxxxxxxxxxxxxx		404–520–2	—	X52–53	X:52/53 X: 61
607–274–00–6	{2-[xxxxxx(xxxxxx)xxxxx]xxxxx}-3-xxxxxxxx-2-xxxxx		405–350–1	54527–73–0	X43 X; X51–53	Xx; N X: 43–51/53 S: (2-)24–37–61
607–275–00–1	xxxxxxx-4-(xxxxxxxxxx)xxxxxx-1-xxxxxxxx		405–450–5	66531–87–1	X43	Xx X: 43 S: (2-)24-37
607–276–00–7	[xxx(2-xxxxxxxxxxxxxx) bis(1-methylimidazol)]zinečnatý xxxxxxx		405–635–0	—	Xx; X38–41 X; X50–53	Xx; X R: 38–41–50/53 X: (2-)26–37/39–60–61
607–277–00–2	Xxxx:2-(xxxxxxxxxxxxx)xxxxxxxxx-xxxxxxxxxxxx x xxxxxxx-xxxxxxxxx		405–720–2	—	Xx; R22 Xx; X41 R43 X; X51–53	Xx; X X: 22–41–43–51/53 X: (2-)24–26–37/39–61
607–278–00–8	Xxxx:xxxxx(X7-X9 xxxxxxxxxx x xxxxxxxxxxxx)-3-[3-(2 X - xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx		405–760–0	—	Xx; X41 X43 X52–53	Xx X: 41–43–52/53 X: (2-)24–26–37/39–61
607–279–00–3	Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) a (xxxxxxxxxxxxxx)xxxxxxxxx-(xxxxxxxx-xxxxxx)-(xxxxxxxx-xxxxxxxx)		405–960–8	—	X43 X; R51–53	Xi; 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 Xx; X36 X43	Xx R: 22–36–43 X: (2-)22–26–36/37
607–281–00–4	Směs:alkyl(C7-C9 xxxxxxxxxx x xxxxxxxx)-3-[3-(2X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx		407–000–3	127519–17–9	X; 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 N; X50–53	Xx; N R: 21/22–38–41–43–50/53 S: (2-)26–36/37/39–60–61
607–284–00–0	Směs (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) x xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx)		410–040–4	136213–76–8	X; X51–53	X X: 51/53 X: 61
607–285–00–6	Xxxx:7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxxx xxxxxxxx, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx x natrium-7-(3-aminobenzensulfonamido)naftalen-1,3-disulfonát		410–065–0	—	R43	Xi X: 43 X: (2-)22–24–37
607–286–00–1	Xxxx:xxxxxx- a xxxxxxx-7-[4-({4-[(2-xxxxxxx-1-xxxxxx)xxx]xxxxx}xxx)xxxxxxxxxxxxxxxxx]xxxxxxxx-1,3-xxxxxxxxxx		410–070–8	141880–36–6	X43 X52–53	Xx R:43–52/53 X: (2-)22–24–37–61
607–287–00–7	xxxxxx-[1-xxxxxx-2-(xxxxxxxxxxxxxxx)xxxxx]-1,2,3,6-xxxxxxxxxxxxxxxx		410–140–8	—	X52–53	X:52/53 X: 61
607–288–00–2	[c-(N -{3-[(1-{3-[(2,6(4,6)-xxxxxxx-5-xxxxxxxxxxxxx-4(2)-xx)xxxxxxxxxxx]xxxxxx}-2-xxxxxxx-4-xxxxxx-6-xxx-1,6-xxxxxxx-3-xxxxxxx)xxx]-4-xxxxxxxxxxxxxx}xxxxxxxxx)-x,x,x -xxxxxxxxxxxxxxxxxxxxxxx]xxxxxxxxx xxxxxxx, xxxxxxxxxx xxx; x = 15, 16, 17 nebo 18, x = 1, 2, 3 xxxx 4, b = 8, 9, 10 xxxx 11, d = 22, 23, 24 nebo 25		410–160–7	148732–74–5	Xx; X36 X43 X52–53	Xx X: 36–43–52/53 X: (2-)22–26–36/37–61
607–288–00–8	3-[(3-{X —[4-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxx]xxxxxxxxx}-4-xxxxxxx-1-xxxxxx)xxxxxxxx]xxxxxxxxx xxxxxxxx		410–370–9	105488–33–3	X53	X:53 X: 61
607–290–00–3	Směs (x xxxxxxxx xxxxxx):xxxxxxx-1-xxxxx(X14-X18)-4-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx a xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx		410–540–2	—	Xx; R38 X43 X; X50–53	Xx; N X: 38–43–50/53 X: (2-)24–37–60–61
607–291–00–9	xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx		410–630–1	104051–92–5	X53	X: 53 X: 61
607–292–00–4	Směs:[2-(alkyl(C12)oxy)-1-(methoxymethyl)ethoxy]octová xxxxxxxx x [2-(xxxxx(X14)xxx)-1-(xxxxxxxxxxxxx)]xxxxxx kyselina		410–640–6	—	Xi; X38–41 X; X50–53	Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61
607–293–00-XSměs:	1-(2-aminoethyl)piperazin-1,4-diium-[(2,4,6-trimethylnonyl)fenoxy]benzendisulfonát x 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx		410–650–0	—	Xx; X41 X43 X; X51–53	Xx; N 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 R: 43 X: (2-)24-37
607–295–00–0	Xxxx:xxxxxxxxxxxx-xxxxxxxxxxxxxxxxx x xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx		410–800–5	—	X43 N; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
607–296–00–6	Směs:tetraestery xxxxxxxxxxxxxxxx, xxxxxxxxx xxxxxxxx x 2-xxxxxxxxxxxxx kyselina		410–830–9	—	R53	R: 53 X: 61
607–297–00–1	3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(2-xxxxxxxxx-10-xxxxxxxxx xxxxxxxx)2,2'-xxxxx-3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(1,7,7-xxxxxxxxxxxxxxxx[2.2.1]xxxxxx-1-xxxxxxxxxxxxxxx xxxxxxxx)		410–960–6	92761–26–7	Xx; X41	Xx R: 41 X: (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; N X: 22–43–50/53 X: (2-)24–37–60–61
607–300–00–6	[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, x-xxxxxxxxxxxxxxxxxxxx]xxxxxxx xxxxxxx, xxxxxxxx sůl; x = 1,2,3 xxxx 4, b = 8, 9, 10 xxxx 11, x = 15, 16, 17 nebo 18, x = 22, 23, 24 nebo 25		411–430–7	—	X43	Xx X: 43 X: (2-)22–24–37
607–301–00–1	Směs:dodekanová kyselina x xxxxxxxxxxx oligo(1-7)laktátů		411–860–5	—	Xi; X38–41 X43 N; X51–53	Xx; X R: 38–41–43–51/53 X: (2-)24–26–37/39–61
607–302–00–7	Xxxx:xxxxxxxxxxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxxx(1-7)xxxxxxx		411–910–6	—	Xx; X38–41 R43 X; R51–53	Xi; X X: 38–41–43–51/53 S: (2-)24–26–37/39–61
607–303–00–2	1-xxxxxxxxxxx-6,7-xxxxxxx-4-xxx-1,4-xxxxxxxxxxxxxxx-3-xxxxxxxxxxx xxxxxxxx		413–760–7	93107–30–3	Xxxx. xxx.3; X62 X52–53	Xx X: 62–52/53 S: (2-)22–36/37–61
608–023–00–3	4-(4-xxxxxxxxxx)-2-xxxxx-2-[(1X- 1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx		406–140–2	114369–43–6	X; X50–53	X X: 50/53 S: 60-61
608–024–00–9	2-{4-[butyl(fenethyl)amino]fenyl}ethen-1,1,2-trikarbonitril		407–650–8	97460–76–9	R53	R:53 X: 61
608–025–00–4	[2-xxxxx-4,5-xxx(xxxxxxxxx)xxxxx]xxxxxxxxxxx		410–970–0	117568–27–1	X53	X:53 X: 61
609–053–00-X	xxxxxxxxxxx-xxxxxxxxxxxxxxxx		414–850–9	—	X; R3 X; X8 Xxxx. xxx. 2; R45 X; X23/25 X43	X; T X: 45–3–8–23/25–43 X: 53-45
610–010–00–2	1-xxxx-2-(2-xxxxx)-1-xxxxxxxxxx		406–110–9	35950–52–8	Xx; X22–48/22 X; X34 X43 X; X50–53	X; X R: 22–34–43–48/22–50/53 X: (1/2-)22–26–36/37/39–45–60–61
611–043–00–5	Xxxx (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx trisodný, [bis{6-[(2-amino-4-hydroxyfenyl)azo]- 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 a[{6-[(2-amino-4-hydroxyfenyl)azo]- 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 X: (2-)26–39–61
611–044–00–0	Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [(5-terc-butyl-3-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)(5-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx a[(4(5)-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato) (3-xxxxx-5-xxxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx		403–720–7	117527–94–3	X; X51–53	Xx; 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 X: 61	N X: 51/53 X: 61
611–046–00–1	4,4'-xxxxxxx-2-xxxxxxxxxxxxxxx2-xxxxxxxxxxxxxxx-4,4'-xxxxxx		407–590–2	43151–99–1	X; R25 Xn; X48/22 X43 X; X50–53	X; N X: 25–43–48/22–50/53 X: (1/2-)22–28–36/37–45–60–61
611–047–00–7	Xxxx (1:1):2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx a 2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx		407–890–3	111381–11–4	X53	X: 53 X: 61
611–048–00–2	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 S: 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 octová x mléčná kyselina (2:1:1)	408–000–6	118658–98–3	Xx; X48/22 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 S: 60-61
611–052–00–4	[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) azo]-6-[(6-sulfonato-1-naftyl)azo]benzen-1,3-diolato}]železnatý komplex, xxxxx xxx		400–720–9	—	X52–53	X: 52/53 X: 61
612–156–00–2	Xxxx:xxxxxxxxxxxx(xxxxxx)xxxxxxx-xxxxxxx x xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx		405–620–9	—	Xx; X41 X; X50–53	Xx; N X: 41–50/53 X: (2-)26–39–60–61
612–157–00–8	(X)-1-(1-xxxxxxxxxxxx-2-xx)xxxxx-1-xx-xxxx-xxxxxxxxxxxx		410–780–8	—	Xx; X22–48/22 Xx; R41 X43 X; R51–53	Xn; X X: 22–41–43–48/22–51/53 X: (2-)22–26–36/37/39–61
612–158–00–3	Xxxx:[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 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 směsi 2,2,4-xxxxxxxxx- a 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x xxxxxxx XXXXXX), xxxxxxxx [(alkyl(C10-C16)oxy)methyl]oxiranu (Xxxxxx 8) x 4-methylbenzen-1-sulfonové xxxxxxxx		410–880–1	—	Xx; X22 X; X34 X; R50–53	C; 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 X: 43–51/53 X: (2-)24–37–61
613–153–00–9	2,3,5-xxxxxxxxxxxxxxx		407–270–2	16063–70–0	X52–53	X:52/53 X: 61
613–154–00–4	2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx		410–050–9	5734–64–5	Xx; R22	Xn R: 22 X: (2-)22
613–155–00-X	5-xxxxx-2,3-xxxxxxxxxxxxxx		410–090–7	89402–43–7	X10 Xx; X22 R52–53	Xn X: 10–22–52/53 X: (2-)23–36–61
613–156–00–5	2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-butyl-5-chlorimidazol-4-karbaldehyd		410–260–0	83857–96–9	R43 X; X51–53	Xx; X R: 43–51/53 X: (2-)24–37–61
613–157–00–0	2,4-xxxxxxx-5-(xxxxxxxxxxxxx)xxxxxxxxx 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx		410–330–0	54236–98–5	Xx; X22–48/22 Xx; X36	Xx X: 22–36–48/22 X: (2-)22–26–36
613–158–00–6	2,3-dichlor-5-(trifluormethyl)pyridin		410–340–5	69045–84–7	Xn; R20/22 Xx; R41 X43 X; X51–53	Xx; X X: 20/22–41–43–51/53 X: (2-)24–26–37/39–61
613–159–00–1	4-[2-(4-xxxx-xxxxxxxxxx)xxxxxx]xxxxxxxxxx		410–580–0	120928–09–8	X; X25 Xx; X20 X; R50–53	T; X X: 20–25–50/53 X: (1/2-)37–45–60–61
613–160–00–7	2-methyl-2,5-diazabicyklo[2.2.1]heptan-dihydrobromid		411–000–9	125224–62–6	R43	Xi R: 43 X: (2-)24-37
615–022–00–1	methyl-3-(isokyanatosulfonyl)thiofen-2-karboxylát		410–550–7	79277–18–2	E; X2 R14 Xn; X48/22 X42/43	X; Xn X: 2–14–42/43–48/22 X: (2-)22–30–35–36/37
615–023–00–7	xxxxxxxxxxx 2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxxx xxxxxxxxxxxxxx-2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxx		410–900–9	83056–32–0	X10 X14 Muta. xxx. 3; X40 Xx; X20–48/22 Xx; R41 X42	Xx X: 10–14–20–40–41–42–48/22 X: (2-)23–26–36/37/39
616–044–00–4	X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)-2-(3-xxxxxxxxxxxxxxxx)xxxxxxxxx		402–510–2	—	X; R51–53	N X: 51/53 S: 61
616–045–00-X	2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxxxxx		405–190–2	122371–93–1	X43 R53	Xi X: 43-53 X: (2-)22–24–37–61
616–046–00–5	X -[2-(6-xxxxx-7-xxxxxxxxxxxxxx[1,5-x][1,2,4]xxxxxxx-4-xx)xxxxxx]-2-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxxxxxx		406–390–2	—	X; X50–53	X X: 50/53 X: 60-61
616–047–00–0	Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x N, X′,X″,X′′′ - tetraalkyl(C18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx		406–640–0	—	X43	Xx R: 43 X: (2-)24-37
616–048–00–6	3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx		406–740–4	1939–27–1	Xx; X48/22 X; X51–53	Xx; X X: 48/22–51/53 X: (2-)22–36–61
616–049–00–1	2-(2,4-xx-xxxx-xxxxxxxxxxx)-X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxx		408–150–2	99141–89–6	X53	X:53 X: 61
616–050–00–7	1-[2,5-xxxxxxx-4-(1,1,2,3,3,3-xxxxxxxxxxxxxxxx)xxxxx]-3-(2,6-xxxxxxxxxxxx)xxxxxxxx		410–690–9	103055–07–8	X43 X; R50–53	Xi; 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'-bis(4-methylfenyl)-1,1'-(2-methyl-1,3-fenylen)dimočovina Směs:2,4-bis[3-(4-methylfenyl)ureido]toluen x 2,6-xxx[(3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx		411–070–0	—	X53	X: 53 X: 61
617–015–00–9	xxx(4-xxxxxxxxxxxxx)xxxxxxx		407–950–9	895–85–2	X; R2 X; X7 N; X50–53	X; X X: 2–7–50/53 S: (2-)7–14–36/37/39–47–60–61
650–032–00-X	xxxxxxxxxxxx (XXX) (2R, 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. xxx. 3; X63 Xn; X22 X; X50–53	Xx; X X: 22–50/53–63 S: (2-)36/37–60–61

PŘÍLOHA 2

POVAHA XXXXXXXXXXXX XXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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

XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX ZACHÁZENÍ X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.

XXXXXXX 3B

STANDARDNÍ POKYNY XXX XXXXXXXX XXXXXXXXX X NEBEZPEČNÝMI LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.

XXXXXXX 4X

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

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx metody XXXX XX 473 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx u savců xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx chromozomové xxxxxxx x savců xx xxxxx xx xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx savců (1, 2, 3). Rozlišují xx xxx typy xxxxxxxxxxxx aberací: chromozomové x chromatidové. X xxxxxxx xxxxxxxxxx mutagenů xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx chemická xxxxx xx xxxxxxxxx indukovat xxxxxxxxx aberace. Tato xxxxxx xxxx není xxxxxx ke stanovení xxxxxxxxxxx aberací x xxxx x tomuto xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx mutace x xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx důkazů o xxx, xx xxxxxxxxxxxx xxxxxx x x xxxx xxxxxxxxxxx jevy xxxxxxxxxxx změny x xxxxxxxxxx a v xxxxxx xxxxxxxxxxx buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxx mohou být xxxxxxx xxxxxxxxxxxxx buněčné xxxxx, xxxxxxx xxxxx xxxx xxxxxxxx buněčné xxxxxxx. Xxxxxxx buňky xxxx vybrány xx xxxxxxx schopnosti růstu x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx četnosti chromozomových xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx zdroje xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Je xxxxx se xxxxx xxxxxxxxx podmínek, xxxxx xx xxxxx k xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx mutagenitu x xxxx x xxx xxxxx xxxxxx xX, xxxxxxxxxx nebo xxxxxxxx úrovní xxxxxxxxxxxx (4, 5).

Xxxx zkouška xx xxxxxxx ke xxxxxxxx možných mutagenů x xxxxxxxxxxx xxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx je xxxx xxxxxxx pozitivní, xxxx xxx xxxxx xxxxxxxxxxx; xxxx touto xxxxxxxx x karcinogenitou xxxx xxxx xxxxxxxxx xxxxxxxx. Korelace xxxxxx xx xxxxxxxx xxxxx x přibývají xxxxxx x tom, xx xxxxxxxx karcinogeny, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxxxxx XXX.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx aberace : strukturní poškození xxxxxxxxxx x xxxxxx xxxxx xxxx zlomu x xxxxxxx xxxx xxxxxxxxx x xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : xxxxxx, xxx xxxxxx v xxxxx po X-xxxx xxxxxxxxx DNA xxxxxxx x xxxxxx, nýbrž xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx jsou chromozomy xx 4, 8, 16… chromatidami.

Gap : xxxxxxxxxxxx léze menší xxx xxxxx jedné xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx xxxxx : podíl xxxxx, xxxxx xx xxxxxxxxx x xxxxxxxx, x xxxxxxxxx xxxxx xxxxx x populaci; xxxxx stupeň xxxxxxxxxxx xxxx xxxxxxxx.

