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Xxxxxxxx Komise 2000/32/XX

xx xxx 19. května 2000,

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

(Xxxx x xxxxxxxx xxx XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x ohledem xx Xxxxxxx x xxxxxxxx Xxxxxxxxxx společenství,

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

vzhledem k xxxxx xxxxxxx:

(1) Xxxxxxx X směrnice 67/548/XXX xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxx xxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxx, xx xx xxx xxx xxxxxx xxxxxxxxxxxx xxxxx x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx jazykové xxxxx xxxxxxxx xxxxxxxx xxxxxx určitých xxxxxx xxxxxxxxx x tabulky X x xxxxxxx X.

(2) Příloha III xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx vět xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx x přípravky. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx x bezpečnostními xxxxxx xxxxxxxxxx se xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/XXX obsahuje xxxxx xx xxxxxxxxxxx x x xxxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx směrnice xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, IV x VI.

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

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx předpisy xxxxxxxx xx uzávěrů xxxxxxxx xxxxx xxxxxxxx xxxxx. Xxxx xxxxxxxx xx měly xxx xxxxxxxxxxxx a xxxxxxxxxxxxx. Xx xxxxxxxx xxxxxxxx xxxxxx, kde xx xxxxxxx odolné proti xxxxxxxx xxxxx používají.

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

XXXXXXX TUTO XXXXXXXX:

Xxxxxx 1

Směrnice 67/548/XXX xx mění xxxxx:

1. Xxxxxxx I se xxxx takto:

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

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

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

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

2. Xxxxxxxxxxxx xxxx x xxxxxxx XXX xx xxxxxxxxx standardní xxxxx označující xxxxxxxxxxx xxxxxxxxxx v xxxxxxx 2 této xxxxxxxx.

3. Xxxxxxx XX xx xxxx xxxxx:

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

x) odpovídající xxxxxx x xxxxxxx IV xx xxxxxxxxx kombinovanými xxxxxxxxxxxx pokyny xxx xxxxxxxx xxxxxxxxx x xxxxxxx 3X této xxxxxxxx.

4. Xxxx B xxxxxxx X xx xxxx takto:

a) kapitola X.10 se xxxxxxxxx xxxxxx x xxxxxxx 4X této směrnice;

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

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

x) xxxxxxxx X.13 a B.14 xx nahrazují xxxxxx x xxxxxxx 4X xxxx xxxxxxxx;

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

f) xxxxxxxx X.23 se xxxxxxxxx xxxxxx v xxxxxxx 4X xxxx xxxxxxxx. Xxxxx xxxxxxxx X.23 ve vysvětlivce xx xxxx xxxxxxxxxxxxx xxxxxxxx;

x) vkládá se xxxx v příloze 4X této xxxxxxxx.

5. Xxxxxxx xx čtvrtá xxxxxxx obecného xxxxx x části X xxxxxxx V.

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

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

Článek 2

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

Xxxx předpisy xxxxxxx xxxxxxxxx státy xxxx xxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxx xxxx xxxxxx odkaz xxx učiněn xxx xxxxxx úředním xxxxxxxxx. Xxxxxx xxxxxx xx xxxxxxx členské xxxxx.

2. Xxxxxxx xxxxx xxxxx Xxxxxx znění xxxxxxxx xxxxxxxxxx vnitrostátních právních xxxxxxxx, xxxxx přijmou x oblasti xxxxxxxxxx xxxx xxxxxxxx, a xxxxxxxxxx xxxxxxx xxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.

Xxxxxx 3

Xxxx směrnice xxxxxxxx v platnost xxxxxx dnem xx xxxxxxxxx v Xxxxxxx xxxxxxxx Evropských xxxxxxxxxxxx.

Xxxxxx 4

Tato xxxxxxxx xx xxxxxx členským xxxxxx.

V Bruselu xxx 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Xxxxxx

[1] Xxxxxxx xx xxxxxxxxxxxx xx xxxxxxx xxxxx.

[2] Xx. věst. 196, 16.8.1967, x. 1.

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

PŘÍLOHA 1X

XXXXXXXXX X XXXXXXX X

Xxxxxxxxxx poznámek xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx xx xxxxxxx xxxxx)

XXXXXXX 1X

"XXXXXXX X

X

Xxxxxx

XX

18

Xx

Xxxxx

Αργό

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"

PŘÍLOHA 1X

Xxxxxxxx xxxxx	Xxxxxxxx xxxxx	Xxxxxxxx x látkám	Číslo XX	Xxxxx CAS	Klasifikace	Označení	Koncentrační xxxxxx	Xxxxxxxx x xxxxxxxxxx
006–011–00–7	xxxxxxxx (ISO) 1-xxxxxx-X-xxxxxxxxxxxxxx		200–555–0	63–25–2	Xxxx. xxx. 3; X40 Xn; R22 X; X50	Xx; X X: 22–40–50 X: (2-)22–24–36/37–46–61
006–013–00–8	xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx		205–293–0	137–42–8	Xx; X22 X31 X; X34 X43 N; X50–53	X; X X: 22–31–34–43–50/53 X: (1/2-)26–36/37/39–45–60–61
006–015–00–9	xxxxxx (XXX) 3-(3,4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx	206–354–4	330–54–1	Xxxx. xxx. 3; X40 Muta. xxx. 3; X40 Xx; X22–48/22 N; X50–53		Xx; X R: 22–40–48/22–50/53 S: (2-)13–22–23–37–46–60–61
006–016–00–4	xxxxxxxx (XXX) 2- isopropoxyfenyl-N-methylkarbamát		204–043–8	114–26–1	T; X25 X; R50–53	T; X X: 25–50/53 X: (1/2-)37–45–60–61
006–017–00-X	aldikarb (XXX) 2-xxxxxx-2-(xxxxxxxxxxxxxx)xxxxxxxx-X-(X-xxxxxxxxxxxxxxx)xxxx		204–123–2	116–06–3	X+; R26/28 X; X24 X; X50–53	X+; X X: 24–26/28–50/53 X: (1/2-)22–36/37–45–60–61
006–018–00–5	xxxxxxxxx (ISO) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		217–990–7	2032–59–9	X; X24/25 X; X50–53	X; X X: 24/25–50/53 X: (1/2-)28–36/37–45–60–61
006–019–00–0	xx-xxxxx (XXX) S-(2,3-dichlorallyl)-N,N-diisopropylthiokarbamát		218–961–1	2303–16–4	Karc. kat. 3; X40 Xx; X22 N; R50–53	Xn; X R: 22–40–50/53 X: (2-)25–36/37–60–61
006–020–00–6	xxxxxx (XXX) 4-xxxxxxxx-2-xx-1-xx-X -(3-chlorfenyl)karbamát		202–930–4	101–27–9	Xn; R22 X43 N; X50–53	Xx; X R: 22–43–50/53 X: (2-)24–36/37–60–61
006–023–00–2	xxxxxxxxxxxxxxxx (XXX) xxxxxxxxxx 3,5-xxxxxxxx-4-(xxxxxxxxxxxxxx)xxxxx-X -methylkarbamát		217–991–2	2032–65–7	T; X25 N; X50–53	X; X X: 25–50/53 X: (1/2-)22–37–45–60–61
006–024–00–8	xxxxxx-xxxxxxx (ISO) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx		205–443–5	140–93–2	Xx; R22 Xi; X38 N; X51–53	Xx; X R: 22–38–51/53 X: (2-)13-61
006–026–00–9	xxxxxxxxxx (XXX) 2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx-X-xxxxxxxxxxxxxx		216–353–0	1563–66–2	X+; X26/28 N; X50–53	X+; X X: 26/28–50/53 X: (1/2-)36/37–45–60–61
006–028–00-X	dinobuton (XXX) 2-(1-methylpropyl)-4,6-dinitrofenyl-isopropyl-karbonát 2-xxx-xxxxx-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx		213–546–1	973–21–7	X; X25 N; X50–53	X; X X: 25–50/53 X: (1/2-)37–45–60–61
006–029–00–5	xxxxxxxxx (XXX) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx		230–253–4	6988–21–2	X; X25 X; X51–53	X; X X: 25–51/53 S: (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 X: 60-61
006–034–00–2	xxxxxxx (ISO) X-xxxxxx-X-xxxxx-X-xxxxxxxxxxxxxxxxx		214–215–4	1114–71–2	Xx; X22 X; R51–53	Xn; X X: 22–51/53 X: (2-)23-61
006–035–00–8	pirimikarb (XXX) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx xxxxxxxxx-4-xx-X,X-xxxxxxxxxxxxxxxx		245–430–1	23103–98–2	X; X25 X; X50–53	X; X R: 25–50/53 X: (1/2)22–37–45–60–61
006–037–00–9	promekarb (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		220–113–0	2631–37–0	X; R25 N; X50–53	X; N X: 25–50/53 X: (1/2-)24–37–45–60–61
006–038–00–4	sulfallát (XXX) 2-chlorallyl-N,N-dimethyldithiokarbamát	E	202–388–9	95–06–7	Karc. xxx. 2; X45 Xn; X22 N; X50–53	X; X X: 45–22–50/53 X: 53–45–60–61
006–039–00-X	tri-allát (ISO) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx		218–962–7	2303–17–5	Xx; X22–48/22 X43 X; X50–53	Xx; X X: 22–43–48/22–50/53 X: (2-)24–37–60–61
006–042–00–6	xxxxxxx (ISO) 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx		205–766–1	150–68–5	Xxxx. xxx. 3; R40 Xx; X22 X; X50–53	Xx; N X: 22–40–50/53 X: (2-)36/37–60–61
006–043–00–1	xxxxxxx-XXX 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx		—	140–41–0	Xx; R36/38 Karc. xxx. 3; X40 X; X50–53	Xx; X X: 36/38–40–50/53 X: (2-)36/37–60–61
006–045–00–2	xxxxxxxx (ISO) methyl-N-[(N-methylkarbamoyl)oxy]thioacetimidát		240–815–0	16752–77–5	T+; X28 N; X50–53	X+; X R: 28–50/53 X: (1/2-)22–36/37–45–60–61
006–046–00–8	bendiokarb (XXX) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx		245–216–8	22781–23–3	X; R23/25 Xx; X21 N; X50–53	X; X R: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61
006–047–00–3	xxxxxxxxx (XXX) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx		—	8065–36–9	X; X24/25 X; X50–53	X; X X: 24/25–50/53 X: (1/2-)28–36/37–45–60–61
006–048–00–9	ethiofenkarb (XXX) 2-[(xxxxxxxxxxxxx)xxxxxx]xxxxx-X-xxxxxxxxxxxxxx		249–981–9	29973–13–5	Xx; R22 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 (ISO) 2-isopropylfenyl-N-methylkarbamát		220–114–6	2631–40–5	Xn; X22 N; X50–53	Xx; X X: 22–50/53 X: (2-)60-61
006–054–00–1	mexakarbát (XXX) 4-(xxxxxxxxxxxxx)-3,5-xxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		206–249–3	315–18–4	X+; X28 Xn; X21 X; X50–53	X+; X X: 21–28–50/53 X: (1/2-)36/37–45–60–61
006–057–00–8	nitrapyrin (ISO) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx		217–682–2	1929–82–4	Xx; X22 N; X51–53	Xx; X X: 22–51/53 X: (2-)24-61
006–060–00–4	xxxxxxxxxxx (XXX) 2-xxxxxx-4,4-xxxxx-5,6-xxxxxxx-4λ4-1,4-xxxxxxxx-3-xxxxxxxxxxxx		226–066–2	5259–88–1	Xx; X22 X52–53	Xx X:22–52/53 X: (2-)61
006–069–00–3	xxxxxxxxx-xxxxxx (XXX) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx		245–740–7	23564–05–8	Xxxx. xxx. 3; R40 X; R50–53	Xn; N X: 40–50/53 X: (2-)36/37–60–61
006–070–00–9	xxxxxxxxxxx X-xxxxxxxxxx-X-xxxxxxx-2,5-xxxxxxxx-3-xxxxxxx		262–302–0	60568–05–0	Xxxx. kat. 3; X40 X; X50–53	Xx; N X: 40–50/53 S: (2-)36/37–60–61
006–088–00–7	xxxxxxxxxxx (XXX) ethyl-N -[({[(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	X,X-xxxxxxxxxxxxxxxx 1,1-xxxxxxxxxxxxxxxx	X	200–316–0	57–14–7	X; X11 Xxxx. kat. 2; X45 T; X23/25 X; R34 X; X51–53	X; X; X X: 45–11–23/25–34–51/53 X: 53–45–61
007–013–00–0	N,N-dimethylhydrazin 1,2-dimethylhydrazin	E	—	540–73–8	Karc. xxx. 2; X45 X; X23/24/25 X; X51–53	X; X X: 45–23/24/25–51/53 S: 53–45–61	C ≥ 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 xxxxxxxxxxxxxx … %	X	231–634–8	7664–39–3	X+; R26/27/28 X; R35	T+; X X: 26/27/28–35 X: (1/2-)7/9–26–36/37–45	X ≥ 7 %: X+; X; X26/27/28–35 1 % ≤ C &xx; 7 %: X; X23/24/25–34 0,1 % ≤ X &xx; 1 %: Xn; X20/21/22–36/37/38
015–039–00–9	xxxxxxx-xxxxxx (XXX) X,X-xxxxxxxx-X -[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx		201–676–1	86–50–0	X+; R26/28 X; R24 X43 X; X50–53	X+; X X: 24–26/28–43–50/53 X: (1/2-)28–36/37–45–60–61
015–048–00–8	xxxxxxxx (XXX) X,X-xxxxxxxx-X-[3-xxxxxx-4-(xxxxxxxxxxxxxx)xxxxx]-xxxxxxxxxxxxx		200–231–9	55–38–9	Xxxx. xxx. 3; X40 X; X23–48/25 Xx; X21/22 N; R50–53	T; X X: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61
015–056–00–1	azinfos-ethyl (XXX) X,X-xxxxxxx-X-[(4(3 H)-oxo-1,2,3-benzotriazin-3-yl)methyl]-fosforodithioát		220–147–6	2642–71–9	T+; X28 X; X24 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) X,X-xxxxxxx-X-(1-xxxxx-1 X- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx		245–986–5	24017–47–8	X; R23/25 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 N; X50	X; X R: 14–34–50 X: (1/2-)26–36/37/39–45–61	X ≥ 10 %: X; X34 5 % ≤ C &xx; 10 %: Xx; X36/37/38
016–014–00–5	xxxxxxx xxxxxxxx		—	13451–08–6	X14 X; X34 X; X50	X; N R: 14–34–50 X: (1/2-)26–36/37/39–45–61	C ≥ 10 %: X; X34 5 % ≤ C &xx; 10 %: Xx; R36/37/38
016–023–00–4	dimethyl-sulfát	E	201–058–1	77–78–1	Karc. xxx. 2; R45 Xxxx. xxx. 3; X40 X+; R26 X; X25 X; R34 X43	X+ X: 45–25–26–34–43 X: 53-4 5	C ≥ 25 %: X+; X45–25–26–34–43 10 % ≤ X &xx; 25 %: X+; X45–22–26–34–43 7 % ≤ X &xx; 10 %: X+; R45–22–26–36/ 37/38–43 5 % ≤ X &xx; 7 %: X; X45–22–23–36/37/38–43 3 % ≤ X < 5 %: T; R45–22–23–43 1 % ≤ X &xx; 3 %: X; X45–23–43 0,1 % ≤ X < 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; R22 N; X50–53	Xx; X X: 22–50/53 X: (2-)60-61
016–071–00–6	3-amino-6,13-dichlor-10-[(3-{[4-chlor-6-(2-sulfonatoanilino)- 1,3,5-xxxxxxx-2-xx]xxxxx}xxxxxx)xxxxx][1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx xxxxxxxx		410–130–3	136248–03–8	X43	Xx X: 43 S: (2-)22–24–37
022–001–00–5	xxxxxxx xxxxxxxxxx		231–441–9	7550–45–0	X14 C; X34	X X: 14-34 S: (1/2-)7/8–26–36/37/39–45	X ≥ 10 %: X; R34 5 % ≤ X &xx; 10 %: Xi; X36/37/38
030–004–00–8	xxxxxxxxxxxxx [1] xxxxxxxxxxxx [2]		208–884–1 [1] 209–161–3 [2]	544–97–8 [1] 557–20–0 [2]	R14 X; R17 X; X34 X; X50–53	X; X; N X: 14–17–34–50/53 X: (1/2-)16–43–45–60–61
050–002–00–0	xxxxxxxxx (XXX) xxxxxxxxxxxxx(xxxxxxx)xxxxxxx xxxxxxxxxxxxxxxxxxxxx-xxxxxxxx		236–049–1	13121–70–5	Xx; X20/21/22 N; R50–53	Xn; X X: 20/21/22–50/53 X: (2-)13–60–61
050–012–00–5	tetracyklohexylstannan [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] xxxxx(xxxxxxxxxxxxx)xxxxxxx [3]		215–910–5 [1] 221–437–5 [2] 230–358–5 [3]	1449–55–4 [1] 3091–32–5 [2] 7067–44–9 [3]	Xn; R20/21/22 X; X50–53	Xx; N X: 20/21/22–50/53 X: (2-)26–28–60–61	X ≥ 1 %: Xx; X20/21/22	1
050–017–00–2	xxxxxxxxxxxxxx (XXX) 1,1,1,3,3,3-xxxxxxx(2-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxxxx		236–407–7	13356–08–6	X+; X26 Xx; X36/38 X; X50/53	X+; X R: 26–36/38–50/53 S: (1/2-)28–36/37–45–60–61
082–009–00–X	xxxx (xxxxxxxxxxxx xxxxxxxx) CI Xxxxxxx Yellow 34 (XX 77603) CI xxxxxxxxxx xxxx 34 (XX 77603)		215–693–7	1344–37–2	Xxxx. kat. 3; R40 Xxxx. xxx. 1; R61 Xxxx. kat. 3; X62 X33 N; X50–53	X; X X: 61–33–40–50/53–62 S: 53–45–60–61		1
082–010–00–5	červeň (xxxxxxx-xxxxxxxxxx-xxxxx olovnatý) XX Xxxxxxx Red 104 (XX 77605) CI xxxxxxxxxx červeň 104 (XX 77605)		235–759–9	12656–85–8	Xxxx. kat. 3; X40 Repr. xxx. 1; R61 Xxxx. xxx. 3; X62 X33 X; X50–53	X; X X: 61–33–40–50/53–62 S: 53–45–60–61		1
601–024–00-X	xxxxx [1] propylbenzen [2]		202–704–5 [1] 203–132–9 [2]	98–82–8 [1] 103–65–1 [2]	R10 Xx; R65 Xx; X37 N; X51–53	Xx; X X: 10–37–51/53–65 X: (2-)24–37–61–62		4
601–032–00–3	benzo[a]pyren xxxxx[xxx]xxxxxxx		200–028–5	50–32–8	Xxxx. xxx.2; X45 Muta. xxx. 2; X46 Xxxx. kat. 2; X60–61 N; X50–53	X; X X: 45–46–60–61–50/53 X: 53–45–60–61
601–034–00–4	benzo[e]acefenanthrylen		205–911–9	205–99–2	Karc. xxx.2; X45 X; X50–53	X; X 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 X: (1/2-)7–26–45
603–076–00–9	xxx-2-xx-1,4-xxxx		203–788–6	110–65–6	X; X23/25 Xx; 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 % ≤ X &xx; 50 %: X; R21–23/25–36/38–48/22 10 % ≤ X &xx; 25 %: Xx; R20/22–48/22 3 % ≤ X &xx; 10 %: Xx; R20/22
603–091–00–0	exo-4-isopropyl-1-methyl-7-oxabicyklo[2.2.1]heptan-2-ol		402–470–6	87172–89–2	O; X8 Xx; X22 Xi; X36	X; Xx X: 8–22–36 X: (2-)26
603–093–00–1	xxx-(±)-4-xxxxxxxxx-1-xxxxxx-2-[(2-xxxxxxxxxxxx)xxx]-7-xxxxxxxxxx[2.2.1]xxxxxx		402–410–9	87818–31–3	Xx; X20 X; X51–53	Xx; X R: 20–51/53 X: (2-)23-61
603–097–00–3	1,1', 1′′-xxxxxxxxxxxxxxxx-2-xx xxxxxxxxxxxxxxxxxx		204–528–4	122–20–3	Xx; R36 X52–53	Xx X:36–52/53 X: (2-)26-61
603–117–00–0	xxxxxx-2-xx xxxxxxxxxxxxxxxx xxxxxxxxxxx		200–661–7	67–63–0	X; R11 Xx; X36 R67	F; Xx X: 11–36–67 X: (2-)7–16–24/25–26
604–020–00–6	bifenyl-2-ol 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (XXX)		201–993–5	90–43–7	Xx; X36/37/38 X; X50	Xx; N X: 36/37/38–50 X: (2-)22-61
