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Xxxxxxxx Xxxxxx 2000/32/XX

xx xxx 19. května 2000,

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

(Text x xxxxxxxx pro XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Xxxxxxx o xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx xx xxxxxxxx Xxxx 67/548/XXX xx xxx 27. června 1967 x xxxxxxxxxx xxxxxxxx x správních xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení x xxxxxxxxxx nebezpečných látek [2], naposledy pozměněnou xxxxxxxx Evropského xxxxxxxxxx x Xxxx 1999/33/XX [3], x xxxxxxx xx xxxxxx 28 xxxxxxx směrnice,

vzhledem x xxxxx xxxxxxx:

(1) Příloha X xxxxxxxx 67/548/XXX xxxxxxxx seznam xxxxxxxxxxxx xxxxx xxxxxxxx s xxxxxxxxxx údaji o xxxxxxxxxxx a xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxx, xx xx měl xxx xxxxxx xxxxxxxxxxxx látek x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx jazykové xxxxx xxxxxxxx xxxxxxxx xxxxxx určitých xxxxxx xxxxxxxxx x tabulky X v xxxxxxx X.

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

(3) X xxxxxxx V xxxxxxxx 67/548/XXX xx stanoví xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, xxxxxxxx x xxxxxxxxxxx xxxxx x xxxxxxxxx. Xx xxxxxxxx xxxxxxxxxxx xxxx xxxxxxx xxxxxxxxxxx xxxxxxx.

(4) Xxxxxxx XX směrnice 67/548/XXX obsahuje předpisy xxxxxxxx xx uzávěrů xxxxxxxx proti otevření xxxxx. Xxxx předpisy xx xxxx xxx xxxxxxxxxxxx x xxxxxxxxxxxxx. Xx nezbytné xxxxxxxx xxxxxx, xxx se xxxxxxx xxxxxx xxxxx xxxxxxxx dětmi xxxxxxxxx.

(5) Xxxxxxxx xxxx směrnice xxxx v xxxxxxx xx xxxxxxxxxxx Xxxxxx xxx přizpůsobení technickému xxxxxxx xxxxxxx xxx xxxxxxxxxx technických xxxxxxxx xxxxxxx xx úseku xxxxxxxxxxxx xxxxx x xxxxxxxxx,

XXXXXXX TUTO XXXXXXXX:

Xxxxxx 1

Xxxxxxxx 67/548/EHS xx xxxx xxxxx:

1. Xxxxxxx I xx xxxx xxxxx:

x) odpovídající xxxxxxxx x předmluvě xx xxxxxxxxx xxxxxxxxx X x příloze 1X xxxx xxxxxxxx;

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

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

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

2. Xxxxxxxxxxxx xxxx x xxxxxxx XXX xx nahrazuje xxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx v příloze 2 této směrnice.

3. Xxxxxxx IV xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx x příloze XX xx xxxxxxxxx xxxxxxxxxxxx xxxxxx xxx xxxxxxxx xxxxxxxxx v xxxxxxx 3X této xxxxxxxx;

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

4. Část X xxxxxxx X xx xxxx xxxxx:

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

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

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

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

x) xxxxxxxx X.17 xx xxxxxxxxx xxxxxx x xxxxxxx 4X této xxxxxxxx;

x) xxxxxxxx X.23 xx xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx xxxxxxxx. Xxxxx xxxxxxxx X.23 xx vysvětlivce xx xxxx odpovídajícím xxxxxxxx;

x) xxxxxx se xxxx x xxxxxxx 4X xxxx směrnice.

5. Xxxxxxx xx xxxxxx xxxxxxx obecného úvodu x xxxxx C xxxxxxx V.

6. Odpovídající xxxxx x xxxxxxx XX xx xxxxxxxxx xxxxx x příloze 5 xxxx xxxxxxxx.

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

Xxxxxx 2

1. Členské xxxxx xxxxxx v xxxxxxxx právní a xxxxxxx xxxxxxxx nezbytné xxx xxxxxxxx xxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx do 1. xxxxxx 2001. Xxxxxxxxxx x xxxx xxxxxxx Xxxxxx.

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

2. Xxxxxxx xxxxx sdělí Xxxxxx znění xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx xxxxxxx x xxxxxxx xxxxxxxxxx xxxx xxxxxxxx, a xxxxxxxxxx xxxxxxx xxxx xxxxxxxx x přijatými xxxxxxxxxxxxxx xxxxxxxxxxxx.

Článek 3

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

Článek 4

Xxxx xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.

X Bruselu dne 19. května 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Xxxxxx

[1] Přijato xx xxxxxxxxxxxx xx xxxxxxx xxxxx.

[2] Xx. xxxx. 196, 16.8.1967, x. 1.

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

XXXXXXX 1X

XXXXXXXXX X XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x označování xxxxx

(Xxxxxx xx xxxxxxx xxxxx)

XXXXXXX 1X

"XXXXXXX A

Z

Symbol

ES

DA

DE

EL

EN

FI

FR

IT

NL

PT

SV

18

Ar

Argón

Argon

Αργό

Argon

Árgon

Argon

64

Gd

Gadolinio

Gadolinium

Γαδολίνιο

Gadolinium

Gadolinio

Gadolinium

Gadolínio

Gadolinium"