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

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

Xxxxxxxxxx aberace : xxxxxxxxxxxxx pozorovatelné změny xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx; xxxx xx jako xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx změny.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx vystaveny xxxxxxxx látce, a xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. X xxxxxx xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxx se xx xxxxxxxxx xxxxxx xxxxx látka xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx), kultury xx xxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxxxxxxx xxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx různé buněčné xxxxx, xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxx lidských buněčných xxxxx (např. fibroblasty xxxxxx xxxxxxxx, xxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx jiných savců).

1.4.1.2 Xxxxx a kultivační xxxxxxxx

Xxx udržování xxxxxx xx měla xxx xxxxxxx vhodná kultivační xxxxx x inkubační xxxxxxxx (kultivační nádoby, xxxxxxxxxxx XX2, xxxxxxx x vlhkost). X xxxxxxxxxxxxxxx buněčných linií x kmenů xx xxxx xxx xxxxxxx xxxxxxxxxxxx stabilita modální xxxxxxx xxxxx xxxxxxxxxx x mělo xx xxx kontrolováno, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Pro xxxxxxx xxxxx x inkubační xxxxxxxx xx xxxx xxx xxxxx xxxxxxxx xxxxx buněčného cyklu.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx x xxxxx: xxxxx xx pomnoží x kmenových xxxxxx, xxxxxx xx xx xxxxxxxxxxxx xxxxx x xxxxxx hustotě, xxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx, x inkubují xx xxx 37 °X.

Xxxxxxxxx: xxxx ošetřená xxxxxxxxxxxxxxx (xxxx. xxxxxxxxx) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx probandů xx xxxxxxx xx xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. xxxxxxxxxxxxxxxx) a xxxxxxxx xx xxx 37 °C.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx metabolickou xxxxxxxx x bez xx. Nejčastěji xxxxxxxxxx xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená x xxxxx xxxxxxxx zpracovaná xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (6, 7, 8 x 9), xxxx xxxx fenobarbitonu x β-naftoflavonu (10, 11 a 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx v xxxxxxxx testovacím xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % obj. Xxxx xxxxxxxxxxxxx aktivačního xxxxxxx může xxxxxxx xx třídě xxxxxxxx xxxxx, která xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx výsledků xxxxxx, včetně přípravy xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, poskytuje xxxxxxxx xxx endogenní xxxxxxxx. Xxxxx použitých xxxxxxxxx xxxxx xx xxxx být vědecky xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 xxx metabolismus xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky mohou xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxx x s xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo by xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx xx xxxx by xxxx xxx použita xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx. Xxxx xxx xxxxxxxxx přidáním molekulového xxxx.

1.4.2.2 Expoziční koncentrace

Mezi xxxxxxxx, která mají xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxx koncentrace, xxxxx xxxxxxxxxxxx, rozpustnost x xxxxxxxxxx xxxxxxx x xxxxx xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx ní x xxxxxxx experimentu xx xxxxxxx xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x růstu, xxxx xxxx xxxxxx konfluence, xxxxx životaschopných xxxxx xxxx xxxxxxxxx xxxxx. Xxxx xxx výhodné xxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx alespoň xxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx xxxxxxxxxxxx xx xxxx tyto xxxxxxxxxxx xxxxxxxx rozmezí xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, což xxxxxxx xxxxxxx, xx xx xx xxxxxxxxxxx neměly xxxxx xxxx nežli xxxxxxxx 2 xx Ö10. V okamžiku xxxxxxx by měla xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx snížení xxxxxx xxxxxxxxxx, xxxxx xxxxx xxxx mitotického indexu (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx a závisí xx xxxx, xxxxx xxxxxxxx xx expozice. Xxxxxxxxx index xx xxxx přijatelný x xxxxxxxxxxx kultur, x xxxxx xxxxx xxx xxxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx a xxxxxxxxxxx. Informace x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (AGT), xxxxx xxx xxxxxxx xxxx xxxxxxxxx xxxxxxxxx. V xxxxxxx XXX xxxx xxx o xxxxxxxx xxxxxxxxx xxxxxxx, x xxx xxxxx xxxxxxx xx existenci xxxxxxxxxx xxxxxxxxxxx, x i xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx doby xxxx xxx za xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx optimálního výtěžku xxxxxxx.

X xxxxxxx relativně xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 mg/ml xxxx 0,01 X, xxxxx xxxx, xxxxx x xxxx je xxxxxxxx.

X xxxxxxx relativně xxxxxxxxxxxxx látek, které xxxxxx toxické při xxxxxxxxxxxxx nižších, xxx xx xxxxxx xxxxxxxxxxx, xx měla xxx xxxxxxx nejvyšší dávka x xxxxxxxxxxx, xxx xx xxx mezí xxxxxxxxxxxx x konečném xxxxxxxxxxx xxxxx na xxxxx xxxx xxxxxxxx. X určitých xxxxxxxxx (xxxx. xxxxxxx-xx xx xxxxxxxx xxxxx při xxxxxxx koncentracích, než xx rozpustnost) xx xxxxxxxxxx xxxxxxxxx více xxxxxxxxxxx, xxx xxxxx xxxxxxx xx xxxxxxx. Xxxx být xxxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x na xxxxx expozice, xxxxx xxxxxxxxxxx v xxxxxxxxxx xxxxxxx xx xxxx x xxxxxxx expozice xxxxx v xxxxxxxx xxxxxxxxxxx buněk, séra X9 atd. Nerozpustnost xxx xxxxxxx vizuálně. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx měly xxx xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx vehikula). Xxx xxxxxxx xxxxxxxxxxx xxxxxxxx xx měla xxx xxx pozitivní kontrolu xxxxxxx xxxxxxxx látka, xxxxx x mutagenní xxxxxx xxxxxxxx aktivaci.

K xxxxxxxxx kontrole xx xxx být použit xxxxx xxxxxxxxx x xxxxxxxxxxx koncentracích, xxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxx, xxxx xx prokáže xxxxxxxxx xxxxxxxxxxx systému.

Koncentrace pozitivních xxxxxxx xx měly xxx xxxxxxx tak, xxx xxx účinek xxxxxxxx, xxx xxx xxx odečtu nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx	Xxxxx	Xxxxx XXX	Xxxxx xxxxx XXXXXX
Xxx 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 monohydrát	6055–19–2	200–015–4

Pro xxxxxxxxx xxxxxxxx xxxxx být xxxxxxx i xxxx xxxxxx xxxxx. Pro xxxxxxxxx xxxxxxxx by xxxx xxx xxxxx xxxxx xxxxx x xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx třídy.

V okamžiku xxxxxxxx by xxxx xxx xxxxxxx negativní xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx rozpouštědla xxxx xxxxxxxx x xxxxxxxxxxx xxxxx x xxxxxxxxxx stejným způsobem xxxx kultury. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx žádné xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxxxxx xxxxxxxx látce xxx za přítomnosti xxxxxxxxxxxxx aktivačního xxxxxxx, xxx xxx něho. Xxxxxxxx lymfocytů by xxxx být zahájena xxx 48 xxxxx xx mitogenní xxxxxxxxx.

1.4.3.2 Xxx xxxxxx xxxxxxxxxxx xx měly být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, a xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx pro xxxxxxxxx xxxxxxxx nebo xxxxxxxx rozpouštědla. Jestliže xxx na xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx duplicitními xxxxxxxxx xx xxxxxxxxx xxxxxx, xxxx xxx xxxxxxxxx xxxxxxx jediné xxxxxxx.

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

1.4.3.3 Xxxx xxxxxxx xxxxxx

X xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxx xxxxxxxxx xxxxxxxx látce, xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx ní, xx dobu 3 — 6 xxxxx, x xxxx by xxx xxxxxxxx xx xxxxxx době od xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (12). Xxxxxxxx xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx jak x xxxxxxxx, tak xxx xxxxxxxx, měl by xxx xxxxxxxx dodatečný xxxxxxxxxx xxx xxxxxxxx x nepřetržitou xxxxxxxx xx xx xxxxxx x xxxx, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx xxxxx xxx xxxxx xxxxxxxxx xxx xxxxxx aplikace xxxx xxxxxx xxxxxxx xxx 1,5násobek délky xxxxx. Xxxxxxxxx xxxxxxxx xxx xxxxxxxxxxx aktivaci xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. X případech, xxx xx nepovažuje potvrzení xxxxxxxxxxx výsledků xx xxxxxxxx, by xxxx xxx xxxxxx zdůvodnění.

1.4.3.4 Xxxxxxxx preparátů pro xxxxxxx chromozomů

Do xxxxxxx xxxxxxx se xxxxxxx 1-3 xxxxxx xxxx xxxxxxxxx xxxxx Xxxxxxxx® xxxx kolchicin. Xxx xxxxxxxx xxxxxxxxx pro xxxxxxx chromozomů se xxxxx xxxxxxx xxxxxxx xxxxxx a zpracovává xxxxxx. Příprava xxxxxxxxx xxx analýzu xxxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx a xxxxxxxx xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x negativních xxxxxxx, xx měly xxx xxxx xxxxxxxx xxx xxxxxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx xxx fixaci xxxxx xxxxxxx ke xxxxx xxxxx buněk x xxxxxxxx a xx xxxxxx xxxxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxx xxxxxxx xxxxxxx ± 2 xxx xxxxxxx xxxx xxxxx. Na xxxxxx xxxxxxxxxxx x xxxxxxxx xx mělo xxx hodnoceno xxxxxxx 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxx duplicitní xxxxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx.

Xxxxxx je xxxxxx xxxxxxx xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx, xx xxxxxxxx xxxxxxxxxx polyploidii x xxxxxxxxxxxxxxx, xxxx-xx xxxxxxxxxx.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx x xxxx xx xxxx být xxxxxxxxxxx množství buněk xx strukturní chromozomovou xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Xxxx xx zaznamenávají xxxxxxxx x xxxxxxx xx, xxx xxxxxxxxxx xx do xxxxxxx xxxxxxxx xxxxxxx.

Xxxx by xxx xxxx xxxxxxxxxxx xxxxxxxx, která xxxx xxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxx u všech xxxxxxxxxxxx kultur x xxxxxxxxxxx kultur x xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

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

Xxxxxxx xxxxx pozitivní xxxxxxxx xx xxxxxxxxxx. Dvojznačné xxxxxxxx xx měly xxx vyjasněny xxxxxx xxxxxxxxx, nejlépe s xxxxxxxx experimentálních xxxxxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx x bodu 1.4.3.3. Xxxxx xxxxxxxxx studie x xxxxx rozšířit xxxxxx posuzovaných podmínek xx měla xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx koncentrací x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x chromozomovými aberacemi x xxxxxxxxxx xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx xxxxxx xxxxx. Xxxxxxxx xx měla xxx uvážena biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků zkoušky xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (3, 13). Xxxxxxxxxxx významnost xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxx znamenat, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxx xxxxx buněk x endoreduplikovanými xxxxxxxxxx xxxx xxxxxxxx, že xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (17, 18).

Xxxxxxxx látka, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx kritéria, se x tomto xxxxxxx xxxxxxxx za nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx poskytne xxxxx xxxxxxxxx nebo xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx o xxxxxxxx xxxxxxxx látky. Xxxxxxxx xxxxx zůstat xxxxxxxxxx xxxx sporné xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx typu xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- informace o xxxxx xxxxxxxxx xxxxx,

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

- xxxxxxxx počet xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx kultury,

- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

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

- složení xxxxx, xxxxxxxx xxxxxxxxxxx XX₂,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx vehikula x xxxxxxx zkoušené xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- xxxxxxxx hustota xxxxx xxx xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx kontroly,

- xxxxxx xxxxxxxx preparátů,

- kritéria xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxxxxx,

- metody xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx, xxxx. stupeň xxxxxxxxxx, xxxxx x xxxxxxxx xxxxx, xxxxx xxxxx, xxxxxxxxx index,

- xxxxxx xxxxxxx,

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

- xxxxxxxx xxxxxxx, xxxxxx xxxx,

- xxxxx buněk s xxxxxxxxxxxxxx xxxxxxxxx x xxxx xxxxxxx zvlášť xxx xxxxxx xxxxxxxxxxx x kontrolní kulturu,

- xxxxx xxxxxxx, pokud xxxx pozorovány,

- xxxxx xxxxxxxx xxxxxxxxx odpovědi xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

- dosavadní xxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx x rozpětími, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X. (1976), Xxxxxxxxxxx Xxxxxxx xxx Detecting Chemical Xxxxxxxx, xx: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx and Xxxxxxx xxx xxxxx Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, X. (xx) Xxxxxx Xxxxx, Xxx Xxxx and Xxxxxx, 1-29.

2) Ishidate, X. Xx., Xxxxxx, X. (1985), The Xx xxxxx Chromozomal Xxxxxxxxxx Xxxx Xxxxx Xxxxxxx Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Xxxxx xx Xxxxxxx, in: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Xxxxx, X. xx al., (xxx) Xxxxxxxx Science Xxxxxxxxxx, Amsterdam-New Xxxx-Xxxxxx, 427-432.

3) Galloway, X. X., Xxxxxxxxx, X. X., Xxxxxx, X., Xxxxxx, X., Brown, X., Cannon, C., Xxxxx, A. D., Xxxxxxxx, X., Xxxxx, X., Xxx, S., Xxxxx, X., Xxxxxxxx, X. H., Resnick, X. X., Anderson, X., Zeiger X. (1978), Chromozome aberration xxx xxxxxx xxxxxxxxx xxxxxxxxx xx Chinese xxxxxxx xxxxx cells: Xxxxxxxxxx xx 108 xxxxxxxxx, Environ. Xxxxx. Xxxxxxx. 10 (suppl. 10), 1-175.

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

5) Xxxxxx, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxx, K., (1992), Xxxxxxxxxxxxxx xx xxx xX xx Xxxxxxx Cultured Xxxxxxxxx Xxxxx, Xxxxxxxxxx Res., 268, 297-305.

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

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

8) Xxxxxxxxx, X. T., Xxxxx, X. X., xxx Xxxx, X. X. X., Xxxxxxx, M., xx Xxxxx, N. (1976), Xxxxxxxxxxx Effects xx Xxxxxxx/Xxxxxxxxxxx xxxxx Xxxxxxxxxx in a Xxxxxxxxxxx Xxxxxx Xx xxxxx, I. Xxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xxx Xxxxxx Chromatid Xxxxxxxx by Diethylnitrosamine (XXX) and Dimethylnitrosamine (XXX) xx XXX Xxxxx xx xxx Xxxxxxxx of Rat-Liver Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

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

10) Xxxxxx, X. M., Combes, X. X., Elcombe, X. X., Xxxxxxxxx, X. X., Gibson, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Party. Alternative xx Aroclor 1254-xxxxxxx X9 in In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, K., Xxxxxxxx, X. (1976), X. Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx of Metabolic Xxxxxxxxxx Systems, in: xx Serres, X. X., Xxxxx, J. X. Xxxx, X. X., Xxxxxxx, R. X. (eds), In xxxxx Xxxxxxxxx Activation xx Mutagenesis Xxxxxxx, Xxxxxxxx, North-Holland, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxx, X. L., Xxxxxxxx, X. X., Xxxxxx, X., Xxxxxxx, X., Xxxxxx, X. (1994), Xxxxxx from Xxxxxxx Xxxxx xx Xx xxxxx Xxxxx xxx Xxxxxxxxxxx Aberrations, Xxxxxxxxxx Res., 312, 241-261.

13) Richardson, X., Xxxxxxxx, X. A., Xxxxx, X. A., Xxxxxxxx, G., Xxxxxxx, X. X., Xxxxxxxx, X. (1989), Analysis xx Xxxx xxxx Xx vitro Xxxxxxxxxxx Xxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Xxxxxxxx, X. J., (xx) Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, 141-154.

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

15) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, K. X. (1982), XXX/XXXXX Mutation Xxxxx: Xxxxxxxxxx xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Tice, X. X., Xxxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, P. X., Xxxxxx, X. X., Xx, A. X., Xxxxxx, X. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx System Xxxxx Cells Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Mutagens in xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxxxxxxxx Mutagen., 5, 795-801.

17) Locke-Huhle, X. (1983), Endoreduplication xx Xxxxxxx xxxxxxx xxxxx during xxxxx-xxxxxxxxx xxxxxxx G2 xxxxxx, Xxxxxxxxxx Xxx., 119, 403-413.

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

PŘÍLOHA 4X

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

1. XXXXXX

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

1.1 ÚVOD

Zkouška xx chromozomové xxxxxxx x xxxxx xx xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx x xxxxxxx xxxxxx xxxxx xxxxx, obvykle xxxxxxxx (1, 2, 3, 4). Rozlišují se xxx xxxx strukturních xxxxxxx — xxxxxxxxxxxx x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx schopnost xxxxxxxxx xxxxxxxxx xxxxxxx. X xxxxxxx většiny xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx jevy xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x existuje xxxxx xxxxxx x xxx, že xxxxxxxxxxxx xxxxxx x související xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx x x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x v xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx této xxxxxxx xxxx xxxxxxx xxxxxxxxx hlodavci. Xxxxxxx xxxxx xx v xxxx zkoušce kostní xxxx, xxxxxxxx je xxxxxx vaskularizovanou xxxxx x xxxxxxxx populaci xxxxx x rychlým xxxxxx, které xx xxxxxx xxxxxxx a xxxxxxxxxxxx. Xxxx xxxxx x cílové tkáně xxxxxx předmětem xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx umožňuje xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx x různých xxxxx x xxxxx měnit. Xxxxxxx xx xxxx xx xxxxxx xxxxxxxx xxx další xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx xx xxxxx.

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

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

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

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

Xxx : achromatická xxxx xxxxx než xxxxx xxxxxxx chromatidu x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

Xxxxxxxxxxx : násobek xxxxxxxxxxx xxxxx xxxxxxxxxxxxxx xxx (x), jiný xxx diploidní (tj. 3 x, 4 x xxx.).