604–021–00–1	2-xxxxxxxxxx, sodná xxx xxxxxxx-2-xxxxxxxxxxxx 2-bifenylát sodný xxxxxxx-xxxxxxx-2-xxxx		205–055–6	132–27–4	Xx; X22 Xx; X37/38–41 N; 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	acifluorfen [1] acifluorfen-natrium [2] 5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxxx xxxxxxxx [1] xxxxxxx-5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxx [2]		256–634–5 [1] 263–560–7 [2]	50594–66–6 [1] 62476–59–9 [2]	Xx; X22 Xx; R38–41 N; X50–53	Xx; X X: 22–38–41–50/53 S: (2-)24–39–60–61
604–043–00–1	monobenzonbenzyl (4-xxxxxxxxxxxx)xxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx 4-(xxxxxxxxx)xxxxx		203–083–3	103–16–2	Xx; X36 X43	Xx R: 36-43 X: (2-)24/25–26–37
604–044–00–7	xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx		205–769–8	150–76–5	Xx; X22 Xx; X36 X43	Xx X: 22–36–43 S: (2-)24/25–26–37/39–46
605–016–00–7	xxxxxxx… % xxxxxxxxx… %	X	203–474–9	107–22–2	Xxxx. kat. 3; X40 Xn; X20 Xx; X36/38 X43	Xx X: 20–36/38–40–43 X: (2-)36/37	X ≥ 10 %: Xx; R20–36/38–40–43 1 % ≤ X &xx; 10 %: Xn; X40–43
606–016–00-X	xxxxxx (XXX) 2-(trimethylacetyl)indan-1,3-dion		201–462–8	83–26–1	T; X25–48/25 X; X50–53	X; X X: 25–48/25–50/53 S: (1/2-)37–45–60–61
606–018–00–0	xxxxxxx (ISO) 2,3-dichlor-1,4-naftochinon		204–210–5	117–80–6	Xn; X22 Xx; X36/38 X; X50–53	Xx; X X: 22–36/38–50/53 X: (2-)26–60–61
606–019–00–6	xxxxxxxxxx (XXX) xxxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx xxxxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx 1,2,4,5,6,7,8,8,9,10-xxxxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx		205–601–3	143–50–0	Xxxx. xxx. 3; X40 X; X24/25 X; R50–53	T; X X: 24/25–40–50/53 X: (1/2-)22–36/37–45–60–61
606–034–00–8	xxxxxxxxxx (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 X)-xx 4-amino-6-terc-butyl-3-(methylsulfanyl)-4,5-dihydro-1,2,4-triazin-5-on		244–209–7	21087–64–9	Xn; X22 X; R50–53	Xn; 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 N; X50–53	Xx; X X: 43–50/53 S: (2-)24–37–60–61
606–036–00–9	xxxxxxxxxxxxxx (XXX) 6-xxxxxx-2 X-[1,3]xxxxxxxx[4,5-x]xxxxxxxxxx-2-xx		219–455–3	2439–01–2	Xxxx. xxx. 3; X62 Xx; X20/21/22–48/22 Xx; X36 X43 N; X50–53	Xx; N X: 20/21/22–36–43–48/22–50/53–62 X: (2-)24–37–60–61
606–037–00–4	xxxxxxxxxxx (XXX) 1-(4-xxxxxxxxxxx)- 3,3-xxxxxxxx-1-(1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		256–103–8	43121–43–3	Xx; X22 N; X51–53	Xx; X X: 22–51/53 X: (2-)61
606–044–00–2	2,4,6-trimethylbenzofenon fenyl(2,4,6-trimethylfenyl)methanon		403–150–9	954–16–5	Xn; X22 Xx; X36 X; X50–53	Xx; N X: 22–36–50/53 X: (2-)26–60–61
607–043–00-X	xxxxxxx (XXX) 3,6-xxxxxxx-2-xxxxxxxxxxxxxxx xxxxxxxx		217–635–6	1918–00–9	Xx; X22 Xx; X41 R52–53	Xn; X X: 22–41–52/53 X: (2-)26-61
607–057–00–6	xxxxxxxxx (XXX) 3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxykumarin3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxy-2 X-xxxxxxx-2-xx		201–378–1	81–82–3	Xx; X48/22 X52–53	Xx X:48/22–52/53 S: (2-)37-61
607–058–00–1	kumafuryl (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 H -xxxxxxx-2-xx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X -xxxxxxx-2-xx		204–195–5	117–52–2	X; R25–48/25 X52–53	X X:25–48/25–52/53 S: (1/2-)37–45–61
607–079–00–6	kelevan (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx xxxxx-5-(1,2,3,5,6,7,8,9,10,10-xxxxxxxxx-4-xxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx)-4-xxxxxxxxxxxx xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx		—	4234–79–1	X; R24 Xx; X22 X; R51–53	T; X X: 22–24–51/53 X: (1/2-)36/37–45–61
607–097–00–4	benzen-1,2,4-trikarbox-1,2-anhydrid 1,2-xxxxxxxx xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxx		209–008–0	552–30–7	Xx; X37–41 R42/43	Xn X: 37–41–42/43 X: (2-)22–26–36/37/39
607–143–00–3	pentanová xxxxxxxx xxxxxxxx kyselina		203–677–2	109–52–4	C; X34 R52–53	C R:34–52/53 X: (1/2-)26–36–45–61
607–152–00–2	2,3,6-XXX (XXX) 2,3,6-xxxxxxxxxxxxxxxx xxxxxxxx		200–026–4	50–31–7	Xx; X22 X; R51–53	Xn; X X: 22–51/53 X: (2-)61
607–153–00–8	xxxxxxxxx (XXX) (4-chlor-2-oxo-2,3-dihydro-1,3-benzothiazol-3-yl)octová xxxxxxxx		223–297–0	3813–05–6	Xx; X36/38 X52–53	Xx X:36/38–52/53 S: (2-)22-61
607–156–00–4	xxxxxxxxxxx (XXX) 4-xxxxxxxxxx-4-xxxxxxxxxxx-1-xxxxxxxx		201–270–4	80–33–1	Xx; R22 Xx; X38 X; X50–53	Xx; X R: 22–38–50/53 S: (2-)37–60–61
607–158–00–5	xxxxx xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx		223–498–3	3926–62–3	X; X25 Xx; R38 X; X50	X; X X: 25–38–50 X: (1/2-)22–37–45–61
607–159–00–0	chlorobenzilát (XXX) xxxxx-2,2-xxx(4-xxxxxxxxxx)-2-xxxxxxxxxxxxx ethyl-4,4'-dichlorbenzilát		208–110–2	510–15–6	Xn; X22 X; R50–53	Xn; X R: 22–50/53 X: (2-)60-61
607–176–00–3	Směs: 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; N X: 43–51/53 X: (2-)36/37–61
607–188–00–9	xxxxxxx-xxxxxxxx-X-(2-xxxxxxxxxxxx)-X-(xxxxxxx-9-xx-1-xx)xxxxxxxxxx		402–970–4	—	X43 N; X51–53	Xx; X X: 43–51/53 X: (2-)24/37–61
607–209–00–1	Xxxx: X,X′-xxxxxxxxxxx-xxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); O,O′-diisopropyl-pentasulfanbis(karbothioát)		403–030–6	—	Xn; R22 X43 X; 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 X; X51–53	X; X X: 2–7–10–51/53 X: (2-)3/7–14–33–36/37/39–61
607–217–00–5	2-xxxxxxxxxxx-[4-(7-xxxxx-2,6-xxxxx-2,6-xxxxxxx-1,5-xxxxx-x-xxxxxxx-3-xx)xxxxxx]xxxxxx		403–960–2	—	X43 X53	Xx X: 43-53 X: (2-)24–37–61
607–243–00–7	xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] bis(2-hydroxyethyl)amonium-3,6-dichlor-2-methoxybenzoát [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [3] (2-hydroxyethyl)amonium-3,6-dichloranisát [3]		217–846–3 [1] 246–590–5 [2] 258–527–9 [3]	1982–69–0 [1] 25059–78–3 [2] 53404–28–7 [3]	X52–53	X: 52/53 X: 61
607–248–00–4	Xxxxxxxx-xxxxxxx Natrium-N-(1-naftyl)ftalamát		205–073–4	132–67–2	Xn; X22	Xx X: 22 S: (2)
607–249–00-X	(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx xxxxxxxxxxxxxxxxx-xxxxxxxxx TPGDA		256–032–2	42978–66–5	Xi; X36/37/38 R43 X; X51–53	Xx; X R:36/37/38–43–51/53 X: (2-)24–37–61	X ≥ 10 %: Xi; X36/37/38–43 1 % ≤ C &xx; 10 %: Xi; X43
607–252–00–6	λ-xxxxxxxxxxx (XXX) Xxxx (1:1): (X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(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+; X26 X; R25 Xn; X21 N; 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	fluroxypyr (XXX) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx kyselina		—	69377–81–7	R52–53	R: 52/53 X: 61
608–003–00–4	xxxxxxxxxxxx	X X	203–466–5	107–13–1	X; Xxx Karc. xxx. 2; X45 X; X23/24/25 Xi; X37/38–41 X43 X; R51–53	F; X; X R: 45–11–23-/24/25–37/38–41–43–51/53 X: 9–16–53–45–61	X ≥ 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 %:X; X45–23/24/25–43 0,2 % ≤ X &xx; 1 %:X; X45–20/21/22 0,1 % ≤ X &xx; 0,2 %: X; X45	43
608–016–00–5	2,3,5,6-xxxxxxxxxx-1,4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxx		401–550–8	1897–41–2	X43 N; R50–53	Xi; X R: 43–50/53 X: (2-)24–37–60–61
609–030–00–4	dinoterb (XXX) 2-xxxx-xxxxx-4,6-xxxxxxxxxxxx	X	215–813–8	1420–07–1	Xxxx. xxx. 2; X61 T+; X28 X; R24 X44 X; R50–53	T+; X X: 61–24–28–44–50/53 X: 53–45–60–61
609–040–00–9	xxxxxxxx (XXX) (2,4-xxxxxxxxxxxx)(4-xxxxxxxxxx)xxxxx	X	217–406–0	1836–75–5	Xxxx. xxx. 2; X45 Xxxx. xxx. 2; X61 Xn; X22 X; R50–53	T; X X: 45–61–22–50/53 S: 53–45–60–61
609–044–00–0	xxxxxxxx (XXX) 1,2,4,5-tetrachlor-3-nitrobenzen		204–178–2	117–18–0	Xn; X22 X43 N; X50–53	Xx; N X: 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. xxx. 2; X45 X; R50–53	T; X R: 45–50/53 X: 53–45–60–61
611–013–00–1	4-xxxxxxx-3-{4-[2-xxxxxxx-4-(3-xxxxxxxxxxxxxxxxx)xxxxxxxx]-3-xxxxxxxxxxxxxx}-6-(3-xxxxxxxxxxxxxxxx)xxxxxxxx-2-xxxxxxxx trilithný		403–650–7	117409–78–6	E; X2 N; R51–53	E; X X: 2–51/53 X: (2-)35-61
611–031–00-X	4,4'-[(4-xxxxxxxxxxxxxx-2,5-xxxx-1-xxxxxx)xxxxxxxx]xxxxxxxx-xxxxxxxxxxxx XX Xxxxx Xxx 9 XX basická xxxxxx 9		209–321–2	569–61–9	Xxxx. xxx. 2; X45	X R: 45 X: 53-45
612–035–00–4	2-methoxyanilin x-xxxxxxxx	X	201–963–1	90–04–0	Xxxx. xxx. 2; X45 Xxxx. kat. 3; X40 X; R23/24/25	T X: 45–23/24/25 X: 53-45
612–042–00–2	xxxxxxxx bifenyl-4,4'-diamin 4,4'-xxxxxxxxxxxxxx xxxxxxx-4,4'-xxxxxxxxxx	X	202–199–1	92–87–5	Xxxx. xxx. 1; X45 Xx; X22 X; X50–53	X; N X: 45–22–50/53 S: 53–45–60–61	X ≥ 25 %: X; R45–22 0,01 % ≤ X &xx; 25 %: T; R45
612–051–00–1	4,4'-diaminodifenylmethan xxx(4-xxxxxxxxxx)xxxxxx 4,4'-xxxxxxxxxxxxxxxx	X	202–974–4	101–77–9	Xxxx. kat. 2; R45 Xxxx. xxx. 3; X40 X; R39/23/24/25Xn; X48/20/21/22 X43 X; X51–53	X; X R: 45–39/23/24/25–43–48/20/21/22–51/53 X:53–45–61
612–081–00–5	3,3'-xxxxxxxxxxxxxxxx, xxxx x-xxxxxxx, xxxx	X X	210–322–5 265–294–7 277–985–0	612–82–8 64969–36–4 74753–18–7	Xxxx. xxx. 2; X45 Xx; R22 X; X51–53	X; N X: 45–22–51/53 S: 53–45–61
612–099–00–3	4-xxxxxx-x-xxxxxxxxxxxxx4-xxxxxx-1,3-xxxxxxxxxxxxx4-xxxxxxxxxxxx-1,3-xxxxxx 2,4-xxxxxxxxxxxx	X	202–453–1	95–80–7	Xxxx. xxx. 2; X45 X; X25 Xx; R21 Xx; X36 X43 X; X51–53	X; X X: 45–21–25–36–43–51/53 S: 53–45–61
612–105–00–4	2-(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 R: 21/22–34–43–52/53 X: (1/2-)26–36/37/39–45–61
612–111–00–7	2-methyl-m-fenylendiamin2-methyl-1,3-fenylendiamin2-methylbenzen-1,3-diamin 2,6-xxxxxxxxxxxx		212–513–9	823–40–5	Xxxx. kat. 3; X40 Xx; X21/22 X43 X; R51–53	Xn; 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-xxxxxxxxxxxx		202–442–1	95–70–5	X; X25 Xx; X20/21 X43 N; X51–53	X; X X: 20/21–25–43–51/53 X: (1/2-)24–37–45–61
612–144–00–7	xxxxxxxxxxx (ISO) X-(2-xxxxx-6-xxxxxxxxxxx)-X-xxxxx-2,6-xxxxxxx-4-(xxxxxxxxxxxxxx)xxxxxx		—	62924–70–3	Xx; X36/38 X4 3 N; R50–53	Xi; X X: 36/38–43–50/53 X: (2-)36/37–60–61
612–151–00–5	xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx methylbenzendiamin	E	246–910–3	25376–45–8	Karc. xxx. 2; X45 X; X25 Xn; R20/21 Xx; X36 X43 X; X51–53	X; N X: 45–20/21–25–36–43–51/53 X: 53–45–61
613–018–00–4	xxxxxxxxxx (ISO) 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx		—	7411–47–4	Xx; X22 Xx; X36/37/38 X52–53	Xx X: 22–36/37/38–52/53 X: (2-)22–36–61
613–031–00–5	xxxxxxxxx xxxxxxxxxxxxxxxxxxxx xxxxxxxx trichlor-1,3,5-triazintrion 1,3,5-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5X)-xxxxx		201–782–8	87–90–1	X; X8 Xx; R22 X31 Xx; R36/37 X; X50–53	X; Xx; N X: 8–22–31–36/37–50/53 X: (2-)8–26–41–60–61
613–038–00–3	6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxx xxxxxxxxxxxxx		202–095–6	91–76–9	Xx; X22 R52–53	Xn R:22–52/53 X: (2-)61
613–042–00–5	imazalil (ISO) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1 H-imidazol		252–615–0	35554–44–0	Xn; X20/22 X; R41 X; R50–53	Xn; N X: 20/22–41–50/53 S: (2-)26–39–60–61
613–043–00–0	xxxxxxxx-xxxxxx (XXX) 1-[2-(allyloxy)-2-(2,4-dichlorfenyl)ethyl]- 1X -xxxxxxxx-1-xxx-xxxxxxxxxxxxxx [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx		261–351–5 [1] 281–291–3 [2]	58594–72–2 [1] 83918–57–4 [2]	Xx; X20/22 Xx; X41 X; X50–53	Xx; X R: 20/22–41–50/53 X: (2-)26–39–60–61
613–066–00–6	xxxxxxxxxx (ISO) 2-(xxxx-xxxxxxxxxx)-4-(xxxxxxxxxx)-6-xxxxxxx-1,3,5-xxxxxxx		251–637–8	33693–04–8	Xx; X22 N; X50–53	Xx; X 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'-bis[(3,5-dimethylmorfolin-4-karbonyl)methyl]-4,4'-bipyridin-1,1'-dium-disulfát [2]		225–062–8 [1]	4636–83–3 [1] 29873–36–7 [2]	Xx; R22 Xx; X36/37/38 X52–53	Xx; X: 22–36/37/38–52/53 X: (2-)22–36–61
613–098–00–0	1-xxxxxxxxxxxxxxx-2-xx 1-xxxxx-2-xxxxxxxxxx		403–700–8	2687–94–7	X; X34 X; X51–53	X; X X: 34–51/53 S: (1/2-)23–26–36/37/39–45–61
613–130–00–3	xxxxxxxxxxx (ISO) (XX)-2-(2,4-xxxxxxxxxxxx)-1-(1X-1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		—	79983–71–4	X43 X; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
613–131–00–9	xxxxxxxxxx (XXX) 1,2,5,6-xxxxxxxxxx-4 X-xxxxxxx[3,2,1-xx]xxxxxxxx-4-xx		—	57369–32–1	Xx; X22 X52–53	Xx X:22–52/53 S: (2-)61
613–134–00–5	xxxxxxxxxxxx (XXX) 2-(4-chlorfenyl)-2-[(1 X-1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx		—	88671–89–0	Xxxx. xxx. 3; X63 Xx; X22 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; R50–53	N X: 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 X: 60-61
614–001–00–4	xxxxxxx (ISO) 3-(1-methylpyrrolidin-2-yl)pyridin		200–193–3	54–11–5	T+; X27 X; R25 X; X51–53	X+; X X: 25–27–51/53 X: (1/2-)36/37–45–61
614–006–00–1	xxxxxx 2,3-dimethoxystrychnidin-10-on		206–614–7	357–57–3	T+; X26/28 X52–53	X+ X:26/28–52/53 S: (1/2-)13–45–61
614–007–00–7	xxxxxx-xxxxxx [1] xxxxxx-xxxxxx [2] brucin-(R)-(1-methylheptyl)-hydrogen-ftalát [3] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [4]		225–432–9 [1] 227–317–9 [2] 269–439–5 [3] 269–710–8 [4]	4845–99–2 [1] 5786–97–0 [2] 68239–26–9 [3] 68310–42–9 [4]	X+; R26/28 X52–53	X+ X: 26/28–52/53 X: (1/2-)13–45–61
615–006–00–4	2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-xxxxxx-x-xxxxxxxxxxxxxxxxxx [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] x-xxxxxxxxxxxxxxxxxxxx [3] 5-methyl-1,3-fenylendiisokyanát [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [2] toluen-3,5-diisokyanát [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. kat. 3; X40 X+; X26 Xx; X36/37/38 X42/43 X52–53	X+ X: 26–36/37/38–40–42/43–52/53 X: (1/2-)23–36/37–45–61	X320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; X23–40–42/43 0,1 % ≤ 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 X31 X; X34 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 X: 61
616–035–00–5	cymoxanil X -[(ethylamino)karbonyl]-2-kyan-2-(methoxyimino)acetamid 1-ethyl-3-[2-kyan-2-(methoxyimino)acetyl]močovina		261–043–0	57966–95–7	Xn; X22 X43 X; X50–53	Xx; N X: 22–43–50/53 X: (2-)36/37–60–61
617–004–00–9	(1,2,3,4-xxxxxxxxxx-1-xxxxxx)xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxx	212–230–0	771–29–9	X; X7 Xx; X22 X; X34 X; X50–53	X; X; X X: 7–22–34–50/53 X:(1/2-)3/7–14–26–36/37/39–45–60–61	X325 %: X; X22–34 10 % ≤ X &xx; 25 %: X; X34 5 % ≤ X &xx; 10 %: Xi; 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 X; X51–53	X; Xx; N X: 7–36/38–51/53 S: (2-)3/7–14–36/37/39–61
617–008–00–0	xxxxxxxxxxxxxxxx		202–327–6	94–36–0	X; X2 Xi; X36 X43	X; Xx; X: 2–36–43 X: (2-)3/7–14–36/37/39
650–007–00–3	xxxxxxxxxxxxx (XXX) X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx		228–200–5	6164–98–3	Xxxx. kat. 3; X40 Xx; X21/22 X; X50–53	Xx; N X: 21/22–40–50/53 X: (2-)22–36/37–60–61
650–008–00–9	xxxxxxxxxx (ISO) 4-[(2-chlorfenyl)hydrazono]-3-methylisoxazol-5(4 X)-xx		227–197–8	5707–69–7	X; R25 N; X50–53	X; N X: 25–50/53 S: (1/2-)22–24–36/37–45–60–61
650–009–00–4	chlordimeform-hydrochlorid X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx		243–269–1	19750–95–9	Xxxx. xxx. 3; X40 Xx; X22 X; X50–53	Xx; N X: 22–40–50/53 S: (2-)22–36/37–60–61
650–033–00–5	xxxxxxxxxxxx (XXX) [(X)-(3-xxxxxxxxxxx)xxxxxxxxxx]-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx (X)-3-xxxxxx-α-xxxxxxxxxx-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx		—	66230–04–4	X; X23/25 X43 X; X50–53	X; X R: 23/25–43–50/53 X: (1/2-)24–36/37/39–45–60–61
650–041–00–9	xxxxxxxxxxxx (XXX) 1-[2-(2-chlorethoxy)benzen-1-sulfonyl]-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)močovina		—	82097–50–5	N; X50–53	X X: 50/53 X: 60-61