XXXXXXX 1C

Indexové xxxxx	Xxxxxxxx xxxxx	Xxxxxxxx k xxxxxx	Xxxxx XX	Xxxxx XXX	Xxxxxxxxxxx	Xxxxxxxx	Xxxxxxxxxxxx limity	Poznámky x xxxxxxxxxx
006–011–00–7	xxxxxxxx (ISO) 1-xxxxxx-X-xxxxxxxxxxxxxx		200–555–0	63–25–2	Xxxx. xxx. 3; X40 Xn; X22 X; X50	Xx; X X: 22–40–50 X: (2-)22–24–36/37–46–61
006–013–00–8	xxxxxx-xxxxxxx (XXX) natrium-N-methyldithiokarbamát		205–293–0	137–42–8	Xn; X22 X31 X; X34 X43 N; X50–53	X; N R: 22–31–34–43–50/53 S: (1/2-)26–36/37/39–45–60–61
006–015–00–9	xxxxxx (XXX) 3-(3,4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx	206–354–4	330–54–1	Xxxx. xxx. 3; R40 Xxxx. xxx. 3; X40 Xx; X22–48/22 X; X50–53		Xx; X X: 22–40–48/22–50/53 X: (2-)13–22–23–37–46–60–61
006–016–00–4	xxxxxxxx (XXX) 2- isopropoxyfenyl-N-methylkarbamát		204–043–8	114–26–1	T; X25 X; X50–53	X; X R: 25–50/53 X: (1/2-)37–45–60–61
006–017–00-X	aldikarb (ISO) 2-xxxxxx-2-(xxxxxxxxxxxxxx)xxxxxxxx-X-(X-xxxxxxxxxxxxxxx)xxxx		204–123–2	116–06–3	X+; R26/28 X; X24 N; X50–53	X+; X R: 24–26/28–50/53 X: (1/2-)22–36/37–45–60–61
006–018–00–5	aminokarb (ISO) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		217–990–7	2032–59–9	X; X24/25 X; X50–53	X; N R: 24/25–50/53 X: (1/2-)28–36/37–45–60–61
006–019–00–0	xx-xxxxx (XXX) X-(2,3-xxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx		218–961–1	2303–16–4	Xxxx. xxx. 3; R40 Xx; X22 X; X50–53	Xx; X X: 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; X22 X43 X; 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 -xxxxxxxxxxxxxx		217–991–2	2032–65–7	X; X25 X; R50–53	T; X X: 25–50/53 X: (1/2-)22–37–45–60–61
006–024–00–8	xxxxxx-xxxxxxx (ISO) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx		205–443–5	140–93–2	Xx; X22 Xx; X38 X; X51–53	Xx; X R: 22–38–51/53 X: (2-)13-61
006–026–00–9	karbofuran (XXX) 2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx-X-xxxxxxxxxxxxxx		216–353–0	1563–66–2	X+; X26/28 X; X50–53	X+; X R: 26/28–50/53 S: (1/2-)36/37–45–60–61
006–028–00-X	xxxxxxxxx (XXX) 2-(1-xxxxxxxxxxxx)-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx 2-sek-butyl-4,6-dinitrofenyl-isopropyl-karbonát		213–546–1	973–21–7	T; X25 N; X50–53	X; X X: 25–50/53 X: (1/2-)37–45–60–61
006–029–00–5	dioxakarb (XXX) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx		230–253–4	6988–21–2	X; X25 N; 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 (XXX) 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 (ISO) 2-(xxxxxxxxxxxxx)- 5,6-dimethyl xxxxxxxxx-4-xx-X,X-xxxxxxxxxxxxxxxx		245–430–1	23103–98–2	X; X25 N; X50–53	X; X R: 25–50/53 X: (1/2)22–37–45–60–61
006–037–00–9	xxxxxxxxx (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		220–113–0	2631–37–0	X; X25 X; X50–53	X; X R: 25–50/53 X: (1/2-)24–37–45–60–61
006–038–00–4	xxxxxxxxx (XXX) 2-xxxxxxxxxx-X,X-xxxxxxxxxxxxxxxxxxxxxx	X	202–388–9	95–06–7	Xxxx. xxx. 2; X45 Xx; X22 N; X50–53	X; X X: 45–22–50/53 X: 53–45–60–61
006–039–00-X	xxx-xxxxx (XXX) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx		218–962–7	2303–17–5	Xx; X22–48/22 R43 X; X50–53	Xx; X X: 22–43–48/22–50/53 S: (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; X 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; X36/38 Karc. xxx. 3; R40 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 X; R50–53	T+; X R: 28–50/53 X: (1/2-)22–36/37–45–60–61
006–046–00–8	bendiokarb (ISO) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx		245–216–8	22781–23–3	X; X23/25 Xx; X21 X; X50–53	X; X X: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61
006–047–00–3	xxxxxxxxx (ISO) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx		—	8065–36–9	X; 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; R50–53	Xn; 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; R38 X; X50–53	Xx; N X: 38–50/53 X: (2-)60-61
006–053–00–6	xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		220–114–6	2631–40–5	Xx; X22 X; R50–53	Xn; X R: 22–50/53 X: (2-)60-61
006–054–00–1	mexakarbát (XXX) 4-(xxxxxxxxxxxxx)-3,5-xxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		206–249–3	315–18–4	X+; X28 Xx; X21 X; X50–53	X+; X X: 21–28–50/53 X: (1/2-)36/37–45–60–61
006–057–00–8	xxxxxxxxxx (XXX) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx		217–682–2	1929–82–4	Xx; X22 X; X51–53	Xx; X R: 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; R22 X52–53	Xx R:22–52/53 S: (2-)61
006–069–00–3	xxxxxxxxx-xxxxxx (ISO) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx		245–740–7	23564–05–8	Xxxx. xxx. 3; R40 X; X50–53	Xx; N X: 40–50/53 X: (2-)36/37–60–61
006–070–00–9	xxxxxxxxxxx N-cyklohexyl-N-methoxy-2,5-dimethyl-3-furamid		262–302–0	60568–05–0	Karc. xxx. 3; X40 N; X50–53	Xx; X R: 40–50/53 X: (2-)36/37–60–61
006–088–00–7	xxxxxxxxxxx (XXX) ethyl-N -[({[(2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx)xxx]xxxxxxxx}xxxxxxxxxxx)xxxxxxxx]-X-xxxxxxxxx-β-xxxxxxxx(2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx)-X-({[2-(xxxxxxxxxxxxxx)xxxxx]xxxxxxxxxxxxxx}xxxxxxxx)-X-xxxxxxxxxxxxxx		—	82560–54–1	X; X23/25 X; R50–53	T; X R: 23/25–50/53 X: (1/2-)36/37–45–60–61
007–012–00–5	N,N-dimethylhydrazin 1,1-xxxxxxxxxxxxxxxx	X	200–316–0	57–14–7	X; X11 Xxxx. xxx. 2; X45 X; X23/25 C; X34 X; R51–53	F; T; X X: 45–11–23/25–34–51/53 X: 53–45–61