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx struktury chromozomů xxx xxxxxxxx xxxxxx xx stadiu metafáze; xxxx se jako xxxxxx x fragmenty, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

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

1.4 POPIS ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxx x xxxxxx čínský, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx savčí xxxx. Xxxx by xxx xxxxxxx xxxxx xxxxxxx laboratorní kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx xxxxxx xx měla být xxxxxxxx x hmotnosti xxxxxx minimální x xxxxxx xx u xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxxxx se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, xxxxx xx xxxxxxx xxxxxxxx xxxxx. Klece by xxxx xxx xxxxxxxxxx xxx, aby xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Nechají xx x laboratorních xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx být xxxx xxxxxxxx zvířatům xxxxxxxxxx nebo suspendovány xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by být xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx údaje o xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx při použitých xxxxxxxx xxxxx toxické xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx látkou. Xxxx-xx použita xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X výjimkou xxxxxxxx xxxxxxxx látky by xxxx zvířata kontrolní xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx skupinách, v xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx strukturní xxxxxxx in xxxx xxx expozičních xxxxxxxx, x nichž xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx odečtu nevyšla xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby byla xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx a xxx xxx xxxxx x xxxxx případě xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxxx xxx použity xxxxxxxx xxxxx xx xxxxxx chemické xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx	Xxxxx XXX	Xxxxx xxxxx EINECS
ethyl-methansulfonát	62–50–0	200–536–7
1-ethyl-1-nitrosomočovina	759–73–9	212–072–2
mitomycin C	50–07–7	200–008–6
cyklofosfamid	50–18–0	200–015–4
cyklofosfamid xxxxxxxxxx	6055–19–2	200–015–4
2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx	51–18–3	200–083–5

X xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx u xxxxxxxxxxx xxxxxxx, xxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx vehikulum a xxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxxxxx xxxxxxx, xxxxx xxxxxx z dosavadních xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx x variabilitě zvířat x četnosti buněk x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx jeden xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx měly být xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, neexistují-li xxxxx kontrolní údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní xxxxxxx xx skládá x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx pro xxxxx xxxxxxx. Jestliže xxxx v době xxxxxx x xxxxxxxxx xxxxx xx studií xx xxxxxxx xxxxxx x za xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx mezi xxxxxxxxx xxxxxx v toxicitě, xxxx postačující xxxxxxxx xxxxxxx pohlaví. Je-li xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx pohlaví, xxxx je tomu xxxxxxxxx x některých xxxxxxxxxxxxxxx xxxxx, měla xx xxx zkouška xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx xxxxx xxx podávány xxxx xx xxxx xxxxxxx, xxx. xxx xxxxx x xxx den x xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Jiné xxxxxx podávání xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx odebrány xx xxxx xxxxxxx intervalech xx aplikace xxxxxx x jednom xxx. X xxxxxxxx xx xxxxx xxxxxxx xx xxxxxx xxxx xx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (xxxx xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx a xxxxxxxxxxxx zkoušené xxxxx x xxxxxx xxx xxxxxx na xxxxxxxx xxxxxxxxx xxxxx xxxx xxx vliv xx xxxxxxxxx okamžik xxx xxxxxxxxx xxxxxxxxxxxxxx aberací, xxxxxxxxxx se xxxxxxx xxxxx xxxxx xx 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx xx xxxx než xxxxxxx xxx, měl xx xxx xxxxx proveden xx xxxxxx xxxx xx xxxxxxxx aplikace, xxxxx odpovídá 1,5násobku xxxxxxxx xxxxx buněčného xxxxx.

Xxxx usmrcením xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® nebo kolchicin). Xxxx xx xx xxxxxx době xxxxxxx x zvířat xxxxx. X xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 x; u křečka xxxxxxxx je xxxx xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xx xx chromozomové xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx xxxxxxx xxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx, xxxxxx, pohlavím x xx xxxxxxxx xxxxxx expozice, xxx xx xxxxxxx v xxxxxx xxxxxx (5). X případě xxxxxxxx xx pro xxxxx xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx rozpětí xxxx maximální x xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx vyšší xxxxx xx xxxxx xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x letalitě. Látky xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx vyhovovat a xxxx xx xxx xxxxxxxxx případ od xxxxxxx. Xxxxxxxx dávka xxxx xxx xxxx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx známky xxxxxxxx (např. více xxx 50 % xxxxxxx mitotického xxxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx nebo ve xxxx dávkách v xxxxxx dni xxxxxxxxxx xxxxx pozorovatelné toxické xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx strukturu, xxxxxxxxx xxxxxxxxxxxx, nepovažuje xx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X xxxx trvajících xxxxxx xx xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den x xxx xxxxx xxx 14xxxxx aplikaci je xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx potřebu xxxxxx v xxxxxxx xxxxxxx vyšší úroveň xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx se xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Maximální objem xxxxxxxx, xxxxx může xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Objem xx xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, než xx xxxxxxx xxxxx, xxxx xxx zdůvodněno. Xx na dráždivé x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx vykazují xxxxxxxx xxxxxx, xx xxxx xxx variabilita xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx xxxxxxxx dávky.

1.5.6 Xxxxxxxx preparátů xxx xxxxxxx chromozomů

Ihned po xxxxxxxx xx xxxxxxx xxxxxx dřeň, hypotonizuje xx x xxxxxx. Xxxxx xx xxxxxxx xx podložní xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx xxxxxxx xxxxxxxxxxxx xx xxx xxx x xxxxx exponovaných xxxxxx (xxxxxx pozitivních xxxxxxx) x x xxxxxxxxxxxxxx xxxxxx pro xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx, x xx alespoň x 1000 xxxxx na xxxxx zvíře.

U každého xxxxxxx by xxxx xxx xxxxxxxxxxx xxxxxxx 100 buněk. Xxxxx xxxxx lze xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx by xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxx xxx xxxxxx často xxxxxxx xx xxxxxxxxxxxxxx zlomům xxxx xx xxxxxx xxxxxxxxxx x xxxxx xxxxx x xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x xxxxx odpovídajícímu xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx zvířata by xxxx být xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx každé xxxxx by xxx xxx xxxxxxxxxx xxxxx xxxxx, xxxxx aberací xx xxxxx a xxxxx xxxxx x xxxxxxxxxxxxx xxxxxxx (chromozomovými xxxxxxxxx) vyjádřený v xxxxxxxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx měly být xxxxxxx xxxxx typy xxxxxxxxxxxx xxxxxxxxxxxxxx aberací x jejich xxxxxx x xxxxxxxx. Gapy xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx se, xxx xxxxxx se xxxxxxxxxx xx celkové xxxxxxxx xxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, mohou být xxx xxxxxxxxxxxx analýzu xxxxx xxx xxx xxxxxxx zkombinovány.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx s xxxxxxxxxxxxxx aberacemi v xxxxxxxxxx na dávce xxxx jasný xxxxxx xxxxx buněk x xxxxxxxxx pro xxxxxxx x xxxxxxx xxxxxx x k určitému xxxxxxxx odběru. Xxxxxxxx xx měla být xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxxx numerické xxxxxxxxxxxx xxxxxxx. Nárůst xxxxx buněk s xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxx progresi xxxxxxxxx xxxxx (7, 8).

Xxxxxxxx xxxxx, jejíž xxxxxxxx xxxxxxxxx výše uvedená xxxxxxxx, se považuje x tomto xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx poskytne xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx xxxxx xxxxxxxx konečný xxxxx x aktivitě xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx dvojznačné xxxx sporné xxx xxxxxx na to, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx výsledky xxxxxxx xx chromozomové aberace xx xxxx xxxxxxxxx, xx zkoušená látka xxxxxxxx x xxxxxx xxxxx testovacího xxxxx xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x kostní xxxxx xxxxxxxxxxx xxxxx chromozomové xxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, stáří x pohlaví zvířat,

- xxxxx, xxxxxxxx chovu, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx na xxxxxxx zkoušky, včetně xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx a negativní (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- zdůvodnění způsobu xxxxxxxx,

- popřípadě metody xxxxxxx, zda se xxxxxxxx xxxxx dostala xx xxxxxxxx oběhu xxxx xx cílové xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx a xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx hodnocení xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- mitotický xxxxx,

- xxx x xxxxx xxxxxxx uvedený xxxxxxxxxx xxx každé xxxxx,

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

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

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx závislost odpovědi xx dávce,

- případné xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx negativní xxxxxxxx,

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

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Xxxxxxx, X. J., Dean, X. J., Galloway, X., Holden, X., XxXxx, X. F., Xxxxxx, M. (1987), Xxxxxxxxx In xxxx Xxxxxxxxxxx Xxxxxx: Xxxxxxxx xx Xxxxxxxxxx Aberrations xx Bone Marrow Xxxxx, Xxxxxxxxxx Xxx., 189, 157-165.

3) Richold, X., Xxxxxxxx, A., Xxxxx, J., Gatehouse, X. G., Xxxxxxx, X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. J. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx Xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx X xxxxxxx, Xxxxxxxxx University Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Melbourne, Xxxxxx, 115-141.

4) Xxxx, X. X., Xxxxxxx, X., XxxXxxxxxx, J. X., Anderson, D., Xxxxxx, D. X., Xxxxxx, X. X., Xxxxxx-Xxxxxxx, X., Oleson Xx., F. B., Xxxxxxxxxxxx, X., Preston, X. X., Xxxxxxx, X., Shimada, X., Xxxxx, X., Xxxxxxx, X. (1994), Xxxxxx xxxx xxx Xxxxxxx Xxxxx xx xxx xx xxxx Mammalian Xxxx Xxxxxx Chromozomal Xxxxxxxxxx Test, Mutatation Xxx., 312, 305-312.

5) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, X. X., Xxx, X., Esdaile, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, D. X., Richold, M. (1992), Xxxxxx of Xxxxxxx Xxxxxxxxxx Society/UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, X., Albanese, X., Xxxxxxxx, X. X., Clare, X., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, D. X., Savage, J. X. K. (1989), Xxxxxxxxxxx Xxxxxxxx of Xx xxxx Cytogenetic Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx on Guidelines xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Evaluation of Xxxxxxxxxxxx Xxxx Data, X. X. Kirkland (xx.) Cambridge Xxxxxxxxxx Xxxxx, Cambridge, 184-232.

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

8) Xxxxx, Y., Xxxxxx, X., Xxxxxx, X. E. (1983), Xxxxxxxxxxx-xxxxxxx endoreduplication xx Xxxxxxx xxxxxxx xxxxx, Xxxxxx Xxx., 43, 1362-1364."

XXXXXXX 4X

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

1. XXXXXX

Xxxx xxxxxx xx replikou xxxxxx XXXX TG 474 — Test xxxxxxx erytrocytárních xxxxxxxxxx xx xxxx (1997).

1.1 XXXX

Xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx in xxxx xx používán xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx látkou, x xx pomocí xxxxxxx xxxxxxxxxx xxxxxxxxxx x kostní xxxxx x/xxxx buněk periferní xxxx, xxxxxxx hlodavců.

Účelem xxxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx je identifikovat xxxxx, které xxxxxxxxx xxxxxxxxxxxxx poškození, jehož xxxxxxxxx je xxxxxx xxxxxxxxxx xxxxxxxxxxxx nereplikující xx (xxxxxxx) xxxxxxxxxxxx xxxxxxxxx nebo celé xxxxxxxxxx.

Xxxx se xxxxxxxxxxx xxxxxx xxxxx mění xx xxxxxxxxxxxxxxx erytrocyt, xxxxxx xxxxx je xxxxxxxx a xxxxxxxxxx, xxxxx xxx xxx xxxxx xxxxxxxxx, xxxxxxxxx x cytoplasmě, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx mikrojader xx x xxxxxx xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx hlavní xxxxx. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx s xxxxxxxxxx x exponovaných xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx xx rutinně xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxxxx tato xxxx produkuje xxxxxxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) erytrocytů x xxxxxxxxxx v xxxxxxxxx xxxx xx rovnocenně xxxxxxxxxx x xxxxxxxxxxx xxxxx, x něhož xxxx prokázána xxxxxxxxxxx xxxxxxx xxxxxxxxxxx erytrocyty x mikrojádry, xxxx xxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx aberace. Mikrojádra xxx rozlišit xxxxx xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx přítomnosti nebo xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX x mikrojádře. Xxxxxxxxx se zejména xxxxxxx xxxxxxxxx (polychromatických) xxxxxxxxxx x xxxxxxxxxx. Xxxxx zralých (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx x periferní xxxx, xxxxx obsahují xxxxxxxxxx, xxxxxxxxxxx xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx lze xxxxxx xxxxxx jako xxxxxxx xxxxxxxx xxxxxxx, xxxxxxxx xxxx xxxxxxx exponována xxxxx týdny xxxx xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxx xxxxxx x posouzení xxxxxxxxx mutagenese, neboť xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx xx vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx xxxxx x xxxxxxx xxxxx x tkání, xxxxx x x xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxx xx rovněž xxxxxxxx xxx xxxxx xxxxxx mutagenních účinků xxxxxxxxxx v xxxxxxxxx xx xxxxx.

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

Xxx xxxx Obecný xxxx, xxxx B.

1.2 XXXXXXXX

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

Xxxxxxxxxx : xxxx xxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx a xxxxx xxxx, vytvářená xxxxx xxxxxxxx mitosy (meiosy) xxxxxxxxxxxxxxx se (xxxxxxx) xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxx chromozomy.

Normochromatický xxxxxxxxx : xxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxx, xxxxx xxx rozlišit xx xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx selektivním pro xxxxxxxx.

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx vystaví xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx xxxxx se xxxxxxx xx xxxxxxx xxxxxxxx xx xxxxxxxx xxxxxx, xxxxxxx se xxxxxx dřeň, xxxxxxxx xx xxxxxxxxx x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx xxxxxxxxx xxxx se xxxx xx vhodném xxxxxxxx xx xxxxxxxx xxxxxxx, xxxxxxxxxx se xxxxxxxx xxxxxxxx a xxxxxx xx (4, 8, 9, 10). Xxx xxxxxxxx x xxxxxxxxx xxxx by xxxx xxxx xxxxxxxx expozicí x xxxxxxxxx buněk xxxxxxxx co nejkratší xxxx. Xxxxxxxxx xxxx xxxxxxxxxxx xx xxxxxxxxxx xxxxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx zvířete

Při xxxxxxx xxxxxx xxxxx xx xxxx xxxxxxxxx zvíře xxxxxxxxxx xxx nebo xxxxxx, ačkoli xxx xxxxxx jakýkoli xxxxxx xxxxx xxxx. Při xxxxxxx periferní xxxx xx xxxxxxxxxx xxx. Xxx však xxxxxx xxxxxxxx xxxxxx xxxx xxxxx xx xxxxxxxxxxx, xx jde x xxxx, x něhož xxxxxxx xxxxxxxxxxxx xxxxxxxxxx x mikrojádry, xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx v hmotnosti xxxxxx xxxxxxxxx x xxxxxx by u xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x skupinu, x xxx xx xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx v laboratorních xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat. Klece xx xxxxxxxxxx xxx, xxx xxx vliv xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx před xxxxxxxx xxxxxxxx rozpuštěny xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx před podáním xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, pokud xxxxx x xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx použitých xxxxxxxx xxxxx toxické účinky x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Jsou-li xxxxxxx xxxx než xxxxx rozpouštědla/vehikula, xxxx xx xxx jejich xxxxxxxx podloženo xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx identický proces xxxx xxxxxxx xx xxxxxxxxx, v nichž xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx xxxxxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, u xxxxx xx xxxxxxx, xx xxxxxxxxx detekovatelný xxxxxx xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx zvoleny xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx při xxxxxx xxxxxxx ihned najevo xxxxxxxx xxxxxxxxxxxx preparátu. Xx přijatelné, aby xxxxxxxxx xxxxxxxx xxxx xxxxxxxx jiným xxxxxxxx xxx zkoušená xxxxx x aby byl xxxxx x xxxxx xxxxxxx prováděn jen xxxxxx. Xxx pozitivní xxxxxxxx xxxxx xxxx xxx xxxxx v xxxxx použití xxxxxxxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx, xxxx-xx x dispozici. Xxxxxxxx xxxxx pro pozitivní 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	200–015–4
2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx	51–18–3	200–083–5

X xxxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a která xxxxx xxxxxxxxxx stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx kontrolních xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx x xxxxxxxxxx. Provádí-li xx xxx negativní xxxxxxxx xxxxx odběr, je xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx odběru. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx dosud xxxx xxxxxx-xx xxxxxxxxxxx kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

Při použití xxxxxxxxx xxxx může xxx jako xxxxxxxxx xxxxxxxx přijatelný xxxx xxxxxx krve xxxxxxxx xxxx xxxxxxxx, pouze xxxx x xxxxxxxx xxxxxx x periferní xxxx (xxxx. 1 — 3 xxxxxxxx) xx předpokladu, že xxxxxxxx xxxxx xxxxx x xxxxxxx, které xx na základě xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Každá xxxxxxxxxx x kontrolní xxxxxxx xx xxxx xxxxxxx x xxxxxxx pěti xxxxxxxxxxxxxxxx zvířat pro xxxxx xxxxxxx (11). Xxxxxxxx xxxx v xxxx studie x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx stejného způsobu xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx postačující xxxxxxxx xxxxxxx pohlaví. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, jako xx xxxx xxxxxxxxx x xxxxxxxxx farmaceutických látek, xxxx xx xxx xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx doporučit xxxxx xxxxxxxxxx xxxx (xx. xxxxx, dvě xxxx xxx xxxxxxxx x xxxxxxxxx 24 xxxxx). Xxxxxx xx xxxxxx s xxxxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxxx se x xxxxxx xxxxxx xxxxxxx xxxxxxxxx výsledky, xxxx –x xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx xxxx prokázána xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxxx xx do xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx ve xxxx xxxxxxx, xxx. xxx xxxxx x týž xxx x xxxxxxx xx více xxx xxxxxxxx hodin, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx být xxxxxxxx xxxxx xxxxxxx:

x) xxxxxxxx xxxxx se aplikuje xxxxxxxx xxxxxx. Xxxxxx xxxxxx dřeně se xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 24 xxxxx po xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx aplikaci x x přiměřeným odstupem xxxx xxxxxx. Xxxxx xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx xxxxxxxxx xxxx xx odeberou alespoň xxxxxxx, xxxxxxx první xxxxx xx xxxxxxx xxxxxxxx 36 xxxxx xx aplikaci x xxxxxxxx nejpozději 72 xxxxx xx xxxxxxxx x po prvnímodběru xx dodrží xxxxxxxxxxxx xxxxxx. Je-li po xxxxxx odběru pozorována xxxxxxxxx odpověď, není xxxxx xxxxx xxxxx;

x) xxxx-xx xxxxxxxx xxx xxxx xxxx dávek xxxxx (xxxx. dvě xxxx xxxx xxxxx x intervalu 24 xxxxx), měly by xxx xxxxxx xxx xxxxxxx xxxxxx xxxxx xxxxxxxx jednou xx 18 xx 24 xxxxxxxx xx xxxxxxxx xxxxxxxx x xxx xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).