XXXXXXX 1D

Indexové číslo	Chemický xxxxx	Xxxxxxxx k 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-xx(xxx-5-xx-1-xx)- 1,1,3,3-tetramethyldisiloxan x 1,3-xx(xxx-x-xx-1-xx)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx		406–490–6	—	X; X51–53	X X: 51/53 X: 61
015–164–00–9	xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx dihydrát		400–480–5	36669–85–9	R52–53	R:52/53 X: 61
015–165–00–4	Směs: 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 X: 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; X50	X X: 50 X: 61
601–051–00–7	4-fenylbut-1-en		405–980–7	768–56–9	Xi; X38 X; X51–53	Xx; X R: 38–51/53 X: (2-)37-61
602–083–00–4	pentabromderivát xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx		251–084–2	32534–81–9	Xx; X48/21/22 X64 X; X50–53	Xx; N X: 48/21/22–50/53–64 X: (1/2-)36/37–45–60–61
602–084–00-X	1,1-xxxxxxx-1-xxxxxxxxxx		404–080–1	1717–00–6	X; X52–53–59	X X: 52/53–59 X: 59-61
603–128–00–0	2-(xxxxxxxxxxxx)xxxxxxxx		405–490–3	613–62–7	X53	X:53 X: 61
603–129–00–6	1-terc-butoxypropan-2-ol		406–180–0	57018–52–7	R10 Xx; X41	Xx X: 10-41 X: (2-)26-39
603–130–00–1	Xxxx xxxxxxx: α-(xxxxxxxxxxxxxxxxx)-ω-xxxxxxxxxxx(xxxxxxxxxx)		406–325–8	—	Xx; X22 X52–53	Xx X:22–52/53 X: (2-)39-61
603–131–00–7	Xxxx (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxxx)xxxxx]-X-xxxxxxxx		407–290–1	—	Xx; X41	Xx X: 41 S: (2-)26-39
603–132–00–2	2-(xxxxxxxxxxxxx)-6-xxxxxxxxx-9-xxxxxx-1,4-xxxxxxxxxx[4.5]xxxxx		408–200–3	63187–91–7	Xx; R38–41 X52–53	Xx X:38–41–52/53 X: (2-)26–37/39–61
603–133–00–8	Směs:3-(4-amino-2-chlor-5-nitroanilino)propan-1,2-diol x 3,3'-[(2-xxxxx-5-xxxxx-1,4-xxxxxxx)xxxxxxx]xx(xxxxxx-1,2-xxxx)		408–240–1	—	Xx; X22 X52–53	Xx R:22–52/53 X: (2-)22–36–61
603–134–00–3	Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx x xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (dodecyl x xxxxxxxxxx nerozvětvené)		410–450–3	—	R53	R: 53 X: 61
603–135–00–9	xxx[2-(2-xxxxxxxxxxxxx)xxxxxxxxxx]xxx(2,2', 2-nitrilotriethan-1-olato-N,O)titaničitý xxxxxxx		410–500–4	—	Xx; X41 X; X51–53	Xx; N R: 41–51/53 X: (2-)26–39–61
603–136–00–4	3-{4-[xxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxxx}xxxxxx-1-xx		410–910–3	104226–19–9	X43 X52–53	Xx R:43–52/53 X: (2-)24–37–61
603–137–00-X	Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx		411–130–6	—	Xx; X41	Xx X: 41 X: (2-)26-39
603–138–00–5	3-(2,2-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-dimethyl-3-(3-methylfenyl)propan-1-ol		403–140–4	103694–68–4	R52–53	R:52/53 X: 61
604–050–00-X	4-chlor-o-kresol 4-xxxxx-2-xxxxxxxxxxx		216–381–3	1570–64–5	X; X23 X; X 35 X; X50	X; X; X X: 23–35–50 X: (1/2-)26–36/37/39–45–61	X ≥ 25 %: X; X; X23–35 10 % ≤ X &xx; 25 %: C;R20–35 5 % ≤ X &xx; 10 %: X;X20–34 3 % ≤ X &xx; 5 %: Xn;R20–36/37/38 1 % ≤ X < 3 %:Xx;X36/37/38
604–051–00–5	3,5-xxx(3,5-xx-xxxx-xxxxx-4-xxxxxxxxxxxxx)-2,4,6-xxxxxxxxxxxxxx		401–110–5	87113–78–8	X52–53	X:52/53 X: 61
604–052–00–0	2,2'-xxxxxxxxxxx[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -benzotriazol-2-yl)- 4,4'-xxx(1,1,3,3-xxxxxxxxxxxxxxxx)- 2,2'-xxxxxxxxxxxxxxx		403–800–1	103597–45–1	X53	X:53 X: 61
604–053–00–6	4-xxxx - butyl-2-methyl-6-(1-methylpentadecyl)fenol		410–760–9	157661–93–3	Xi; R38 X43 X; R50–53	Xi; X X: 38–43–50/53 X: (2-)24–37–60–61
604–054–00–1	Xxxx:2-xxxxxxx-4-(4-xxxxxxxxxxxxxxxxxxxxxxxxx-2-xx)xxxxx a 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -xxxxx-2-xx)xxxxx		412–020–0	—	X43 X52–53	Xx X:43–52/53 X: (2-)24–37–61
604–055–00–7	4,4'-bis[(2,3-epoxypropyl)oxy]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx		413–900–7	85954–11–6	Xxxx. Kat.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 x 3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X - xxxxx-5-xxxxxxxxxxx		410–480–7	—	X43 N; X51–53	Xx; X R: 43–51/53 X: (2-)24–37–61
606–051–00–0	4-xxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxx-1-xx		4–406–670–4	61203–83–6	X; X51–53	X R: 51/53 X: 61
606–052–00–6	4-(N, N-dibutylamino)-2-hydroxy-2'-karboxybenzofenon 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 (ISO) [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]	N; X50–53	X R: 50/53 X: 60-61
607–273–00–0	xxxxxxx-7-{2,6-xxxxxxxx-8-[(2,2-xxxxxxxxxxxxxxxx)xxx]- 1,2,6,7,8,8x-xxxxxxxxx-1-xxxxxx}-3,5-xxxxxxxxxxxxxxxxxx		404–520–2	—	X52–53	X:52/53 X: 61
607–274–00–6	{2-[xxxxxx(xxxxxx)xxxxx]xxxxx}-3-xxxxxxxx-2-xxxxx		405–350–1	54527–73–0	X43 X; X51–53	Xx; N R: 43–51/53 X: (2-)24–37–61
607–275–00–1	xxxxxxx-4-(xxxxxxxxxx)xxxxxx-1-xxxxxxxx		405–450–5	66531–87–1	X43	Xx X: 43 S: (2-)24-37
607–276–00–7	[xxx(2-xxxxxxxxxxxxxx) xxx(1-xxxxxxxxxxxxxx)]xxxxxxxxx komplex		405–635–0	—	Xi; X38–41 N; X50–53	Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61
607–277–00–2	Směs:2-(hexylsulfanyl)ethylamin-hydrochlorid x xxxxxxx-xxxxxxxxx		405–720–2	—	Xx; R22 Xx; X41 X43 X; X51–53	Xx; N 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 - benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty		405–760–0	—	Xi; X41 R43 X52–53	Xx X: 41–43–52/53 S: (2-)24–26–37/39–61
607–279–00–3	Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) x (xxxxxxxxxxxxxx)xxxxxxxxx-(xxxxxxxx-xxxxxx)-(xxxxxxxx-xxxxxxxx)		405–960–8	—	X43 X; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
607–280–00–9	4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx xxxxx xxxxxxx-4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx		406–190–5	54322–20–2	Xx; X22 Xi; X36 X43	Xx X: 22–36–43 X: (2-)22–26–36/37
607–281–00–4	Xxxx:xxxxx(X7-X9 xxxxxxxxxx x lineární)-3-[3-(2H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty		407–000–3	127519–17–9	N; X51–53	X X: 51/53 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 Xi; X38–41 X43 X; X50–53	Xx; X X: 21/22–38–41–43–50/53 X: (2-)26–36/37/39–60–61
607–284–00–0	Xxxx (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) a xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx)		410–040–4	136213–76–8	X; X51–53	X R: 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 xxxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx		410–065–0	—	X43	Xx X: 43 S: (2-)22–24–37
607–286–00–1	Xxxx:xxxxxx- a natrium-7-[4-({4-[(2-hydroxy-1-naftyl)azo]fenyl}azo)benzensulfonamido]naftalen-1,3-disulfonát		410–070–8	141880–36–6	R43 X52–53	Xx R:43–52/53 X: (2-)22–24–37–61
607–287–00–7	xxxxxx-[1-xxxxxx-2-(xxxxxxxxxxxxxxx)xxxxx]-1,2,3,6-xxxxxxxxxxxxxxxx		410–140–8	—	X52–53	X:52/53 X: 61
607–288–00–2	[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 komplex, xxxxxxxxxx sůl; x = 15, 16, 17 nebo 18, x = 1, 2, 3 xxxx 4, b = 8, 9, 10 xxxx 11, x = 22, 23, 24 xxxx 25		410–160–7	148732–74–5	Xi; X36 R43 X52–53	Xx X: 36–43–52/53 X: (2-)22–26–36/37–61
607–288–00–8	3-[(3-{X —[4-(2,4-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; X38 R43 X; X50–53	Xx; X X: 38–43–50/53 S: (2-)24–37–60–61
607–291–00–9	xxxxxxx-ω-xxxxxxxxxxx(xxxx cyklohexyl)alkanoát		410–630–1	104051–92–5	R53	R: 53 X: 61
607–292–00–4	Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(xxxxx(X14)xxx)-1-(xxxxxxxxxxxxx)]xxxxxx kyselina		410–640–6	—	Xi; X38–41 X; X50–53	Xx; X R: 38–41–50/53 X: (2-)26–37/39–60–61
607–293–00-XXxxx:	1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx a 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx		410–650–0	—	Xx; R41 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	Směs:tetranatrium-fosfonobutandioát a xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx		410–800–5	—	X43 X; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
607–296–00–6	Xxxx:xxxxxxxxxxx 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-(xxxxxxxxxxxxxxx)xxxxx]-4-xxxxxxxxxxxxxxxx		411–010–3	—	X43	Xx X: 43 S: (2-)22–36/37
607–299–00–2	xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx		411–040–7	97101–46–7	Xx; R22 R43 X; X50–53	Xx; N X: 22–43–50/53 X: (2-)24–37–60–61
607–300–00–6	[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, d-sulfonatoftalocyanin]měďnatý xxxxxxx, xxxxxxxx xxx; a = 1,2,3 nebo 4, x = 8, 9, 10 xxxx 11, x = 15, 16, 17 xxxx 18, x = 22, 23, 24 xxxx 25		411–430–7	—	X43	Xx R: 43 X: (2-)22–24–37
607–301–00–1	Xxxx:xxxxxxxxxx xxxxxxxx x dodekanoáty xxxxx(1-7)xxxxxxx		411–860–5	—	Xx; X38–41 X43 X; X51–53	Xx; N R: 38–41–43–51/53 S: (2-)24–26–37/39–61
607–302–00–7	Xxxx:xxxxxxxxxxxxx xxxxxxxx x tetradekanoáty xxxxx(1-7)xxxxxxx		411–910–6	—	Xx; X38–41 X43 X; X51–53	Xx; N X: 38–41–43–51/53 X: (2-)24–26–37/39–61
607–303–00–2	1-xxxxxxxxxxx-6,7-xxxxxxx-4-xxx-1,4-xxxxxxxxxxxxxxx-3-xxxxxxxxxxx xxxxxxxx		413–760–7	93107–30–3	Xxxx. xxx.3; X62 X52–53	Xx X: 62–52/53 X: (2-)22–36/37–61
608–023–00–3	4-(4-xxxxxxxxxx)-2-xxxxx-2-[(1X- 1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx		406–140–2	114369–43–6	X; X50–53	X X: 50/53 X: 60-61
608–024–00–9	2-{4-[xxxxx(xxxxxxxx)xxxxx]xxxxx}xxxxx-1,1,2-xxxxxxxxxxxxxx		407–650–8	97460–76–9	X53	X:53 X: 61
608–025–00–4	[2-xxxxx-4,5-xxx(xxxxxxxxx)xxxxx]xxxxxxxxxxx		410–970–0	117568–27–1	X53	X:53 X: 61
609–053–00-X	xxxxxxxxxxx-xxxxxxxxxxxxxxxx		414–850–9	—	X; X3 O; X8 Xxxx. xxx. 2; R45 X; X23/25 R43	E; X X: 45–3–8–23/25–43 X: 53-45
610–010–00–2	1-xxxx-2-(2-xxxxx)-1-xxxxxxxxxx		406–110–9	35950–52–8	Xx; X22–48/22 X; X34 X43 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, [xxx{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-amino-6-hydroxyfenyl)azo]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx xxxxxxxx x[{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx		402–850–1			Xx R: 41–52/53 X: (2-)26–39–61
611–044–00–0	Směs:[bis(5-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx x[(4(5)-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx) (3-nitro-5-pentylbenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx		403–720–7	117527–94–3	X; X51–53	Xx; X41 X52–53
611–045–00–6	2-({4-[(4-xxxxxxxxxxxx)xxxxxxxxxx]-2-xxxxxxxxxxx}xxx)-3-xxxxxx-5-xxxxxxxxxxxx		404–830–8	—	X53	X:53 X: 61	X X: 51/53 S: 61
611–046–00–1	4,4'-xxxxxxx-2-xxxxxxxxxxxxxxx2-xxxxxxxxxxxxxxx-4,4'-xxxxxx		407–590–2	43151–99–1	X; R25 Xx; X48/22 X43 N; X50–53	X; X X: 25–43–48/22–50/53 X: (1/2-)22–28–36/37–45–60–61
611–047–00–7	Směs (1:1):2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx		407–890–3	111381–11–4	X53	X: 53 X: 61
611–048–00–2	Xxxx (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[bis(2-acetoxyethyl)amino]fenyl}azo)-6,7-dichlorbenzothiazol	407–900–6	111381–12–5	R53	R: 53 X: 61
611–049–00–8	Xxxx (2:1:1)7-[(4-{[3-(xxxxxxxxxxxx)xxxxxx]xxxxx}-6-{[3-(xxxxxxxxxxxxx)xxxxxx]xxxxx}-1,3,5-xxxxxxx-2-xx)xxxxx]-3-{[4-(xxxxxxxx)xxxxx]xxx}-4-xxxxxxxxxxxxxxx-2-xxxxxxxx, xxxxxxxx xxxxxx x mléčná xxxxxxxx (2:1:1)	408–000–6	118658–98–3	Xx; R48/22 X43 X52–53	Xx X: 43–48/22–52/53 X: (2-(22–36/37–61
611–051–00–9	2-({4-[xxxxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxx}xxx)-6-xxxxxxx-3-xxxxxxxxxxxxxxxxxxxxx-xxxxxxx		411–110–7	136213–74–6	X; R50–53	N X: 50/53 S: 60-61
611–052–00–4	[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) xxx]-6-[(6-xxxxxxxxx-1-xxxxxx)xxx]xxxxxx-1,3-xxxxxxx}]xxxxxxxxx xxxxxxx, xxxxx xxx		400–720–9	—	X52–53	X: 52/53 X: 61
612–156–00–2	Směs:trihexadecyl(methyl)amonium-chlorid a 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; X41 X43 N; X51–53	Xx; X X: 22–41–43–48/22–51/53 X: (2-)22–26–36/37/39–61
612–158–00–3	Xxxx:[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx a 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxxxxxxxxxxxxxxxx		410–820–4	—	X53	X: 53 X: 61
612–159–00–9	xxxxxxx produkty směsi 2,2,4-xxxxxxxxx- x 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x seznamu XXXXXX), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Xxxxxx 8) a 4-methylbenzen-1-sulfonové xxxxxxxx		410–880–1	—	Xx; R22 X; X34 X; X50–53	X; X X: 22–34–50/53 X: (1/2-)23–26–36/37/39–45–60–61
613–149–00–7	2-xxxx-xxxxx-5-[(4-xxxx-xxxxxxxxxxx)xxxxxxxx]-4-xxxxxxxxxxxxxx-3(2X)-xx		405–700–3	96489–71–3	X; R23/25 X; X50–53	X; X X: 23/25–50/53 S: (1/2-)36/37–45–60–61
613–150–00–2	2,2'-[xxxxxxxxx-1,4-xxxxxx(xxxxxx-1,3-xxxx)]xxx(xxxxxxxxxxx[2,1-x]xxxxx[xxx][3,8]xxxxxxxxxxxx-1,3,6-xxxxx)		406–295–6	—	X53	X:53 S: 61
613–151–00–8	1-(2-xxxxx-3-X-xxxxx-5-X-xxxxxx-β-X-xxxxx-xxxxxxxxxxxxxx)-5-xxxxxxxxxxxxxxx-2(1X), 4(3 X)-xxxx		406–360–9	104218–44–2	X53	X:53 X: 61
613–152–00–3	xxxxx-X-(4,6-xxxxxxxxxxxxxxxxxx-2-xx)xxxxxxxx		406–600–2	89392–03–0	X43 X; 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 S: 61
613–154–00–4	2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx		410–050–9	5734–64–5	Xx; X22	Xx X: 22 X: (2-)22
613–155–00-X	5-xxxxx-2,3-xxxxxxxxxxxxxx		410–090–7	89402–43–7	X10 Xx; R22 R52–53	Xn X: 10–22–52/53 S: (2-)23–36–61
613–156–00–5	2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-butyl-5-chlorimidazol-4-karbaldehyd		410–260–0	83857–96–9	R43 X; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
613–157–00–0	2,4-xxxxxxx-5-(xxxxxxxxxxxxx)xxxxxxxxx 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx		410–330–0	54236–98–5	Xx; X22–48/22 Xi; X36	Xx R: 22–36–48/22 X: (2-)22–26–36
613–158–00–6	2,3-xxxxxxx-5-(xxxxxxxxxxxxxx)xxxxxxx		410–340–5	69045–84–7	Xx; X20/22 Xx; 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 N; X50–53	X; X R: 20–25–50/53 X: (1/2-)37–45–60–61
613–160–00–7	2-xxxxxx-2,5-xxxxxxxxxxxx[2.2.1]xxxxxx-xxxxxxxxxxxxx		411–000–9	125224–62–6	X43	Xx X: 43 X: (2-)24-37
615–022–00–1	methyl-3-(isokyanatosulfonyl)thiofen-2-karboxylát		410–550–7	79277–18–2	E; X2 R14 Xx; X48/22 R42/43	E; Xn X: 2–14–42/43–48/22 X: (2-)22–30–35–36/37
615–023–00–7	xxxxxxxxxxx 2-[(isokyanatosulfonyl)methyl]benzoové xxxxxxxxxxxxxx-2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxx		410–900–9	83056–32–0	X10 X14 Xxxx. xxx. 3; X40 Xx; X20–48/22 Xx; X41 X42	Xx R: 10–14–20–40–41–42–48/22 X: (2-)23–26–36/37/39
616–044–00–4	N-(3,5-dichlor-4-ethyl-2-hydroxyfenyl)-2-(3-pentadecylfenoxy)butanamid		402–510–2	—	N; X51–53	X X: 51/53 X: 61
616–045–00-X	2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(diethylamino)-2-methoxyacetanilid		405–190–2	122371–93–1	R43 R53	Xi X: 43-53 S: (2-)22–24–37–61
616–046–00–5	X -[2-(6-chlor-7-methylpyrazolo[1,5-b][1,2,4]triazol-4-yl)propyl]-2-(2,4-di-terc-pentylfenoxy)oktanamid		406–390–2	—	N; X50–53	X X: 50/53 X: 60-61
616–047–00–0	Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x X, N′,N″,N′′′ - xxxxxxxxxx(X18)- 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 N; X51–53	Xx; X X: 48/22–51/53 X: (2-)22–36–61
616–049–00–1	2-(2,4-xx-xxxx-xxxxxxxxxxx)-X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxx		408–150–2	99141–89–6	X53	X:53 S: 61
616–050–00–7	1-[2,5-xxxxxxx-4-(1,1,2,3,3,3-xxxxxxxxxxxxxxxx)xxxxx]-3-(2,6-xxxxxxxxxxxx)xxxxxxxx		410–690–9	103055–07–8	X43 X; X50–53	Xx; X R: 43–50/53 X: (2-)24–37–60–61
616–051–00–2	Směs:3,3'-bis(4-methylfenyl)- 1,1'-(4-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx x 3,3'-xxx(4-xxxxxxxxxxx)-1,1'-(2-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx Xxxx:2,4-xxx[3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx x 2,6-xxx[(3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx		411–070–0	—	X53	X: 53 X: 61
617–015–00–9	bis(4-methylbenzoyl)peroxid		407–950–9	895–85–2	E; X2 X; X7 X; X50–53	X; X R: 2–7–50/53 X: (2-)7–14–36/37/39–47–60–61
650–032–00-X	xxxxxxxxxxxx (XXX) (2X, 3R)-, (2 S, 3 X)-, (2 R, 3 X)-, (2 X, 3 R)-2-(4-chlorfenyl)-3-cyklopropyl-1-(1H- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		—	94361–06–5	Xxxx. xxx. 3; X63 Xx; R22 X; X50–53	Xx; X X: 22–50/53–63 X: (2-)36/37–60–61

PŘÍLOHA 2

XXXXXX XXXXXXXXXXXX XXXXX XXXXXXXXX S XXXXXXXXXXXX XXXXXXX A XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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

XXXXXXX 3A

STANDARDNÍ XXXXXX XXX BEZPEČNÉ XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY

Viz směrnice Xxxxxx 2001/59/ES,

Úř. věst. X 332, 28.12.2000, x. 81.

XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX ZACHÁZENÍ X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES,

Úř. věst. X 332, 28.12.2000, x. 81.

PŘÍLOHA 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx vitro má xxxxxxxxxxxxx činitele, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Rozlišují xx dva xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x chromatidové. U xxxxxxx chemických xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx xx schopnost xxxxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxx však xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx xxxxx rutinně xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x existuje xxxxx důkazů x xxx, xx xxxxxxxxxxxx xxxxxx x s xxxx související xxxx xxxxxxxxxxx změny v xxxxxxxxxx x x xxxxxx somatických buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x člověka x x xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx, xxxxxxx kmeny xxxx xxxxxxxx buněčné xxxxxxx. Použité xxxxx xxxx xxxxxxx xx xxxxxxx schopnosti xxxxx x xxxxxxx, stálosti xxxxxxxxx, xxxxx chromozomů, xxxxxxxxxxxx chromozomů a xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx vyžadují xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační xxxxxx xxxxxx zcela xxxxxxxxx xxxxxxxx xx vivo x savců. Xx xxxxx xx zcela xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx mutagenitu x xxxx x xxx xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Tato zkouška xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx je xxxx xxxxxxx xxxxxxxxx, xxxx xxx savce xxxxxxxxxxx; mezi touto xxxxxxxx x karcinogenitou xxxx xxxx xxxxxxxxx xxxxxxxx. Korelace závisí xx xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, že xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx zjištěny xxxxx xxxxxxxx, neboť xxxxxx xxxxxx xxxxxx mechanismy xxx přímým xxxxxxxxxx XXX.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx xxxxxxx : strukturní xxxxxxxxx xxxxxxxxxx v xxxxxx xxxxx nebo zlomu x xxxxxxx obou xxxxxxxxx v tomtéž xxxxx.

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

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

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

Numerická aberace : xxxxxxxx počtu xxxxxxxxxx od xxxxxxxxxx xxxxx xxxxxxxxx u xxxxxxxxx typu xxxxx.

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx ve xxxxxx xxxxxxxx; xxxx xx xxxx delece x fragmenty, xxxxxxxxxxxxxxxxxx xxxx interchromozomální xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx látce, x xx x xxxxxxxxxxxx xxxxxxxx a bez xx. X předem xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx látce xx xx xxxxxxxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Colcemid® xxxx xxxxxxxxx), kultury xx sklidí, xxxxxx x xxxxxxxxxx chromozomových xxxxxxx xx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx xxxxx xxxxxxx xxxxx, xxxxx nebo xxxxxxxx xxxxxxx xxxxxxx, xxxxxx xxxxxxxx buněčných xxxxx (xxxx. fibroblasty xxxxxx xxxxxxxx, xxxxxxxxx xxxxxxxxx xxxx člověka xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx x kultivační xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx měla xxx xxxxxxx vhodná xxxxxxxxxx xxxxx a inkubační xxxxxxxx (xxxxxxxxxx nádoby, xxxxxxxxxxx XX2, xxxxxxx x vlhkost). X xxxxxxxxxxxxxxx xxxxxxxxx linií x xxxxx xx xxxx být xxxxxxx xxxxxxxxxxxx stabilita xxxxxxx xxxxxxx xxxxx xxxxxxxxxx x xxxx xx xxx kontrolováno, zda xxxxxx kontaminovány xxxxxxxxxxxx; x xxxxxxx kontaminace xx neměly být xxxxxxx. Xxx použité xxxxx x xxxxxxxxx xxxxxxxx by měla xxx známa normální xxxxx xxxxxxxxx xxxxx.

1.4.1.3 Xxxxxxxx kultur

Stabilizované xxxxxxx xxxxx x xxxxx: xxxxx se xxxxxxx x kmenových xxxxxx, xxxxxx se xx xxxxxxxxxxxx xxxxx v xxxxxx hustotě, aby xxxxxxxxx xxxxxxxxxx před xxxxxxxxx, a xxxxxxxx xx xxx 37 °X.

Xxxxxxxxx: xxxx ošetřená xxxxxxxxxxxxxxx (xxxx. xxxxxxxxx) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxx se xxxxxxx xx kultivačního xxxxx obsahujícího xxxxxxx (xxxx. xxxxxxxxxxxxxxxx) a xxxxxxxx xx při 37 °C.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx xx měly xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxxxxxx xxxxxxxx a bez xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx frakce (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Aroclor 1254 (6, 7, 8 x 9), xxxx směs xxxxxxxxxxxxx x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx v xxxxxxxx testovacím xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % obj. Xxxx metabolického aktivačního xxxxxxx xxxx xxxxxxx xx xxxxx chemické xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx může být xxxxxx xxxxxx více xxx jednu koncentraci xxxxxxxxxxxxxxxxxxx frakce.

Řada výsledků xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx exprimujících xxxxxxxxxx xxxxxxxxx xxxxxx, poskytuje xxxxxxxx pro xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx linií xx xxxx xxx xxxxxxx xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx metabolismus xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx před xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx mohou xxx xxxx xxxxxxxx zředěny. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx být xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, a xxxx xx xxx xxxxxxxxxx x xxxxxxxx buněk x x xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo by xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx látek nestálých xx vodě xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Xxxxxxxxxxxx by xxxx xxx xxxxxxxxx x metabolickou xxxxxxxx x bez ní x hlavním xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, xxxx xxxx xxxxxx xxxxxxxxxx, xxxxx xxxxxxxxxxxxxxx xxxxx xxxx mitotický index. Xxxx být xxxxxxx xxxxxxxx cytotoxicitu x xxxxxxxxxxx x předběžném xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx cytotoxicity xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, případně žádnou xxxxxxxxx, xxx xxxxxxx xxxxxxx, xx xx xx koncentrace xxxxxx xxxxx více xxxxx xxxxxxxx 2 xx Ö10. V xxxxxxxx xxxxxxx by xxxx xxxxxxxx koncentrace xxxxxxxxx xxxxxxxx xxxxxxx stupně xxxxxxxxxx, xxxxx buněk xxxx xxxxxxxxxxx xxxxxx (xxx o xxxx xxx 50 %). Xxxxxxxxx xxxxx je xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x xxxxxx xx xxxx, která xxxxxxxx od xxxxxxxx. Xxxxxxxxx xxxxx je xxxx xxxxxxxxxx u xxxxxxxxxxx xxxxxx, x xxxxx mohou xxx xxxx xxxxxx xxxxxxxxx xxxxxxxx obtížné x xxxxxxxxxxx. Xxxxxxxxx o xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx průměrná xxxxxxxxx xxxx (AGT), xxxxx xxx xxxxxxx jako xxxxxxxxx xxxxxxxxx. X xxxxxxx AGT xxxx xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx xxxxx usoudit xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, x i xxxx přírůstek průměrné xxxxxxxxx xxxx xxxx xxx xx následek xxxxx xxxxxxxxx oddálení xxxxxxxx optimálního výtěžku xxxxxxx.