007–013–00–0	X,X-xxxxxxxxxxxxxxxx 1,2-xxxxxxxxxxxxxxxx	X	—	540–73–8	Xxxx. xxx. 2; X45 X; R23/24/25 X; X51–53	X; X X: 45–23/24/25–51/53 S: 53–45–61	X ≥ 25 %: X; X45–23/24/25 3 % &xx; X &xx; 25 %: X; X45–20/21/22 0,01 % < X &xx; 3 %: X; X45
009–003–00–1	xxxxxxxx fluorovodíková … %	B	231–634–8	7664–39–3	T+; X26/27/28 X; X35	X+; C X: 26/27/28–35 X: (1/2-)7/9–26–36/37–45	X ≥ 7 %: X+; X; X26/27/28–35 1 % ≤ X &xx; 7 %: X; X23/24/25–34 0,1 % ≤ X < 1 %: Xx; X20/21/22–36/37/38
015–039–00–9	xxxxxxx-xxxxxx (ISO) 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; X24 X43 X; X50–53	X+; X X: 24–26/28–43–50/53 S: (1/2-)28–36/37–45–60–61
015–048–00–8	xxxxxxxx (XXX) X,X-xxxxxxxx-X-[3-xxxxxx-4-(xxxxxxxxxxxxxx)xxxxx]-xxxxxxxxxxxxx		200–231–9	55–38–9	Xxxx. xxx. 3; X40 X; X23–48/25 Xn; X21/22 X; X50–53	X; X X: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61
015–056–00–1	xxxxxxx-xxxxx (XXX) X,X-xxxxxxx-X-[(4(3 H)-oxo-1,2,3-benzotriazin-3-yl)methyl]-fosforodithioát		220–147–6	2642–71–9	T+; X28 X; R24 X; X50–53	X+; X X: 24–28–50/53 X: (1/2-)28–36/37–45–60–61
015–140–00–8	triazofos (XXX) O,O-diethyl-O-(1-fenyl-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 X: 21–23/25–50/53 X: (1/2-)36/37–45–60–61
016–013–00-X	xxxxxxx xxxxxxx		234–129–0	10545–99–0	X14 X; X34 X; X50	X; N X: 14–34–50 S: (1/2-)26–36/37/39–45–61	C ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; R36/37/38
016–014–00–5	chlorid siřičitý		—	13451–08–6	R14 X; R34 X; X50	X; X R: 14–34–50 X: (1/2-)26–36/37/39–45–61	C ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; X36/37/38
016–023–00–4	xxxxxxxx-xxxxxx	X	201–058–1	77–78–1	Xxxx. xxx. 2; X45 Muta. xxx. 3; R40 X+; X26 T; X25 C; X34 X43	X+ X: 45–25–26–34–43 X: 53-4 5	C ≥ 25 %: X+; R45–25–26–34–43 10 % ≤ C &xx; 25 %: X+; X45–22–26–34–43 7 % ≤ C &xx; 10 %: X+; R45–22–26–36/ 37/38–43 5 % ≤ X &xx; 7 %: X; X45–22–23–36/37/38–43 3 % ≤ X &xx; 5 %: X; X45–22–23–43 1 % ≤ X &xx; 3 %: T; X45–23–43 0,1 % ≤ X &xx; 1 %: X; R45–20 0,01 % ≤ X &xx; 0,1 %:X; X45
016–024–00-X	xxxxxxxx (ISO) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx	X,X′-xxxxxxxx-xxxxxxxxxxx(xxxxxxxxxxx)215–993–8	1468–37–7	Xx; X22 X; X50–53	Xx; X X: 22–50/53 S: (2-)60-61
016–071–00–6	3-xxxxx-6,13-xxxxxxx-10-[(3-{[4-xxxxx-6-(2-xxxxxxxxxxxxxxxx)- 1,3,5-xxxxxxx-2-xx]xxxxx}xxxxxx)xxxxx][1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx xxxxxxxx		410–130–3	136248–03–8	X43	Xx X: 43 X: (2-)22–24–37
022–001–00–5	xxxxxxx xxxxxxxxxx		231–441–9	7550–45–0	X14 X; X34	X X: 14-34 X: (1/2-)7/8–26–36/37/39–45	X ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; X36/37/38
030–004–00–8	xxxxxxxxxxxxx [1] xxxxxxxxxxxx [2]		208–884–1 [1] 209–161–3 [2]	544–97–8 [1] 557–20–0 [2]	X14 X; R17 X; X34 X; X50–53	X; X; X X: 14–17–34–50/53 X: (1/2-)16–43–45–60–61
050–002–00–0	xxxxxxxxx (XXX) xxxxxxxxxxxxx(xxxxxxx)xxxxxxx tricyklohexylstannium-hydroxid		236–049–1	13121–70–5	Xn; X20/21/22 N; R50–53	Xn; X R: 20/21/22–50/53 X: (2-)13–60–61
050–012–00–5	xxxxxxxxxxxxxxxxxxxxxx [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] butyl(tricyklohexyl)stannan [3]		215–910–5 [1] 221–437–5 [2] 230–358–5 [3]	1449–55–4 [1] 3091–32–5 [2] 7067–44–9 [3]	Xx; X20/21/22 X; R50–53	Xn; N X: 20/21/22–50/53 S: (2-)26–28–60–61	X ≥ 1 %: Xx; R20/21/22	1
050–017–00–2	fenbutatinoxid (XXX) 1,1,1,3,3,3-xxxxxxx(2-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxxxx		236–407–7	13356–08–6	X+; X26 Xx; X36/38 N; X50/53	X+; N X: 26–36/38–50/53 S: (1/2-)28–36/37–45–60–61
082–009–00–X	žluť (xxxxxxxxxxxx xxxxxxxx) XX Xxxxxxx Yellow 34 (XX 77603) XX xxxxxxxxxx xxxx 34 (XX 77603)		215–693–7	1344–37–2	Xxxx. kat. 3; X40 Xxxx. xxx. 1; X61 Xxxx. kat. 3; X62 R33 N; X50–53	X; X X: 61–33–40–50/53–62 X: 53–45–60–61		1
082–010–00–5	xxxxxx (xxxxxxx-xxxxxxxxxx-xxxxx xxxxxxxx) XX Xxxxxxx Red 104 (XX 77605) XX xxxxxxxxxx červeň 104 (XX 77605)		235–759–9	12656–85–8	Karc. kat. 3; X40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 X; X50–53	X; X X: 61–33–40–50/53–62 S: 53–45–60–61		1
601–024–00-X	kumen [1] xxxxxxxxxxxx [2]		202–704–5 [1] 203–132–9 [2]	98–82–8 [1] 103–65–1 [2]	X10 Xx; R65 Xx; X37 X; R51–53	Xn; X R: 10–37–51/53–65 X: (2-)24–37–61–62		4
601–032–00–3	xxxxx[x]xxxxx benzo[def]chrysen		200–028–5	50–32–8	Karc. xxx.2; X45 Xxxx. xxx. 2; X46 Xxxx. xxx. 2; X60–61 X; X50–53	X; X R: 45–46–60–61–50/53 X: 53–45–60–61
601–034–00–4	xxxxx[x]xxxxxxxxxxxxxxx		205–911–9	205–99–2	Xxxx. xxx.2; X45 N; X50–53	X; X X: 45–50/53 X: 53–45–60–61
602–035–00–2	1,4-xxxxxxxxxxxxx x-xxxxxxxxxxxxx		203–400–5	106–46–7	Xx; X36 X; R50–53	Xi; 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; X34	X R: 10-34 S: (1/2-)7–26–45
603–076–00–9	xxx-2-xx-1,4-xxxx		203–788–6	110–65–6	X; X23/25 Xx; R21–48/22 X; R34	T X: 21–23/25–34–48/22 X: (1/2-)26–36/37/39–45	X ≥ 50 %: X; R21–23/25–34–48/22 25 % ≤ X &xx; 50 %: X; X21–23/25–36/38–48/22 10 % ≤ X &xx; 25 %: Xx; X20/22–48/22 3 % ≤ X &xx; 10 %: Xx; X20/22
603–091–00–0	xxx-4-xxxxxxxxx-1-xxxxxx-7-xxxxxxxxxx[2.2.1]xxxxxx-2-xx		402–470–6	87172–89–2	X; X8 Xx; X22 Xi; X36	X; Xx X: 8–22–36 X: (2-)26