Xxxxx xxxxxxx xxxxx xxx xxxxx xxxxxxx xxxx doby xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, pohlavím x za stejného xxxxxx expozice, xxx xx xxxxxxx x xxxxxx studii (13). X xxxxxxx xxxxxxxx xx pro xxxxx xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx pokrývat rozpětí xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Při xxxxxxxxx odběru xxxxx, xxxx xxxx použita xxxxx nejvyšší xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že xxxxx xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x letalitě. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx dávkách (např. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx vyhovovat x xxxx xx xxx xxxxxxxxx případ xx xxxxxxx. Nejvyšší dávka xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x kostní xxxxx xxxx v xxxxxxxxx krvi).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx xxxxxx x xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx dni xxxxxxxxxx xxxxx pozorovatelné toxické xxxxxx a není-li xx xxxxxxx xxxxx x xxxxxxx, které xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx xxxxx xxxxxx xx xxxxx úrovněmi xxxxx xx nezbytnou. X xxxx trvajících xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den x xxx delší xxx 14xxxxx aplikaci xx xxxxxxx dávkou 1000 xx/xx tělesné hmotnosti/den. Xxxxxxxxx expozice člověka xxxx xxxxxxxx xxxxxxx xxxxxx v xxxxxxx xxxxxxx vyšší úroveň xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx obvykle xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx nebo xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx podávání xxxx xxxxxxxxxx v xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx může xxx xxxxxxxx xxxxx xxxxxxxxx sondou nebo xxxxxxxx, závisí na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 ml/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx zesílené účinky, xx měla xxx xxxxxxxxxxx zkušebního objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx nebo xxxx

Xxxxx xxxxxx xxxxx se xxxxxxx xxxxxxxxx x xxxxxx nebo xxxxx xxxxx xx usmrcení. Xxxxx xx odeberou x xxxxxx xxxx xxxxx x xxxxxxxxxx xxxxxxxx se xxxxxxxxx x obarví. Xxxxxxxxx xxxx xx xxxxxxx x ocasní žíly xxxx xxxx xxxxxx xxxxxx xxxx. Xxxxxx xxxxx xx ihned xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx xxxxxxxx preparáty xxxxxxxx a xxxx xx xxxxxx. Xxxxxxxx xxxxxxx specifického xxx XXX (xxxx. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 a xxxxxxx-X (15)) xx xxx xxxxxxx xxxxxxxx xxxxxxxxxx spojeným x xxxxxxxx xxxxxxx nespecifického xxx XXX. Xxxx xxxxxx nebrání použití xxxxxxxxxxx xxxxxx (např. Xxxxxx). Přídavné xxxxxxx (xxxx. xxxxxxxxxx xxxxxx x xxxxxxxxxx buněk xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx za xxxxxxxxxxx, xx xx xxxxxxxxx odpovídající xxxxxxxxx xxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Analýza

Pro xxxxx xxxxx se xxxxxxx xxxxx nezralých xxxxxxxxxx x xxxxxxxxx (xxxxxxx + zralé) xxxxxxxx xxxxxxxxxx, xxxxxxx se x případě kostní xxxxx použije celkově xxxxxxx 200 xxxxxxxxxx x x případě xxxxxxxxx krve alespoň 1000 erytrocytů (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx pozitivních a xxxxxxxxxxx xxxxxxx, by xxxx xxx xxxx xxxxxxxx xxx mikroskopem xxxxxxxxx kódovány. U xxxxxxx xxxxxxx xx xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx zralých erytrocytů xx xxxxxx xxxxxxxxxx. Xxx xxxxxxxxxxxxx analýze xx neměl xxx xxxxx nezralých erytrocytů x xxxxxxxxx xxxxxxxx xxxxxxxxxx menší než 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxx xxxx xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx xx xxxxx zvíře. Systémy xxx xxxxxxxxxxxx analýzu (xxxxxxx obrazu a xxxxxxxxx xxxxxxxxxxxx analýza xxxxxxx xxxxxxxx) xxxx xx xxxxxxxxxxxxx zdůvodnění x xxxxxxxx přijatelnými xxxxxxxxxxxxx manuálního xxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Experimentální xxxxxxxxx xx xxxxx. Pro xxxxx analyzované zvíře xx měl být xxxxxx počet xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx x počet xxxxxxxxx xxxxxxxxxx z xxxxxxxxx množství xxxxxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx nebo déle, xxxx xx být xxxx xxxxxxx xxxxx x zralých erytrocytech, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx zvíře xx xxxxx xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, xxxxx být xxx xxxxxxxxxxxx analýzu xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, xxxx. xxxxxx počtu xxxxx x mikrojádry x xxxxxxxxxx xx xxxxx nebo jasný xxxxxx xxxxx xxxxx x xxxxxxxxxx xxx xxxxxxx s určitou xxxxxx x x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx by xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx použity xxxx xxxxxxx prostředek xxxxxxxxxxx metody (18, 19). Statistická xxxxxxxxxx xx xxxxxx být xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx vyjasněny xxxxxx zkoušením, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx na xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx na xxxxxxxxxx xxxxxxxxx, xx zkoušená xxxxx indukuje mikrojádra, xxx jsou xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxxxxx mitotického aparátu xxxxxxxxxxxx testovacího xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx zkoušená xxxxx xx podmínek zkoušky xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx testovacího xxxxx.

Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx nebo její xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx do xxxxxx xxxxx (např. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- rozpustnost a xxxxxxx zkoušené xxxxx x rozpouštědle/vehikulu, je-li xxxxx.

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, stáří x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx hodnota x xxxxxxxxxx xxxxxxxx pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

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

- xxxxxxxxxx zvolených xxxxxx dávek,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx způsobu podávání,

- xxxxxxxxx xxxxxx ověření, xxx se xxxxxxxx xxxxx xxxxxxx do xxxxxxxx xxxxx nebo xx xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x vody,

- xxxxxxxx popis rozvrhu xxxxxxxx x odběru,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxx mikrojader x nezralých erytrocytech,

- xxxxx analyzovaných buněk xx jedno zvíře,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx erytrocytů,

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

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx statistické xxxxxxx x metody,

- xxxxx x souběžné x xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx o souběžné xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxxx, X. X. (1973), X Xxxxx In vivo Xxxx xxx Chromozomal Xxxxxx, Xxxxxxxxxx Res., 18, 187-190.

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

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

4) Xxxxxxxxx, K. H., Xxxxxx, D. X., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxx, J. X. (1990), The Xx xxxx Xxxxxxxxxxxx Assay xx Xxxxxxxxx Xxxx Xxxxxx and Xxxxxxxxxx Xxxxx. X xxxxxx xx the X. X. Environmental Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 239, 29-80.

5) MacGregor, J. X., Schlegel, X., Xxxx, W. N., Xxxx, X. M. (1983), Xxxxxxxxxxx in Xxxxxxxxxxx Xxxxxxxxxxxx: A Xxxxx Screen for Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Xxxxxxxx Xxxxxxx xx Xxxx, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx xx Xxxxxxxxxx, xx. X. X. Xxxxx, X. X. Xxxxxxx, X. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) MacGregor, X. T., Xxxxxx, X. A. Xxxx, X., Margolin, X. X., Ramel, C., Xxxxxxxx, X. X., Xxxx, R. X., Xxxx, D. (1987), Xxxxxxxxxx for xxx Xxxxxxx of Micronucleus Xxxxxx xx Mammalian Xxxx Xxxxxx Erythrocytes, Xxxxxxxxxx Xxx., 189, 103-112.

7) XxxXxxxxx, J. X., Xxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X. (1990), Xxx xx xxxx Erythrocyte Xxxxxxxxxxxx Xxxx: Measurement xx Xxxxxx Xxxxx Xxxxxxxxx Assay Xxxxxxxxxx xxx Xxxxxxx Xxxxxxxxxxx xxxx Toxicity Studies, Xxxxxx. Appl. Toxicol. 14, 513-522.

8) Xxxxxxx, X., Morita, X., Xxxxxx, X., Xxxxxx, X., Ishidate, X. Xx. (1990), Xxx Xxxxxxxxxxxx Xxxxx xxxx Xxxxx Xxxxxxxxxx Blood 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 Xxxxx Xxxxxxxxxxxx by Acridine Xxxxxx Xxxxxxxxxx Xxxxxxxx: Xxx Xxxxxxx Xxxxxx xx xxx 5xx Xxxxxxxxxxxxx Study xx XXXXX/XXXXX, XXX, Xxxxxxxxxx Xxx., 278, 83-98.

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx for xxx Xxxxxxxxxxxx Xxxx (CSGMT/JEMMS, XXX: Xxx Mammalian Xxxxxxxxxxx Xxxxx Group xx xxx Environmental Xxxxxxx Xxxxxxx of Xxxxx) (1995), Protocol xxxxxxxxxxx for xxx xxxxx-xxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx test, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, M., Xxxx, X. R., MacGregor, X. T., Xxxxxxxx, X., Xxxxxxx, D. X., Kirsch-Volders, X., Xxxxxx, Xx. X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, B. (1994), Xx vivo Xxxxxx Xxxxxxxxxxx Xxxxxxxxxxxx Xxxxx, Xxxxx. Res., 312, 293-304.

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

13) Xxxxxxx, X. X., Xxxxx, X. X., Boobis, X. X., Botham, X. X., Doe, X., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Morton, X. B., Xxxxxxxx, X. X., Xxxxxxx, X. (1992), Report xx Xxxxxxx Toxicology Xxxxxxx/XX Environmental Mutagen Xxxxxxx Working Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

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

15) XxxXxxxxx, J. T., Xxxx, C. M., Xxxxxxxx, X. X. (1983), X Xxxxxx Xxxxxxxxxxx Staining Xxxxxxxxx xxx Xxxxxxxxxxx and XXX in Xxxxxxxxxxxx Xxxxx Hoechst 33258 xxx Pyromin X, Xxxxxxxx Xxx., 120, 269-275.

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

17) Xxxxxxxxx, X., XxXxxxxx, L. X. (1995), Sample Xxxx xxx the Xxxxxxxxxx xx Xxxxxxxxxxxxx xx Normochromatic Xxxxxxxxxxx Xxxxx xx the Xxxx Marrow Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 347, 97-99.

18) Xxxxxxx, X., Xxxxx, X., Xxxxxxx, J., Xxxxxxxx, X., Gatehouse, X. X., Henderson, X. (1990), Xx vivo Xxxxxxxxxxxx Xxxxx, in: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, XXXXX Recommended Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

19) Lovell, X. P., Anderson, X., Xxxxxxxx, X., Xxxxxxxx, X. E., Xxxxx, X., Xxxxxxxx X., Xxxxxxx, M., Xxxxxxxx, D. G., Xxxxxx, X. X. X. (1989), Xxxxxxxxxx Xxxxxxxx of Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. J. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx of Mutagenicity Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx III, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."

XXXXXXX 4X

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

1. XXXXXX

Xxxx metoda xx replikou metody XXXX XX 471 — Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xx xxxxxxxxx bakteriální xxxxx závislé xx xxxxxxxxxxxxxxx Salmonella typhimurium x Xxxxxxxxxxx xxxx, x xxxxxxx xxxxxxxx xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxx x xxxxxx xxxxxxx nebo xxxxxxxx párů xxxx XXX (1, 2, 3). Podstata této xxxxxxx na reverzní xxxxxx x xxxxxxxxxx xxxxxxx x xxxxxxx xxxxxx, xxxxx xxxxxxxxx xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxx x xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx xxxx xxx xxxxxxxxxx xxxx v xxxxxxxxxxxxx aminokyselin, xxxxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx xxxxxx x podobné xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxx xxxxxx x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx xxxxxx mají xxxxx xx tvorbě xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx. Xxxxxxx xx xxxxxxxx mutace x xxxxxxxxxx je xxxxxx, xxxxxxxxxx x relativně xxxxxx. Mnoho xxxxxxxxxxx xxxxx xx xxxx xxxxxxxxxx, xxxx xxxx xxxx xxxxxxxxxx na xxxxxxx mutací, včetně xxxxxxxxxxxxx sekvencí XXX xx xxxxxxxxxx místech, xxxxxxx xxxxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx x xxxxxxxxx reparačních xxxxxxx XXX nebo xxxxxxxx xxxxxxxxxxx xxxxxxx XXX náchylných x xxxxxx. Xxxxxxxxxxxx testovacích xxxxx může xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxx x xxxxxx xxxxxx, xxx xxxx indukovány xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx k dispozici xxxxx rozsáhlá xxxxxxxx xxxxxxxx pro xxxxxxx xxxxx struktur a xxxx byly xxxxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx xxxxxxxx xxxxxxxxx, x různými xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxx xx reverzní xxxxxx s bakteriemi Xxxxxxxxxx typhimurium xxxx Xxxxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (xxxxxxxx resp. xxxxxxxxx), xxxxxxx vzniká xxxx xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx párů bází xxxx xxxxxxxx, xxx xxxxxxxxx změny x xxxxxx DNA. Xxx xxxxxxx xxxxxxxxxx mutací xx mohou xxxx xxxxx xxxxxxxxxx xx xxxxx xxxxxxx xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx xxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx nebo xxxxxx xxxxxxx xxxx xxxx xxxx xxxx XXX x posunují xxx čtecí xxxxx XXX.

1.3 XXXXXXX ÚVAHY

Při xxxxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx se xxxx od xxxxx xxxxx xxxxxxx, xxxx xxxx příjem, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx x xxxxxxxxx procesy XXX. Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx vyžadují xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx zcela xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx x karcinogenním xxxxxxxxxx látky xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xx zpravidla xxxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx, a xxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxxx, xx xxxxx xxxxxxxxxx xxxxx, které jsou x xxxx xxxxxxx xxxxxxxxx, xxxxxxxx mutagenní xxxxxxxx x x xxxxxx zkouškách. Xxxxxxxx xxxxxxxx mutagenních činitelů, xxxxx nejsou detekovány xxxxx zkouškou. Xxxxxxx xxxxxx skutečností lze xxxxxxxxx ve xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx xxxx, x rozdílech x xxxxxxxxxxx xxxxxxxx xxxx x xxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx. Na xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxx xxxxxxx na reverzní xxxxxx xx xxxxxxxxxx, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx aktivity.

Zkouška xx xxxxxxxx xxxxxx x bakteriemi nemusí xxx xxxxxx xxx xxxxxx xxxxx chemických xxxxx, například xxxxxx xxxxxxxxxxxx sloučeniny (xxxx. xxxxxx xxxxxxxxxxx) x xxx xxxxxxxx xxxxx, x xxxxx xx xxxxxxxxxxx (xxxx x xxxxx xx ví), xx xxxxxxxxxx zasahují xx xxxxxxxxxxxx xxxxxxx xxxxx xxxxx (např. xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). V takových xxxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx mnoho xxxxxxxxx, pro xxx xx xxxx xxxxxxx xxxxxxxxx, xx karcinogenní xxx xxxxx, xxxx xxxxxxxx xxxxxxxxx. Závisí xx chemické xxxxx x existuje xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx touto xxxxxxxx, xxxxx xxxxxx jinými, xxxxxxxxxxxxxxx xxxxxxxxxx, nebo xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx buněk xxxx xxxxxxxxx zkoušené xxxxx, x xx xx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx x xxx xxxx. Ve xxxxxxxxxxx xxxxxxxx testu xx suspenze xxxxxxxx x xxxxxxx xxxxxx x xxxxx se xxxxxxx xx xxxxxxxxx xxxx. X xxxxxxxxxxxx xxxxxx xx xxxxxxxx xxxx inkubuje x xxxx xx xxxx xxxxxxxxx na xxxxxxxxx xxxx xxxxxx s xxxxxxx agarem. Xxx xxxx xxxxxxxxxx xx xx xxxx xxxx xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx revertantů x provede xx xxxxxxxx s xxxxxx xxxxxxx spontánních xxxxxxxxxx xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

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

Xxx xxxxxxx postupy xx xxxxxx xxxxxx standardního xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Každá x xxxx xx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx jak s xxxxxxxxxxxx aktivací, tak xxx ní. Xxxxxxx xxxxx xxx účinněji xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx metody. Xxxx xxxxx xxxxx xx xxxxxxxxxx xxxx, xx xxxxx xxxxx xxxx xxxxx krátké alifatické xxxxxxxxxxx, xxxxxxxxx kovy, xxxxxxxx, xxxxxxxxxx x xxxxxxxxxx sloučeniny, xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx xxxxxxxxx, xx xxxxxx třídy xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx xx xxxxxxxxxx xxxxxxx test xxxx xxxxxxxxxxxx xxxxxx. Měly xx xxx xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x k xxxxxx xxxxxxx xx důrazně xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (společně s xxxxxxxx postupů jejich xxxxxxx): azobarviva x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx x xxxxxx xxxxxxxx látky (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx od xxxxxxxxxxxx xxxxxxx 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 xx xxxxxx exponenciální xxxx xxxx do xxxxx xxxxxxxxxxx fáze růstu (xxxxxxxxx 109 xxxxx xx xx). Xxxxx x xxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx použity. Xx xxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx xxxxxx xxxx životaschopných xxxxxxxx. Xxxx xxxx xxx xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, nebo xxx xxxxxx zkoušku xxxxxxxxxx xxxxx životaschopných xxxxx xx xxxxxxx.

Xxxxxxxxxx inkubační xxxxxxx je 37 °X.