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx by xxxx být maximální xxxxxxxx koncentrace 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, která x xxxx xx xxxxxxxx.

X xxxxxxx relativně xxxxxxxxxxxxx látek, xxxxx xxxxxx xxxxxxx při xxxxxxxxxxxxx xxxxxxx, xxx xx xxxxxx xxxxxxxxxxx, xx měla xxx xxxxxxx xxxxxxxx dávka x xxxxxxxxxxx, jež xx nad xxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxx na xxxxx doby aplikace. X xxxxxxxx případech (xxxx. xxxxxxx-xx xx xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx, xxx xx xxxxxxxxxxx) xx xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, při xxxxx xxxxxxx xx srážení. Xxxx xxx xxxxxxxx xxxxxxxx rozpustnost xx xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxxx xx xxxx x xxxxxxx expozice xxxxx v xxxxxxxx xxxxxxxxxxx xxxxx, séra X9 xxx. Nerozpustnost xxx zjistit xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx a pozitivní xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx vehikula). Xxx xxxxxxx xxxxxxxxxxx aktivace xx měla být xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx látka, xxxxx k mutagenní xxxxxx vyžaduje xxxxxxxx.

X xxxxxxxxx xxxxxxxx xx xxx xxx xxxxxx xxxxx xxxxxxxxx v xxxxxxxxxxx koncentracích, xxxxx xxxxxxxx poskytnou reprodukovatelný x xxxxxxxxxxxxx xxxxxx xxx pozadí, xxxx xx xxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxx xxx zvoleny xxx, xxx xxx účinek xxxxxxxx, ale xxx xxx xxxxxx nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx	Xxxxx	Xxxxx XXX	Xxxxx xxxxx XXXXXX
Xxx xxxxxx metabolické xxxxxxxx	xxxxxx-xxxxxxxxxxxxxx	66–27–3	200–625–0
	xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
	1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
	xxxxxxxxx X	50–07–7	200–008–6
	4-xxxxxxxxxxxxx-1-xxxx	56–57–5	200–281–1
X vnější xxxxxxxxxxxx xxxxxxxx	xxxxx[x]xxxxx	50–32–8	200–028–5
	xxxxxxxxxxxxx	50–18–0	200–015–4
	xxxxxxxxxxxxx monohydrát	6055–19–2	200–015–4

Pro xxxxxxxxx xxxxxxxx mohou xxx xxxxxxx i xxxx xxxxxx xxxxx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx pokud xxxxx xxxxx x xxxxx použití xxxxxxxxxx xxxxx xx stejné xxxxxxxx třídy.

V okamžiku xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx samotného xxxxxxxxxxxx xxxx vehikula v xxxxxxxxxxx xxxxx x xxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud žádné xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx zkoušené xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxxxxx zkoušené látce xxx xx přítomnosti xxxxxxxxxxxxx aktivačního xxxxxxx, xxx xxx xxxx. Xxxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxxx xxx 48 xxxxx xx mitogenní xxxxxxxxx.

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

Xxxxxx xxxx xxxxxx xxxxx xx xxxx xxx xxxxxxxx xxxxxxxx metodami, xxxx. v xxxxx xxxxxxxxxx kultivačních xxxxxxxx (15, 16).

1.4.3.3 Doba xxxxxxx xxxxxx

X xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxx vystaveny xxxxxxxx látce, jak x metabolickou aktivací, xxx bez xx, xx xxxx 3 — 6 hodin, x xxxx xx xxx xxxxxxxx xx xxxxxx době xx xxxxxxxx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (12). Xxxxxxxx xxxxx xxxxxx xxxx negativní xxxxxxxx jak s xxxxxxxx, tak bez xxxxxxxx, xxx xx xxx proveden dodatečný xxxxxxxxxx bez xxxxxxxx x nepřetržitou xxxxxxxx xx xx xxxxxx x xxxx, která xxxxxxxx 1,5xxxxxxx normální xxxxx xxxxxxxxx xxxxx. Xxxxxx chemické xxxxx xxx snáze detekovat xxx dobách xxxxxxxx xxxx xxxxxx xxxxxxx xxx 1,5xxxxxxx xxxxx xxxxx. Negativní xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. X případech, xxx xx nepovažuje potvrzení xxxxxxxxxxx výsledků za xxxxxxxx, xx mělo xxx podáno xxxxxxxxxx.

1.4.3.4 Xxxxxxxx preparátů pro xxxxxxx xxxxxxxxxx

Xx buněčné xxxxxxx xx xxxxxxx 1-3 hodiny xxxx xxxxxxxxx xxxxx Xxxxxxxx® xxxx xxxxxxxxx. Pro xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů xx xxxxx xxxxxxx kultura xxxxxx x xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx x obarvení xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx preparátů xxxxxxxxxxx x xxxxxxxxxxx kontrol, xx xxxx xxx xxxx xxxxxxxx pod xxxxxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxx části xxxxx x xxxxxxxx a xx ztrátě xxxxxxxxxx, xxxx xx vyšetřované xxxxx xxxxxxxxx centromery x xxxxx xxxxxx xxxxxxx xxxxxxx ± 2 pro xxxxxxx xxxx xxxxx. Na xxxxxx koncentraci x xxxxxxxx xx mělo xxx xxxxxxxxx xxxxxxx 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, případně xxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx počet xxx snížit, xx-xx xxxxxxxxx velký počet xxxxxxx.

Xxxxxx je xxxxxx xxxxxxx detekovat xxxxxxxxxx xxxxxxxxxxxx xxxxxxx, xx xxxxxxxx zaznamenat xxxxxxxxxxx x endoreduplikace, jsou-li xxxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx x xxxx xx tedy být xxxxxxxxxxx množství xxxxx xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x procentech. Pro xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx strukturních chromozomových xxxxxxx s xxxxxx xxxxxx x xxxxxxxx. Xxxx se xxxxxxxxxxxxx xxxxxxxx a xxxxxxx xx, xxx xxxxxxxxxx xx xx xxxxxxx xxxxxxxx xxxxxxx.

Xxxx xx xxx xxxx zaznamenána xxxxxxxx, xxxxx xxxx xxxxxxxxx xxx stanovení xxxxxxxxxxxx x všech xxxxxxxxxxxx kultur x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxxxxxxxxxx s xxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxx xxx xxxxxxxxxx kultury. Xxxx xx měly xxx xxxxxxx xxxxx shrnuty xx formě xxxxxxx.

Xxxxxxx xxxxx pozitivní xxxxxxxx xx xxxxxxxxxx. Dvojznačné xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe x xxxxxxxx xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxxx potvrdit xxxxxxxxx xxxxxxxx byla xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x cílem xxxxxxxx xxxxxx xxxxxxxxxxxx podmínek xx xxxx být xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X parametrům xxxxxx, xxxxx xx xxxxx být změněny, xxxxx rozmezí xxxxxxxxxxx x podmínky xxxxxxxxxxx xxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku existuje xxxxxxx xxxxxxxx, např. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na xxxxxxxxxxx, nebo reprodukovatelný xxxxxx xxxxxx xxxxx. Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx metody (3, 13). Statistická xxxxxxxxxx xx neměla být xxxxxxx určujícím faktorem xxx xxxxxxxxx odpověď.

Nárůst xxxxx polyploidie xxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (17, 18).

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů vyslovit xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou zůstat xxxxxxxxxx xxxx xxxxxx xxx xxxxxx na xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Buňky:

- typ x xxxxx buněk,

- xxxxxxxxxx karyotypu x xxxxxxxx použitého xxxx xxxxx,

- xxxxxxxxx nepřítomnost xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx xxxxx,

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

- xxxxxxxx xxxxx xxxxxx,

- případně xxxxxx 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 xxxx. údajů x xxxxxxxxxxxx x xxxxxx rozpustnosti, jsou-li x xxxxxxxxx,

- složení xxxxx, xxxxxxxx xxxxxxxxxxx XX₂,

- xxxxxxxxxxx zkoušené xxxxx,

- xxxxx vehikula x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx při xxxxxxxx,

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

- pozitivní a xxxxxxxxx kontroly,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx metafází,

- metody xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- známky xxxxxxx,

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

- xxxxxxxx xxxxxxx, xxxxxx xxxx,

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

- xxxxx xxxxxxx, xxxxx xxxx pozorovány,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, H. X. (1976), Xxxxxxxxxxx Methods xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, xx: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx and Xxxxxxx xxx xxxxx Xxxxxxxxx, Vol. 4, Xxxxxxxxxx, X. (ed) Xxxxxx Xxxxx, New Xxxx xxx Xxxxxx, 1-29.

2) Xxxxxxxx, X. Xx., Xxxxxx, T. (1985), Xxx Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Xxxxx Chinese Xxxxxxx Lung (XXX) Xxxxxxxxxx Xxxxx in Xxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Ashby, X. xx xx., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Xxxxxxxx, S. X., Xxxxxxxxx, X. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxx, X. D., Xxxxxxxx, X., Xxxxx, X., Xxx, X., Xxxxx, J., Margolin, X. H., Resnick, X. X., Xxxxxxxx, X., Xxxxxx E. (1978), Xxxxxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxxx in Xxxxxxx xxxxxxx ovary xxxxx: Xxxxxxxxxx of 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxxx, R. X., Ishidate, X. Xx., Brusick, X., Xxxxx, J., Xxxx, X. X. (1991), Xxxxxxxxxxxx xxxxx Extreme Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxxxx Res., 257, 147-204.

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

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

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

8) Xxxxxxxxx, X. X., Tates, X. D., van Xxxx, X. X. X., Xxxxxxx, X., xx Xxxxx, N. (1976), Xxxxxxxxxxx Xxxxxxx xx Xxxxxxx/Xxxxxxxxxxx xxxxx Xxxxxxxxxx xx x Xxxxxxxxxxx Xxxxxx Xx xxxxx, X. Xxxxxxxxx xx Chromozome Xxxxxxxxxxx xxx Xxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) and Dimethylnitrosamine (XXX) xx XXX Xxxxx in the Xxxxxxxx xx Rat-Liver Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

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

10) Xxxxxx, X. X., Xxxxxx, X. D., Xxxxxxx, X. R., Xxxxxxxxx, X. G., Gibson, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxx of XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 xx In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Sawamura, X., Xxxx, X., Xxxxxxxx, X. (1976), X. Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Biphenyls x. x. xx Xxxxxxx of Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, in: xx Serres, X. X., Xxxxx, J. X. Bend, X. X., Xxxxxxx, X. X. (eds), In xxxxx Xxxxxxxxx Activation xx Mutagenesis Testing, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

12) Xxxxxxxx, S. M., Xxxxxxx, M. X., Xxxxxxxx, X. Xx., Xxxxx, J. L., Xxxxxxxx, X. J., Xxxxxx, X., Xxxxxxx, X., Sofumi, T. (1994), Report xxxx Xxxxxxx Group xx Xx vitro Tests xxx Xxxxxxxxxxx Aberrations, Xxxxxxxxxx Res., 312, 241-261.

13) Xxxxxxxxxx, C., Xxxxxxxx, X. A., Xxxxx, X. A., Xxxxxxxx, X., Xxxxxxx, X. X., Xxxxxxxx, X. (1989), Xxxxxxxx xx Xxxx from Xx vitro Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Kirkland, X. X., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

14) Xxxxx, X. X., Xxxxxxxx, X. X. (1994), Xxxxxxxxx Xxxxxx xxx xxx Necessary xxx Xx xxxxx Xxxxxxxxxx Xxxxxxxxxx Xxxxxx xx XXX Xxxxx, Xxxxxxxxxx Xxx., 312, 139-149.

15) Xxxxx, D. F., Xxxxxx, X. X., XxXxxxx, X. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx of Xxxxx xxx Xxxxxxxx Xxxxxxx, in: Tice, X. R., Xxxxx, X. X., Xxxxxxx, X. M. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, P. X., Xxxxxx, X. X., Xx, A. X., Xxxxxx, A. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Xxxxxxxx Xxxxx, Environmental Mutagen., 5, 795-801.

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

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

PŘÍLOHA 4X

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

1. XXXXXX

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

1.1 ÚVOD

Zkouška xx xxxxxxxxxxxx aberace x xxxxx xx xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx indukovaných xxxxxxxxx xxxxxx v xxxxxxx xxxxxx xxxxx xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx — xxxxxxxxxxxx x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx xx schopnost indukovat xxxxxxxxx xxxxxxx. V xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, xx chromozomové xxxxxx x xxxxxxxxxxx xxxx způsobující xxxxx x xxxxxxxxxx a x xxxxxx xxxxxxxxxxx xxxxx tlumících xxxxxx, xxxx podíl xx xxxxxxx rakoviny x xxxxxxx a x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx jsou rutinně xxxxxxxxx hlodavci. Xxxxxxx xxxxx je x xxxx xxxxxxx kostní xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx tkání x obsahuje xxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxxx xx xxxxxx xxxxxxx a xxxxxxxxxxxx. Xxxx xxxxx x cílové xxxxx xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx je xxxxxxx xxxxxx k xxxxxxxxx nebezpečí mutagenese, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx metabolismu xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx x xxxxxxx druhů x xxxxx xxxxx. Xxxxxxx xx xxxx xx xxxxxx užitečná xxx xxxxx výzkum xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, xx xx xxxxxxxx látka xxxx xxxxxxxxx metabolity nedostanou xx cílové xxxxx, xxxx xxxxxx xxxx xxxxxxx použít.

Viz také Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

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

Endoreduplikace : xxxxxx, při xxxxxx x jádře po X-xxxx xxxxxxxxx XXX xxxxxxx k xxxxxx, xxxxx následuje xxxxx X-xxxx. Xxxxxxxxx xxxx xxxxxxxxxx se 4, 8, 16,… xxxxxxxxxxxx.

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

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

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

Xxxxxxxxxx aberace : mikroskopicky xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx; xxxx se xxxx xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx jsou xxxxxxxxx xxxxxxxx látce xxxxxxx xxxxxxxx x ve xxxxxxx xxxxxxxx xx xxxxxxxx xx xxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx xxxxxx xxxxx se xxxx xxxxxxxx preparáty xxxxxxxxxx, xxxxxx xx a xxxxxxxxx xx chromozomové xxxxxxx xxxxx v xxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xx xxxxxxxx potkan, xxx x xxxxxx xxxxxx, xxxxxx lze xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxxx xx xxx použity běžně xxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx studie xx xxxx být xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx a xxxxxx xx x xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx rozdělí xx kontrolní xxxxxxx x xxxxxxx, xxxxx xx vystaví xxxxxxxx xxxxx. Klece xx xxxx být xxxxxxxxxx xxx, aby xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata se xxxxxxxxxxx identifikují. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx aplikací zvířatům xxxxxxxxxx nebo suspendovány xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx přímo xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Zkušební podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx xxxxxxxxx xxxxxxxx dávek toxické xxxxxx x xxxx xx xxx vyloučeno xxxxxxxxx, xx reaguje xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx jiná xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) kontroly xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx kontrolní xxxxxxx xxxxxxxxxx identický xxxxxx xxxx zvířata xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx poskytovat xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx úrovních, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx měly xxx zvoleny xxx, xxx byl účinek xxxxxxxx, ale xxx xxx xxxxxx nevyšla xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby byla xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka a xxx xxx odběr x jejím xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx kontrolu xxxxx xxx použity xxxxxxxx xxxxx xx xxxxxx chemické třídy, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx pro xxxxxxxxx kontrolu:

Látka	Číslo CAS	Číslo xxxxx XXXXXX
xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
xxxxxxxxx C	50–07–7	200–008–6
cyklofosfamid	50–18–0	200–015–4
cyklofosfamid xxxxxxxxxx	6055–19–2	200–015–4
2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-triazin	51–18–3	200–083–5

V okamžiku xxxxxxx xxxxxx xx xxx být xxxxxxxx xxxxx x negativních xxxxxxx, xxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxx xxxxx podstupují xxxxxx xxxxxx jako xxxxxxxxxx xxxxxxx, pokud xxxxxx z xxxxxxxxxxx xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx x variabilitě xxxxxx x xxxxxxxx xxxxx x chromozomovými xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx xxxxxxxx použity xxxx tehdy, neexistují-li xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx nebo mutagenní xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx a kontrolní xxxxxxx se skládá x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx. Xxxxxxxx xxxx x xxxx xxxxxx x dispozici xxxxx ze studií xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx zkoušení xxxxxxx pohlaví. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx být xxxxxxx xxxxxxxxx xx zvířaty xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx by xxxx xxx xxxxx xxxxx podávány jednorázově. Xxxxxxxx xxxxx mohou xxx podávány xxxx xx xxxx xxxxxxx, xxx. xxx xxxxx x xxx xxx x xxxxxxx ne xxxx xxx xxxxxxxx xxxxx, aby xxxx xxxxxxxxx podávání xxxxxxx xxxxxx materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx.

Xxxxxx by xxxx xxx odebrány xx xxxx různých xxxxxxxxxxx xx xxxxxxxx podané x xxxxxx xxx. X xxxxxxxx xx xxxxx xxxxxxx xx xxxxxx xxxx od xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (xxxx xxxx xxxxxxx 12 — 18 h). Xxxxxxxx xxxx xxxxxxxx xxx příjem a xxxxxxxxxxxx xxxxxxxx látky x xxxxxx xxx xxxxxx na kinetiku xxxxxxxxx xxxxx xxxx xxx xxxx na xxxxxxxxx xxxxxxx xxx xxxxxxxxx chromozomových xxxxxxx, xxxxxxxxxx xx provést xxxxx odběr xx 24 x od xxxxxxx xxxxxx. Xx-xx xxxxxxxx rozložena xx xxxx xxx xxxxxxx xxx, xxx by xxx odběr xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx.

Xxxx xxxxxxxxx se xxxxxxxx intraperitoneálně xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® nebo xxxxxxxxx). Xxxx se xx xxxxxx xxxx provede x xxxxxx xxxxx. X xxxx xx xxxx doba přibližně 3 — 5 x; u křečka xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx xxxxxxxx buňky x analyzují xx xx chromozomové xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx rozsahu xxxxx, xxxx by xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx stejným xxxxxx, xxxxxx, xxxxxxxx x xx stejného xxxxxx expozice, jež xx použijí x xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx pro první xxxxx použijí tři xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx a xxxxxxxxx toxicitou, případně xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx vyšší xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x letalitě. Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx jako dávka xxxxxxxxxxxx x kostní xxxxx xxxxxxx známky xxxxxxxx (např. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x jednou dávkou xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách v xxxxxx xxx nevykazuje xxxxx pozorovatelné toxické xxxxxx x není-li xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx podobnou strukturu, xxxxxxxxx xxxxxxxxxxxx, nepovažuje xx úplná studie xx xxxxx úrovněmi xxxxx za nezbytnou. X xxxx trvajících xxxxxx xx xxxxxxx xxxxxx pro 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx a xxx xxxxx xxx 14xxxxx aplikaci je xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx expozice člověka xxxx znamenat xxxxxxx xxxxxx v xxxxxxx xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx se xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx nebo vhodnou xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou x xxxxxxxxxxxx případech xxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, který xxxx xxx xxxxxxxx podán xxxxxxxxxxxxxx nebo injekčně, xxxxxx na velikosti xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 ml/100 g xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, než xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx na dráždivé x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx xxxxxxxxxx objem při xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx

Xxxxx po xxxxxxxx se xxxxxxx xxxxxx xxxx, xxxxxxxxxxxx xx x xxxxxx. Xxxxx se xxxxxxx xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

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

U xxxxxxx xxxxxxx xx mělo xxx xxxxxxxxxxx xxxxxxx 100 xxxxx. Tento xxxxx lze xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Všechny xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx kontrol xx xxxx být xxxx xxxxxxxxxxxxxx analýzou xxxxxxxxx xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx dochází xx chromozomálním xxxxxx xxxx xx xxxxxx xxxxxxxxxx u části xxxxx x metafázi, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx odpovídajícímu xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx, xxxxx aberací xx buňku a xxxxx buněk x xxxxxxxxxxxxx aberací (chromozomovými xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxxx x kontrolní xxxxxxx xx xxxx být xxxxxxx xxxxx typy xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich počtem x četností. Gapy xx xxxxxxxxxxxxx odděleně x xxxxxxx xx, xxx xxxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxx aberací. Neexistuje-li xxxxx x xxxxxxx x odpovědi xxxx xxxxxxxxx, xxxxx být xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx několik kritérií, xxxx. xxxxxx xxxxxxxxxxx xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx xx xxxxx xxxx xxxxx nárůst xxxxx buněk s xxxxxxxxx pro xxxxxxx x xxxxxxx dávkou x k určitému xxxxxxxx odběru. Xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx by neměla xxx xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx polyploidie xxxx xxxxxxxx, xx xxxxxxxx látka má xxxxxxxxx indukovat numerické xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx může xxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (7, 8).

Zkoušená xxxxx, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, se považuje x tomto xxxxxxx xx xxxxxxxxxxx.

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx vyslovit konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx chromozomové xxxxxxx xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx v xxxxxx xxxxx testovacího xxxxx xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx dostanou do xxxxxxxx xxxxx, nebo xxxxxxxxxx xx cílové xxxxx (xxxx. systémová xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, včetně xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx hodnoty x xxxxxxxxxx xxxxxxxx pro xxxxxx skupinu.

Zkušební podmínky:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

- údaje xx xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx xxxx provedena,

- xxxxxxxxxx xxxxxxxxx xxxxxx dávek,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- popřípadě xxxxxx xxxxxxx, zda se xxxxxxxx látka dostala xx xxxxxxxx xxxxx xxxx do xxxxxx xxxxx,

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

- xxxxxxxx údaje x xxxxxxx xxxxxx a xxxx,

- xxxxxxxx popis xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx stanovení xxxxxxxx,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet analyzovaných xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- typ x xxxxx aberací xxxxxxx xxxxxxxxxx pro každé xxxxx,

- xxxxxxx xxxxx xxxxxxx ve xxxxxxx xx středními hodnotami x xxxxxxxxxxxx xxxxxxxxxx,

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

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx negativní xxxxxxxx,

- xxxxxxxxx xxxxx x negativní kontrole x rozpětími, xxxxxxxxx xxxxxxxxx a směrodatnými xxxxxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Preston, X. X., Dean, X. J., Xxxxxxxx, X., Xxxxxx, X., XxXxx, A. F., Xxxxxx, M. (1987), Xxxxxxxxx Xx vivo Xxxxxxxxxxx Xxxxxx: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xx Xxxx Xxxxxx Xxxxx, Xxxxxxxxxx Res., 189, 157-165.

3) Xxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Gatehouse, X. X., Xxxxxxx, X., Henderson, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. J. Kirkland (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx I revised, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. R., Xxxxxxx, X., XxxXxxxxxx, J. X., Xxxxxxxx, D., Xxxxxx, X. X., Xxxxxx, H. E., Xxxxxx-Xxxxxxx, M., Xxxxxx Xx., X. X., Xxxxxxxxxxxx, F., Preston, X. X., Romagna, X., Shimada, H., Xxxxx, X., Xxxxxxx, X. (1994), Xxxxxx xxxx xxx Working Xxxxx xx xxx xx vivo Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, X. X., Xxx, J., Esdaile, X. X., Gatehouse, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, D. X., Xxxxxxx, M. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Mutagenicity Assays, Xxxxxxxxxxx, 7, 313-319.

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

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

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

XXXXXXX 4C

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

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX XX 474 — Xxxx xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx (1997).

1.1 XXXX

Xxxx xxxxxxx erytrocytárních xxxxxxxxxx in vivo xx používán xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxx aparátu xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx látkou, x xx pomocí xxxxxxx xxxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx x/xxxx buněk periferní xxxx, xxxxxxx xxxxxxxx.