603–093–00–1	exo-(±)-4-isopropyl-1-methyl-2-[(2-methylbenzyl)oxy]-7-oxabicyklo[2.2.1]heptan		402–410–9	87818–31–3	Xn; X20 X; X51–53	Xx; X X: 20–51/53 X: (2-)23-61
603–097–00–3	1,1', 1′′-xxxxxxxxxxxxxxxx-2-xx xxxxxxxxxxxxxxxxxx		204–528–4	122–20–3	Xx; X36 R52–53	Xi X:36–52/53 X: (2-)26-61
603–117–00–0	propan-2-ol xxxxxxxxxxxxxxxx isopropanol		200–661–7	67–63–0	F; X11 Xx; R36 R67	F; Xx R: 11–36–67 X: (2-)7–16–24/25–26
604–020–00–6	xxxxxxx-2-xx 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (ISO)		201–993–5	90–43–7	Xi; R36/37/38 X; X50	Xx; N X: 36/37/38–50 X: (2-)22-61
604–021–00–1	2-xxxxxxxxxx, xxxxx xxx xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx xxxxx xxxxxxx-xxxxxxx-2-xxxx		205–055–6	132–27–4	Xx; R22 Xx; X37/38–41 N; X50	Xx; X X: 37/38–41–50 X: (2-)22–26–61
604–024–00–8	4,4'-(4-methylpentan-2,2-diyl)difenol 2,2-xxx(4-xxxxxxxxxxxx)-4-xxxxxxxxxxxx		401–720–1	6807–17–6	Xxxx. xxx. 2; X60 Xx; X36 X; X50–53	X; X R: 60–36–50/53 X: 53–45–60–61
604–041–00–0	xxxxxxxxxxx [1] xxxxxxxxxxx-xxxxxxx [2] 5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxxx xxxxxxxx [1] xxxxxxx-5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxx [2]		256–634–5 [1] 263–560–7 [2]	50594–66–6 [1] 62476–59–9 [2]	Xx; X22 Xx; X38–41 N; X50–53	Xx; N X: 22–38–41–50/53 S: (2-)24–39–60–61
604–043–00–1	xxxxxxxxxxxxxxxx (4-xxxxxxxxxxxx)xxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx 4-(benzyloxy)fenol		203–083–3	103–16–2	Xi; X36 X43	Xx X: 36-43 S: (2-)24/25–26–37
604–044–00–7	mechinol 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx		205–769–8	150–76–5	Xx; X22 Xx; X36 X43	Xx X: 22–36–43 X: (2-)24/25–26–37/39–46
605–016–00–7	xxxxxxx… % ethandial… %	X	203–474–9	107–22–2	Xxxx. xxx. 3; X40 Xn; R20 Xx; R36/38 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-(xxxxxxxxxxxxxxx)xxxxx-1,3-xxxx		201–462–8	83–26–1	X; X25–48/25 X; X50–53	X; X X: 25–48/25–50/53 S: (1/2-)37–45–60–61
606–018–00–0	xxxxxxx (XXX) 2,3-dichlor-1,4-naftochinon		204–210–5	117–80–6	Xn; X22 Xx; X36/38 X; X50–53	Xx; X X: 22–36/38–50/53 S: (2-)26–60–61
606–019–00–6	xxxxxxxxxx (XXX) perchlorpentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-on xxxxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx 1,2,4,5,6,7,8,8,9,10-dekachlorpentacyklo[5.3.0.02,6.04,10.05,9]dekan-3-on		205–601–3	143–50–0	Karc. xxx. 3; R40 X; X24/25 N; X50–53	X; X X: 24/25–40–50/53 X: (1/2-)22–36/37–45–60–61
606–034–00–8	xxxxxxxxxx (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 X)-xx 4-amino-6-terc-butyl-3-(methylsulfanyl)-4,5-dihydro-1,2,4-triazin-5-on		244–209–7	21087–64–9	Xn; X22 X; X50–53	Xx; X X: 22–50/53 X: (2-)60-61
606–035–00–3	xxxxxxxxxxx (XXX) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx xxxxxxx		216–920–2	1698–60–8	X43 X; X50–53	Xx; X X: 43–50/53 X: (2-)24–37–60–61
606–036–00–9	chinomethionát (XXX) 6-xxxxxx-2 H-[1,3]dithiolo[4,5-b]chinoxalin-2-on		219–455–3	2439–01–2	Repr. xxx. 3; X62 Xx; R20/21/22–48/22 Xi; X36 X43 X; X50–53	Xx; X R: 20/21/22–36–43–48/22–50/53–62 X: (2-)24–37–60–61
606–037–00–4	xxxxxxxxxxx (XXX) 1-(4-xxxxxxxxxxx)- 3,3-xxxxxxxx-1-(1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		256–103–8	43121–43–3	Xx; X22 X; R51–53	Xn; X X: 22–51/53 X: (2-)61
606–044–00–2	2,4,6-xxxxxxxxxxxxxxxxxxx fenyl(2,4,6-trimethylfenyl)methanon		403–150–9	954–16–5	Xn; X22 Xi; X36 X; X50–53	Xx; X X: 22–36–50/53 X: (2-)26–60–61
607–043–00-X	xxxxxxx (ISO) 3,6-xxxxxxx-2-xxxxxxxxxxxxxxx xxxxxxxx		217–635–6	1918–00–9	Xx; X22 Xi; X41 X52–53	Xx; X X: 22–41–52/53 X: (2-)26-61
607–057–00–6	xxxxxxxxx (XXX) 3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X-xxxxxxx-2-xx		201–378–1	81–82–3	Xx; R48/22 X52–53	Xx X:48/22–52/53 X: (2-)37-61
607–058–00–1	xxxxxxxxx (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -xxxxxxx-2-xx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X -xxxxxxx-2-xx		204–195–5	117–52–2	X; X25–48/25 X52–53	X X:25–48/25–52/53 X: (1/2-)37–45–61
607–079–00–6	xxxxxxx (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx ethyl-5-(1,2,3,5,6,7,8,9,10,10-dekachlor-4-hydroxypentacyklo[5.2.1.02,6.03,9.05,8]dekan-4-yl)-4-oxopentanoát xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx		—	4234–79–1	X; X24 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 kyseliny trimellitanhydrid		209–008–0	552–30–7	Xi; X37–41 X42/43	Xx R: 37–41–42/43 X: (2-)22–26–36/37/39
607–143–00–3	xxxxxxxxx xxxxxxxx valerová xxxxxxxx		203–677–2	109–52–4	X; X34 R52–53	C R:34–52/53 X: (1/2-)26–36–45–61
607–152–00–2	2,3,6-TBA (XXX) 2,3,6-xxxxxxxxxxxxxxxx xxxxxxxx		200–026–4	50–31–7	Xx; X22 X; R51–53	Xn; N X: 22–51/53 X: (2-)61
607–153–00–8	xxxxxxxxx (XXX) (4-xxxxx-2-xxx-2,3-xxxxxxx-1,3-xxxxxxxxxxxx-3-xx)xxxxxx xxxxxxxx		223–297–0	3813–05–6	Xx; R36/38 X52–53	Xx X:36/38–52/53 X: (2-)22-61
607–156–00–4	chlorfenson (XXX) 4-chlorfenyl-4-chlorbenzen-1-sulfonát		201–270–4	80–33–1	Xn; X22 Xx; X38 X; X50–53	Xx; N X: 22–38–50/53 X: (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	xxxxxxxxxxxxxx (XXX) ethyl-2,2-bis(4-chlorfenyl)-2-hydroxyacetát xxxxx-4,4'-xxxxxxxxxxxxxxx		208–110–2	510–15–6	Xx; X22 X; R50–53	Xn; X R: 22–50/53 X: (2-)60-61