Xxxx by xxx xxxxxxx xxxxxxx xxx xxxxx bakterií. Mezi xxxx xx xxxx xxx xxxxx kmeny X. typhimurium (TA1535; XX1537 xxxx TA97a xxxx TA97; TA98 x XX100), xxxxxxx xxxxxxx xx ukázala x různých xxxxxxxxxxxx xxxx spolehlivá x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx X. xxxxxxxxxxx xxxx xxx xxxx XX xx xxxxxxxxx xxxxxxxxx xxxxx a xx xxxxx, že xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx určité oxidační xxxxxxxx, činitele způsobující xxxxxxxxxx vláken XXX x hydraziny. Xxxx xxxxx xxxxx být xxxxxxxxxx kmeny X. xxxx WP2 xxxx X. typhimurium TA102 (19), xxxxx mají xx primárním xxxxxxxxx xxxxx xxx xxxx XX. Xxxxxxxxxx xxxxxxxxx xxxxx xx tedy xxxx:

- S. typhimurium XX1535 x

- X. xxxxxxxxxxx TA1537 xxxx XX97x x

- X. xxxxxxxxxxx XX98 a

- X. typhimurium XX100 x

- X. xxxx XX2 uvrA, xxxx X. coli XX2 xxxX (xXX101), xxxx X. xxxxxxxxxxx XX102.

Xxx xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx XXX xxxx xxx vhodnější xxxxxxx XX102 nebo xxxxxx xxxx E. xxxx s xxxxxxx xxxxxxxxxx xxxxxxxx XXX, (xxxx. X. coli XX2 (pKM101)).

Měly xx xxx xxxxxxx zavedené xxxxxxx xxxxxxxx xxxxxxx xxxxxxx, verifikace xxxxxxx x xxxxxxxxxx. Potřeba xxxxxxxxxxxxx xxx růst xx měla xxx xxxxxxxxx pro xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx xxx xxxxx X. xxxxxxxxxxx x xxxxxxxxx pro X. xxxx). Xxxxxxx by xxxx být xxxxxxxxxxxx xxxx fenotypové charakteristiky, xxxxxxxxx xxxxx xxxxxxx xxxxxxxxxx xxxx nepřítomnost X-xxxxxxx xxxxxxxx (tj. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, XX100 x XX97x xxxx XX97, XX2 xxxX x WP2 uvrA (xXX101) x ampicilinová x tetracyklinová xxxxxxxxxx x kmene XX102), xxxxxxxxxx charakteristických xxxxxx (xx. xxx mutací x S. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx xxxxxx a uvrA xxxxxx u X. xxxx nebo uvrB xxxxxx u X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx světlo) (2, 3). Xxxxx by xxxx rovněž xxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx na xxxxx x rozmezí xxxxxxxx xxxxxxxxxxx xx základě xxxxxxxxxxx údajů xxxxxxxxxxxxx xxxxxxx x xxxxxxx x xxxxxxx uvedeném x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx minimální xxxx (např. xxxxxxxxxx xxxxxxxxx půdu E (Xxxxx-Xxxxxx) x glukosu) x xxxxxx agar xxxxxxxxxx histidin a xxxxxx xxxx tryptofan xxxxxxxxxx několik buněčných xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx xxxxxxxx

Xxxxxxxx xx xxxx být xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x xxx xxxx. Nejčastěji xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx z xxxxx hlodavců xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (1, 2) xxxx fenobarbitonu x β-xxxxxxxxxxxx (18, 20, 21). Postmitochondriální xxxxxx xx obvykle používána x xxxxxxxxxxxxx x xxxxxxx 5 xx 30 % xxx. xx xxxxx X9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx na xxxxx xxxxxxxx xxxxxxxx xxxxx. X některých xxxxxxxxx xxxx xxx xxxxxx xxxxxx více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. U xxxxxxxxx x diazoniových xxxxxxxxx může xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx přípravek

Pevné xxxxxxxx xxxxx xx xxxx být xxxx xxxxxxxx xx bakterie xxxxxxxxxx xxxx suspendovány xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x testovacím xxxxxxxx x/xxxx xxxxx xxx xxxx aplikací xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, a xxxx by být xxxxxxxxxx x přežitím xxxxxxxx x x xxxxxxxxx S9 (22). Xxxx-xx xxxxxxx xxxx xxx známá rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při zkoušení xxxxx xxxxxxxxx xx xxxx by měla 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 xxxxxxxx, xxxxx mají xxx xxxxxxxxxx při xxxxxxxxx xxxxxxxxxx xxxxxxxx zkoušené xxxxx patří cytotoxicita x rozpustnost v xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx xxxx xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx xx může xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx aktivačních xxxxxxx. Xxxxxxxxxxxxx xx xxxx xxx posouzena xx xxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxxx směsi xx skutečných xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx xx 5 xx/xxxxx xxxx 5 μx/xxxxx. X xxxxxxxxxxxxxxx látek xxxxxxxxxxxxx xxx koncentracích 5 xx/xxxxx xxxx 5 μx/xxxxx xx xxxx xxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, xxx xxxxx xxxx v konečné xxxxx pro xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, xx xxxx xxx zkoušeny až xx cytotoxické koncentrace. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx koncentrací zkoušené xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx by xxxx být xxxxxxxxx xxxx xxxxxxxxxx xxxx xxxxx přibližně polovině xxxxx logaritmické stupnice (xx. Ö10). Menší xxxxxxxxx jsou xxxxxx x xxxxxxx, kdy xx xxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx než 5 xx/xxxxx nebo 5 μx/xxxxx xxxx xxx xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx významné xxxxxxxx xxxxxxxxxxx mutagenních xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx kontroly

Součástí každého xxxxxxxxx xx xxxx xxx xxxxxxx specifické xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx x metabolickou xxxxxxxx a xxx xx. Xxx xxxxxxxxx xxxxxxxx xx měly xxx vybrány koncentrace xxxxxxxxxxx účinnost xxxxx xxxxxxx.

X xxxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxx (xxxxx) xxx xxxxxxxxx xxxxxxxx vybrána (xxxxxxx) xx xxxxxxx xxxx xxxxxxxxx xxxxx bakterií.

Příkladem xxxxxx xxxxxxxxx kontroly x xxxxxxx x xxxxxxxxxxxx aktivací xxxx xxxx xxxxx:

Xxxxx	Xxxxx XXX	Xxxxx xxxxx XXXXXX
9,10-xxxxxxxxxxxxxxxxx	781–43–1	212–308–4
7,12-xxxxxxxxxxxxx[x]xxxxxxxxx	57–97–6	200–359–5
xxxxx[x]xxxxx	50–32–8	200–028–5
2-xxxxxxxxxxxxxx	613–13–8	210–330–9
Xxxxxxxxxxxxx	50–18–0	200–015–4
xxxxxxxxxxxxx monohydrát	6055–19–2	200–015–4

Tato xxxxx xx vhodnou xxxxxxxxx kontrolou 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 jako xxxxxx indikátor xxxxxxxxx xxxxx X9. Xxx xxxxxxx 2-xxxxxxxxxxxxxxx xx xxxx být xxxxx xxxxx X9 xxxxxxxxxxxxxxxx xxxxxxxxx, který xxxxxxxx xxxxxxxxxxxx xxxxxxxx mikrosomálními xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-dimethylbenzo[a]anthracen.

Příkladem kmenověspecifické xxxxxxxxx xxxxxxxx u xxxxxxx bez 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 XX97x
XXX 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 xxxX x XX2 uvrA (xXX101)
4-xxxxxxxxxxxxx-1-xxxx	56–57–5	200–281–1	XX2, XX2 xxxX a XX2 uvrA (pKM101)
α-[(5-nitro-2-furyl)methyliden]furan-2-acetamid (XX2)	3688–53–7		xxxxx xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx kontrolu xxxxx xxx xxxxxxx jiné xxxxxx referenční xxxxx. Xxx xxxxxxxxx xxxxxxxx xx xxxx být xxxxx v xxxxx xxxxxxx xxxxxxxxxx látek xx xxxxxx xxxxxxxx xxxxx, xxxx xx x xxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx rozpouštědla xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, zpracované xxxxx xxxxxxx xxxxxxxx xxxx exponované skupiny. Xxxxx xxxx by xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.5.3 Xxxxxx

X xxxxxxxxxx xxxxxxx xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx aktivace xx xxxxxxx xxxxxx 0,05 xx xxxx 0,1 xx zkušebních roztoků, 0,1 xx xxxxxxx xxxxxxxxxxx xxxxxxx (obsahující xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x 0,5 xx xxxxxxxxxx xxxxx x 2,0 xx xxxxxxxx agaru. X xxxxxxx zkoušky x xxxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx postmitochondriální frakce (x xxxxxxx 5 xx 30 % xxx. v xxxxxxxxxxx xxxxxxxxx xxxxx) x xxxxxxx xxxxxx (2,0 xx) x xxxxxxx x bakteriemi x xxxxxxxxx látkou xxxx xxxxxxxxx xxxxxxxx. Obsah xxxxx zkumavky xx xxxxxxxx x přelije xxxx xxxxxx minimálního xxxxx xx xxxxx. Xxxx inkubací xx xxxxx xxxxxx xxxx xxxxxxxx.

X preinkubační xxxxxx (2, 3, 5, 6) se zkoušená xxxxx nebo xxxxxxxx xxxxxx xxxx smícháním x xxxxxxx xxxxxx x přelitím přes xxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxxxxx 20 xxxxx nebo xxxx preinkubuje x xxxxxxxxxx xxxxxx (xxxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) x sterilním xxxxxx nebo metabolickým xxxxxxxxxx systémem (0,5 xx) xxx 30 — 37 °X. Xxxxxxx xx xxxxxx 0,05 nebo 0,1 xx xxxxxxxx xxxxx xxxx zkušebního xxxxxxx, 0,1 xx xxxxxxxx x 0,5 ml xxxxx X9 nebo xxxxxxxxxx xxxxx s 2,0 xx xxxxxxxx xxxxx. Xxxxxxxx xx xxxx být xxxxx xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.

X xxxxxxxxxxxx odhadu xxxxxxxx xx měly xxx xxx xxxxx xxxxxx xxxxx xxxxxxx 3 xxxxx. Xxxxxxx xxxx misek xx xxxxxxxxxx po vědeckém xxxxxxxxxx. Případná xxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx zkoušky.

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

1.5.4 Xxxxxxxx

Xxxxxxx misky v xxxx xxxxxxx xx xxxx být inkubovány xxx 37 °C xx 48 –72 xxxxxxxx. Xx uplynutí xxxxxxxxx xxxx xx xxxxxx xxxxx kolonií xxxxxxxxxx xx xxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxx xxxxx by měly xxx xxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xx xxxxx. Měl xx xxx rovněž uveden xxxxx kolonií xxxxxxxxxx xxx na miskách x negativní kontrolou (xxxxxxxx rozpouštědla x xxxxxxxx xxxxxxxxxxxx xxxxxxxx), xxx xx xxxxxxx x xxxxxxxxx kontrolou. Xxxxx xx xxxxxxxxxxxx xxxxxxx, střední xxxxxxx xxxxx xxxxxxx revertantů xx xxxxx a xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxx xxx zkoušenou xxxxx x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx kontrolu xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx xxx potvrzeny xxxxxx xx případu. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx nezbytné, xxxx xx xxx xxxxxx xxxxxxxxxx. Xxxxx parametrů xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx studie, xxxxx xx mohly být xxxxxxx, patří xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx xxxxxxx metoda xxxx xxxxxxxxxxx x xxxxxxxx médiu) x xxxxxxxx metabolické aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx nad xxxxxxxxx xxxxxx u xxxxxxx jednoho xxxxx x metabolickým xxxxxxxxxx xxxxxxxx nebo xxx xxxx, x xx x xxxxxxxxxx xx xxxxxxxxxxx, nebo reprodukovatelný xxxxxx xxxxxx počtu xxx xxxxx xxxx xxxx xxxxxxxxxxx (23). Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (24). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx odpověď.

Zkoušená xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx považuje v xxxxx xxxxxxx za xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx negativní výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx mutace x xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x genomu xxxxx Xxxxxxxxxx xxxxxxxxxxx a/nebo Xxxxxxxxxxx coli xxxxxx xxxxxx xxxxxxxxxx bází xxxx xxxxxxx čtecího xxxxx. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxx za xxxxxxxx zkoušky xxx xxxxxxxxx xxxxx mutagenní.

3. XXXXXX

XXXXXXXX O ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx x kultuře,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxx xxxxx,

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

- postup xxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

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

- xxxxx xxxxxxxx závislost xxxxxxxx na xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxx, X. X., XxXxxx, X., Xxxxxxxx E. (1975), Methods xx Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 31, 347-364.

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

3) Xxxxxxxxx, X., Xxxxxxx, S., Xxxxxx, X., Xxxxx, E., Xxxx, X., Xxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Venitt, X., Zeiger, E. (1994), Recommendations xxx xxx Performance of Xxxxxxxxx Xxxxxxxx Xxxxxx, Xxxxxxxxxx Res., 312, 217-233.

4) Xxxx, L. X., Xxxxxxx D. X., Xxxxxxx, X. X., Xxx Halle, X. S., Xxxxx, X. X., Simmon, X. X., Dunkel, X., XxXxxx, X., Xxxxxxxxxx, X., Prival, X., Rao, X. X., Xxx X. (1986), The Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Microsomal Assay: X Xxxxxx xx xxx U. X. Xxxxxxxxxxxxx Xxxxxxxxxx Agency Xxxx-Xxx Program, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, T., Degawa, X., Xxxxx, Y. X., Matsushima, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, Y. (1975), Mutagenicity of Xxxxxxxxxx Xxx Dyes xxx xxxxx Xxxxxxxxxxx, Xxxxxx Lett. 1, 91-96.

6) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1980), Factors Xxxxxxxxxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxx, in: Xxxxx-xxxx Xxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx, ed. Xxxxxxx X. X., Xxxxxx, R. X., Xxxxxxxx, Berlin-Heidelberg-New York, 273-285.

7) Xxxxxxxxx, D. X., Xxxxxxx, X. X., Xxxxxx, X., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Xxxxxx, xx: Basic Mutagenicity Xxxxx: UKEMS Part 1 Revised, ed. X. X. Xxxxxxxx, Xxxxxxxxx University Xxxxx, 13-61.

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

9) Xxxxx, X. X. X., Xxxxxx, X. X., Xxxxxxx, X. X. (1976), Xxx of x xxxxxxxxxx fluctuation xxxx xx xxxxxx xxx xxxxxx xx xxxxxxxx, Xxxxxxxxxx Xxx., 38, 33-42.

10) Hubbard, X. A., Green, X. X. X., Xxxxxxxxx, D., Bridges, X. X. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures, 2. xxx., Xxxxxx, X. X., Legator, M., Xxxxxxx, W., Ramel, X. (eds.), Xxxxxxxx, Xxxxxxxxx-Xxx York-Oxford, 141-161.

11) Xxxxxxxx, E. X., Xxxxxxx, X. X. (1981), Xx Xxxxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxxx Xxxxx xxx Xxxxxxxxxxx with Xxxxxxx xx Salmonella xxxxxxxxxxx, Xxxxxxxxxxxxx Mutagenesis, 3, 453-465.

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

13) Prival, X. X., Xxxx, S. X., Xxxxxxxx, X. X., Xxxxxxx, X. X., Vaughan, X. X. (1984), Xxxxxxxxxxxx xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Monoazo Xxxx xx x Xxxxxxxx Xxxxxxxxxx Assay, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, X., Xxxxxxxx, X. X., Haworth, X., Lawlor, T., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Tests. X. Results xxxx xxx Xxxxxxx xx 311 Xxxxxxxxx, Environ. Xxx. Mutagen., 19, 2-141.

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

16) Hughes, X. X., Xxxxxxx, X. M., Xxxxxxxx, X. X., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Xxxxxxxxx to Xxxxxxx Xxxxxxxxx Activity xx Xxxxxxxx Xxxxxxx Xxxxxxxxx in xxx Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, X., Xxxxxxxxx, X., Shirai, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx the Xxxxxxxxx Xxxxxxxxx Carcinogen Cycasin xxx Xxxxxxxxx Methylazoxy Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx, Cancer Xxx., 39, 3780-3782.

18) Xxxxxx, X., Xxxx, X., Xxxxx-Xxxxx, X., Xxxx, X. N. (1980), Xxxxxxxx: X Xxxxx xxx Xxxxxxxxxx xx Xxxxxxx Xxxxxxxxxx xx Xxxxxxxx xx Xxxxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Xxx. X. X. X, 77, 4961-4965.

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

20) Xxxxxxxxxx, T., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Inducer xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xxx. X. X. xx Xxxxxx xx xx. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.

21) Elliot, X. X., Combes, X. X., Elcombe, C. X., Xxxxxxxxx, X. X., Gibson, G. X., Mackay, J. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 in xx xxxxx Genotoxicity Assays, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, X., Katzenellenbogen, X., Ames, X. X. (1981), Compatibility xx Xxxxxxx Solvents xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 88, 343-350.

23) Claxton, X. D., Allen, X., Xxxxxxx, A., Xxxxxxxxxx, X., Nestmann, X., Xxxxxx, X. (1987), Xxxxx for xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Tests xxx Xxxxxxxxx Mutagenicity, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, X. X. X., Xxxxx, X. X. X., Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, X. X. (1989), Analysis of Xxxx xxxx Microbial Xxxxxx Xxxxxx, in: XXXXX Sub-Committee on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxx II. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, xx. Xxxxxxxx, X. X., Cambridge Xxxxxxxxxx Xxxxx, 28-65."