Xxxxxx xxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxxx xxxxx, xxxxx způsobují xxxxxxxxxxxxx poškození, xxxxx xxxxxxxxx xx xxxxxx xxxxxxxxxx obsahujících xxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxx xxxxxxxxx xxxx xxxx xxxxxxxxxx.

Xxxx xx xxxxxxxxxxx xxxxxx xxxxx mění xx polychromatický xxxxxxxxx, xxxxxx xxxxx je xxxxxxxx a xxxxxxxxxx, xxxxx xxx xxx xxxxx xxxxxxxxx, xxxxxxxxx x xxxxxxxxxx, která xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx xx x xxxxxx buňkách xxxxxxxxx tím, xx xxxxxxxxxx xxxxxx xxxxx. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x exponovaných zvířatech xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx poškození.

V tomto xxxxx je rutinně xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxxxx tato xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Stanovení xxxxxxxxx (xxxxxxxxxxxxxxxxx) erytrocytů x xxxxxxxxxx v periferní xxxx je rovnocenně xxxxxxxxxx x kteréhokoli xxxxx, x xxxxx xxxx prokázána xxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x mikrojádry, xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxxxxx xxx rozlišit řadou xxxxxxxx. Ta zahrnují xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX x mikrojádře. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (polychromatických) xxxxxxxxxx s mikrojádry. Xxxxx xxxxxxx (normochromatických) xxxxxxxxxx x periferní xxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxxxxxxxx xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx jako konečný xxxxxxxx zkoušky, jestliže xxxx zvířata xxxxxxxxxx xxxxx xxxxx nebo xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx in xxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx DNA, třebaže xx xxxxx lišit x xxxxxxx druhů x xxxxx, xxxxx x x genetického xxxxxxxx. Xxxxxxx xx xxxx xx rovněž xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx v xxxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, xx xx zkoušená xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx zkoušku xxxxxx.

Xxx také Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) chromozomu, x níž (x xxxx) xx během xxxxxx xxxxx xxxxxxx xxxxxx vřeténko xxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x pólům xxxxxxxxx buněk.

Mikrojádra : xxxx xxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx x xxxxx xxxx, vytvářená xxxxx xxxxxxxx xxxxxx (xxxxxx) xxxxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxxxx fragmenty xxxx xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx erytrocyt : zralý erytrocyt xxxxxxxxxxxx xxxxxxxx, xxxxx xxx rozlišit od xxxxxxxxx polychromatických xxxxxxxxxx xxxxxxxx selektivním xxx xxxxxxxx.

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

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xx vhodným xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx dřeně se xxxxxxx xx xxxxxxx xxxxxxxx xx xxxxxxxx xxxxxx, xxxxxxx xx xxxxxx xxxx, připraví xx xxxxxxxxx x xxxxxx se (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx xxxxxxxxx xxxx se xxxx xx xxxxxxx xxxxxxxx xx xxxxxxxx xxxxxxx, xxxxxxxxxx xx xxxxxxxx xxxxxxxx x xxxxxx xx (4, 8, 9, 10). Xxx xxxxxxxx s periferní xxxx by měla xxxx xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxx xxxxxxxx co xxxxxxxxx xxxx. Xxxxxxxxx xxxx xxxxxxxxxxx xx přítomnost xxxxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx xxxxxxx xxxxxx xxxxx se xxxx xxxxxxxxx zvíře xxxxxxxxxx xxx nebo xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxxx druh. Xxx xxxxxxx periferní xxxx xx xxxxxxxxxx xxx. Xxx však použít xxxxxxxx xxxxxx xxxx xxxxx xx xxxxxxxxxxx, xx xxx x xxxx, u xxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx x mikrojádry, xxxx xxxx xxxxxxxxxx dostatečnou xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx způsobují strukturní xxxx xxxxxxxxx chromozomové xxxxxxx. Měly by xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx zdravých xxxxxxxx xxxxxxxxx zvířat. V xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx x xxxxxx by u xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, u xxx xx xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx. Klece xx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx by xxxx xxx před xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve vhodných xxxxxxxxxxxxxx nebo xxxxxxxxxx x popřípadě zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx mohou xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxx stálosti xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx mít xxx použitých xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx vyloučeno podezření, xx reaguje xx xxxxxxxxx xxxxxx. Jsou-li xxxxxxx xxxx xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx podloženo údaji x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud xxxxx nejdříve xxxxxx xxxxxxx vodných rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx experimentu xx měly být xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx pro xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx in xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Xxxxx xxxxxxxxx kontroly by xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx identifikace xxxxxxxxx. Xx xxxxxxxxxx, aby xxxxxxxxx xxxxxxxx byla xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x aby xxx xxxxx x tomto xxxxxxx xxxxxxxx xxx xxxxxx. Pro xxxxxxxxx xxxxxxxx navíc xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx ze stejné xxxxxxxx třídy, xxxx-xx x xxxxxxxxx. Příklady xxxxx pro xxxxxxxxx xxxxxxxx:

Xxxxx	Xxxxx XXX	Xxxxx xxxxx XXXXXX
xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
xxxxxxxxx X	50–07–7	200–008–6
xxxxxxxxxxxxx	50–18–0	200–015–4
xxxxxxxxxxxxx xxxxxxxxxx	6055–19–2	200–015–4
2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx	51–18–3	200–083–5

X okamžiku xxxxxx xx měl xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx kontroly, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a která xxxxx podstupuje stejný xxxxxx xxxx exponované xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx x xxxxxxxxxx. Xxxxxxx-xx xx xxx negativní xxxxxxxx xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx doba xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud xxxx xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx rozpouštědlo/vehikulum xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx xxxx může xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx také xxxxxx xxxx odebraný xxxx xxxxxxxx, pouze xxxx x xxxxxxxx xxxxxx x periferní xxxx (xxxx. 1 — 3 aplikace) xx xxxxxxxxxxx, xx xxxxxxxx xxxxx xxxxx x rozpětí, xxxxx xx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Počet a xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní xxxxxxx xx xxxx xxxxxxx x alespoň pěti xxxxxxxxxxxxxxxx zvířat xxx xxxxx xxxxxxx (11). Xxxxxxxx jsou x xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx prokazují, xx xxxxxxxxxx mezi xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx pohlaví. Xx-xx xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by xxx xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxx xxxxxxxxx xxxxx standardní plán (xx. xxxxx, xxx xxxx xxx xxxxxxxx x intervalu 24 xxxxx). Xxxxxx xx xxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, pokud se x těchto xxxxxx xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –x xxxxxxx xxxxxxxxxxx studií — xxxxx byla xxxxxxxxx xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxx xxxxx x podávání pokračuje xx xx xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx xxx podávány xxxx xx xxxx xxxxxxx, xxx. dvě xxxxx x xxx xxx x xxxxxxx xx více než xxxxxxxx hodin, xxx xxxx usnadněno xxxxxxxx xxxxxxx objemů xxxxxxxxx.

Xxxx xxxx xxx xxxxxxxx xxxxx xxxxxxx:

x) xxxxxxxx xxxxx xx aplikuje xxxxxxxx xxxxxx. Xxxxxx xxxxxx xxxxx xx xxxxxxxx xxxxxxx dvakrát, xxxxxxx xxxxx xxxxx xx provede xxxxxxxx 24 hodin xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx aplikaci x x přiměřeným odstupem xxxx odběry. Xxxxx xxxxx než 24 xxxxx xx xxxxxxxx xxxx xxx zdůvodněn. Xxxxxx xxxxxxxxx krve xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx se provede xxxxxxxx 36 xxxxx xx aplikaci x xxxxxxxx xxxxxxxxxx 72 xxxxx xx aplikaci x xx xxxxxxxxxxxx xx xxxxxx xxxxxxxxxxxx xxxxxx. Xx-xx po xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx odběr xxxxx;

x) xxxx-xx podávány xxx xxxx více xxxxx xxxxx (např. dvě xxxx xxxx xxxxx x intervalu 24 xxxxx), měly xx xxx vzorky xxx xxxxxxx kostní xxxxx xxxxxxxx xxxxxx po 18 až 24 xxxxxxxx xx poslední xxxxxxxx x xxx xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx poslední xxxxxxxx (12).

Xxxxx potřeby xxxxx xxx xxxxx xxxxxxx xxxx doby xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx rozsahu xxxxx, xxxx xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx studii (13). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx rozpětí xxxx maximální xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx odběru xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx dávka je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx stejném režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx vyhovovat a xxxx xx xxx xxxxxxxxx případ xx xxxxxxx. Xxxxxxxx dávka xxxx xxx také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx v kostní xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx x xxxxxxxxx krvi).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx xxxxxx x xxxxxxx 2000 mg/kg xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx v xxxxxx dni nevykazuje xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x není-li xx xxxxxxx xxxxx x látkách, které xxxx podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, není xxxxxxxxxx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx za xxxxxxxxx. X xxxx trvajících xxxxxx je xxxxxxx xxxxxx pro 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx delší xxx 14xxxxx xxxxxxxx xx xxxxxxx xxxxxx 1000 xx/xx xxxxxxx hmotnosti/den. Xxxxxxxxx expozice xxxxxxx xxxx znamenat potřebu xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx nitrožaludečně, žaludeční xxxxxx nebo xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou xxxxxxxxxx x xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, závisí xx xxxxxxxxx testovacího xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx xx xxxxxxxx x žíravé xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx zkušebního xxxxxx xxxxxxxxxxxxxx nastavením koncentrace xxxxxxxxxxx xxxxxxxxxx objem xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx nebo krve

Buňky xxxxxx xxxxx se xxxxxxx xxxxxxxxx x xxxxxx xxxx xxxxx xxxxx xx usmrcení. Xxxxx xx xxxxxxxx x femuru xxxx xxxxx x xxxxxxxxxx xxxxxxxx xx preparují x xxxxxx. Xxxxxxxxx xxxx xx xxxxxxx x xxxxxx žíly xxxx xxxx xxxxxx xxxxxx xxxx. Xxxxxx xxxxx xx xxxxx xxxxxxxxxxxx obarví (8, 9, 10), nebo xx připraví xxxxxxxxx xxxxxxxx x xxxx xx obarví. Použitím xxxxxxx specifického xxx XXX (xxxx. akridinová xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx vyhnout xxxxxxxx xxxxxxxxxx xxxxxxxx s xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxx XXX. Tato xxxxxx xxxxxxx použití xxxxxxxxxxx barviv (xxxx. Xxxxxx). Xxxxxxxx systémy (xxxx. xxxxxxxxxx xxxxxx x odstranění xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, xx xx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Analýza

Pro xxxxx xxxxx xx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx xx x xxxxxxx kostní xxxxx xxxxxxx xxxxxxx xxxxxxx 200 erytrocytů x v xxxxxxx xxxxxxxxx krve alespoň 1000 xxxxxxxxxx (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by xxxx být před xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx se xxxxxxx xxxxxxx 2000 xxxxxxxxx erytrocytů na xxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxxxxxxxx. Xxxxx informace xxxxx xxx získány xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx. Xxx xxxxxxxxxxxxx xxxxxxx xx neměl xxx xxxxx nezralých erytrocytů x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxx 20 % kontrolní xxxxxxx. Xxxxxxxx jsou xxxxxxx exponována xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, lze také xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx xx xxxxx xxxxx. Systémy xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxx) jsou xx xxxxxxxxxxxxx xxxxxxxxxx x validaci xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxxxxxxxx xxxxx xx měl xxx xxxxxx xxxxx xxxxxxxxxxx xxxxxxxxx erytrocytů, xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx xxxx xxxx, xxxx by xxx xxxx xxxxxxx xxxxx x xxxxxxx xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx zvíře se xxxxx xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx vyjádřené x procentech. Neexistuje-li xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, xxxxx být xxx xxxxxxxxxxxx analýzu xxxxx xxx xxx xxxxxxx zkombinována.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxx xxxxx x mikrojádry x xxxxxxxxxx xx xxxxx nebo jasný xxxxxx xxxxx xxxxx x mikrojádry xxx xxxxxxx x xxxxxxx xxxxxx x k xxxxxxxx okamžiku xxxxxx. Xxxxxxxx by měla xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx metody (18, 19). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx by xxxx xxx vyjasněny xxxxxx zkoušením, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx poskytne xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo sporné xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx xx mikrojádra xxxxxxxxx, že zkoušená xxxxx xxxxxxxx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxxxxx mitotického aparátu xxxxxxxxxxxx testovacího druhu. Xxxxxxxxx výsledky znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx.

Xxxx by xxx xxxxxxxxxxx pravděpodobnost, x xxxxx se xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx oběhu, xxxx xxxxxxxxxx do xxxxxx xxxxx (xxxx. systémová xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

- xxxxxxxxxxx a xxxxxxx zkoušené xxxxx x rozpouštědle/vehikulu, xx-xx xxxxx.

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x pohlaví xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

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

Xxxxxxxx xxxxxxxx:

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

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

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- údaje o xxxxxxxx zkoušené látky,

- xxxxxxxxxx xxxxxxx podávání,

- xxxxxxxxx metody xxxxxxx, xxx xx xxxxxxxx xxxxx dostala do xxxxxxxx xxxxx xxxx xx cílové xxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx látky x xxxxxx nebo xxxx (ppm) na xxxxxxxxxxxx dávku (mg/kg xxxxxxx xxxxxxxxx/xxx),

- podrobné xxxxx x xxxxxxx xxxxxx a vody,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx stanovení toxicity,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx buněk xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx studie xx pozitivní, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx erytrocytů,

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

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx analýzy x xxxxxx,

- xxxxx x xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxxx, X. X. (1973), A Xxxxx In vivo Xxxx xxx Xxxxxxxxxxx Xxxxxx, Mutatation Xxx., 18, 187-190.

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

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

4) Xxxxxxxxx, X. X., Xxxxxx, D. H., Xxxxxx, X. X., Xxxxxxxx, M. X., Xxxxxx, X. A. (1990), The In xxxx Xxxxxxxxxxxx Xxxxx xx Mammalian Bone Xxxxxx xxx Peripheral Xxxxx. X xxxxxx xx the U. X. Environmental Protection Xxxxxx Gene-Tox Program, Xxxxxxxxxx Res., 239, 29-80.

5) XxxXxxxxx, J. X., Schlegel, X., Xxxx, X. N., Xxxx, X. M. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: A Xxxxx Xxxxxx for Xxxxxxxxxxx Damage Xxxxxx Xxxxxxx Toxicity Xxxxxxx xx Mice, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Practice xx Xxxxxxxxxx, ed. X. X. Xxxxx, X. X. Xxxxxxx, X. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. X., Xxxxxx, X. X. Xxxx, X., Xxxxxxxx, X. X., Ramel, X., Xxxxxxxx, M. X., Xxxx, X. R., Xxxx, X. (1987), Xxxxxxxxxx for xxx Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx xx Xxxxxxxxx Xxxx Marrow Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) XxxXxxxxx, X. X., Xxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X. (1990), Xxx xx vivo Erythrocyte Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Xxxxxx State Xxxxxxxxx Assay Xxxxxxxxxx xxx Xxxxxxx Integration xxxx Xxxxxxxx Studies, Xxxxxx. Xxxx. Xxxxxxx. 14, 513-522.

8) Hayashi, X., Morita, X., Xxxxxx, X., Sofumi, X., Xxxxxxxx, M. Xx. (1990), Xxx Xxxxxxxxxxxx Xxxxx with Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxxx Xxxxx Xxxxxxxx Xxxxxx-Xxxxxx Xxxxxx, Mutatation Xxx., 245, 245-249.

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

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx for xxx Xxxxxxxxxxxx Xxxx (CSGMT/JEMMS, XXX: Xxx Mammalian Xxxxxxxxxxx Study Xxxxx xx the Environmental Xxxxxxx Xxxxxxx xx Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx for the xxxxx-xxxx xxxxx peripheral xxxxx xxxxxxxxxxxx test, Xxxxxxxxxxx, 10, 53-159.

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

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

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

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

15) XxxXxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, R. X. (1983), A Xxxxxx Xxxxxxxxxxx Xxxxxxxx Xxxxxxxxx xxx Micronuclei and XXX in Xxxxxxxxxxxx Xxxxx Hoechst 33258 xxx Pyromin X, Xxxxxxxx Res., 120, 269-275.

16) Romagna, F., Xxxxxxxxxx, X. X. (1989), The xxxxxxxxx xxxx marrow micronucleus xxxx, Mutatation Xxx., 213, 91-104.

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

18) Richold, X., Ashby, X., Xxxxxxx, J., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, L. (1990), Xx xxxx Xxxxxxxxxxxx Xxxxx, in: X. J. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, UKEMS Recommended Xxxxxxxxxx, XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Melbourne, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Anderson, X., Xxxxxxxx, X., Xxxxxxxx, X. E., Xxxxx, G., Xxxxxxxx X., Xxxxxxx, X., Xxxxxxxx, D. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx of Xx xxxx Cytogenetic Assays, xx: D. J. Xxxxxxxx (xx.), Statistical Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data. UKEMS Xxx-Xxxxxxxxx xx Guidelines xxx Mutagenicity Testing. Xxxxxx, Xxxx XXX, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."

XXXXXXX 4X

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

1. XXXXXX

Xxxx metoda xx xxxxxxxx xxxxxx XXXX TG 471 — Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 ÚVOD

Při xxxxxxx na reverzní xxxxxx x xxxxxxxxxx xx používají xxxxxxxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Xxxxxxxxxxx xxxx, x detekci xxxxxxxx xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, adici x xxxxxx xxxxxxx xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Podstata xxxx xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxx x detekci xxxxxx, které revertují xxxxxx obsažené x xxxxxxxxxxx xxxxxxx x xxxxxxxx xxx xxxxxxx xxxxxxxxx bakterií xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Bakterie xx reverzi xxxx xxxxxxxxxx xxxx xxx xxxxxxxxxx xxxx x xxxxxxxxxxxxx xxxxxxxxxxxx, xxxxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx mutace x xxxxxxx xxxx xxxx xxxxxxxx mnoha xxxxxxxxx podmíněných xxxxxx x xxxxxxx x xxxxxxxx mnoho důkazů x xxx, xx xxxxxx xxxxxx v xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxx xx tvorbě xxxxxxxx u člověka x x pokusných xxxxxx. Zkouška xx xxxxxxxx mutace x xxxxxxxxxx xx xxxxxx, xxxxxxxxxx a relativně xxxxxx. Xxxxx xxxxxxxxxxx xxxxx má xxxx xxxxxxxxxx, díky xxxx xxxx xxxxxxxxxx na xxxxxxx xxxxxx, včetně xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx buněk xxx xxxxx molekuly x xxxxxxxxx reparačních xxxxxxx XXX xxxx xxxxxxxx reparačních xxxxxxx XXX náchylných x xxxxxx. Xxxxxxxxxxxx xxxxxxxxxxx xxxxx xxxx poskytnout xxxxxxx xxxxxxxx xxxxxxxxx x xxxxxx mutací, xxx jsou xxxxxxxxxx xxxxxxxxxxxxx činiteli. Xxx xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xx x dispozici xxxxx xxxxxxxx xxxxxxxx xxxxxxxx pro xxxxxxx xxxxx xxxxxxxx x xxxx xxxx xxxxxxxx xxxxx vyzkoušené xxxxxx xxxxxxxx chemických xxxxx, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx také xxxxxx xxxx, část X.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx xxxxxx x detekci xxxxxx x kmeni xxxxxxxxxxx xxxxxxxxxxxxx (xxxxxxxx resp. xxxxxxxxx), xxxxxxx xxxxxx xxxx xxxxxxxxx na xxxxxxx přísunu xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx x xxxxxx DNA. Při xxxxxxx reverzních xxxxxx xx xxxxx xxxx xxxxx xxxxxxxxxx xx xxxxx původní mutace xxxx xxxxx místě xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx mutageny xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx nebo xxxxxx xxxxxxx nebo xxxx párů bází XXX x xxxxxxxx xxx čtecí xxxxx XXX.

1.3 XXXXXXX XXXXX

Xxx xxxxxxxxx xx xxxxxxxx xxxxxx s bakteriemi xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, které xx xxxx xx xxxxx xxxxx faktory, jako xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx struktura a xxxxxxxxx procesy XXX. Xxxxxxx xxxxxxxxx in xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx zcela xxxxxxxxx xxxxxxxx xx xxxx x savců. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx využívána xxx počáteční xxxxxxxxx xxxxxxxxxxx aktivity, a xxxxxxx xxxxxxxx vyvolávající xxxxxx mutace. X xxxxxxxx xxxxxxxx xxxxxxx, xx mnoho xxxxxxxxxx xxxxx, xxxxx jsou x xxxx xxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx x x xxxxxx zkouškách. Xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx xxxxxx xxxxxxxxxx xxxxx zkouškou. Xxxxxxx xxxxxx xxxxxxxxxxx xxx xxxxxxxxx xx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx xxxx, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx xxxx x xxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx citlivost xxxxxxx xx reverzní xxxxxx xx bakteriích, xxxxx vést x xxxxxxxxxxxx xxxxxxxxx aktivity.

Zkouška xx reverzní mutace x xxxxxxxxxx xxxxxx xxx vhodná pro xxxxxx xxxxx chemických xxxxx, například xxxxxx xxxxxxxxxxxx xxxxxxxxxx (např. xxxxxx antibiotika) x xxx xxxxxxxx xxxxx, x nichž xx xxxxxxxxxxx (nebo x xxxxx xx xx), xx specificky zasahují xx xxxxxxxxxxxx xxxxxxx xxxxx savců (xxxx. xxxxxxx xxxxxxxxxx topoisomerasy x xxxxxxx analogy xxxxxxxxxx). X takových xxxxxxxxx mohou být xxxxxxxxx xxxxxxx mutagenity x savců.

Přestože mnoho xxxxxxxxx, xxx xxx xx tato xxxxxxx xxxxxxxxx, xx xxxxxxxxxxxx xxx xxxxx, xxxx xxxxxxxx absolutní. Závisí xx xxxxxxxx xxxxx x xxxxxxxx xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx touto xxxxxxxx, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, nebo xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx neexistují.

1.4 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxxx xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, x to xx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx x xxx něho. Xx xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx x xxxxxxx xxxxxx x xxxxx xx xxxxxxx na xxxxxxxxx xxxx. X preinkubační xxxxxx xx zkoušená xxxx xxxxxxxx a xxxx se xxxx xxxxxxxxx na minimální xxxx xxxxxx x xxxxxxx xxxxxx. Xxx xxxx technikách xx xx xxxx xxxx xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx x provede se xxxxxxxx x xxxxxx xxxxxxx spontánních xxxxxxxxxx xx kontrolní xxxxx x rozpouštědlem.

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

Xxx xxxxxxx xxxxxxx xx xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Xxxxx x nich xx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx jak x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxx xx použití xxxxxxxxxxxx xxxxxx. Tyto xxxxx xxxxx xx xxxxxxxxxx tříd, xx xxxxx xxxxx xxxx xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx kovy, xxxxxxxx, azobarviva x xxxxxxxxxx xxxxxxxxxx, pyrrolizidinové xxxxxxxxx, xxxxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx se xxxxxxxxx, xx xxxxxx xxxxx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx xx standardní xxxxxxx xxxx nebo xxxxxxxxxxxx metoda. Měly xx xxx xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x x jejich xxxxxxx xx xxxxxxx xxxxxxxxxx použít xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "zvláštní xxxxxxx" (xxxxxxxx x xxxxxxxx postupů xxxxxx xxxxxxx): xxxxxxxxxx x xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxx xxx xxxxxxx xxxxxxxxxx.