607–176–00–3	Xxxx: α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-xxxxxxxxxxx(xxxxxxxxxx);α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-({3-[3-(2 H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propionyl}oxy)poly(oxyethylen)		400–830–7	—	R43 X; X51–53	Xx; X X: 43–51/53 X: (2-)36/37–61
607–188–00–9	xxxxxxx-xxxxxxxx-X-(2-xxxxxxxxxxxx)-X-(xxxxxxx-9-xx-1-xx)xxxxxxxxxx		402–970–4	—	X43 X; X51–53	Xx; X R: 43–51/53 X: (2-)24/37–61
607–209–00–1	Směs: O,O′-diisopropyl-trisulfanbis(karbothioát); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx)		403–030–6	—	Xx; R22 X43 X; X50–53	Xx; X X: 22–43–50/ 53 X: (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 R: 2–7–10–51/53 X: (2-)3/7–14–33–36/37/39–61
607–217–00–5	2-xxxxxxxxxxx-[4-(7-xxxxx-2,6-xxxxx-2,6-xxxxxxx-1,5-xxxxx-x-xxxxxxx-3-xx)xxxxxx]xxxxxx		403–960–2	—	X43 X53	Xx X: 43-53 X: (2-)24–37–61
607–243–00–7	xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-hydroxyethyl)amonium-3,6-dichlor-2-methoxybenzoát [3] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [3]		217–846–3 [1] 246–590–5 [2] 258–527–9 [3]	1982–69–0 [1] 25059–78–3 [2] 53404–28–7 [3]	X52–53	X: 52/53 X: 61
607–248–00–4	Xxxxxxxx-xxxxxxx Xxxxxxx-X-(1-xxxxxx)xxxxxxxx		205–073–4	132–67–2	Xx; R22	Xn X: 22 X: (2)
607–249–00-X	(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx xxxxxxxxxxxxxxxxx-xxxxxxxxx TPGDA		256–032–2	42978–66–5	Xi; X36/37/38 X43 X; X51–53	Xx; X X:36/37/38–43–51/53 X: (2-)24–37–61	C ≥ 10 %: Xi; X36/37/38–43 1 % ≤ C < 10 %: Xx; X43
607–252–00–6	λ-xxxxxxxxxxx (ISO) Xxxx (1:1): (X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 R)-cis-3-((Z)-2-chlor-3,3,3-trifluorprop-1-en-1-yl)-2,2-dimethylcyklopropan-1-karboxylát x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 S)-cis-3-((Z)-2-chlor-3,3,3-trifluorprop-1-en-1-yl)-2,2-dimethylcyklopropan-1-karboxylát		415–130–7	91465–08–6	T+; R26 X; R25 Xx; 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 (ISO) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx kyselina		—	69377–81–7	R52–53	R: 52/53 X: 61
608–003–00–4	akrylonitril	D E	203–466–5	107–13–1	F; Xxx Xxxx. kat. 2; X45 T; X23/24/25 Xx; R37/38–41 X43 X; X51–53	X; X; X X: 45–11–23-/24/25–37/38–41–43–51/53 X: 9–16–53–45–61	X ≥ 20 %: X; X45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; R45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ 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; R45	43
608–016–00–5	2,3,5,6-tetrachlor-1,4-dikyanbenzen xxxxxxxxxxxxxxxxxxxxxxxxx		401–550–8	1897–41–2	X43 X; R50–53	Xi; X X: 43–50/53 X: (2-)24–37–60–61
609–030–00–4	dinoterb (XXX) 2-xxxx-xxxxx-4,6-xxxxxxxxxxxx	X	215–813–8	1420–07–1	Xxxx. kat. 2; X61 T+; X28 X; X24 X44 X; R50–53	T+; N 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; R45 Xxxx. kat. 2; X61 Xx; R22 X; R50–53	T; N X: 45–61–22–50/53 X: 53–45–60–61
609–044–00–0	xxxxxxxx (ISO) 1,2,4,5-xxxxxxxxxx-3-xxxxxxxxxxx		204–178–2	117–18–0	Xx; X22 R43 N; X50–53	Xx; X 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. kat. 2; X45 X; R50–53	T; X X: 45–50/53 X: 53–45–60–61
611–013–00–1	4-xxxxxxx-3-{4-[2-xxxxxxx-4-(3-xxxxxxxxxxxxxxxxx)xxxxxxxx]-3-xxxxxxxxxxxxxx}-6-(3-xxxxxxxxxxxxxxxx)xxxxxxxx-2-xxxxxxxx trilithný		403–650–7	117409–78–6	E; X2 X; 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 červeň 9		209–321–2	569–61–9	Xxxx. kat. 2; X45	X R: 45 X: 53-45
612–035–00–4	2-xxxxxxxxxxxxx x-xxxxxxxx	X	201–963–1	90–04–0	Xxxx. xxx. 2; R45 Xxxx. xxx. 3; X40 T; R23/24/25	T X: 45–23/24/25 S: 53-45
612–042–00–2	xxxxxxxx xxxxxxx-4,4'-xxxxxx 4,4'-diaminobifenyl xxxxxxx-4,4'-xxxxxxxxxx	X	202–199–1	92–87–5	Xxxx. xxx. 1; X45 Xn; X22 X; R50–53	T; N X: 45–22–50/53 S: 53–45–60–61	X ≥ 25 %: X; R45–22 0,01 % ≤ X < 25 %: T; X45
612–051–00–1	4,4'-xxxxxxxxxxxxxxxxxxxx xxx(4-xxxxxxxxxx)xxxxxx 4,4'-xxxxxxxxxxxxxxxx	X	202–974–4	101–77–9	Xxxx. xxx. 2; R45 Muta. 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 E	210–322–5 265–294–7 277–985–0	612–82–8 64969–36–4 74753–18–7	Xxxx. xxx. 2; R45 Xx; X22 X; X51–53	X; X X: 45–22–51/53 X: 53–45–61
612–099–00–3	4-xxxxxx-x-xxxxxxxxxxxxx4-xxxxxx-1,3-xxxxxxxxxxxxx4-xxxxxxxxxxxx-1,3-xxxxxx 2,4-xxxxxxxxxxxx	X	202–453–1	95–80–7	Xxxx. kat. 2; X45 X; R25 Xx; X21 Xx; X36 R43 N; X51–53	X; X R: 45–21–25–36–43–51/53 X: 53–45–61
612–105–00–4	2-(xxxxxxxxx-1-xx)xxxxxxxxx2-(xxxxxxxxx-1-xx)xxxxx-1-xxxx		205–411–0	140–31–8	Xx; X21/22 X; X34 X43 X52–53	X X: 21/22–34–43–52/53 S: (1/2-)26–36/37/39–45–61
612–111–00–7	2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,3-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,3-xxxxxx 2,6-xxxxxxxxxxxx		212–513–9	823–40–5	Xxxx. xxx. 3; X40 Xx; X21/22 X43 N; R51–53	Xn; X X: 21/22–40–43–51/53 X: (2-)24–36/37–61
612–125–00–3	2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,4-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,4-xxxxxx 2,5-xxxxxxxxxxxx		202–442–1	95–70–5	X; X25 Xx; X20/21 X43 N; R51–53	T; X X: 20/21–25–43–51/53 X: (1/2-)24–37–45–61
612–144–00–7	xxxxxxxxxxx (XXX) X-(2-xxxxx-6-xxxxxxxxxxx)-X-xxxxx-2,6-xxxxxxx-4-(xxxxxxxxxxxxxx)xxxxxx		—	62924–70–3	Xx; R36/38 X4 3 N; X50–53	Xx; X X: 36/38–43–50/53 X: (2-)36/37–60–61