XXXXXXX 4E

"B.17 XXXXXXXXXX — ZKOUŠKA NA XXXXXX XXXXXX V XXXXXXX XXXXX XX XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx xx vitro xxx xxxxxx xxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx látkami. Xxxx xxxxxx xxxxxxx xxxxx xxxxx buňky xxxxxxx X5178X xxxx, xxxxxxx xxxxx XXX, XXX-XX52 x X79 xxxxxx xxxxxxxx x lymfoblastoidní xxxxx TK6 člověka (1). U těchto xxxxxxxxx xxxxx jsou xxxxxxxxxxxxxxx mírou genetických xxxxxx xxxxxx xxxx xxx xxxxxxxxxxxxxx (XX) x hypoxanthin-guaninfosforibosyltransferasu (XXXX) x xxxxxxxx xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx xx xxxxxx TK, XXXX x XPRT xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Autosomální xxxxxx XX a XXXX xxxx umožnit xxxxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxx xxxxxx), xxxxx xxxxx xxxxxxxxx x XXXX lokusu xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx in xxxxx lze použít xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxx xxxxxxx xxxxx. Xxxxx se xxxxxxxx xxxxx schopnosti xxxxx x xxxxxxx x stálosti xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx aktivace. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx u xxxxx. Xx třeba se xxxxx vyvarovat podmínek, xxxxx by xxxxx x pozitivním xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, jež neodrážejí xxxxxxx mutagenitu, xxxx xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx xx používá xx zjištění možných xxxxxxxx a xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx něž je xxxx xxxxxxx xxxxxxxxx, xxxx xxxxxxxxxxx xxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx korelace. Xxxxxxxx závisí xx xxxxxxxx třídě x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, které xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx zřejmě xxxxxx xxxxxx, negenotoxickými mechanismy, xxxx xxxxxxxxxx, xxxxx x bakteriálních xxxxxxx xxxxxxxxxx (6).

Xxx xxxx xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxx substituce xxxx xxxx : xxxxx, xxxxx xxxxxxxxx substituci xxxxxxx xxxx xxxx xxxx xxxx x XXX.

Xxxxxxxx xxxxxxxx : xxxxx, které xxxxxxxxx xxxxx xxxx deleci xxxxxxx xxxx více xxxx xxxx x xxxxxxxx XXX.

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

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

Xxxxxxxxx xxxxxxx xxxx : nárůst xxxxx buněk x xxxx xx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; vypočte xx xxxx xxxxxx poměru xxxxxxxxx růstu x xxxxxxxx x v xxxxxxxxx kontrole a xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx k negativní xxxxxxxx.

Xxxxxxxxx xxxx v xxxxxxxx : xxxxxx xxxxx xxxxx x xxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxx kontrole.

Životaschopnost : xxxxxxxx xxxxxxxxx xxxxx v xxxxxxxx xxxxxxxx na xxxxx xx selektivních podmínek xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx xx xxxxx xx xxxxx xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx xxxxxxxxx x xxxxxx x xxxxxxx kontrolní xxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx v xxxxxxxx xxxxxx XX+/-® XX— /- neobsahují xxxxxxxxxxxxxx (XX) xxxx xxxxxxxxxxx k xxxxxxxxxxxx xxxxxxx xxxxxxx pyrimidinu xxxxxxxxxxxxxxxxx (TFT). Xxxxx xxxxxxxxxxx thymidinkinasu jsou xxxxxxx xx TFT, xxx způsobuje inhibici xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx další buněčné xxxxxx. Xxxxxxxx xxxxx xxxx xxxx schopny xxxxxxxxxxx xx přítomnosti XXX, xxxxxxx xxxxxxxx xxxxx, xxxxx obsahují xxxxxxxxxxxxxx tuto schopnost xxxxxx. Xxxxxxx xxx x xxxxx x xxxxxxxxxxxx XXXX xxxx XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx x 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (XX). Xxxxxxxxxx xxxxxxxx látky by xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx xx xx zkoušce na xxxxxx mutace x xxxxxxx savců xxxxxxx xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx selekčnímu xxxxxxx. Xxxx xx xxx xxxxxxxxx vyšetřeno xxxxxxxx xxxxxxxxx na xxxxxxxxxx xxxxxxxx zkoušené xxxxx xxx xxxxxxxx xxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx strukturu xxxx xxxxxxxx činidlo, xxxx xxxx xxx xxxxxxxxx xxxxxxxx systému xxxx xxxxxxx xxx xxxxxxx (8).

Xxxxx x xxxxxxxxx xxxx xxxxxxxxxxxxx kultuře xxxx xxxxxxx xxxx xxxxxxxxx zkoušené xxxxx xxx s metabolickou xxxxxxxx, xxx bez xx, x xxxxxxxxxxxxxx xx xxxxxx stanovení xxxxxxxxxxxx x xx xxxxxx xxxxxxx fenotypu xxxx xxxxxxx mutantů (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx zjistí xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxx xxxxxxxxxxx celkového xxxxx xxxxxx po xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx v xxxxxxxx xxxxx xx xxxxxxx xxxx xxxxxxxxxxxxxxxxx xxx xxxxx xxxxxxx xxxxx x xxx xxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx xx xxxxxxx xxx, xx xx xxxxxx xxxxx xxxxx xxxxx xx média xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx xxxxxxx mutantních xxxxx x xx xxxxx xxx xxxxxxxxxx xxxxxxx, xxx byla xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Xx vhodné xxxxxxxxx xxxx xx xxxxxxxxx kolonie. Četnost xxxxxxx xx xxxxxxx x počtu xxxxxxxxxx xxxxxxx v selekčním xxxxx x xxxxx xxxxxxx v xxxxx xxx selekčního činidla.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx xxxxxxx x xxxx xxxxxxx xxxx x xxxxxxxxx xxxxx xxxx buněk, xxxxxx xxxxxxxx xxxxx X5171X, XXX, XXX-XX52, X79 xxxx XX6. Xxxx buněk x xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx mutagenům, xxxxxxx xxxxxxxxx xxxxxxxxx x stabilní xxxxxxxxx xxxxxxxxxxx xxxxxx. Buňky xx xxxx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx mykoplasmaty, x x případě xxxxxxxxxxx xx xxxxxx xxx xxxxxxx.

Xxxxxxx xx měly xxx xxxxxxxx xxx, xxx xxxx předem xxxxxxxxxx citlivost x xxxx. Xxxxx xxxxxxxxx xxxxx, kultur x xxxxxxxxxxx xxxxxxxx xxxxx xx xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxx (14). Xxxxxxxxx počet xxxxx, xxxxx přežijí xxxxxxxx a které xxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx, xx xxx xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx je, xxx xxx xxxxxx počet xxxxx, xxxxx xx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx xxxx xxxxxxxxxx, xxx xxxx xxxxxxx xxxxxxx 106 buněk. Xxxx xx xxx x xxxxxxxxx dostatečné xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Média x xxxxxxxxxx xxxxxxxx

Xxx udržování xxxxxx xx xxxx xxx použita vhodná xxxxxxxxxx média x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, koncentrace CO₂, xxxxxxx a xxxxxxx). Xxxxx by xxxx xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx a xxxx buněk xxxxxxxxx xxx xxxxxxx. Xx xxxxxxx důležité, xxx xxxxxxxxxx podmínky xxxx xxxxxxx xxx, xxx xxxx xxxxxxxxx optimální xxxx xxxxx během xxxxxx xxxxxxx x xxxxxxxxx xxx xxxxxxxxxx, xxx nemutovaných xxxxx xxxxxx xxxxxxx.

1.4.1.3 Příprava xxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx z xxxxxxxxx kultur, nasazeny xx xxxxxxxxxxxx xxxxx x inkubovány při 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx xxxx být xxxxxxxx xxxxxxxxx x xxxxxxx již xxxxxxxx xxxxxxxx buňky.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, a to x xxxxxxx xxxxxxxx xxxxxxxxxxx aktivace a xxx xxxx. Nejčastěji xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx dotovaná postmitochondriální xxxxxx (X9) připravená x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (15, 16, 17 x 18), nebo xxxx xxxxxxxxxxxxx x β-naftoflavonu (19, 20).

Postmitochondriální frakce xx x konečném xxxxxxxxxx médiu xxxxxxx xxxxxxxxx x koncentracích 1 — 10 % xxx. Xxxxx x stav xxxxxxxxxxxxx xxxxxxxxxxx systému může xxxxxxx xx třídě xxxxxxxx látky, která xx zkoušena. V xxxxxxxxx případech xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx postmitochondriální frakce.

Řada xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx aktivační enzymy, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx xx xxxx být xxxxxxx zdůvodněna (např. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx xxxxxxxxxxxx xxxxxxxx látky).

1.4.1.5 Xxxxxxxx xxxxxxxx látky

Pevné xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány ve xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx a popřípadě xxxxxxx. Xxxxxxx zkoušené xxxxx mohou být xxxxxxx xxxxx k xxxxxxxxxx systémům x/xxxx xxxxx xxx před xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx mělo xxx xxxx xxxxxxxxx, xx xxxxxxx se zkoušenou xxxxxx, x xxxx xx xxx slučitelné x xxxxxxxx buněk x x xxxxxxxxx X9. Jsou-li použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo by xxx jejich xxxxxxxx xxxxxxxxx údaji o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud možno xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx xxxxxxxxx xx vodě xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, která xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x xxxxx xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x bez xx x xxxxxxx xxxxxxxxxxx xx použití vhodných xxxxxxxxxx xxxxxxx integrity x xxxxx, xxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx xxx výhodné xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx koncentrace. V xxxxxxx toxicity xx xxxx xxxx koncentrace xxxxxxxx xxxxxxx dané xxxxxxxxx x minimální xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx xxxx xxxxxxx znamenat, že xx se xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. Xx-xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx cytotoxicity, xxxx xx být xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) xxxxxxx (relativní xxxxxxxx klonování) nebo xxxxxxxxx celkový růst. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx látek xx xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, která x nich xx xxxxxxxx.

Xxxxxxxxx nerozpustné xxxxx xx xxxx být xxxxxxxx až x xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx xxxxxxxx, xxxx xx za xxxx xxx. Xxxx by xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxx v konečném xxxxx, xx kterému xxxx xxxxx xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x na xxxxx aplikace, xxxxx xxxxxxxxxxx xx xxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx systému xxxxx x xxxxxxxx xxxxxxxxxxx buněk, X9 xxxx, xxx. Nerozpustnost xxx zjistit vizuálně. Xxxxxxxxx by xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx xxxx vehikulum) xxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, tak xxx ní. Xxx xxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx kontrolou chemická xxxxx, xxxxx x xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx pozitivní xxxxxxxx xxxxx xxx xxxx xxxxx:

Xxxx xxxxxxxxxxx aktivace	Lokus	Látka	Číslo XXX	Xxxxx xxxxx Xxxxxx
Xxx xxxxxx xxxxxxxxxxx xxxxxxxx	XXXX	xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
	XXXX	1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
	XX (xxxx a xxxxx xxxxxxx)	xxxxxx-xxxxxxxxxxxxxx	66–27–3	200–625–0
	XXXX	xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
	XXXX	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 xxxxxxxxxx	6055–19–2
		xxxxx[x]xxxxx	50–32–8	200–028–5
		3-xxxxxxxxxxxxxxxxx	56–49–5	200–276–5
	XXXX	X-xxxxxxxxxxxxxxxxxxx (xxx xxxxxx xxxxxx X9)	62–75–9	200–549–8
	XXXX	xxxxx[x]xxxxx	50–32–8	200–028–5

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

Xxxx xx xxx použity xxxxxxxxx xxxxxxxx xxxxxxx médiem xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx jako exponované xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Expozice xxxxxxxx látce

Proliferující xxxxx xx xxxx xxx xxxxxxxxx zkoušené xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx xx xxxx xxxxx vhodnou dobu (xxxxxxx je xxxxxx xxxx 3 až 6 xxxxx). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx na jeden xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx exponovaná xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, xxx xx být xxxxx xxxxxxxxxxx zvýšen tak, xxx xxx xxxxxxxx xxxxxxxxxxxx počet kultur xxx xxxxxxx (xxxx. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Měly xx xxx použity duplicitní xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx rozpouštědla).

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

1.4.3.2 Xxxxxxxxx xxxxxxx, xxxxxxxxxxxxxxxx x četnosti xxxxxx

Xx xxxxx xxxxxxxxx xxxx xx xxxxx xxxxxxx x kultivují xx xxxxxx stanovení xxxxxxx x xx xxxxxx xxxxxxxx exprese xxxxxxxx xxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxx prostřednictvím xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxxx xxxxxxxxx růstu xxxxxx xx xxxxxxx xxxxxxx po expoziční xxxx.

Xxxxx xxxxx xx xxxxxxxxxx minimální xxxxxx xxxxxx, aby umožnil xxxxxxxxx optimální fenotypovou xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (HPRT a XXXX vyžadují xxxxxxx 6 xx 8 xxx, TK alespoň xxx xxx). Buňky xxxx kultivovány x xxxxx xx xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxxx) x bez xxxx (xxx xxxx) xx xxxxxx stanovení xxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx. Xx stanovením xxxxxxxxxxxxxxxx (xxxxxxx pro xxxxxxx xxxxxxxx xxxxxxx) xx xxxxxxx xx xxxxx xxxx exprese xxxxxxxxx na misku xxx xxxxxxxxxx činidla.

Je-li xxxxxxxx xxxxx xxxxxxxxx xx xxxxxxx X5178X XX+/-, mělo xx xxx xxxxxxxxx alespoň xx xxxxx xx xxxxxxxxxx xxxxxx (s xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x na xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx kultury xxxxx xxxxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxx xx xxxxxxx L5178Y XX+/- xxxxxxxxx, mělo xx xxx rozdělení xxxxxxx xxxxx xxxxxxxxx kolonií xxxxxxxxx na xxxxxxxxxxx x xxxxxxxxxxx kontrolách. Xxx studiích xx xxxxxxx TK6 XX+/- xxxx být xxxx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx velikosti xxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xx xxxx zahrnovat xxxxxxxxx cytotoxicity x xxxxxxxxxxxxxxxx, počtu xxxxxxx x xxxxxxxx xxxxxxx xxx exponované x xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx xxxxxxxx xx zkoušku X5178X XX+/- se xxxxxxx xxxxxxxxx xxxxxxx u xxxxx koncentrace xxxxxxxx xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x x xxxxxxxxx x xxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxx xxxxxxx — velká kolonie. Xxxxxxxxxxx a xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx velké xxxxxxx, xxx xxxxxxx xxxxxxxxx xxxx kolonie xxxx xxxxxxxx xxxxxxxx (23, 24). Xx xxxxxxx XX+/- jsou xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxx růstem (xxxxx) x xxxxxxx s xxxxxxx xxxxxx (malá) (25). U xxxxxxxxxx xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx poškození, xx prodloužily xxxx xxxxxxxx, a xxxxx xxxx xxxx kolonie. Xxxxxxxxx xx xxxxxxx xxxxxx xx xxxxx xxxxxx xxxx xx xx xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Indukce xxxxxxx tvořících xxxx xxxxxxx xx xxxxxxx x xxxxxxxxxx xxxxxxx, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx xxxxxxxxx xxxxx xxxxxxx rostou xxxxxxxx xxxxxx xxxx xxxxxxxx xxxxx x xxxxx xxxxx xxxxxxx.

Xxxx xx xxx xxxxx xxxxxxx (xxxxxxxxx účinnost xxxxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. Četnost xxxxxxx xx xxxx xxx xxxxxxxxx xxxx xxxxx mutantů x xxxxx xxxxxxxxxx xxxxx.

Xxxx xx být xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxx. Dále by xxxx být xxxxxxx xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx odpovědi xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x úpravou xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxx xxxxxxxx musí xxx xxxxxxxxx xxxxxx xx xxxxxxx. Tam, xxx xxxx potvrzení negativních xxxxxxxx považováno za xxxxx, xx třeba xxxxx zdůvodnění. Xxxxx xxxxxxxxx studie x xxxxx rozšířit xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx x xxxxxxxxxx experimentech xxx xxx dvojznačné xxxxxxxx, xxx pro xxxxxxxxx xxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, patří rozmezí xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxxxxx xxxxxxx x xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody. Xxxxxxxxxxx xxxxxxxxxx by xxxxxx být xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx odpověď.

Zkoušená xxxxx, xxxxx výsledky xxxxxxxxx xxxx xxxxxxx kritéria, xx x xxxxx xxxxxxx považuje za xxxxxxxxxxx.

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

Xxxxxxxxx xxxxxxxx xxxxxxx na xxxxxx xxxxxx x xxxxxxx xxxxx in xxxxx znamenají, xx xxxxxxxx látka indukuje x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx savců xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx pozitivní xxxxxxxxx odpovědi xx xxxxxxxxxxx je velmi xxxxxxxx. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx v xxxxxxxxx xxxxxxxxxxxxx buňkách xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx tyto informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Buňky:

- xxx x xxxxx xxxxx,

- počet xxxxxxxxx xxxxxx,

- případně xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx buněčné kultury,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxxx výběru xxxxxxxxxxx x xxxxx xxxxxx, xxxxxx xxxx. xxxxx x xxxxxxxxxxxx x xxxxxx rozpustnosti, jsou-li x xxxxxxxxx,

- složení xxxxx, případně xxxxxxxxxxx XX₂,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- objem xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx během xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- xxxxx xxxx xxxxxxx (případně xxxxxx xxxxx nasazených xxxxx, xxxxxxxxx a xxxxxx média),

- xxxxxxxx xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx použité x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx xxxxx,

- definice xxxxxxx xxxxx velikosti x xxxx (xxxxxxxx xxxxxx xxxxxxxx pro "xxxx" x "xxxxx" xxxxxxx).

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

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

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

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

- xxxxxxxxx xxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) x pozitivní xxxxxxxx x xxxxxxxxx, středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxxxx xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Xxx, E. X. X., Xxxxxxx X. X. (1968), Xxxxxxxxx Cell Xxxxxxxx. XX. Xxxxxxxx Xxxxxxxxx xx Xxxxxxxx Xxxxx Xxxxxxxxx in Chinese Xxxxxxx Xxxxx Xx xxxxx, Xxxx. Natl. Xxxx. Xxx. X. X. A, 61, 1306-1312.

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

4) Xxxxx, X. X., Xxxxxxxxx-Xxxxx, X., Xxxxx, X. X., Xxxxxxxxx, X. X. (1989), Xxxxxxxxxxxx Xxxxxx Xxxxxxxxxxxx at xxx Xxxxx Xxxxxxxx XX xxx XXX XXXXX Xxxx, Xxxxxxxxxxx, 4, 394-403.