1.5 XXXXX ZKUŠEBNÍ XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Bakterie

Čerstvé xxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxxxx do xxxxxx exponenciální xxxx xxxx do xxxxx xxxxxxxxxxx fáze xxxxx (xxxxxxxxx 109 xxxxx xx ml). Xxxxx x pozdní stacionární xxxx xx xxxxxx xxx použity. Xx xxxxxxxx, aby měly xxxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx xxxx být xxxxxxxx xxx xx xxxxxxx dosavadních xxxxxxxxxxx xxxxx x růstové xxxxxx, nebo xxx xxxxxx xxxxxxx stanovením xxxxx xxxxxxxxxxxxxxx xxxxx xx xxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxx je 37 °X.

Xxxx xx xxx xxxxxxx alespoň xxx xxxxx bakterií. Xxxx xxxx xx xxxx xxx čtyři xxxxx X. xxxxxxxxxxx (XX1535; XX1537 xxxx XX97x xxxx XX97; XX98 x XX100), xxxxxxx xxxxxxx xx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx S. xxxxxxxxxxx xxxx xxx xxxx XX na xxxxxxxxx xxxxxxxxx místě x xx známo, že xxxxxx xxxxxxxxxxxxxxx nelze xxxxxxxxx určité xxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Xxxx xxxxx xxxxx xxx xxxxxxxxxx xxxxx X. xxxx WP2 xxxx X. xxxxxxxxxxx XX102 (19), xxxxx mají xx xxxxxxxxx reverzním xxxxx xxx xxxx XX. Xxxxxxxxxx kombinace xxxxx xx tedy xxxx:

- S. xxxxxxxxxxx XX1535 a

- X. xxxxxxxxxxx XX1537 xxxx XX97x x

- S. xxxxxxxxxxx XX98 a

- X. typhimurium XX100 x

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

Xxx xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx vláken DNA xxxx být xxxxxxxxx xxxxxxx TA102 xxxx xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx xxxxxxxx XXX, (xxxx. X. xxxx XX2 (pKM101)).

Měly by xxx xxxxxxx zavedené xxxxxxx přípravy xxxxxxx xxxxxxx, xxxxxxxxxx xxxxxxx x xxxxxxxxxx. Potřeba xxxxxxxxxxxxx xxx xxxx xx xxxx být xxxxxxxxx pro každou xxxxxxxxx kmenovou xxxxxxx (xxxxxxxx pro xxxxx X. xxxxxxxxxxx x xxxxxxxxx pro X. xxxx). Xxxxxxx xx xxxx být kontrolovány xxxx xxxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxxxx xxxxx potřeby xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx xxxxxxxxxx u xxxxx TA98, TA100 x TA97a xxxx XX97, XX2 xxxX x WP2 xxxX (xXX101) a xxxxxxxxxxxx x tetracyklinová xxxxxxxxxx x kmene TA102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. xxx xxxxxx x S. typhimurium xxxxxxxxxx xx xxxxxxxxxxx xxxxxx x xxxX xxxxxx x E. xxxx xxxx xxxX xxxxxx u X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxxx) (2, 3). Xxxxx xx xxxx rovněž xxxxx xxxxx kolonií xxxxxxxxxxx xxxxxxxxxx na misce x rozmezí xxxxxxxx xxxxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx a xxxxxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

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

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx xxxx být xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je xxxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx z xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx indukujícím xxxxxx, xxxx xx Xxxxxxx 1254 (1, 2) xxxx fenobarbitonu x β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx frakce xx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx x xxxxxxx 5 až 30 % xxx. xx směsi X9. Xxxxx a xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx záviset xx xxxxx zkoušené xxxxxxxx xxxxx. V některých xxxxxxxxx xxxx být xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce. X xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx může xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému (6, 13).

1.5.1.4 Zkoušená xxxxx nebo xxxxxxxxx

Xxxxx xxxxxxxx xxxxx by xxxx být xxxx xxxxxxxx xx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx aplikací xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě připravené xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx by xxxx xxx xxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx, a xxxx by xxx xxxxxxxxxx x xxxxxxxx xxxxxxxx a x xxxxxxxxx S9 (22). Xxxx-xx xxxxxxx xxxx xxx známá rozpouštědla/vehikula, xxxx by být xxxxxx xxxxxxxx podloženo xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx podmínky

1.5.2.1 Zkušební xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx koncentrace

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

Xxxx být užitečné xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx xxxx xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx nebo xxxxxxxx xxxxxx přežití xxxxxxxxxxxx kultur. Xxxxxxxxxxxx xxxxx xx xxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx aktivačních xxxxxxx. Xxxxxxxxxxxxx xx měla xxx xxxxxxxxx xx xxxxxxx viditelného srážení x xxxxxxx směsi xx skutečných xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxxx látky je 5 mg/misku xxxx 5 μx/xxxxx. U xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx by xxxx xxx xxxxx xxxx xxxx zkušebních xxxxxxxxxxx xxxxxxxx, xxx xxxxx xxxx x xxxxxxx xxxxx xxx aplikaci xxxxxxxxxxx. Zkoušené látky, xxxxx jsou xxxxxxxxxxx xxx při koncentracích xxxxxxx než 5 xx/xxxxx nebo 5 μx/xxxxx, xx xxxx xxx xxxxxxxx xx xx xxxxxxxxxxx koncentrace. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx koncentrací zkoušené xxxxx, přičemž při xxxxxx experimentu xx xxxx xxx intervaly xxxx zkušebními xxxx xxxxx xxxxxxxxx polovině xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx xxxx vhodné x xxxxxxx, xxx xx xxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx může xxx xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx potenciálně xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx x negativní (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx s xxxxxxxxxxxx xxxxxxxx x xxx xx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx vybrány koncentrace xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X xxxxxxx zkoušek x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xx xxxx být xxxxx (xxxxx) xxx pozitivní xxxxxxxx vybrána (xxxxxxx) xx základě typu xxxxxxxxx xxxxx xxxxxxxx.

Xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx x xxxxxxxxxxxx aktivací jsou xxxx xxxxx:

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

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

Xxxxx	Xxxxx XXX	Xxxxx podle XXXXXX
XX Xxxxxx Xxx 28	573–58–0	209–358–4

2-xxxxxxxxxxxxxx xx xxxxx xxx xxxxxx jako xxxxxx xxxxxxxxx účinnosti xxxxx S9. Při xxxxxxx 2-xxxxxxxxxxxxxxx xx xxxx xxx každá xxxxx X9 charakterizována xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxx, xxxxxxxxx xxxxx[x]xxxxx xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

Xxxxxxxxx kmenověspecifické xxxxxxxxx kontroly u xxxxxxx bez xxxxxx xxxxxxxxxxx aktivace xxxx xxxx xxxxx:

Xxxxx	Xxxxx CAS	Číslo xxxxx XXXXXX	Xxxx
xxxx xxxxx	26628–22–8	247–852–1	XX1535 x XX100
2-xxxxxxxxxxxx	607–57–8	210–138–5	XX98
9-xxxxxxxxxxxx	90–45–9	201–995–6	XX1537, 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 a TA102
1-methyl-3-nitro-1-nitrosoguanidin	70–25–7	200–730–1	WP2, XX2 xxxX a XX2 xxxX (pKM101)
4-nitrochinolin-1-oxid	56–57–5	200–281–1	WP2, XX2 xxxX a XX2 xxxX (xXX101)
α-[(5-xxxxx-2-xxxxx)xxxxxxxxxx]xxxxx-2-xxxxxxxx (XX2)	3688–53–7		xxxxx xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxxxx mohou xxx xxxxxxx xxxx xxxxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxxx kontrolu xx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx, jsou xx x xxxxxxxxx.

Xxxx xx xxx xxxxxxx negativní xxxxxxxx skládající xx xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx, bez xxxxxxxx látky, xxxxxxxxxx xxxxx stejným xxxxxxxx xxxx xxxxxxxxxx skupiny. Xxxxx toho xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.5.3 Xxxxxx

X xxxxxxxxxx xxxxxxx xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx aktivace xx xxxxxxx xxxxxx 0,05 xx xxxx 0,1 xx zkušebních xxxxxxx, 0,1 xx xxxxxxx xxxxxxxxxxx kultury (obsahující xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x 0,5 xx xxxxxxxxxx xxxxx x 2,0 xx xxxxxxxx xxxxx. V xxxxxxx zkoušky x xxxxxxxxxxxx aktivací se xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx aktivační xxxxx obsahující přiměřené xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x xxxxxxx 5 xx 30 % xxx. x metabolické xxxxxxxxx xxxxx) x xxxxxxx agarem (2,0 xx) x zároveň x bakteriemi a xxxxxxxxx látkou xxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxx xxxxxxxx se xxxxxxxx x přelije xxxx povrch xxxxxxxxxxx xxxxx xx xxxxx. Xxxx xxxxxxxx se xxxxx vrchní xxxx xxxxxxxx.

X xxxxxxxxxxxx metody (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx xxxxxxxx xxxxxx xxxx smícháním x xxxxxxx xxxxxx x xxxxxxxx přes xxxxxx xxxxxxxxxxx xxxxx xx xxxxx obvykle 20 xxxxx nebo xxxx xxxxxxxxxxx x xxxxxxxxxx kmenem (xxxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x sterilním xxxxxx nebo metabolickým xxxxxxxxxx systémem (0,5 xx) xxx 30 — 37 °X. Xxxxxxx se xxxxxx 0,05 xxxx 0,1 xx xxxxxxxx xxxxx xxxx zkušebního xxxxxxx, 0,1 xx bakterií x 0,5 xx xxxxx S9 xxxx xxxxxxxxxx xxxxx s 2,0 xx xxxxxxxx xxxxx. Xxxxxxxx by xxxx být xxxxx xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.

X dostatečnému xxxxxx xxxxxxxx xx xxxx xxx xxx xxxxx xxxxxx xxxxx použity 3 misky. Xxxxxxx xxxx xxxxx xx xxxxxxxxxx xx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxx.

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

1.5.4 Xxxxxxxx

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

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx na xxxxx. Xxx xx xxx xxxxxx xxxxxx xxxxx kolonií xxxxxxxxxx xxx xx xxxxxxx x xxxxxxxxx kontrolou (xxxxxxxx rozpouštědla x xxxxxxxx neexponovaná xxxxxxxx), xxx xx xxxxxxx x xxxxxxxxx xxxxxxxxx. Xxxxx xx jednotlivých xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx revertantů xx misku x xxxxxxxxxx odchylka xx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx látku x pozitivní a xxxxxxxxx xxxxxxxx (neexponovanou xxxxxxxx x/xxxx kontrolu xxxxxxxxxxxx).

Xxxxxxx jasně xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx výsledky by xxxx xxx vyjasněny xxxxxx zkoušením, xxxxxxx x úpravou experimentálních xxxxxxxx. Negativní xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. Xxxxxxxx se xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx nezbytné, xxxx xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx s xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx experimentech. X xxxxxxxxxx studie, xxxxx xx mohly xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, metoda xxxxxxxxxx (xxxxxxxxxx xxxxxxx metoda xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) a xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx xxx xxxxxxxxx xxxxxx x xxxxxxx xxxxxxx kmene x xxxxxxxxxxxx aktivačním xxxxxxxx nebo xxx xxxx, x to x xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx xxxxxx počtu xxx xxxxx xxxx xxxx xxxxxxxxxxx (23). Xxxxxxxx by xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx významnost xx xxxxxx xxx jediným xxxxxxxxx faktorem pro xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx zkoušené xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x genomu xxxxx Xxxxxxxxxx typhimurium x/xxxx Xxxxxxxxxxx coli xxxxxx xxxxxx xxxxxxxxxx bází xxxx xxxxxxx čtecího xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx není xx xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxx xxxxxxxxx.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Kmeny:

- xxxxxxx xxxxx,

- xxxxx xxxxx x kultuře,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx podmínky:

- xxxxxxxx zkoušené látky xx xxxxx (xx/xxxxx xxxx μx/xxxxx) x xxxxxxxxxxx xxxxxx dávky x xxxxx xxxxx xx xxxxxxxxxxx,

- použitá xxxxx,

- typ x xxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- počty xx xxxxxxxxxxxx xxxxxxx,

- střední xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Ames, X. X., McCann, X., Xxxxxxxx X. (1975), Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 31, 347-364.

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

3) Gatehouse, D., Xxxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxx, X., Xxxxxxxxxx, X., Melcion, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, E. (1994), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx of Xxxxxxxxx Mutation Xxxxxx, Xxxxxxxxxx Xxx., 312, 217-233.

4) Kier, X. X., Xxxxxxx D. X., Xxxxxxx, X. X., Von Xxxxx, X. S., Xxxxx, X. X., Simmon, X. X., Dunkel, X., XxXxxx, X., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, X. X., Xxx X. (1986), The Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Assay: X Report xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Agency Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, T., Degawa, X., Seino, X. X., Xxxxxxxxxx, T., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. (1975), Xxxxxxxxxxxx of Xxxxxxxxxx Azo Xxxx xxx xxxxx Xxxxxxxxxxx, Xxxxxx Lett. 1, 91-96.

6) Matsushima, X., Xxxxxxxx, T., Xxxxx, X., Xxxxxx, T., Xxxxxx, A., Sawamura, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxx, xx: Xxxxx-xxxx Xxxx Xxxxxxx xxx Xxxxxxxxx Carcinogens, xx. Xxxxxxx K. X., Xxxxxx, X. C., Xxxxxxxx, Berlin-Heidelberg-New Xxxx, 273-285.

7) Xxxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxx, X., Xxxxxxxxx, R. X., Xxxxxx, X. (1980), Xxxxxxxxx Mutation Xxxxxx, xx: Xxxxx Xxxxxxxxxxxx Xxxxx: UKEMS Xxxx 1 Revised, xx. X. J. Xxxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, 13-61.

8) Xxxxxxxxxx, X. X., Xxxxxx, U., Xxxxxxx, X. (1987), Xxxxxx Preincubation Xxxxxxxxxxxx Xxxx xxx Foods, X. Xxxx Xxxxxx., 8, 167-177.

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

10) Xxxxxxx, X. X., Xxxxx, X. H. X., Xxxxxxxxx, D., Bridges, X. X. (1984), Xxx Fluctuation Test xx Bacteria, in: Xxxxxxxx of Xxxxxxxxxxxx Xxxx Procedures, 2. xxx., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (xxx.), Xxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

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

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

13) Xxxxxx, X. X., Bell, X. X., Mitchell, X. X., Xxxxxxx, X. X., Vaughan, V. X. (1984), Mutagenicity xx Benzidine and Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Xxxx xx x Xxxxxxxx Xxxxxxxxxx Assay, Mutatation Xxx., 136, 33-47.

14) Xxxxxx, X., Xxxxxxxx, X. X., Haworth, X., Xxxxxx, T., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx xxxx xxx Testing of 311 Xxxxxxxxx, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

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

16) Hughes, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Xxxxxxxxx xx Xxxxxxx Mutagenic Xxxxxxxx xx Xxxxxxxx Xxxxxxx Xxxxxxxxx xx xxx Xxxx/Xxxxxxxxxx Assay, Environmental Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, X., Matsumoto, X., Xxxxxx, X., Xxxxxxxx, M., Xxxxxxxx, X. (1979), Mutagenicity xx xxx Xxxxxxxxx Xxxxxxxxx Carcinogen Xxxxxxx xxx Xxxxxxxxx Methylazoxy Xxxxxxx Xxxxxxxxxx in Xxxxxxxxxx xxxxxxxxxxx, Cancer Xxx., 39, 3780-3782.

18) Xxxxxx, X., Gold, X., Xxxxx-Xxxxx, A., Xxxx, X. N. (1980), Xxxxxxxx: X Xxxxx xxx Activation xx Dietary Xxxxxxxxxx xx Mutagens xx Xxxxxxxxxx Xxxxx, Xxxx. Xxxx. Xxxx. Xxx. X. X. A, 77, 4961-4965.

19) Xxxxxx, X., Xxxxxx, X., Xxxx, X. X., Xxxxxxxxx, X. X. (1990), Xxxxxxxxxx of Xxxxxxxxxx typhimurium TA 102 with Xxxxxxxxxxx xxxx XX2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Matsushima, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), A Safe Xxxxxxxxxx for Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Activation Xxxxxxx, xx: Xx vitro Xxxxxxxxx Activation xx Xxxxxxxxxxx Testing, eds. X. X. xx Xxxxxx et al. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.

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

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

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

24) Xxxxx, G. X. X., Xxxxx, X. X. X., Xxxxxxxxx, X., Mitchel, X., Xxxxxxxx, X. D., Xxxxxx, X. J. (1989), Xxxxxxxx of Xxxx from Microbial Xxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxx XX. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Test Xxxx, xx. Kirkland, X. X., Xxxxxxxxx University Xxxxx, 28-65."

XXXXXXX 4X

"X.17 MUTAGENITA — XXXXXXX XX XXXXXX MUTACE V XXXXXXX SAVCŮ XX XXXXX

1. METODA

Tato xxxxxx xx replikou metody XXXX XX 476 — Xxxxxxx xx xxxxxx mutace v xxxxxxx xxxxx xx xxxxx (1997).

1.1 ÚVOD

Zkoušku xx xxxxxx mutace x buňkách xxxxx xx vitro xxx xxxxxx xxx detekci xxxxxxxx xxxxxx indukovaných xxxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxxxxx xxxxx xxxxx buňky xxxxxxx X5178X myší, xxxxxxx xxxxx XXX, CHO-AS52 x X79 xxxxxx xxxxxxxx a xxxxxxxxxxxxxxx xxxxx XX6 člověka (1). U xxxxxx xxxxxxxxx linií xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx mutace genů xxx xxxxxxxxxxxxxx (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x xxxxxxxx xanthin-guaninfosforibosyltransferasy (XXXX). Xxxxxxx xx xxxxxx XX, XXXX x XXXX xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX a XXXX xxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxx xxxxxx), xxxxx xxxxx detekovat x XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx zkoušce xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxx xxxxxx xxxxxxx xxxxxxxxxx linií xxxxx xxxx xxxxxxx xxxxx. Xxxxx se xxxxxxxx xxxxx xxxxxxxxxx xxxxx v xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx metabolické xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační xxxxxx xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x pozitivním xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, jež xxxxxxxxxx xxxxxxx xxxxxxxxxx, může xxxxx xxxxxx xX, xxxxxxxxxx nebo vysokých xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx se xxxxxxx xx xxxxxxxx možných xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx sloučenin, xxx něž xx xxxx xxxxxxx xxxxxxxxx, xxxx xxxxxxxxxxx xxxxx; xxxx touto zkouškou x xxxxxxxxxxxxxx xxxx xxxx absolutní korelace. Xxxxxxxx xxxxxx na xxxxxxxx xxxxx x xxxxxxxxx xxxxxx o xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx zkouškou, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx mechanismy, xxxxx x xxxxxxxxxxxxx buňkách xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxx xxxxxx : xxxxxx mutace xxxxxxxxx typu xxxxxxxx xxxxx, která xxxxxxxxx xxxxx nebo ztrátu xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx : xxxxx, xxxxx xxxxxxxxx substituci xxxxxxx nebo xxxx xxxx xxxx v XXX.

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

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

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

Xxxxxxxxx xxxxxxx xxxx : xxxxxx xxxxx xxxxx x xxxx xx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx se xxxx součin poměru xxxxxxxxx růstu x xxxxxxxx a x xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx klonování xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxx růst x xxxxxxxx : xxxxxx xxxxx buněk v xxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx v xxxxxxxx xxxxxx TK+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (TK) xxxx xxxxxxxxxxx k xxxxxxxxxxxx xxxxxxx analogu pyrimidinu xxxxxxxxxxxxxxxxx (XXX). Xxxxx xxxxxxxxxxx thymidinkinasu jsou xxxxxxx xx TFT, xxx způsobuje xxxxxxxx xxxxxxxxx metabolismu x xxxxxxxxx další buněčné xxxxxx. Mutantní xxxxx xxxx xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxxxxx XXX, xxxxxxx xxxxxxxx xxxxx, xxxxx obsahují xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Podobně xxx x xxxxx s xxxxxxxxxxxx HPRT xxxx XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx x 6-xxxxxxxxxxx (XX) nebo 8-xxxxxxxxxx (XX). Xxxxxxxxxx xxxxxxxx látky by xxxx být xxxxxxx xxxxxxx, xxxxxxxx xx xx zkoušce xx xxxxxx xxxxxx x xxxxxxx xxxxx zkoušen xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx selekčnímu xxxxxxx. Mělo xx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx xx xxxxxxxxxx toxicitu zkoušené xxxxx pro xxxxxxxx xxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx jako xxxxxxxx xxxxxxx, xxxx xxxx xxx potvrzena xxxxxxxx xxxxxxx nebo xxxxxxx pro xxxxxxx (8).

Xxxxx x xxxxxxxxx xxxx jednovrstevné xxxxxxx xxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx látce xxx x xxxxxxxxxxxx xxxxxxxx, xxx bez xx, x xxxxxxxxxxxxxx xx účelem xxxxxxxxx xxxxxxxxxxxx x za xxxxxx exprese fenotypu xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx obvykle zjistí xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxxx xxxxxxxxxxx celkového xxxxx kultur po xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx x xxxxxxxx xxxxx po vhodnou xxxx xxxxxxxxxxxxxxxxx pro xxxxx zvolený xxxxx x xxx xxxxx, xxx xxxxxxx přibližně xxxxxxxxx fenotypová xxxxxxx xxxxxxxxxxxx mutací. Xxxxxxx xxxxxxx xx xxxxxxx xxx, xx se xxxxxx známý xxxxx xxxxx do média xxxxxxxxxxxx selekční xxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxx x xx xxxxx bez selekčního xxxxxxx, xxx byla xxxxxxxxx účinnost xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx xx xxxxxxxxx kolonie. Xxxxxxx xxxxxxx xx xxxxxxx x xxxxx xxxxxxxxxx xxxxxxx v xxxxxxxxx xxxxx x xxxxx xxxxxxx v xxxxx xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Pro použití x xxxx xxxxxxx xxxx k xxxxxxxxx xxxxx xxxx xxxxx, xxxxxx xxxxxxxx xxxxx X5171X, CHO, CHO-AS52, X79 xxxx XX6. Xxxx xxxxx x xxxx xxxxxxx by xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x stabilní xxxxxxxxx xxxxxxxxxxx xxxxxx. Buňky xx měly xxx xxxxxxxxxxxx, zda nejsou xxxxxxxxxxxxx mykoplasmaty, x x xxxxxxx xxxxxxxxxxx xx neměly xxx xxxxxxx.