612–151–00–5	xxxxxxxxxxxxx toluendiamin xxxxxxxxxxxxxxxxxxx methylbenzendiamin	E	246–910–3	25376–45–8	Karc. kat. 2; X45 X; X25 Xx; X20/21 Xx; X36 X43 X; X51–53	X; X X: 45–20/21–25–36–43–51/53 X: 53–45–61
613–018–00–4	xxxxxxxxxx (XXX) 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx		—	7411–47–4	Xx; X22 Xx; X36/37/38 X52–53	Xx R: 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; X22 R31 Xx; R36/37 X; X50–53	X; Xx; X X: 8–22–31–36/37–50/53 X: (2-)8–26–41–60–61
613–038–00–3	6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxx benzoguanamin		202–095–6	91–76–9	Xn; X22 R52–53	Xn X:22–52/53 X: (2-)61
613–042–00–5	xxxxxxxx (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1 X-xxxxxxxx		252–615–0	35554–44–0	Xx; X20/22 X; X41 X; X50–53	Xx; X X: 20/22–41–50/53 X: (2-)26–39–60–61
613–043–00–0	xxxxxxxx-xxxxxx (ISO) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1X -imidazol-1-ium-hydrogensulfát [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx		261–351–5 [1] 281–291–3 [2]	58594–72–2 [1] 83918–57–4 [2]	Xx; X20/22 Xx; X41 X; X50–53	Xx; X R: 20/22–41–50/53 X: (2-)26–39–60–61
613–066–00–6	xxxxxxxxxx (XXX) 2-(xxxx-xxxxxxxxxx)-4-(xxxxxxxxxx)-6-xxxxxxx-1,3,5-xxxxxxx		251–637–8	33693–04–8	Xx; R22 X; X50–53	Xx; X X: 22–50/53 X: (2-)60-61
613–091–00–2	xxxxxxxxxx-xxxxxxxxx [1] xxxxxxxxxx-xxxxxx [2] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx-xxxxxxxxx [1] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxx-xxxxxxxx [2]		225–062–8 [1]	4636–83–3 [1] 29873–36–7 [2]	Xx; X22 Xx; X36/37/38 X52–53	Xx; X: 22–36/37/38–52/53 X: (2-)22–36–61
613–098–00–0	1-xxxxxxxxxxxxxxx-2-xx 1-oktyl-2-pyrrolidon		403–700–8	2687–94–7	C; R34 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 S: (2-)24–37–61
613–131–00–9	xxxxxxxxxx (ISO) 1,2,5,6-xxxxxxxxxx-4 X-xxxxxxx[3,2,1-xx]xxxxxxxx-4-xx		—	57369–32–1	Xx; X22 X52–53	Xx X:22–52/53 X: (2-)61
613–134–00–5	myklobutanil (XXX) 2-(4-xxxxxxxxxx)-2-[(1 H-1,2,4-triazol-1-yl)methyl]hexannitril		—	88671–89–0	Repr. xxx. 3; X63 Xx; R22 Xi; X36 X; X51–53	Xx; X X: 22–36–51/53–63 X: (2-)36/37–46–61
613–137–00–1	xxxxxxxxxxxxxxxxxx (XXX) 1-(1,3-xxxxxxxxxxxx-2-xx)-1,3-xxxxxxxxxxxxxxxx		242–505–0	18691–97–9	X; X50–53	X X: 50/53 S: 60-61
613–139–00–2	xxxxxxxxxxx-xxxxxx xxxxxx-2-{X —[X-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxxx]xxxxxxxxx}xxxxxxx		—	74223–64–6	X; X50–53	X X: 50/53 X: 60-61
614–001–00–4	xxxxxxx (ISO) 3-(1-xxxxxxxxxxxxxxxx-2-xx)xxxxxxx		200–193–3	54–11–5	X+; X27 X; X25 X; R51–53	T+; X X: 25–27–51/53 X: (1/2-)36/37–45–61
614–006–00–1	xxxxxx 2,3-xxxxxxxxxxxxxxxxxxxx-10-xx		206–614–7	357–57–3	X+; R26/28 X52–53	X+ X:26/28–52/53 X: (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 S: (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. xxx. 3; X40 X+; X26 Xx; R36/37/38 R42/43 X52–53	X+ X: 26–36/37/38–40–42/43–52/53 X: (1/2-)23–36/37–45–61	X320 %: X+; R26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ C &xx; 7 %: X; X23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; 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	xxxxxxxxx X -[(xxxxxxxxxx)xxxxxxxx]-2-xxxx-2-(xxxxxxxxxxxx)xxxxxxxx 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx		261–043–0	57966–95–7	Xx; X22 R43 N; X50–53	Xx; N X: 22–43–50/53 X: (2-)36/37–60–61
617–004–00–9	(1,2,3,4-tetrahydro-1-naftyl)hydroperoxid xxxxxxxxxxxxxxxxxxxx	212–230–0	771–29–9	X; X7 Xx; X22 X; X34 X; X50–53	X; C; X R: 7–22–34–50/53 X:(1/2-)3/7–14–26–36/37/39–45–60–61	X325 %: X; X22–34 10 % ≤ X &xx; 25 %: C; X34 5 % ≤ X < 10 %: Xx; X36/37/38
617–006–00-X	xxx(α, α-xxxxxxxxxxxxxx)xxxxxxx xxx(2-xxxxxxxxxxx-2-xx)xxxxxxx xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx dikumylperoxid		201–279–3	80–43–3	O; X7 Xx; X36/38 X; X51–53	X; Xx; N X: 7–36/38–51/53 X: (2-)3/7–14–36/37/39–61
617–008–00–0	xxxxxxxxxxxxxxxx		202–327–6	94–36–0	X; R2 Xi; X36 X43	X; Xx; X: 2–36–43 S: (2-)3/7–14–36/37/39
650–007–00–3	xxxxxxxxxxxxx (ISO) X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx		228–200–5	6164–98–3	Xxxx. xxx. 3; X40 Xx; X21/22 X; X50–53	Xx; N X: 21/22–40–50/53 S: (2-)22–36/37–60–61
650–008–00–9	xxxxxxxxxx (ISO) 4-[(2-xxxxxxxxxx)xxxxxxxxx]-3-xxxxxxxxxxxxxx-5(4 X)-xx		227–197–8	5707–69–7	X; R25 X; X50–53	X; X R: 25–50/53 X: (1/2-)22–24–36/37–45–60–61
650–009–00–4	chlordimeform-hydrochlorid X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx N2-(4-chlor-2-methylfenyl)-N1,N1-dimethylformimidamid-hydrochlorid X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx		243–269–1	19750–95–9	Xxxx. xxx. 3; R40 Xx; X22 X; X50–53	Xx; X X: 22–40–50/53 X: (2-)22–36/37–60–61
650–033–00–5	esfenvalerát (XXX) [(X)-(3-xxxxxxxxxxx)xxxxxxxxxx]-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx (S)-3-fenoxy-α-kyanbenzyl-(S)-2-(4-chlorfenyl)-3-methylbutanoát		—	66230–04–4	T; X23/25 X43 X; X50–53	X; N X: 23/25–43–50/53 S: (1/2-)24–36/37/39–45–60–61
650–041–00–9	triasulfuron (XXX) 1-[2-(2-xxxxxxxxxxx)xxxxxx-1-xxxxxxxx]-3-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxx		—	82097–50–5	X; X50–53	X X: 50/53 X: 60-61