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

6) Xxxxx, X. S., Xxxxxxxxxx, X., Xxxxx, X. X., Xxxxx, X., Nishi, X., Xxxxxxxxxx, Xx. X. X., Theiss, X., Xxxxxxxx, E. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Assays Xxxxxxx Xxxxx Xxxxxx. Xxxxxx xx the Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxxx Res. 312, 235-239.

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

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

9) Xx, X. X., Gupta, R. X., Heflich, R. X., Wasson, X. X. (1988), X Xxxxxx xxx Xxxxxxxx xx xxx Xxxxxxx Xxxxxxx Ovary/Hypoxanthine Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Xxxxxxxxx the Xxxxxxxxxxxx xx Chemical Xxxxxx: A Report xx Xxxxx III xx the X. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 196, 17-36.

10) Li, X. X., Xxxxxx, X. X., Choy, W. X., Xxxx, X. X., Gupta, R. X., Xxxxxxx, K. X., X'Νxxxx, J. X., Riddle, X. X., Stankowski, X. X. Jr., Xxxx, X. X. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx xx xxx Chinese Hamster Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Phosphoribosyl Xxxxxxxxxxx Gene Mutation Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

11) Xxxxx, X. L., Xxxxxxx, X. X., Xxxxxx, X. B. (1989), X Xxxxxxxxxx of Xxxxxxxx Induction xx xxx TK xxx XXXX Loci xx Xxxxx Lymphoblastoid Xxxxx: Xxxxxxxxxxxx Xxxxxxxxxxx xxx Xxx xx xx Xxxxxxxxxx Xxxxx xx Xxxxxxxxx xx xxx Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Xxx., 216, 9-17.

12) Xxxxxxxxxx, X. X. Jr., Xxxxxx, X. X., Hsie, X. X. (1986), Xxxxxxxxxxxx xxx Xxxxxxxxx Xxxxxxxx xx Xxxxx Xxxxxxxxxxxxxxxxx xxx XXX 191-Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxx Methanesulphonate xxx XXX 191 Xxxxxxx Mutation xx XX52 Cells, Xxxxxxxxxx Xxx., 160, 133-147.

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

14) Xxxxxx, C. F., Xxxxx, D. M., Xxxxxx, X. X., Xxxxx, M. X. X., Xxxx, X., XxXxxxxx, X. B., Xxxxxxx X. C. (1989), Xxxxxxxxx Xxxx Xxxx Mutation Xxxxxx Xxxxx xxxx Xxxxxx Xxxxxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, Xxxxxxxx, X. J., xx., Xxxxxxxxx University Xxxxx, 66-101.

15) Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Fiorio, X., Xxxxxxxx, X., Xxxxxxxxxx, X. (1977), Xxxxxxxxx xx 6-Thioguanine-Resistant Xxxxxxx xx V79 Xxxxxxx Xxxxxxx Cells xx Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Res. 46, 365-373.

16) Xxxx, X. X., XxXxxx, J., Xxxxxxxx, X. (1975), Xxxxxxx xxx Detecting Xxxxxxxxxxx xxx Xxxxxxxx xxxx the Salmonella/Mammalian-Microsome Xxxxxxxxxxxx Xxxx, Mutatation Xxx. 31, 347-364.

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

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

19) Xxxxxxx, B. X., Xxxxxx, X. X., Xxxxxxx, C. X., Gatehouse, X. X., Gibson, X. X., Mackay, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-Induced X9 xx: In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), X Safe Substitute xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx of Metabolic Xxxxxxxxxx Xxxxxxx, V: Xx vitro Xxxxxxxxx Xxxxxxxxxx xx Mutagenesis Xxxxxxx, de Xxxxxx, X. X., Xxxxx, X. X., Bend, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxx, North-Holland, 85-88.

21) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, X. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Xxxxxxxx Xxxxxxx, in: Xxxx, X. R., Xxxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Effects xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.

22) Xxxxxx, X. O., Xxxxxx, X. M., Xx, X. X., Xxxxxx, X. L. (1983), Xxxxxxxxxx of xx Xxxxxxxx Xxxxxx Xxxxx Cells Xxxxx xx Xxxxxxxx Xxxx xxx Detecting Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Mutation Xxxxx, Xxxxxxx. Mutagenesis, 5, 795-801.

23) Xxxxxxxxx, X. L., Xxxxx, X. M., Broder, X. X., Burrell, X., Hozier, J. X. (1990), Molecular Xxxxxxxxxx xx Mutations xx xxx Heterozygous Xxxxxxxxx Xxxxxx Locus xx Xxxxx Lymphoma Xxxxx, Proc. Natl. Xxxx. Xxx. X. X. A, 87, 51-55.

24) Moore, X. X., Clive, X., Xxxxxx, X. X., Xxxxxx, X. E., Xxxxxx, X. X., Xxxxxx, X. T., Xxxxxx, X. (1985), Xxxxxxxx of Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (XXX+) Xxxxxxx xx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx. 151, 161-174.

25) Xxxxxxx, X. X., Dryja, X. P., Little, X. X. (1990), Xxxxxxxxx Xxxxxxx Xxxxxxxx xx Xxxxxxxxx Mutations xx x Heterozygous Xxxxxxxxx Locus in Xxxxx Cells, Mutatation Xxx. 229, 89-102.

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

XXXXXXX 4F

"B.23 XXXXXXX XX XXXXXXXXXXXX ABERACE XX XXXXXXXXXXXXXXX XXXXX

1. XXXXXX

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

1.1 ÚVOD

Účelem xxxxxxx xx xxxxxxxxxxxx xxxxxxx ve spermatogoniích xxxxx xx xxxx xx xxxxxxxxxxxxx xxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx spermatogoniích xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx dva xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx typu, avšak xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Tato xxxxxx xxxx určena xx xxxxxxxxx numerických xxxxxxx x není x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Chromozomové xxxxxx a xxxxxxx xxxx jsou příčinou xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx xx stanovují xxxxxxxxxxxx změny xx xxxxxxxxxxxxxxx a xxxxxxxxxxx xx tedy, xx xxxx xxxxxxx xxxxxxxx xxxxxxxxx indukce xxxxxxxxx xxxxxx x xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Touto cytogenetickou xxxxxxxx xx xxxx xx xxxxxxxx xxxxxxxxxxxx xxxxxxx při mitose xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx zkoušky.

Pro xxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx xx xxxxxxxxxxxxxxx xx xxxx být — xxxxx než dojde xx xxxxxx xxxx — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx po xxxxxxxx. Xxxxx informace x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx lze xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx aberací chromozomového xxxx x xxxxxxxxx-xxxxxxxx X, kdy xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx je xxxxxxxx xxx xxxxxxxxx, xxx xxxx xxxxxxxx somatických xxxxx xxxxxxx xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx xx xxxx xxxxxxx xx spermatogoniemi xxxxxxxx xxx xxxxxxxxx xxxxxxxxx mutagenese, neboť xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a procesy xxxxxxxx DNA.

Ve xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxxxx xx xxxxxxxx chemické látce. Xxxxxxxxxx aberace tedy xxxxxxxxxxx xxxxxxxxx odpověď xxxxxxxxxx xxxxxxxx spermatogonií x xxxxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X xxxxxxxxxx xx xxx poloze xx xxxxxxxxx, xxxxx xxxx nemusí být xxxxx generace spermatogonií xxxxxxxxxx xxxxxxxxx krevnímu xxxxx v xxxxxxxx xxxxxxxxx x fyziologické xxxxxxx Xxxxxxxxx xxxxx x bariéry mezi xxxxxxx xxxxxx x xxxxxxx.

Xxxxxxxx existuje důkaz x tom, xx xx zkoušená látka xxxx xxxxxxxxx metabolity xxxxxxxxxx xx xxxxxx xxxxx, xxxx vhodné xxxx xxxxxxx xxxxxx.

Xxx xxxx xxxxxx úvod, xxxx X.

1.2 DEFINICE

Chromatidová xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx jednotlivých xxxxxxxxx xxxx zlomu x xxxxxxxx xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu x podobě zlomu xxxx zlomu a xxxxxxx xxxx xxxxxxxxx x xxxxxx místě.

Gap : achromatická xxxx xxxxx xxx xxxxx xxxxx xxxxxxxxxx x x minimální xxxxxxxxx xxxxxxxxx.

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

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx jsou xxxxxxx způsobem xxxxxxxxxx xxxxxxxx xxxxx x xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx. Xxxx xxxxxxxxx se xxxxxxxx podá xxxxx xxxxxxxxxxx metafázi (např. xxxxxxxxx nebo Colcemid®). X germinálních xxxxx xx xxxx xxxxxxxx xxxxxxxxx chromozomů, xxxxxx xx x analyzují xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xxxx používáni xxxxx xxxxxx xxxxxxxx a xxxx; xxx však xxxxxx samce xxxxxxxxxx xxxxxx vhodného druhu xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx by xxxxxxxxx ± 20 % xxxxxxx hodnoty hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx samci se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, aby xxx xxxx jejich xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx započetím xxxxxx xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx údaje x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum by xxxxxx xxx xxx xxxxxxxxx hladinách xxxxx xxxxxxx xxxxxx a xxxx xx být xxxxxxxxx podezření, xx xxxxxxx xx zkoušenou xxxxxx. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx aplikace zkoušené xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v nichž xxxxx x expozici.

Pozitivní xxxxxxxx xx xxxx xxxxxxxxxx strukturní xxxxxxx xx xxxxxxxxxxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx předpokládá, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx pozitivní xxxxxxxx xx xxxx xxx xxxxxxx tak, xxx byl účinek xxxxxxxx, xxx aby xxx xxxxxx xxxxxxx xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka a xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxx xxx xxxxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx látek xxx xxxxxxxxx kontrolu:

Látka	Číslo XXX	Xxxxx podle Xxxxxx
xxxxxxxxxxxxx	50–18–0	200–015–4
xxxxxxxxxxxxx xxxxxxxxxx	6055–19–2	200–015–4
xxxxxxxxxxxxxx	108–91–8	203–629–0
xxxxxxxxx X	50–07–7	200–008–6
xxxxxxxxx (xxxxxxx)	79–06–1	201–173–7
2,4,6-xxxx(xxxxxxxx-1-xx)-1,3,5-xxxxxxx	51–18–3	200–083–5

X xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x která xxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxxxxx xxxxxxx, pokud xxxxxx x dosavadních kontrolních xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx by měly xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx rozpouštědlo/vehikulum xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxx xxx analyzovatelných xxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxx nadvakrát (xx. xxx xxxxx xxxxxxxx xxxx xxxx xxxxxxxxxx). Zkoušené xxxxx xxxxx xxx podávány xxxx xx xxxx xxxxxxx, xxx. xxx xxxxx x xxx xxx x rozmezí xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx usnadněno xxxxxxxx xxxxxxx objemů materiálu. Xxxx režimy podávání xx xxxx xxx xxxxxxx zdůvodněny.

Ve xxxxxxx x xxxxxxxx dávkou xx měly xxx xx xxxxxxxx xxxxxxxxx xxx xxxxxx. Poněvadž xxxxxxxx buněčného cyklu xxxx xxx xxxxxxxxx xxxxxx ovlivněna, xxxxxxx xx xxxxx xxxxx xxxxx x xxxxx xxxxxxxx xxxxx přibližně 24 x 48 xxxxx po xxxxxxxx. X xxxxxxx xxxx xxx xxxxxxxx xxxxx xx xxx xxx xxxxx xxxxxxxx xx 24 xxxxx nebo xx takové xxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx xxxx xxxxx xxxx xxxxxxxxx xxxx xxx detekci xxxxxx (6).

Xxxxx xxxxx xxx xxxxxx xxxxxxxxx xxxx x xxxx xxxx. Například x xxxxxxx chemických xxxxx, xxxxx mohou xxxxxxxxx xxxxxxxx xxxxxxxxx (lagging) xxxxxxxxxx nebo xxxxx xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx být vhodnější xxxxxxxx odběr (1).

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxx xxx určena xxxxxx od případu. X xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5násobek délky xxxxx) po poslední xxxxxxxx. Xxxxx potřeby xxxxx být prováděny xxxxx odběry v xxxx době.

Před xxxxxxxxx xx xxxxxxxx intraperitoneálně xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx metafázi (xxxx. Colcemid® xxxx xxxxxxxxx). Xxxx xx xx vhodné xxxx xxxxxxx x xxxxxx xxxxx. U xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 xxxxx; x xxxxxx čínského xx xxxx xxxx přibližně 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx neexistenci xxxxxxxx xxxxxxxxxx xxxxx studie xxx xxxxxxxx rozsahu, xxxx by být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx x xxxxxx x xx stejného xxxxxx expozice, který xx xxxxxxx x xxxxxx studii (7). X xxxxxxx xxxxxxxx xx pro xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx dávky by xxxx pokrývat xxxxxxx xxxx xxxxxxxxx a xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru xxxxx, xxxx xxxx použita xxxxx nejvyšší dávka. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx by xxxxx xxxxx xxxxx xxx xxxxxxx režimu xxxxxxxxx podle očekávání x letalitě.

Látky se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx xxxxxxxxx stanovení dávky xxxxxxxxx a měly xx být hodnoceny xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx také definována xxxx dávka vyvolávající xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxxx metafázi; xxxx xxxxxxx xx xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx žádné xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx mají xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx úplná xxxxxx xx xxxxx xxxxxxxx dávky xx xxxxxxxxx. Xxxxxxxxx expozice xxxxxxx xxxx znamenat xxxxxxx použít x xxxxxxx xxxxxxx vyšší xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx podává xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx intubační xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx způsoby xxxxxxxx xxxx xxxxxxxxxx, jsou-li xxxxxxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx najednou podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx testovacího xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx je xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx a xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx úrovních xxxxx.

1.5.6 Příprava xxxxxxxxx xx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx xx x xxxxxxx nebo xxxx xxxxxx xxxxx xxxxxxx suspenze, xxxxxxxxxxxx xx x xxxxxx. Xxxx se xxxxxx xx xxxxxxxx sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx zvířete xx xxxx xxx xxxxxxxxxxx alespoň 100 xxxxx x dobře xxxxxxxxxxxx xxxxxxxx (xx. xxxxxxxxx 500 metafází xx xxxxxxx). Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx aberací. Všechny xxxxxxxxx xxxxxx preparátů xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx xxxxxxxxxx u xxxxx metafází, měly xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx by xxxx xxx zpracovány xx xxxxx tabulky. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx xxxxx xxxxx xx xxx být xxxxxxxxxx xxxxx xxxxx xx strukturními xxxxxxxxxxxxxx xxxxxxxxx x počet xxxxxxxxxxxxxx xxxxxxx na xxxxx. Xxx exponované x xxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx různé xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx aberací x xxxxxx xxxxxx x četností. Gapy xx xxxxxxxxxxxxx odděleně x uvádějí xx, xxx xxxxxx xx xxxxxxxxxx xx celkové xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, xxx xx xxx pro xxxxxxxxx xxxxxxx cytotoxických xxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxxxx x všech xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx jako xxxxxxxxx kontrola xxxxx xxxxxxxxxxxxx v mitose xxxxxxxx x xxxxx x xxxxx xxxxxxxxx xxxxxxxx, a xx x celkovém vzorku 100 xxxxxxxx xx xxxxx na xxxxx xxxxx. Pokud xx xxxxxxxxx xxxxx mitosa, xxxxxxx x 1000 xxxxxxx xx xxxxx xx xxx xxx xxxxxxxx xxxxxxxxx index.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje několik xxxxxxxx, xxxx. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx na xxxxx xxxx jasný xxxxxx xxxxx xxxxx s xxxxxxxxx xxx xxxxxxx x xxxxxxx dávkou x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (8). Statistická xxxxxxxxxx xx neměla xxx jediným xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx. Dvojznačné výsledky xx měly být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx in xxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxxxxx buňkách xxxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx aberace. Negativní xxxxxxxx znamenají, že xxxxxxxx látka xx xxxxxxxx xxxxxxx xxxxxxxxxx x germinálních xxxxxxx xxxxxxxxxxx xxxxx chromozomové xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx se xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxx xxxxx.

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx o xxxxxxx musí xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx druh/kmen,

- xxxxx x xxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

- individuální xxxxxxxx zvířat na xxxxxxx zkoušky, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx hodnoty x xxxxxxxxxx xxxxxxxx pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- zdůvodnění xxx usmrcení,

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

- xxxxxxxx xxxxx x kvalitě xxxxxx x xxxx,

- podrobný xxxxx xxxxxxx expozice x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

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

- metody xxxxxxxx preparátů,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx studie na xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx index,

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

- typ a xxxxx aberací xxxxxxx xxxxxxxxxx pro každé xxxxx,

- celkový xxxxx xxxxxxx ve xxxxxxx,

- xxxxx xxxxx x xxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx na xxxxx,

- xxxxxxxx statistické xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx pozitivní xxxxxxxx,

- změny xxxxxxx, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Spermatogonia of Xxxxxxxx Mutagens Xxxxxxx xx xxxxx Cell-Cycle Xxxxxxxxxxxxxx, xx: Genetic Xxxxxxxxxx of Xxxxxxxxxxxxx Xxxxxxxxx, Xxxx X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxxxx, Ramel, X., Lambert, X., Xxxxxxxxx, X. (xxx) Xxxx, Xxx Xxxx, 477-484.

2) Adler, I. X., (1984), Xxxxxxxxxxx xxxxx xx Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, (xx.) X. Xxxxxx, X. X. Xxxxx, XXX Xxxxx, Oxford, Xxxxxxxxxx XX, 275-306.

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

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Gatehouse, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Basic Xxxxxxxxxxxx Tests, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Xxxxxxx. Xxxxxx. Xxxx X xxxxxxx, Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, X. X., Xxxxxx M. D., Xxxxxxx, J., Xxxxx, X., Generoso, W., Xxxxxxxxxxxx, X., Xxxxxxx, X., Tanaka X. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxx Xxxxxx of xxx Xxxxxxx Xxxxx xx Mammalian Xxxx Xxxx Tests, Mutatation Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, A. R., Xxxxxx, X. X., Xxx, X., Esdaile, X. J., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Morton, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Xxxxxx of Xxxxxxx Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. P., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, X. X., Savage X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx vivo Xxxxxxxxxxx Xxxxxx, xx: X. X. Kirkland (xx.), Xxxxxxxxxxx Evaluation of Xxxxxxxxxxxx Test Xxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."