Xxxxxxx xx xxxx xxx xxxxxxxx xxx, xxx xxxx předem xxxxxxxxxx xxxxxxxxx x xxxx. Počet použitých xxxxx, kultur a xxxxxxxxxxx zkoušené látky xx měl xxxx xxxxxxxxxx xxxxxxxxx odrážet (14). Xxxxxxxxx xxxxx xxxxx, xxxxx přežijí xxxxxxxx x xxxxx xxxxx použity x xxxxxx xxxxxx zkoušky, xx xxx být xxxxxxx xx xxxxxxxx xxxxxxxxxxx mutací. Xxxxxxx xxxxxxxxx je, xxx xxx použit počet xxxxx, xxxxx je xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx mutací. Xx xxxx xxxxxxxxxx, xxx xxxx použito xxxxxxx 106 xxxxx. Xxxx by xxx x xxxxxxxxx dostatečné xxxxxxxxx údaje x xxxxxxxx buněčném xxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx podmínky

Pro udržování xxxxxx by xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx média a xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX₂, xxxxxxx x xxxxxxx). Xxxxx xx měla xxx zvolena podle xxxxxxxxxx systémů a xxxx xxxxx použitých xxx zkoušce. Xx xxxxxxx xxxxxxxx, aby xxxxxxxxxx podmínky byly xxxxxxx tak, xxx xxxx xxxxxxxxx xxxxxxxxx xxxx xxxxx xxxxx xxxxxx exprese x xxxxxxxxx xxx xxxxxxxxxx, xxx nemutovaných buněk xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxx, xxxxxxxx xx kultivačního xxxxx x inkubovány xxx 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx xxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxx již přítomné xxxxxxxx buňky.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx aktivace x xxx něho. Nejčastěji xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx dotovaná xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx indukujícím xxxxxx, jako je Xxxxxxx 1254 (15, 16, 17 a 18), xxxx xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (19, 20).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx xxxxxxxxxx médiu xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % obj. Volba x xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx na xxxxx xxxxxxxx látky, xxxxx xx xxxxxxxx. V xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, xxxxxx xxxxxxxx geneticky xxxxxxxxxxxxxx xxxxxxxxx linií xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx enzymy, xxxxxxxxx možnosti pro xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx buněčných xxxxx xx xxxx být xxxxxxx zdůvodněna (např. xxxxxxxxxxx xxxxxxxxx cytochromu X450 pro metabolismus xxxxxxxx xxxxx).

1.4.1.5 Příprava xxxxxxxx látky

Pevné zkoušené xxxxx xx xxxx xxx před xxxxxxxx xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx být xxxxxxx přímo k xxxxxxxxxx systémům a/nebo xxxxx být před xxxxxxxx xxxxxxx. Měly xx xxx použity xxxxxxx připravené xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x stálosti xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx být xxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx být xxxxxxxxxx x přežitím xxxxx x s aktivitou X9. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx jejich xxxxxxxx xxxxxxxxx údaji o xxxxxx kompatibilitě. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx vodě by xxxx xxx xxxxxxx xxxxxxxxx rozpouštědla xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, xxxxx mají xxx zohledněna při xxxxxxxxx nejvyšší xxxxxxxxxxx, xxxxx cytotoxicita, xxxxxxxxxxx x testovacím xxxxxxx x změny xX xxxx osmolality.

Cytotoxicita by xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx x hlavním xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, xxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxx celkový růst. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx alespoň xxxxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxx xx xxxx tyto xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx xxxx xxxxxxx znamenat, xx xx xx xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. Xx-xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx, xxxx xx xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx nejméně 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx klonování) nebo xxxxxxxxx xxxxxxx xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx toho, xxxxx x nich xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxx xx k xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx podmínek, xxxx xx xx xxxx xxx. Měla by xxx xxxxxxxxx případná xxxxxxxxxxxxx x xxxxxxxx xxxxx, xx xxxxxxx xxxx xxxxx exponovány. Xxxx xxx výhodné xxxxxxxx rozpustnost xx xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx xx může x průběhu xxxxxxxx x xxxxxxxxxx xxxxxxx xxxxx v xxxxxxxx xxxxxxxxxxx xxxxx, X9 xxxx, atd. Nerozpustnost xxx zjistit xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při vyšetřování.

1.4.2.3 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx xxx x xxxxxxxxxxxx aktivací, xxx xxx ní. Při xxxxxxx metabolické xxxxxxxx xx měla xxx xxxxxxxxx xxxxxxxxx chemická xxxxx, která x xxxxxxxxx xxxxxxxx vyžaduje xxxxxxxx.

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxx xxxxx:

Xxxx xxxxxxxxxxx aktivace	Lokus	Látka	Číslo XXX	Xxxxx podle 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 x 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 vnější xxxxxxxxxxxx xxxxxxxx	XXXX	3-xxxxxxxxxxxxxxxxx	56–49–5	200–276–4
		X-xxxxxxxxxxxxxxxxxxx	62–75–9	200–549–8
		7,12-xxxxxxxxxxxxxxxxxxxxxx	57–97–6	200–359–5
	XX (malé x xxxxx kolonie)	cyklofosfamid	50–18–0	200–015–4
		cyklofosfamid 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 xxxxxxxxxx xxxxx xxx pozitivní xxxxxxxx, např. xx-xx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxx o 5-brom-2′-deoxyuridinu (XXX 59–14–3, XXXXXX 200–415–9), xxxx xxx xxxx xxxxxxxxxx xxxxx xxxxxx xxxxxxx. Pro xxxxxxxxx kontrolu by xxxx xxx xxxxx x úvahu xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxxxxxxx jinak stejným xxxxxxxx jako exponované xxxxxxx. Kromě xxxx xx měly být xxxxxxxxxxxx kontroly použity xxxx xxxxx, neexistují-li xxxxx kontrolní xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx nebo mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx zkoušené xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx bez xxxx. Xxxxxxxx xx xxxx xxxxx vhodnou xxxx (xxxxxxx xx xxxxxx xxxx 3 xx 6 hodin). Xxxxxxxxx xxxx xxxx být xxxxxxxxxxx na jeden xxxx více buněčných xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx exponovaná xxxxxxx. Xx-xx použita xxxxx kultura, měl xx být počet xxxxxxxxxxx xxxxxx xxx, xxx xxx xxxxxxxx xxxxxxxxxxxx xxxxx xxxxxx xxx analýzu (např. xxxxxxx xxx analyzovatelných xxxxxxxxxxx). Xxxx xx xxx použity xxxxxxxxxx xxxxxxxxx kontrolní kultury (xxxxxxxx xxxxxxxxxxxx).

Xxxxxx nebo xxxxxx xxxxx by xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Xxxxxxxxx přežití, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx konci xxxxxxxxx xxxx xx xxxxx xxxxxxx a xxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxx x xx xxxxxx umožnění xxxxxxx xxxxxxxx xxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (přežití) xxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx se xxxxxxx xxxxxxx xx expoziční xxxx.

Xxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (HPRT x XXXX xxxxxxxx alespoň 6 xx 8 xxx, TK xxxxxxx xxx xxx). Buňky xxxx xxxxxxxxxxx x xxxxx xx xxxxxxxxx xxxxxxxx (selekčními xxxxxxx) x xxx něho (xxx xxxx) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx a xxxxxxxxx xxxxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx četnosti xxxxxxx) xx započne na xxxxx xxxx exprese xxxxxxxxx xx misku xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx látka pozitivní xx xxxxxxx X5178X XX+/-, xxxx by xxx xxxxxxxxx alespoň xx jedné xx xxxxxxxxxx xxxxxx (x xxxxxxxx xxxxxxxxx koncentrací) x xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx podle xxxxxxxxx xxxxxxx. Xx-xx xxxxxxxx látka ve xxxxxxx X5178X XX+/- xxxxxxxxx, xxxx xx xxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx studiích xx xxxxxxx XX6 TK+/- xxxx xxx xxxx xxxxxxxxx rozdělení xxxxxxx xxxxx xxxxxxxxx kolonií.

2. XXXXX

2.1 ZPRACOVÁNÍ VÝSLEDKŮ

Údaje xx xxxx xxxxxxxxx xxxxxxxxx cytotoxicity a xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x xxxxxxxx mutantů xxx exponované a xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx odpovědi xx xxxxxxx X5178X XX+/- se xxxxxxx xxxxxxxxx xxxxxxx x xxxxx koncentrace xxxxxxxx xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x u xxxxxxxxx x pozitivní xxxxxxxx za použití xxxxxxxx malá xxxxxxx — velká xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx velké kolonie, xxx xxxxxxx tvořících xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Xx zkoušce XX+/- xxxx xxxxxxx xxxxxxxxxxx za xxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxx (velká) x xxxxxxx x xxxxxxx xxxxxx (malá) (25). U xxxxxxxxxx xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx genetické poškození, xx xxxxxxxxxxx xxxx xxxxxxxx, a tvoří xxxx xxxx xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx xx xxxxx xxxxxx genu xx xx karyotypické viditelné xxxxxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx tvořících malé xxxxxxx xx spojuje x chemickými xxxxxxx, xxxxx xxxxxxxx silné xxxxxxxxxxxx xxxxxxx (26). Xxxx závažně xxxxxxxxx xxxxx xxxxxxx rostou xxxxxxxx xxxxxx xxxx xxxxxxxx xxxxx x xxxxx velké xxxxxxx.

Xxxx xx xxx xxxxx xxxxxxx (relativní účinnost xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx růst. Četnost xxxxxxx by xxxx xxx xxxxxxxxx xxxx xxxxx xxxxxxx x xxxxx xxxxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxx xxxxx pro jednotlivé xxxxxxx. Dále by xxxx xxx všechny xxxxx xxxxxxx xx xxxxx tabulky.

Ověření xxxxx xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxx xxxxxxxx musí xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxx, kde xxxx xxxxxxxxx negativních xxxxxxxx považováno xx xxxxx, je xxxxx xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx rozšířit rozsah xxxxxxxxxxxx podmínek xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx xxx pro xxxxxxxxxx xxxxxxxx, xxx pro xxxxxxxxx xxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x podmínky xxxxxxxxxxx aktivace.

2.2 HODNOCENÍ X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx četností xxxxxxx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx jako pomocný xxxxxxxxxx xxxxxxxxxxx metody. Xxxxxxxxxxx významnost xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné nebo xxxxxx bez xxxxxx xx to, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x použitých xxxxxxxxxxxxx xxxxxxx xxxxx genové xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx xx xxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx v xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x zkoušce xxxx xxxxxxxxx tyto informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx volby xxxxxxxxxxxx/xxxxxxxx,

- xxxxxxxxxxx x stálost xxxxxxxx látky v xxxxxxxxxxxx/xxxxxxxx, xx-xx známa.

Buňky:

- xxx a zdroj xxxxx,

- počet xxxxxxxxx xxxxxx,

- xxxxxxxx počet xxxxxx,

- případně metody xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxx xxxxx, případně koncentrace XX₂,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x xxxxxxx zkoušené xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- případně xxxxxxx xxxxx xxxxx expozice,

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

- xxxxxxxxx x xxxxxxxxx kontroly,

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

- xxxxxxxx xxxxxxx,

- kritéria xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx a xxxxxxxxxx xxxxx,

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

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxx xxxxxxx,

- údaje x xX a xxxxxxxxxx xxxxx expozice xxxxxxxx látce, pokud xxxx stanoveny,

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

- xxxxxxxxx předpoklady xxxxxxxxxx xxxxxxxxx mutanty xxxxxxx xxxx xxxxxxx systémem X5178X XX+/-,

- xxxxx xxxxxxxx závislost xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

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

- četnost xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., DeMarini, X. M., XxXxxxxx, X. X., Xxxxxx, X. X. (xxx.) (1987), Xxxxxxx Report 28; Xxxxxxxxx Cell Xxxxxxxxxxx, Xxxx Xxxxxx Xxxxxx Xxxxxxxxxx, New Xxxx.

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

3) Liber, X. X., Thilly, X. X. (1982), Xxxxxxxx Xxxxx xx the Xxxxxxxxx Kinase Xxxxx xx Diploid Human Xxxxxxxxxxxx, Mutation Res. 94, 467-485.

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

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

6) Xxxxx, X. X., Xxxxxxxxxx, X., Glatt, X. X., Moore, X., Xxxxx, X., Xxxxxxxxxx, Xx. L. X., Xxxxxx, J., Xxxxxxxx, X. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Xxxxxx. Xxxxxx xx the Xxxxxxxxxxxxx Xxxxxxxx on Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, S. X., Marshall, R. X., Ishidate, X., Xxxxxxx, X., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx ICPEMC Xxxx Xxxxx 9, Mutation Xxx. 257, 147-204.

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

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

10) Li, X. X., Xxxxxx, X. X., Choy, W. X., Hsie, X. X., Xxxxx, X. X., Loveday, X. X., X'Νxxxx, J. X., Xxxxxx, J. X., Stankowski, X. X. Jr., Yang, X. X. (1987), X Xxxxx xxx xxx Performance of xxx Chinese Hamster Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxx Mutation Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

11) Liber, X. L., Xxxxxxx, X. X., Xxxxxx, X. X. (1989), X Comparison of Xxxxxxxx Induction xx xxx TK xxx XXXX Xxxx in Xxxxx Lymphoblastoid Xxxxx: Xxxxxxxxxxxx Differences are Xxx to xx Xxxxxxxxxx Xxxxx of Xxxxxxxxx xx xxx Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Res., 216, 9-17.

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

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

14) Xxxxxx, X. X., Xxxxx, X. X., Xxxxxx, G. X., Xxxxx, X. H. X., Xxxx, J., XxXxxxxx, X. X., Xxxxxxx X. C. (1989), Xxxxxxxxx Xxxx Xxxx Mutation Assays Xxxxx upon Colony Xxxxxxxxx, xx: Statistical Xxxxxxxxxx xx Mutagenicity Xxxx Data, Kirkland, X. X., ed., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 66-101.

15) Xxxxxxxxxxxx, X., Xxxxxxx, X., Corti, X., Fiorio, R., Xxxxxxxx, X., Xxxxxxxxxx, X. (1977), Xxxxxxxxx xx 6-Xxxxxxxxxxx-Xxxxxxxxx Mutants xx V79 Xxxxxxx Xxxxxxx Xxxxx xx Xxxxx-Xxxxx Microsome-Activated Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Xxx. 46, 365-373.

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

17) Xxxxx, D., Xxxxxxx, X. X., Spector, X. X. X., Xxxxxx X. X., Xxxxx M. X. X. (1979), Xxxxxxxxxx xxx Xxxxxxxxxxxxxxxx of xxx L5178Y/TK+/--Mouse Lymphoma Xxxxxxx Assay Xxxxxx, Xxxxx. Xxx. 59, 61-108.

18) Xxxxx, X. X., Xxxx, B. X. (1983), Revised Xxxxxxx xxx the Xxxxxxxxxx Mutagenicity Test, Xxxxxxxxxx Xxx. 113, 173-215.

19) Elliott, X. X., Xxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, J. X., Xxxx, X. X. (1992), Alternatives xx Xxxxxxx 1254-Xxxxxxx X9 in: In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X Xxxx Substitute xxx Polycholrinated Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, X: Xx xxxxx Metabolic Xxxxxxxxxx xx Mutagenesis Xxxxxxx, de Xxxxxx, X. X., Fouts, X. X., Xxxx, X. X., Xxxxxxx, X. M. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, K. T. (1982), XXX/XXXXX Mutation Xxxxx: Xxxxxxxxxx of Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Xxxxx, X. L., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Agents, Xxx Xxxx, Plenum, 91-103.

22) Xxxxxx, P. X., Xxxxxx, X. X., Xx, X. X., Xxxxxx, X. X. (1983), Evaluation xx xx Xxxxxxxx System Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Xxxxxxxx Xxxxx, Xxxxxxx. Mutagenesis, 5, 795-801.

23) Applegate, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, X., Hozier, X. X. (1990), Molecular Xxxxxxxxxx of Xxxxxxxxx xx xxx Heterozygous Xxxxxxxxx Xxxxxx Xxxxx xx Xxxxx Xxxxxxxx Xxxxx, Proc. Natl. Xxxx. Xxx. U. X. X, 87, 51-55.

24) Xxxxx, X. X., Clive, D., Xxxxxx, J. X., Xxxxxx, X. E., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, J. (1985), Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (XXX+) Mutants xx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx. 151, 161-174.

25) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxx Xxxxxxxx xx Xxxxxxxxx Xxxxxxxxx xx x Heterozygous Xxxxxxxxx Locus in Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.

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

XXXXXXX 4X

"X.23 XXXXXXX XX CHROMOZOMOVÉ ABERACE XX XXXXXXXXXXXXXXX XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx ve xxxxxxxxxxxxxxx xxxxx in xxxx xx xxxxxxxxxxxxx takové xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx chromozomové aberace xx spermatogoniích xxxxx (1, 2, 3, 4, 5). Rozlišují xx dva typy xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx typu, avšak xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx změny xx xxxxxxxxxxxxxxx a předpokládá xx tedy, xx xxxx xxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx x xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Xxxxx cytogenetickou xxxxxxxx xx xxxx xx detekují chromozomové xxxxxxx xxx mitose xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx chromatidového typu xx xxxxxxxxxxxxxxx by xxxx xxx — xxxxx xxx xxxxx xx xxxxxx xxxx — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx xx xxxxxxxx. Další xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx buněk xxx xxxxxx meiotickou chromozomovou xxxxxxxx aberací xxxxxxxxxxxxxx xxxx x xxxxxxxxx-xxxxxxxx X, kdy se xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx aktivní xxxx x xxxxxxxxxxxx buňkách. Xxxxx xx tato xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx xxx posouzení xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx a procesy xxxxxxxx DNA.

Ve xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxxxx xx xxxxxxxx chemické xxxxx. Xxxxxxxxxx aberace xxxx xxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx populace xxxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. V závislosti xx své xxxxxx xx xxxxxxxxx, xxxxx xxxx nemusí xxx xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx celkovému xxxxxxxx xxxxx x důsledku xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx xxxxx x xxxxxxx xxxx xxxxxxx xxxxxx a xxxxxxx.

Xxxxxxxx xxxxxxxx xxxxx x tom, že xx xxxxxxxx xxxxx xxxx xxxxxxxxx metabolity xxxxxxxxxx xx cílové xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx obecný úvod, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu x xxxxxx xxxxx jednotlivých xxxxxxxxx nebo xxxxx x xxxxxxxx spojení xxxxxxxxx.

Xxxxxxxxxxxx aberace : xxxxxxxxxx poškození xxxxxxxxxx x podobě zlomu xxxx zlomu x xxxxxxx xxxx chromatid x xxxxxx xxxxx.

Xxx : achromatická xxxx xxxxx xxx xxxxx xxxxx xxxxxxxxxx x x xxxxxxxxx odchylkou xxxxxxxxx.

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

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

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

1.3 XXXXXXXX XXXXXXXX METODY

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

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx x xxxx; lze xxxx xxxxxx xxxxx xxxxxxxxxx xxxxxx vhodného xxxxx xxxxx. Měly xx xxx xxxxxxx xxxxx xxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx xx xxxx být xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx x xxxxxx xx překročit ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladí xxxxxxxx xxxxxxx xxxxx xx xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx xxxxxxx x skupinu, xxxxx xx xxxxxxxx. Xxxxx xx měly být xxxxxxxxxx xxx, xxx xxx vliv xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx xxxxxxxxx xxxxxx xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xxxxxxxx rozpuštěny xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx podávány xxxxx nebo xxxxx xxx xxxx podáním xxxxxxx. Xxxx by xxx xxxxxxx čerstvě xxxxxxxxxx zkoušené chemické xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx by být xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx použita xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo by xxx jejich zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx experimentu xx xxxx být souběžné xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by xxxx xxxxxxx kontrolní skupiny xxxxxxxxxx identický xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx měly xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx in xxxx při xxxxxxxxxxx xxxxxxxx, u xxxxx xx předpokládá, xx xxxxxxxxx detekovatelný xxxxxx xxx pozadí.

Dávky pozitivní xxxxxxxx by měly xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx xxx xxxxx x xxxxx případě xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx kontrolu xxxx xxx xxxxx xxxxx v xxxxx xxxxxxx chemických xxxxx xx stejné xxxxxxxx xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx látek xxx xxxxxxxxx kontrolu:

Látka	Číslo XXX	Xxxxx xxxxx Einecs
cyklofosfamid	50–18–0	200–015–4
cyklofosfamid xxxxxxxxxx	6055–19–2	200–015–4
xxxxxxxxxxxxxx	108–91–8	203–629–0
xxxxxxxxx X	50–07–7	200–008–6
xxxxxxxxx (monomer)	79–06–1	201–173–7
2,4,6-tris(aziridin-1-yl)-1,3,5-triazin	51–18–3	200–083–5

V xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx odběr x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x která xxxxx podstupuje stejný xxxxxx jako xxxxxxxxxx xxxxxxx, xxxxx nejsou x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 XXXXXX

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxx xxx xxxxxxxxxxxxxxxx samců.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx měly xxx xxxxx xxxxx podávány xxxxxxxxxxx xxxx xxxxxxxxx (xx. xxx xxxxx xxxxxxxx xxxx xxxx xxxxxxxxxx). Zkoušené látky xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, tzn. xxx xxxxx x xxx xxx x rozmezí xx více xxx xxxxxxxx hodin, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxxxxxx xx měly xxx xxxxxxx zdůvodněny.

Ve xxxxxxx x xxxxxxxx dávkou xx xxxx xxx xx xxxxxxxx xxxxxxxxx xxx xxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxx cyklu xxxx xxx xxxxxxxxx xxxxxx ovlivněna, provede xx jeden xxxxx xxxxx x xxxxx xxxxxxxx xxxxx přibližně 24 x 48 xxxxx po xxxxxxxx. X xxxxxxx xxxx xxx xxxxxxxx dávky xx měl xxx xxxxx xxxxxxxx xx 24 xxxxx xxxx xx xxxxxx xxxx xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx délky xxxxxxxxx xxxxx, xxxxx xxxx xxxxx xxxx xxxxxxxxx xxxx xxx detekci xxxxxx (6).

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

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxx xxx xxxxxx xxxxxx xx xxxxxxx. X xxxxxxx xxxxx x opakovanou xxxxxxxx xx xxxx xxx xxxxxxx usmrcena 24 xxxxx (1,5násobek xxxxx xxxxx) xx xxxxxxxx xxxxxxxx. Xxxxx xxxxxxx xxxxx být prováděny xxxxx odběry x xxxx xxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx vhodná xxxxx xxxxx zastavující xxxxxxxx (xxxx. Colcemid® xxxx xxxxxxxxx). Poté xx xx xxxxxx xxxx xxxxxxx u xxxxxx xxxxx. U myši xx tato doba xxxxxxxxx 3 — 5 hodin; x xxxxxx čínského je xxxx xxxx přibližně 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx, xxxx xx xxx xxxxxxxxx ve stejné xxxxxxxxxx, xx xxxxxxx xxxxxx a xxxxxx x xx stejného xxxxxx expozice, který xx xxxxxxx v xxxxxx xxxxxx (7). X případě xxxxxxxx xx xxx xxxxx xxxxx použijí tři xxxxxx xxxxx. Tyto xxxxxx xxxxx by xxxx xxxxxxxx rozmezí xxxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx by xxxxx xxxxx xxxxx xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx aktivitou xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx od případu. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xx spermatogoniích xxxxxxx xxxxxx toxicity (xxxx. xxxxxxx xxxxx xxxxxxxxxxxxx x mitose xxxxxxxx x xxxxx x xxxxx xxxxxxxxx metafázi; xxxx xxxxxxx by xxxxxx překročit 50 %).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x jednou xxxxxx xxxxxxx 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx dvou dávkách x xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx se xxxxx xxxxxx se třemi xxxxxxxx xxxxx za xxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx podává xxxxxxxxxxxxxx, xxxxxxxxx sondou xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx testovacího xxxxxxx. Xxxxx by neměl xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx je xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx x žíravé xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx zesílené účinky, xx xxxx xxx xxxxxxxxxxx zkoušeného xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxx

Xxxxx xx usmrcení xx x xxxxxxx nebo xxxx xxxxxx xxxxx xxxxxxx suspenze, hypotonizuje xx x fixuje. Xxxx xx xxxxxx xx podložní xxxxxxx x obarví xx.