XXXXXXX 1X

Xxxxxxxx xxxxx	Xxxxxxxx xxxxx	Xxxxxxxx x xxxxxx	Xxxxx XX	Xxxxx XXX	Xxxxxxxxxxx	Xxxxxxxx	Xxxxxxxxxxxx xxxxxx	Xxxxxxxx x xxxxxxxxxx
006–090–00–8	2-[(3-xxxxxxx-2-xx-1-xx)xxx]xxxxx-X-xxxxxxxxxxxxx		408–010–0	88558–41–2	Xx; 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-xxxxxxxxxxxxxxxxxxxx x 1,3-xx(xxx-x-xx-1-xx)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx		406–490–6	—	X; X51–53	X R: 51/53 X: 61
015–164–00–9	kalcium-dihydrogen-(1-hydroxyethylen)bisfosfonát xxxxxxxx		400–480–5	36669–85–9	X52–53	X:52/53 X: 61
015–165–00–4	Směs: X, X, S', X''-xxxxxxxxxx-4,4'-xxxxxxxxxxxxx(xxxxxxxxxxxxxx)-xxx(xxxxxxxxxxxxxxxx) x xxxxxxx[4-(xxxxxxxxxxxxx)xxxxx]xxxxxxxxx-xxxxxxxxxxxxxxxx		404–986–7	—	Xx; X41 X; R50–53	Xi; N X: 41–50/53 X: (2-)15–26–39–60–61
015–166–00-X	3,9-xxx(2,6-xx-xxxx-xxxxx-4-xxxxxxxxxxxx)-2,4,8,10-xxxxxxxx-3,9-xxxxxxxxxxxx[5.5]xxxxxxx		410–290–4	80693–00–1	X53	X:53 S: 61
015–167–00–5	3-[hydroxy(fenyl)fosfinoyl]propanová xxxxxxxx		411–200–6	14657–64–8	Xx; X41	Xx X: 41 X: (2-)26-39
601–050–00–1	X10-X13-xxxxxxxxxxxxx xxxxxxx		267–051–0	67774–74–7	X; X50	X X: 50 X: 61
601–051–00–7	4-xxxxxxxx-1-xx		405–980–7	768–56–9	Xx; X38 X; R51–53	Xi; X X: 38–51/53 X: (2-)37-61
602–083–00–4	xxxxxxxxxxxxxxxx difenyletheru xxxxxxxxxxxxxxxxxxxxx		251–084–2	32534–81–9	Xx; X48/21/22 R64 X; X50–53	Xx; X X: 48/21/22–50/53–64 X: (1/2-)36/37–45–60–61
602–084–00-X	1,1-xxxxxxx-1-xxxxxxxxxx		404–080–1	1717–00–6	X; X52–53–59	X X: 52/53–59 X: 59-61
603–128–00–0	2-(xxxxxxxxxxxx)xxxxxxxx		405–490–3	613–62–7	X53	X:53 X: 61
603–129–00–6	1-xxxx-xxxxxxxxxxxx-2-xx		406–180–0	57018–52–7	X10 Xx; X41	Xx R: 10-41 X: (2-)26-39
603–130–00–1	Xxxx xxxxxxx: α-(xxxxxxxxxxxxxxxxx)-ω-xxxxxxxxxxx(xxxxxxxxxx)		406–325–8	—	Xx; R22 X52–53	Xx X:22–52/53 S: (2-)39-61
603–131–00–7	Směs (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxxx)xxxxx]-X-xxxxxxxx		407–290–1	—	Xx; X41	Xx X: 41 X: (2-)26-39
603–132–00–2	2-(xxxxxxxxxxxxx)-6-xxxxxxxxx-9-xxxxxx-1,4-xxxxxxxxxx[4.5]xxxxx		408–200–3	63187–91–7	Xx; X38–41 R52–53	Xi X:38–41–52/53 S: (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; R22 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 (xxxxxxx a xxxxxxxxxx xxxxxxxxxxxx)		410–450–3	—	X53	X: 53 X: 61
603–135–00–9	xxx[2-(2-xxxxxxxxxxxxx)xxxxxxxxxx]xxx(2,2', 2-xxxxxxxxxxxxxxx-1-xxxxx-X,X)xxxxxxxxxx xxxxxxx		410–500–4	—	Xx; X41 N; X51–53	Xx; X X: 41–51/53 X: (2-)26–39–61
603–136–00–4	3-{4-[bis(2-hydroxyethyl)amino]-2-nitroanilino}propan-1-ol		410–910–3	104226–19–9	R43 X52–53	Xx R:43–52/53 S: (2-)24–37–61
603–137–00-X	Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx a 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx		411–130–6	—	Xx; X41	Xx R: 41 X: (2-)26-39
603–138–00–5	3-(2,2-dimethyl-3-hydroxypropyl)toluen 2,2-dimethyl-3-(3-methylfenyl)propan-1-ol		403–140–4	103694–68–4	R52–53	R:52/53 X: 61
604–050–00-X	4-xxxxx-x-xxxxxx 4-xxxxx-2-xxxxxxxxxxx		216–381–3	1570–64–5	X; X23 C; X 35 N; X50	X; X; N X: 23–35–50 S: (1/2-)26–36/37/39–45–61	X ≥ 25 %: X; X; R23–35 10 % ≤ X &xx; 25 %: X;X20–35 5 % ≤ X &xx; 10 %: X;X20–34 3 % ≤ X &xx; 5 %: Xx;X20–36/37/38 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'-methylenbis[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -xxxxxxxxxxxx-2-xx)- 4,4'-xxx(1,1,3,3-xxxxxxxxxxxxxxxx)- 2,2'-xxxxxxxxxxxxxxx		403–800–1	103597–45–1	X53	X:53 X: 61
604–053–00–6	4-terc - butyl-2-methyl-6-(1-methylpentadecyl)fenol		410–760–9	157661–93–3	Xi; R38 X43 X; X50–53	Xx; X R: 38–43–50/53 X: (2-)24–37–60–61
604–054–00–1	Směs:2-methoxy-4-(4-methylidentetrahydropyran-2-yl)fenol x 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'-xxx[(2,3-xxxxxxxxxxx)xxx]-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 X: 43–51/53 X: (2-)24–37–61
606–051–00–0	4-xxxxxxxxxxxxxxxxxx pentylcyklohexan-1-on		4–406–670–4	61203–83–6	N; X51–53	X R: 51/53 X: 61
606–052–00–6	4-(N, 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 (XXX) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-butoxy-1-methylethyl)-[(4-amino-3,5-dichlor-6-fluor-2-pyridyl)oxy]acetát [2]		279–752–9 [1] —	81406–37–3 [1] 154486–27–8 [2]	X; X50–53	X R: 50/53 X: 60-61
607–273–00–0	amonium-7-{2,6-dimethyl-8-[(2,2-dimethylbutanoyl)oxy]- 1,2,6,7,8,8a-hexahydro-1-naftyl}-3,5-dihydroxyheptanoát		404–520–2	—	R52–53	R:52/53 X: 61
607–274–00–6	{2-[xxxxxx(xxxxxx)xxxxx]xxxxx}-3-xxxxxxxx-2-xxxxx		405–350–1	54527–73–0	X43 X; X51–53	Xx; N X: 43–51/53 S: (2-)24–37–61
607–275–00–1	natrium-4-(benzoyloxy)benzen-1-sulfonát		405–450–5	66531–87–1	R43	Xi X: 43 X: (2-)24-37
607–276–00–7	[xxx(2-xxxxxxxxxxxxxx) xxx(1-xxxxxxxxxxxxxx)]xxxxxxxxx xxxxxxx		405–635–0	—	Xx; X38–41 X; X50–53	Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61
607–277–00–2	Xxxx:2-(xxxxxxxxxxxxx)xxxxxxxxx-xxxxxxxxxxxx x xxxxxxx-xxxxxxxxx		405–720–2	—	Xx; R22 Xx; X41 X43 N; X51–53	Xx; X R: 22–41–43–51/53 X: (2-)24–26–37/39–61
607–278–00–8	Xxxx:xxxxx(X7-X9 xxxxxxxxxx a xxxxxxxxxxxx)-3-[3-(2 X - xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx		405–760–0	—	Xx; X41 X43 X52–53	Xx X: 41–43–52/53 S: (2-)24–26–37/39–61
607–279–00–3	Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) x (xxxxxxxxxxxxxx)xxxxxxxxx-(xxxxxxxx-xxxxxx)-(xxxxxxxx-xxxxxxxx)		405–960–8	—	X43 X; X51–53	Xx; N X: 43–51/53 S: (2-)24–37–61
607–280–00–9	4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx sodný xxxxxxx-4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx		406–190–5	54322–20–2	Xx; X22 Xx; X36 X43	Xx R: 22–36–43 X: (2-)22–26–36/37
607–281–00–4	Xxxx:xxxxx(X7-X9 xxxxxxxxxx x lineární)-3-[3-(2H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty		407–000–3	127519–17–9	N; X51–53	X X: 51/53 X: 61
607–282–00-X	2-(xxxxxxxxxxxxx)-4-(xxxxxxxxx)xxxxx-xxxxxx		407–140–5	131266–10–9	X52–53	X: 52/53 S: 61
607–283–00–5	xxxxx-(X)-4-xxxxx-4-xxxxxx-2-xxxxxxxxxx-(X)-4-xxxxx-4-xxxxxxxxxxx		408–040–4	15121–89–8	Xx; R21/22 Xx; X38–41 X43 N; X50–53	Xx; X R: 21/22–38–41–43–50/53 X: (2-)26–36/37/39–60–61
607–284–00–0	Směs (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) x xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx)		410–040–4	136213–76–8	X; X51–53	X X: 51/53 X: 61
607–285–00–6	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 X: (2-)22–24–37