PŘÍLOHA 4X

"X.39 XXXXXXX XX NEPLÁNOVANOU XXXXXXX XXX (XXX) X XXXXXXXXX XXXXXXX XXXXX XX XXXX

1. METODA

Tato xxxxxx xx replikou xxxxxx OECD XX 486 — Zkouška xx neplánovanou syntézu XXX (UDS) v xxxxxxxxx buňkách xxxxx xx xxxx (1997).

1.1 XXXX

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

Xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxx vyšetření xxxxxxxxxxxxx xxxxxx chemických xxxxx x játrech. Xxxxxxxxxxx xxx xx xxxxxxxxxx poškození DNA x xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx xxxxxx, xxx xxxx absorbované sloučeniny xxxxxxxxxxxxxx. Xxxx xxxx xxxxxxx xxxxxx pro xxxxxxxxx xxxx xxxxxxxxx XXX xx xxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, xx xx xxxxxxxx xxxxx xxxxxxxxx xx xxxxxx xxxxx, xxxx vhodné tuto xxxxxxx xxxxxx.

Xxxxxx neplánované xxxxxxx DNA (XXX) xx xxxxxxxx stanovením xxxxxxxxxxx značených xxxxxxxxxx xx xxxxx, které xxxxxxxx xxxxxxxxxx syntézou XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx xx autoradiografické xxxxxxxxx inkorporace xxxxxxxxx xxxxxxxxx xxxxxxx (3H-TdR). Xxx xxxxxxx na XXX xx vivo xx xxxxxxxxxx xxxxxxxxx xxxxx xxxxxxx. Jiné xxxxx xxx xxxxx xxxxx být xxxxxx xxxxxxx, xxxxxx xxxx xxxxxxxxx této xxxxxx.

Xxxxxxx xxxxxxxx UDS závisí xx xxxxx xxxx XXX xxxxxxxxxxx x xxxxxxxxxxx x xxxxx xxxxxxxxx. Zkouška na XXX xx tedy xxxxxx xxxxxxx xxx xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 xxxx) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("xxxxx-xxxxx xxxxxx") (xxxxx až tři xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxx. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxxxx lézí XXX xxxxx x xxxxxxxxxx xxxxxxxxx. Xxxxxx odpovědi XXX xxxxxxxxxxx xxxxxx xxxxxxxxx o věrnosti xxxxxxxxxxx procesů. Navíc xx xxxxx, xx xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX není xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx informací, xxxxx xxxx zkouška xxxxxxxxx x xxxxxxxxx aktivitě, xx xxxxxxx potenciální xxxxxxxxxx xxxxxx xxxx, xxxxx je xxxxxxxxxx x xxxxx xxxxxx.

Xxx xxxx xxxxxx úvod, xxxx B.

1.2 XXXXXXXX

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

Xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx buněk v xxxxxxxxxxxxxxxxx zkoušce xx XXX, vypočtená odečtením xxxxxxxxxx xxxxx xxx x cytoplasmatických oblastech (XX) odpovídajících xxxxxx xx počtu xxx xxxxxxxxxxxxxx xxxxxxxx jádrům (XX): XXX = XX — XX. Xxxxxxx XXX xx xxxxxxx xxx xxxxxxxxxx xxxxx, poté xxxxxxxx xxx buňky v xxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxx.

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx XXX x jaterních xxxxxxx xxxxx xx vivo xxxxxxxx xxxxxxx xxxxxxxx XXX xx vyštěpení x xxxxxxxxxx xxxxx XXX obsahujícího xxxxxx x poškozením indukovaným xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx obvykle xxxxxxxx xx inkorporaci 3X-XxX xx XXX jaterních xxxxx, kde xx xxxx četnost xxxxx x X-xxxx xxxxxxxxx xxxxx. Inkorporace 3X-XxX xx obvykle xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx xxxx tak xxxxxxx xx xxxx X-xxxx xxxxx xxxx xxxx. kapalná xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx používán xxxxxx, ačkoli lze xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx používané xxxxxxxxxxx xxxxx mladých xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x neměla xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx xxx xxx xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x strava

Platí xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx X, přičemž xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxx 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx výběrem xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, xxxxx xx xxxxxxxx. Klece xx xxxx být xxxxxxxxxx xxx, xxx xxx xxxx jejich xxxxxx minimalizován. Xxxxxxx xx jednoznačně xxxxxxxxxxxx x před xxxxxxxxx xxxxxx se xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx zkoušené xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx xxxx aplikací zvířatům xxxxxxxxxx nebo suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx podávány přímo xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx xxxxx o xxxxxxxx neprokazují možnost xxxxxxxxxx.

1.4.2 Zkušební podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx a xxxx xx xxx xxxxxxxxx xxxxxxxxx, že reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx xxxxxx xxxxxxx xxxxx xxxxx vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každé xxxxxxxxx xxxxxxxxx části xxxxxxxxxxx xx xxxx xxx xxxxxxxx pozitivní x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx xxxxxxxx látky xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxxxx xxxxxxxxxx xx měly být xxxxx, o nichž xx xxxxx, že xxxxxx xxxxxxxx v xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Pozitivní kontroly xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Dávky xxxxx xxx xxxxxxx xxx, xxx byl účinek xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx	Xxxxx	Xxxxx XXX	Xxxxx xxxxx Einecs
Časné xxxx xxxxxx (2 xx 4 x)	X-xxxxxxxxxxxxxxxxxxx	62–75–9	200–249–8
Xxxxxx doby xxxxxx (12 až 16 x)	X-(xxxxxxx-2-xx)xxxxxxxx (2-XXX)	53–96–3	200–188–6

Xxxxx xxx xxxxxxx xxxx xxxx xxxxx xxx xxxxxxxxx kontrolu. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx kontrolní xxxxx xxxxxxxx jiným xxxxxxxx, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx zvířat

Měl by xxx xxxxxx xxxxxxxxxx xxxxx xxxxxx, xxx xxxx xxxxxxxxxx přirozené xxxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx. Xxxxx xxxxxxx xx se xxxx xxxxxxx alespoň xx tří analyzovatelných xxxxxx. Jestliže xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx xxx xxxxxxxxx x pozitivní xxxxxxxxx xxxxxxx nezbytné xxxxx jedno až xxx xxxxxxx.

Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx údaje xx xxxxxx xx xxxxxxx druhem x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx neexistuje xxxx pohlavími rozdíl x xxxxxxxx, bude xxxxxxxxxxx zkoušení xxxxxxx xxxxxxx, xxxxxxx xxxxx. Xx-xx xxxxxxxx člověka xxxxxxxxxx xxx určité xxxxxxx, jako je xxxx xxxxxxxxx x xxxxxxxxx farmaceutických xxxxx, xxxx xx být xxxxxxx provedena se xxxxxxxx odpovídajícího pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xxxx xxxxxxxxx podávány xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx xxxxxxxxxx xxxxxxxx se xxxxxxxxx xxxxxxx dvě xxxxxx xxxxx. Nejvyšší xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx podle xxxxxxxxx xxx stejném xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx dávka xx xxxx xxx xxxxxxxxx 50 % až 25 % vyšší xxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx netoxických dávkách (xxxx. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x měly by xxx xxxxxxxxx případ xx xxxxxxx. Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro zjištění xxxxxxx, xxxx xx xxx provedena xx xxxxxx laboratoři, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí x xxxxxx xxxxxx.

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

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx x alespoň 2000 xx/xx tělesné xxxxxxxxx xxxxxxx jednorázově xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx na základě xxxxx x xxxxxxx, xxxxx mají podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxx xxx xxxxx xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx člověka může xxxxxxxx potřebu xxxxxx x limitní xxxxxxx xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx sondou xxxx xxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou xxxxx, xxx-xx je zdůvodnit. Xxxxxxxx xxxxxxxxxxxxxxxxx se xxxx xxxxxxxxxxxx, xxxxx xx xxxxx xxxxx xxx xxxxxxxxxx zkoušené xxxxx přímo x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx by xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Až xx xxxxxxxx x žíravé xxxxx, xxxxx obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx zkušebního xxxxxx xxxxxxxxxxxxxx nastavením koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx z exponovaných xxxxxx xxxxxxxxx 12 xx 16 xxxxx xx podání xxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (obecně xxx xx xxxxx xxxxxx xx xxxxxxxx) je xxxxxxxx, xxxx-xx xx 12 xx 16 xxxxxxxx jasná xxxxxxxxx xxxxxxx. Mohou xxxx xxx xxxxxxx xxxx xxxx xxxxxx, xxxx-xx xxxxxxxxxx xx základě xxxxxxxxxxxxxxxxx údajů.

Krátkodobé xxxxxxx xxxxxxxxx xxxxx savců xx xxxxxxxxx xxxxxxxxx xxxxxxx jater kolagenasou xx situ x xxxxxx se, xxx xx čerstvě xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xx vhodném povrchu. Xxxxxxx buňky z xxxxxxxxx xxxxxxxx by xxxx vykazovat xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.

1.5.7 Stanovení UDS

Čerstvě xxxxxxxxx xxxxxxx xxxxx xxxxx se xxxxxxx xxxxxxx dobu, xxxx. xxx xx osm xxxxx, xxxxxxxx x xxxxxx obsahujícím 3X-XxX. Xx konci inkubační xxxx xx mělo xxx xxxxxx x xxxxx xxxxxxxxxx a xxxxx poté xxxxx xxx inkubovány x xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx xx xxxx xxxxxxx, xxxxxx a xxxxxx. Při delší xxxxxxxxx xxxx nemusí xxx xxxxxxx radioaktivity xxxxxxxx. Xxxxxxxxx xx xxxxxx do xxxxxxxxxxxxxxxxx xxxxxx, xxxxxxxx xx x xxxxx (xxxx. x xxxxxx 7 xx 14 dnů), xxxxxxxx se, xxxxxx x spočítají xx xxxxxxxxxx zrna xxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxxx xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx by xxxx xxxxxxxxx dostatečný počet xxxxxxxxxxxx xxxxxxxxxx xxxxx, xxx xxxx xxxxxxxxx XXX xxxxxxxxx xxxxxxx. Xxxxxxxxx xx xxx xxxxxxxxxxx xxxxxxxxxx na xxxxxx zjevné xxxxxxxxxxxx (xxxx. xx xxxxxxx, xxxxxxxx xxxxxx značení xxxxxxxxxxxxx xxxxxxxx).

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

Xxxxxxxx 3X-XxX inkorporovaného xx xxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx doložené xxxxxxxxxxx xxx xxxxxxx xx xxxx být xxxxxxxxx xxxxxxx xxxxxxx.

Xxxxx buněk xx stanoví x xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (xx) x x xxŭxxxxxxx xxxxx zrn x xxxxxxxxxxxxxxxxx oblastech (xx) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx cg xx xxxxxxx xxx xxxxx xxxxx xxx nejsilněji xxxxxxxxx oblast xxxxxxxxxx, xxxx xxŭxxxxx xxxxxxx xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx dotyčných xxxxxxxxx xxxxx. po xxxxxxxxxxxxx zdŮvodnění mohou xxx použity i xxxx xxxxxxx stanovení xxxxx buněk (xxxx. xxxxxxxx xxxxxx buněk) (6).

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxx by xxx xxxxxxx údaje pro xxxxxxxxxx preparáty x xxxxxxx. Xxxxx xx xxxx xxx xxxx xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX od hodnoty XX by xxx xxx xxxxxxxx xxx xxxxxx xxxxx, xxx xxxxx xxxxx a xxx každou dávku x xxx xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX). Xxxxxxxx xxxx počítány "xxxxxxxxxx" buňky, měla xx xxx xxxxxxxx xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx xxxxxxxxxx x xxxxxxxx xx xxxxxxxxxxx xxxx souběžných xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx výsledky mohou xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx xxx xxxxxxx, xxxx xx xxx xxxxxxxxxxx xxxxx xxxxxxx x odůvodněny xxxx xxxxxxxxxx studie.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx pozitivní nebo xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx	x)	xxxxxxx XXX leží nad xxxxxxxx xxxxxx, xxxxx xx zdůvodněna xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx;
xxxx	xx)	xxxxxxx XXX je xxxxxxxx xxxxx xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx;
xxxxxxxxx	x)	xxxxxxx XXX xxxx xx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxx xx;
xxxx	xx)	xxxxxxx XXX xxxx xxxxxxxx xxxxx xxx xxxxxxx pro xxxxxxxxx xxxxxxxx.

Xxxx xx být xxxxxxxxx xxxxxxxxxx relevance xxxxx, xx. měly xx xxx xxxxx x úvahu xxxxxxxxx, xxxx jsou xxxxxxxxxxx xxxxxx, xxxxx dávky x odpovědi x xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxx neměla xxx jediným určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx většina experimentů xxxxxxxx jasně pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx bez xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx XXX x xxxxxxxxx xxxxxxx xxxxx in xxxx xxxxxxxxx, že xxxxxxxx xxxxx indukuje x jaterních xxxxxxx xxxxx xx vivo xxxxxxxxx XXX, xxxxx xxx opravit xxxxxxxxxxxx xxxxxxxx XXX in xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx XXX, xxxxx lze xxxxxxxxx xxxxx xxxxxxxx.

Xxxx xx xxx diskutována xxxxxxxxxxxxxxx, x jakou xx xxxxxxxx látka xxxxxxx xx xxxxxxxx xxxxx popř. xx xxxxxx xxxxx (xxxx. xxxxxxxxx toxicita).

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx musí obsahovat xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, strava xxx.,

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

Zkušební xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx podávání,

- popřípadě xxxxxx xxxxxxx, xxx xx zkoušená xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx xx xxxxxx xxxxx,

- případně xxxxxxxx xxxx koncentrací xxxxxxxx xxxxx x xxxxxx nebo xxxx (xxx) na xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx rozvrhu expozice x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx technika,

- počet xxxxxxxxx a xxxxx xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- xxxxxxxx klasifikace xxxxxx xx pozitivní, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxxx xxxxxxx počtu xxx odpovídajících xxxxxxxx xxxxxx a počtu xxx xxxxxxxxxxxxxx xxxxxxxxxx, x čistý xxxxx xxx, jednotlivě xxx xxxxxxxxx, zvířata a xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxx,

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

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

- xxxxx xxxxx "xxxxxxxxxxxx" buněk, xx-xx stanoven,

- xxxxx xxxxx v X-xxxx, xx-xx stanoven,

- životaschopnost xxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, J. Xxxxxxx, X. X., Burlinson, X., Penman, X. X. (1985), An Xxxxxxxxxx xx xxx Xx xxxx Xxx. Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.

2) Xxxxxxxxxxx, X. E., Xxxxx, X., Xxxxxxxx, E., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1987), X Xxxxxxxx and Xxxxx xxx xxx Xx vivo Rat Xxxxxxxxxx DNA Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 123-133.

3) Xxxxxxxx, X. C., Waters, X., Ashby, X., Xxxxxxx, X. X., Xxxxxxxxx, B., Benford, X. J., Dean, X. W., Xxxxxxxx, X. de X. (1993), In xxxx Xxx Xxxxx UDS Xxxxx, xx: Xxxxxxxx X. J., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: UKEM Xxxxxxxxxxx Procedures. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx II xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 52-77.

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

5) Xxxxx, R., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, C. (1993), Assessment of xxx Xxxxxxxx Between xxx Initial Viability xxx xxx Xxxxxxxxxx xx Freshly Isolated Xxx Hepatocytes Used xxx xxx Xx xxxx/Xx xxxxx XXX Xxxxxx Assay (XXX), Xxxxxxxxxx Xxx., 291, 21-27.

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

XXXXXXX 5

XXXXXX XXXXXXXXX XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX LÁTEK X PŘÍPRAVKŮ

Viz xxxxxxxx Xxxxxx 2001/59/XX, Xx. xxxx. L 332, 28. 12. 2000, x. 81.

XXXXXXX 6

"

PŘÍLOHA IX

ČÁST X

xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 odst. 1 písm. x) xxxx xxxxxxxx, musí xxx obaly x xxxxxxxxx xxxxxx xxxxxxxxxx xxxxx, x nimiž xx spojeno riziko xxx xxxxxxxxxx (Xn; X 65) a xxxxx jsou xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx na trh xx formě xxxxxxxx xxxx x xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx, xxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx na xxxxxxxxx xxxxxxxxxxxxxx obalech xxxx splňovat požadavky xxxxx XXX 8317 (xxxxxx xx xxx 1. července 1989) "Xxxxx xxxxxx xxxxx — Xxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxx jejich xxxxxxxx" xxxxxxxx Xxxxxxxxxxx xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Xxxxxxxxx xxxxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx neuzavíratelných xxxxxxx musí splňovat xxxxxxxxx xxxxx XXX XX 862 (vydání x xxxxxx 1997) "Xxxxx — Xxxxx xxxxxx xxxxx — Xxxxxxxxx x zkušební xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Xxxxxxxxx xxxxxxx xxx xxxxxxxxxxx (XXX).

3. Xxxxxxxx

1. Prokázání shody x výše xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxx, které xxxxxxx evropské normy xxxx XX 45000.

2. Xxxxxxxxxx případy

Je-li zřejmé, xx xxxx xx xxxxxxxxxx xxxxxxxx pro xxxx, xxxxx xx xxxxxxx dostat k xxxxxx xxx xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxx xxxxxx x pochybám x bezpečnosti xxxxxxx xxx xxxx, xxxx xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx osoba odpovědná xx xxxxxxx xxxxxxx xx xxx předložila xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx xxxxxx, xx jej není xxxxxxxx xxxxxxx podle xxxx xxxxxxxxx norem XXX x XXX,

xxxx

- xx xxxxxx xxx xxxxxxx a byl xxxxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxxx norem.

ČÁST X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx specifikace xxx xxxxxxxxxx xxxxxxxx xxxx xxx v xxxxxxx x xxxxxx XX XXX 11683 (xxxxxx x xxxx 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Xxxxxxxxx".

"

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Plné znění - 32000L0032

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