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx mělo xxx xxxxxxxxxxx xxxxxxx 100 xxxxx v dobře xxxxxxxxxxxx metafázi (tj. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Xxxxx xxxxx xxx xxxxxx, xx-xx pozorován xxxxx xxxxx xxxxxxx. Všechny xxxxxxxxx včetně xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx ke xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx xxxxxxxxxx u xxxxx xxxxxxxx, měly xx vyšetřované xxxxx xxxxxxxxx centromery x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx xxxxx zvíře xx měl xxx xxxxxxxxxx xxxxx buněk xx strukturními chromozomovými xxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx xxxxxxxxxx x kontrolní xxxxxxx xx xxxx xxx xxxxxxx různé xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich xxxxxx x xxxxxxxx. Xxxx xx zaznamenávají xxxxxxxx x uvádějí xx, xxx xxxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, xxx by xxx pro stanovení xxxxxxx xxxxxxxxxxxxx účinků xxxx xxxx xxxxxxxxxxxx xxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxx poměr xxxxxxxxxxxxx v mitose xxxxxxxx x první x druhé xxxxxxxxx xxxxxxxx, x xx x xxxxxxxx vzorku 100 xxxxxxxx se xxxxx xx xxxxx xxxxx. Xxxxx je xxxxxxxxx pouze xxxxxx, xxxxxxx x 1000 xxxxxxx xx zvíře xx xxx xxx xxxxxxxx mitotický xxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, např. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx buněk x xxxxxxxxx pro xxxxxxx x určitou dávkou x x určitému xxxxxxxx xxxxxx. Xxxxxxxx xx měla xxx xxxxxxx biologická relevance xxxxxxxx. Xxx hodnocení xxxxxxxx zkoušky xxxxx xxx použity jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x aktivitě zkoušené xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xxxxx xx xxxx xxxxxxxxx, že xxxxxxxx xxxxx indukuje x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx strukturní xxxxxxxxxxxx aberace. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx chromozomové xxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx druh/kmen,

- xxxxx x stáří xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

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

Xxxxxxxx podmínky:

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- údaje o xxxxxxxx zkoušené xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxx usmrcení,

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

- podrobné xxxxx x kvalitě xxxxxx x xxxx,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x odběru,

- xxxxxx xxxxxxxxx toxicity,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx buněk na xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxxxxx xxxxx,

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

- xxx a xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx xx xxxxxxx,

- xxxxx xxxxx x xxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx statistické xxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx kontrole,

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

- xxxxx x xxxxxxxx pozitivní xxxxxxxx,

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Spermatogonia xx Xxxxxxxx Mutagens Xxxxxxx xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, in: Genetic Xxxxxxxxxx of Environmental Xxxxxxxxx, Xxxx X: Xxxxxxx Effects and Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Xxxxxxx, X., Xxxxxxxxx, J. (eds) Xxxx, Xxx York, 477-484.

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

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

4) Xxxxxxx, X., Ashby, X., Xxxxxxxx, A., Xxxxxxxxx, X. G., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. J. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Tests, XXXXX Xxxxxxxxxxx Procedures. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Mutagenicity Testing. Xxxxxx. Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Chester, Xxxxxxxxx, Xxxxxx, 115-141.

5) Xxxxxxxx, X., Xxxxxxx, X. (1978), X Xxx Xxxxxx xxx Xxxxxxxxxxx of Xxxxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 52, 207-209.

6) Xxxxx, X. X., Xxxxxx X. D., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, W., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx X. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Standardisation xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxx Xxxxxx xx xxx Xxxxxxx Group xx Xxxxxxxxx Xxxx Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. A., Xxxxxx, X. X., Xxxxxx, P. X., Xxx, J., Xxxxxxx, X. X., Gatehouse, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, D. X., Xxxxxxxx, X. X., Richold, M. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx In xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, D. X., Xxxxxxxx, D., Albanese, X., Xxxxxxxx, G. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Savage J. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Subcommittee xx Xxxxxxxxxx for Mutagenicity Xxxxxxx, Xxxxxx, Part XXX. Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."

PŘÍLOHA 4X

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

1. METODA

Tato xxxxxx xx replikou xxxxxx OECD XX 486 — Xxxxxxx xx neplánovanou syntézu XXX (XXX) x xxxxxxxxx xxxxxxx savců xx xxxx (1997).

1.1 XXXX

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

Tato xxxxxxx in xxxx xxxxxxxxx xxxxxx vyšetření xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx v játrech. Xxxxxxxxxxx xxx je xxxxxxxxxx xxxxxxxxx XXX x xxxxxxxx xxxxxxxx x jaterních xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx místem, xxx xxxx xxxxxxxxxxx sloučeniny xxxxxxxxxxxxxx. Xxxx tedy xxxxxxx xxxxxx xxx xxxxxxxxx xxxx poškození XXX in xxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, že xx xxxxxxxx xxxxx nedostane xx cílové xxxxx, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx DNA (UDS) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx značených xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx zkoušky xx XXX xx xxxx xx xxxxxxxxxx používají xxxxx xxxxxxx. Jiné xxxxx než xxxxx xxxxx být xxxxxx xxxxxxx, xxxxxx však xxxxxxxxx této metody.

Detekce xxxxxxxx XXX xxxxxx xx počtu xxxx XXX vyštěpených x xxxxxxxxxxx x xxxxx xxxxxxxxx. Zkouška xx XXX xx xxxx xxxxxx zvláště xxx xxxxxxx dlouhých xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 xxxx) xxxxxxxxxxxx xxxxxx. Krátké xxxxxx ("xxxxx-xxxxx xxxxxx") (xxxxx xx xxx xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxx. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx chybné xxxxxxxxx xxxx XXX xxxxx x mutagenním xxxxxxxxx. Xxxxxx xxxxxxxx XXX neposkytuje xxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, xx xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX není xxxxxxxx xxxxxxxxxxx reparací. Nedostatek xxxxxxxxxxxx xxxxxxxxx, které xxxx zkouška xxxxxxxxx x xxxxxxxxx aktivitě, xx xxxxxxx potenciální xxxxxxxxxx xxxxxx xxxx, xxxxx xx xxxxxxxxxx x celém genomu.

Viz xxxx obecný úvod, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : xxxxx xxxxx zrn odpovídajících xxxxxxxx xxxxxx (XXX), xxxxx než xxxxxxxxxx xxxxxxx xxxxxxxxx laboratoří xxxxxxxxxxx xxxxxxx.

Xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx míra XXX xxxxxxxx xxxxx x xxxxxxxxxxxxxxxxx xxxxxxx na XXX, vypočtená odečtením xxxxxxxxxx počtu xxx x cytoplasmatických xxxxxxxxx (XX) odpovídajících xxxxxx xx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): NNG = XX — CG. Xxxxxxx XXX se xxxxxxx pro xxxxxxxxxx xxxxx, xxxx xxxxxxxx xxx buňky v xxxxxxx, x xxxxxxxxxxx xxxxxxxxx atd.

Neplánovaná xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx vyštěpení a xxxxxxxxxx úseku DNA xxxxxxxxxxxx xxxxxx x xxxxxxxxxx indukovaným chemickými xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx na XXX x jaterních xxxxxxx xxxxx xx xxxx xxxxxxxx syntézu xxxxxxxx XXX po xxxxxxxxx x odstranění xxxxx XXX xxxxxxxxxxxx xxxxxx x poškozením xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx xxxxxxxx xx inkorporaci 3H-TdR xx DNA xxxxxxxxx xxxxx, xxx xx xxxx xxxxxxx xxxxx x S-fázi xxxxxxxxx xxxxx. Xxxxxxxxxxx 3X-XxX xx obvykle xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx tato xxxxxxxx není xxx xxxxxxx xx vliv X-xxxx xxxxx jako xxxx. kapalná xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 XXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxx savce. Xxxx xx xxx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxx mladých xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx xx xxxx xxx odchylka v xxxxxxxxx xxxxxx xxxxxxxxx x neměla xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx xxx xxx xxxxxxx.

1.4.1.2 Podmínky xxxxx x strava

Platí xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x části X, přičemž by xxxx být xxxxxxxx xxxxxxxx vzduchu 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x skupinu, která xx exponuje. Klece xx xxxx být xxxxxxxxxx tak, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx xx xxxxxxx x laboratorních xxxxxxxxxx xxxxxxx pět dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx zkoušené xxxxx

Xxxxx xxxxxxxx xxxxx xx měly být xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx podávány xxxxx xxxx xxxxx být xxxx podáním zředěny. Xxxx xx být xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx dávek xxxxxxx xxxxxx x xxxx xx být xxxxxxxxx xxxxxxxxx, xx reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o jejich xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxxxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxx části xxxxxxxxxxx xx měly xxx xxxxxxxx xxxxxxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx. X výjimkou xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxx xx skupinách, x xxxxx xxxxx x expozici.

Pozitivními kontrolami xx xxxx xxx xxxxx, x xxxxx xx xxxxx, xx xxxxxx xxxxxxxx x xxxxxxxxxxx expozičních koncentracích xxxx k nárůstu XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Pozitivní kontroly xxxxxxxxxx metabolickou xxxxxxxx xx měly xxx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Dávky xxxxx xxx xxxxxxx tak, xxx byl účinek xxxxxxxx, xxx xxx xxx odečtu nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx	Xxxxx	Xxxxx XXX	Xxxxx xxxxx Einecs
Časné doby xxxxxx (2 až 4 h)	N-nitrosodimethylamin	62–75–9	200–249–8
Pozdní xxxx 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 xxxxxxxx. Xx xxxxxxxxx, xxx byla xxxxxxxxx kontrolní látka xxxxxxxx jiným xxxxxxxx, xxx zkoušená xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Měl xx xxx xxxxxx xxxxxxxxxx xxxxx xxxxxx, aby xxxx zohledněno xxxxxxxxx xxxxxxxxxx xxxxxxxx odpovědi xx xxxxxxx. Xxxxx xxxxxxx xx xx xxxx xxxxxxx xxxxxxx xx tří analyzovatelných xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx dostatečné xxxxxxxxx xxxxx, je xxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxx nezbytné xxxxx jedno až xxx xxxxxxx.

Xxxxxxxx xxxx x xxxx studie x dispozici xxxxx xx xxxxxx xx xxxxxxx druhem a xx použití xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx pohlavími rozdíl x toxicitě, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, nejlépe samců. Xx-xx xxxxxxxx člověka xxxxxxxxxx pro xxxxxx xxxxxxx, xxxx je xxxx například u xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx xx být xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xxxx xxxxxxxxx podávány xxxxxxxxxxx.

1.5.3 Dávkování

Za xxxxxxxxxx xxxxxxxx xx používají xxxxxxx xxx xxxxxx xxxxx. Nejvyšší dávka xx definována xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že xxxxx xxxxx xx xxxxx xxxxx očekávání xxx xxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx xx xxxx xxx zpravidla 50 % xx 25 % xxxxx xxxxx.

Xxxxx se specifickou xxxxxxxxxxx aktivitou xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. hormony a xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx případ xx xxxxxxx. Provádí-li xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx zjištění xxxxxxx, xxxx xx xxx xxxxxxxxx ve xxxxxx laboratoři, se xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx expozice, xxx se xxxxxxx x xxxxxx studii.

Nejvyšší xxxxx xxxx xxx xxxxxxxxxx také xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxxxx x xxxxxxx (xxxx. xxxxxxxxxx xxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže zkouška x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx dvou dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx být úplná xxxxxx xxxxxxxx. Očekávaná xxxxxxxx xxxxxxx může xxxxxxxx potřebu xxxxxx x limitní zkoušce xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx podává xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou možné, xxx-xx je xxxxxxxxx. Xxxxxxxx xxxxxxxxxxxxxxxxx xx xxxx nedoporučuje, xxxxx xx xxxxx xxxxx xxx xxxxxxxxxx zkoušené xxxxx xxxxx x xxxxxx prostřednictvím xxxxxxxxx xxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx xx xxxxxxx xxxxx, musí xxx xxxxxxxxxx. Až xx xxxxxxxx a žíravé xxxxx, které xxxxxxx xxx vyšších koncentracích xxxxxxxx zesílené xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx všech úrovních xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxxxx

Xxxxxxx buňky xx xxxxxxxxxx x xxxxxxxxxxxx xxxxxx zpravidla 12 xx 16 hodin xx xxxxxx xxxxx. Xxxxxxxxxx dřívější odebrání xxxxxx (obecně dvě xx čtyři xxxxxx xx expozici) je xxxxxxxx, xxxx-xx xx 12 až 16 xxxxxxxx jasná xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx xxxxxxx xxxx xxxx odběru, jsou-li xxxxxxxxxx na základě xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx xxxxxxx xxxxxxxxx buněk xxxxx xx xxxxxxxxx zakládají xxxxxxx xxxxx xxxxxxxxxxx xx xxxx x xxxxxx se, aby xx xxxxxxx disociované xxxxxxx xxxxx zachytily xx vhodném xxxxxxx. Xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxx životaschopnost (5) xxxxxxx 50 %.

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx jaterní buňky xxxxx xx obvykle xxxxxxx xxxx, xxxx. xxx xx osm xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3X-XxX. Xx konci xxxxxxxxx xxxx by xxxx xxx xxxxxx z xxxxx xxxxxxxxxx x xxxxx xxxx xxxxx xxx inkubovány x xxxxxx xxxxxxxxxxx přebytek xxxxxxxxxxx xxxxxxxxx, aby xxxx xxxxxxx neinkorporovaná xxxxxxxxxxxxx ("cold xxxxx"). Xxxxx xx poté xxxxxxx, xxxxxx x xxxxxx. Xxx xxxxx xxxxxxxxx xxxx nemusí xxx xxxxxxx radioaktivity xxxxxxxx. Xxxxxxxxx se xxxxxx do xxxxxxxxxxxxxxxxx xxxxxx, exponují xx x xxxxx (např. x chladu 7 xx 14 dnů), xxxxxxxx se, xxxxxx x xxxxxxxxx xx xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx xxxxxxx xx připraví xxx xx tři xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx xx xxxx xxxxxxxxx dostatečný xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx, xxx mělo xxxxxxxxx XXX xxxxxxxxx xxxxxxx. Xxxxxxxxx xx xxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxx zjevné cytotoxicity (xxxx. na pyknosu, xxxxxxxx úroveň xxxxxxx xxxxxxxxxxxxx xxxxxxxx).

Xxxx xxxxxxxxx xxx xx xxxx xxx xxxxxxxxx xxxxxxxx. Xxxxxxxxx se xxxxxxxxx 100 xxxxx na xxxxx xxxxx alespoň xx xxxx xxxxxxxxx; xxxxxxxxx méně než 100 xxxxx/xxxxx by xxxx xxx zdůvodněno. Xxx počítání zrn xx xxxxx x X-xxxx nevyšetřují, ale xxxxx buněk v X-xxxx xxxx být xxxxxxxxxx.

Xxxxxxxx 3X-XxX xxxxxxxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxx navrstvením xxx xxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxx.

Xxxxx xxxxx xx xxxxxxx x xxxxx xxx odpovídajících xxxxxxxx xxxxŭx (xx) x x xxŭxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx oblastech (xx) xxxxxxxxxxxxxx jádrŭm. xxxx xxxxxxx xx xx xxxxxxx xxx xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx xxŭxxxxx xxxxxxx xxxx xx tří xxxxxxx vybraných xxxxxxx x blízkosti xxxxxxxxx xxxxxxxxx xxxxx. xx xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx xxxxxxx x xxxx xxxxxxx stanovení xxxxx xxxxx (xxxx. xxxxxxxx celých buněk) (6).

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx by xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx a xxxxxxx. Xxxxx xx xxxx xxx xxxx xxxxxxx xx formě xxxxxxx. Xxxxxxxxx xxxxxxx XX od hodnoty XX by měl xxx xxxxxxxx xxx xxxxxx xxxxx, xxx xxxxx zvíře x xxx xxxxxx xxxxx x xxx čistý xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX). Xxxxxxxx xxxx počítány "xxxxxxxxxx" xxxxx, měla xx xxx kritéria xxx xxxxxxxxxx "opravovaných" xxxxx xxxxxxxxxx x xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx údajích x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx zhodnoceny statistickými xxxxxxxx. Mají-li xxx xxxxxxx, xxxx xx xxx xxxxxxxxxxx xxxxx xxxxxxx x xxxxxxxxxx xxxx provedením studie.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx příklady xxxxxxxx xxx pozitivní nebo xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx	x)	xxxxxxx XXX xxxx xxx xxxxxxxx xxxxxx, xxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxx;
xxxx	xx)	xxxxxxx NNG xx xxxxxxxx xxxxx xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx;
xxxxxxxxx	x)	xxxxxxx NNG xxxx xx xxxxxxxxx prahové xxxxxxx nebo xxx xx;
xxxx	xx)	xxxxxxx XXX xxxx xxxxxxxx vyšší než xxxxxxx xxx xxxxxxxxx xxxxxxxx.

Xxxx by xxx xxxxxxxxx biologická xxxxxxxxx xxxxx, tj. xxxx xx být vzaty x úvahu parametry, xxxx jsou variabilita xxxxxx, vztah dávky x xxxxxxxx a xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky mohou xxx použity jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxx xxxxxx xxx jediným určujícím xxxxxxxx pro pozitivní xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x aktivitě zkoušené xxxxx. Výsledky mohou xxxxxx xxxxxxxxxx nebo xxxxxx bez ohledu xx xx, kolikrát xx experiment opakován.

Pozitivní xxxxxxxx xxxxxxx xx XXX v xxxxxxxxx xxxxxxx savců in xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x jaterních buňkách xxxxx xx xxxx xxxxxxxxx DNA, xxxxx xxx opravit xxxxxxxxxxxx xxxxxxxx XXX xx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx podmínek xxxxxxx xxxxxxxxxx xxxxxxxxx XXX, které xxx xxxxxxxxx touto xxxxxxxx.

Xxxx xx xxx diskutována xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx. xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx zvířat xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, střední hodnoty x směrodatné xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (vehikulum/rozpouštědlo) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

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

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx látky v xxxxxx nebo vodě (xxx) na xxxxxxxxxxxx xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx údaje x xxxxxxx xxxxxx x xxxx,

- podrobný xxxxx rozvrhu xxxxxxxx x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- počet xxxxxxxxx x počet xxxxxxxxxxx buněk,

- xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxxx xxxxxxx počtu xxx xxxxxxxxxxxxxx buněčným xxxxxx a počtu xxx xxxxxxxxxxxxxx xxxxxxxxxx, x xxxxx počet xxx, jednotlivě xxx xxxxxxxxx, zvířata a xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- známky xxxxxxxx,

- xxxxx o souběžné xxxxxxxxx (rozpouštědlo/vehikulum) a xxxxxxxxx kontrole,

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

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

- xxxxx xxxxx x X-xxxx, xx-xx stanoven,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. Xxxxxxx, X. X., Xxxxxxxxx, X., Penman, M. X. (1985), Xx Xxxxxxxxxx of xxx Xx vivo Xxx. Xxxxxxxxxx DNA Xxxxxx Xxxxx, Xxxxxxxxxx Res., 156, 1-18.

2) Xxxxxxxxxxx, X. X., Ashby, X., Xxxxxxxx, X., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxx, G., Xxxxxxxx, X. (1987), X Protocol and Xxxxx for xxx Xx xxxx Xxx Xxxxxxxxxx XXX Xxxxxx Xxxxx, Mutatation Xxx., 189, 123-133.

3) Xxxxxxxx, X. X., Xxxxxx, X., Xxxxx, X., Xxxxxxx, X. A., Xxxxxxxxx, X., Benford, X. X., Dean, X. X., Mitchell, X. xx X. (1993), Xx xxxx Xxx Xxxxx XXX Xxxxx, xx: Xxxxxxxx X. J., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: UKEM Xxxxxxxxxxx Procedures. UKEMS Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx II xxxxxxx, Xxxxxxxxx University Xxxxx, Cambridge, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Sydney, 52-77.

4) Xxxxx, X., Dean, X. W., Xxxxxx, X., Xxxxxxxxx. G., Xxxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxx, X., Hertner, X., XxXxxxx, X. A., Xxxx, H. (1993), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx of UDS Xxxxx Xx xxxxx xxx Xx vivo, Xxxxx. Xxx., 312, 263-285.

5) Fautz, X., Xxxxxxx, B., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, X. (1993), Assessment of xxx Xxxxxxxx Between xxx Initial Xxxxxxxxx xxx xxx Xxxxxxxxxx xx Xxxxxxx Xxxxxxxx Xxx Hepatocytes Used xxx xxx Xx xxxx/Xx xxxxx DNA Xxxxxx Xxxxx (XXX), Xxxxxxxxxx Xxx., 291, 21-27.

6) Xxxxxxxx, J. X., Tyson, C. X., Xxxxxxxxxxx, B. X. (1982), Detection xx Xxxxxxxxx Xxxxxxxxxxx xx the In xxxx/Xx vitro Xxxxxxxxxx XXX Repair Xxxxx, Xxxxxxx.Xxxxxxx. 4, 553-562."

XXXXXXX 5

OBECNÉ XXXXXXXXX XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX LÁTEK X XXXXXXXXX

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

PŘÍLOHA 6

"

XXXXXXX XX

XXXX X

xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx proti xxxxxxxx xxxxx

Xxxxx ustanovení xx. 22 odst. 1 xxxx. x) xxxx směrnice, musí xxx xxxxx x xxxxxxxxx xxxxxx obsahující xxxxx, x xxxxx xx spojeno xxxxxx xxx xxxxxxxxxx (Xn; X 65) a xxxxx xxxx klasifikovány x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x výjimkou xxxxx xxxxxxxxx xx trh xx xxxxx aerosolů xxxx x xxxxxxxx xxxxxxxxxx xxxxxxxxxxx rozprašovačem, xxxxxxxx uzávěry odolnými xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx uzavíratelné obaly

Uzávěry xxxxxx proti xxxxxxxx xxxxx použité xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx XXX 8317 (xxxxxx ze dne 1. xxxxxxxx 1989) "Xxxxx xxxxxx xxxxx — Požadavky na xxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxx xxxxxxxx" přijatou Xxxxxxxxxxx xxxxxxxxxx pro xxxxxxxxxxx (XXX).

2. Xxxxxxxxx neuzavíratelné xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx použité xx xxxxxxxxx xxxxxxxxxxxxxxxx xxxxxxx musí splňovat xxxxxxxxx normy CEN XX 862 (vydání x března 1997) "Xxxxx — Xxxxx xxxxxx xxxxx — Xxxxxxxxx a zkušební xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxxxxxxxxx výrobků" xxxxxxxx Xxxxxxxxx výborem xxx xxxxxxxxxxx (CEN).

3. Xxxxxxxx

1. Xxxxxxxxx xxxxx x xxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxx laboratoře, xxxxx xxxxxxx evropské xxxxx xxxx XX 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx zřejmé, xx obal je xxxxxxxxxx xxxxxxxx xxx xxxx, xxxxx se xxxxxxx xxxxxx x xxxxxx xxx xxxxxx xxxxxxxx, xxxxxx být xxxxxxx provedena.

Ve všech xxxxxxxxx xxxxxxxxx x xxxxx existují xxxxxxxxx xxxxxx x xxxxxxxx x xxxxxxxxxxx uzávěru xxx dítě, xxxx xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx osoba xxxxxxxxx xx xxxxxxx výrobku xx xxx předložila xxxxxxxxxx xxxxxx laboratoří xxxxx xxxx. 3 xxxx 1 konstatující, xx xxx

- xxx xxxxxxx xx xxxxxx, xx xxx xxxx xxxxxxxx zkoušet xxxxx xxxx xxxxxxxxx xxxxx XXX x CEN,

nebo

- xx xxxxxx byl xxxxxxx x xxx xxxxxxx xxxxxxxxxxx xxxxx xxxx uvedených xxxxx.

XXXX X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx xxxxxxxxxxx xxx xxxxxxxxxx výstrahy xxxx být x xxxxxxx x normou XX XXX 11683 (xxxxxx x xxxx 1997) "Obaly — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Xxxxxxxxx".

"

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