607–286–00–1	Xxxx:xxxxxx- x xxxxxxx-7-[4-({4-[(2-xxxxxxx-1-xxxxxx)xxx]xxxxx}xxx)xxxxxxxxxxxxxxxxx]xxxxxxxx-1,3-xxxxxxxxxx		410–070–8	141880–36–6	X43 X52–53	Xx X:43–52/53 S: (2-)22–24–37–61
607–287–00–7	xxxxxx-[1-xxxxxx-2-(xxxxxxxxxxxxxxx)xxxxx]-1,2,3,6-xxxxxxxxxxxxxxxx		410–140–8	—	X52–53	X:52/53 S: 61
607–288–00–2	[x-(X -{3-[(1-{3-[(2,6(4,6)-xxxxxxx-5-xxxxxxxxxxxxx-4(2)-xx)xxxxxxxxxxx]xxxxxx}-2-xxxxxxx-4-xxxxxx-6-xxx-1,6-xxxxxxx-3-xxxxxxx)xxx]-4-xxxxxxxxxxxxxx}xxxxxxxxx)-x,x,x -xxxxxxxxxxxxxxxxxxxxxxx]xxxxxxxxx xxxxxxx, xxxxxxxxxx xxx; x = 15, 16, 17 xxxx 18, x = 1, 2, 3 xxxx 4, x = 8, 9, 10 xxxx 11, d = 22, 23, 24 xxxx 25		410–160–7	148732–74–5	Xi; X36 R43 X52–53	Xx X: 36–43–52/53 S: (2-)22–26–36/37–61
607–288–00–8	3-[(3-{X —[4-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxx]xxxxxxxxx}-4-xxxxxxx-1-xxxxxx)xxxxxxxx]xxxxxxxxx kyselina		410–370–9	105488–33–3	R53	R:53 X: 61
607–290–00–3	Xxxx (x xxxxxxxx xxxxxx):xxxxxxx-1-xxxxx(X14-X18)-4-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx x xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx		410–540–2	—	Xx; X38 X43 X; X50–53	Xx; N X: 38–43–50/53 X: (2-)24–37–60–61
607–291–00–9	xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx		410–630–1	104051–92–5	X53	X: 53 X: 61
607–292–00–4	Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(alkyl(C14)oxy)-1-(methoxymethyl)]octová xxxxxxxx		410–640–6	—	Xx; X38–41 N; X50–53	Xx; X R: 38–41–50/53 X: (2-)26–37/39–60–61
607–293–00-XSměs:	1-(2-aminoethyl)piperazin-1,4-diium-[(2,4,6-trimethylnonyl)fenoxy]benzendisulfonát 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; X X: 41–43–51/53 S: (2-)26–36/37/39–61
607–294–00–5	xxxxxxx-2-(xxxxxxxxxx)-1-xxxxxxxxxxxx-1-xxxxxxxx		410–680–4	—	X43	Xx R: 43 X: (2-)24-37
607–295–00–0	Směs:tetranatrium-fosfonobutandioát x xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx		410–800–5	—	X43 X; R51–53	Xi; 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-fenylendimethyliden)bis(2-oxobornan-10-sulfonová xxxxxxxx)2,2'-xxxxx-3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(1,7,7-xxxxxxxxxxxxxxxx[2.2.1]xxxxxx-1-xxxxxxxxxxxxxxx xxxxxxxx)		410–960–6	92761–26–7	Xx; X41	Xx R: 41 S: (2-)26-39
607–298–00–7	[2-(xxxxxxxxxxxxxxx)xxxxx]-4-xxxxxxxxxxxxxxxx		411–010–3	—	X43	Xx X: 43 X: (2-)22–36/37
607–299–00–2	xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx		411–040–7	97101–46–7	Xx; X22 X43 X; R50–53	Xn; X X: 22–43–50/53 X: (2-)24–37–60–61
607–300–00–6	[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, d-sulfonatoftalocyanin]měďnatý komplex, xxxxxxxx xxx; a = 1,2,3 nebo 4, x = 8, 9, 10 xxxx 11, c = 15, 16, 17 xxxx 18, x = 22, 23, 24 nebo 25		411–430–7	—	X43	Xx R: 43 X: (2-)22–24–37
607–301–00–1	Xxxx:xxxxxxxxxx kyselina x xxxxxxxxxxx oligo(1-7)laktátů		411–860–5	—	Xi; X38–41 X43 X; X51–53	Xx; X X: 38–41–43–51/53 X: (2-)24–26–37/39–61
607–302–00–7	Xxxx:xxxxxxxxxxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxxx(1-7)xxxxxxx		411–910–6	—	Xx; X38–41 X43 X; X51–53	Xx; X X: 38–41–43–51/53 X: (2-)24–26–37/39–61
607–303–00–2	1-xxxxxxxxxxx-6,7-xxxxxxx-4-xxx-1,4-xxxxxxxxxxxxxxx-3-xxxxxxxxxxx kyselina		413–760–7	93107–30–3	Repr. 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-nitro-4,5-bis(benzyloxy)fenyl]acetonitril		410–970–0	117568–27–1	R53	R:53 X: 61
609–053–00-X	xxxxxxxxxxx-xxxxxxxxxxxxxxxx		414–850–9	—	X; X3 X; X8 Karc. kat. 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 C; X34 X43 N; X50–53	X; N X: 22–34–43–48/22–50/53 X: (1/2-)22–26–36/37/39–45–60–61
611–043–00–5	Xxxx (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx, [xxx{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx xxxxxxxx a[{6-[(2-amino-4-hydroxyfenyl)azo]- xxxx 6-[(2-amino-6-hydroxyfenyl)azo]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx		402–850–1			Xx X: 41–52/53 X: (2-)26–39–61
611–044–00–0	Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [bis(4-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan 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; R51–53	Xi; X41 X52–53
611–045–00–6	2-({4-[(4-xxxxxxxxxxxx)xxxxxxxxxx]-2-xxxxxxxxxxx}xxx)-3-xxxxxx-5-xxxxxxxxxxxx		404–830–8	—	X53	X:53 S: 61	X X: 51/53 X: 61
611–046–00–1	4,4'-xxxxxxx-2-xxxxxxxxxxxxxxx2-xxxxxxxxxxxxxxx-4,4'-xxxxxx		407–590–2	43151–99–1	X; X25 Xn; X48/22 R43 N; X50–53	X; X X: 25–43–48/22–50/53 S: (1/2-)22–28–36/37–45–60–61
611–047–00–7	Xxxx (1:1):2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx		407–890–3	111381–11–4	X53	X: 53 X: 61
611–048–00–2	Xxxx (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx a 2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx	407–900–6	111381–12–5	X53	X: 53 X: 61
611–049–00–8	Xxxx (2:1:1)7-[(4-{[3-(xxxxxxxxxxxx)xxxxxx]xxxxx}-6-{[3-(xxxxxxxxxxxxx)xxxxxx]xxxxx}-1,3,5-xxxxxxx-2-xx)xxxxx]-3-{[4-(xxxxxxxx)xxxxx]xxx}-4-xxxxxxxxxxxxxxx-2-xxxxxxxx, kyselina xxxxxx x xxxxxx kyselina (2:1:1)	408–000–6	118658–98–3	Xx; X48/22 X43 X52–53	Xx X: 43–48/22–52/53 X: (2-(22–36/37–61
611–051–00–9	2-({4-[xxxxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxx}xxx)-6-xxxxxxx-3-xxxxxxxxxxxxxxxxxxxxx-xxxxxxx		411–110–7	136213–74–6	X; X50–53	X X: 50/53 X: 60-61
611–052–00–4	[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) xxx]-6-[(6-xxxxxxxxx-1-xxxxxx)xxx]xxxxxx-1,3-xxxxxxx}]xxxxxxxxx xxxxxxx, xxxxx sůl		400–720–9	—	R52–53	R: 52/53 X: 61
612–156–00–2	Xxxx:xxxxxxxxxxxx(xxxxxx)xxxxxxx-xxxxxxx x xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx		405–620–9	—	Xx; R41 X; X50–53	Xx; X X: 41–50/53 X: (2-)26–39–60–61
612–157–00–8	(Z)-1-(1-benzothiofen-2-yl)ethan-1-on-oxim-hydrochlorid		410–780–8	—	Xn; X22–48/22 Xx; X41 X43 X; R51–53	Xn; X X: 22–41–43–48/22–51/53 X: (2-)22–26–36/37/39–61
612–158–00–3	Xxxx:[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx a 4-xxxxxxxxxxxxxxxxxxxxx		410–820–4	—	X53	X: 53 X: 61
612–159–00–9	xxxxxxx xxxxxxxx xxxxx 2,2,4-xxxxxxxxx- x 2,4,4-trimethylhexan-1,6-diaminu (x xxxxxxx XXXXXX), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Epoxid 8) x 4-xxxxxxxxxxxx-1-xxxxxxxxx xxxxxxxx		410–880–1	—	Xx; X22 C; X34 X; R50–53	C; X X: 22–34–50/53 X: (1/2-)23–26–36/37/39–45–60–61
613–149–00–7	2-xxxx-xxxxx-5-[(4-xxxx-xxxxxxxxxxx)xxxxxxxx]-4-xxxxxxxxxxxxxx-3(2X)-xx		405–700–3	96489–71–3	X; X23/25 X; X50–53	X; N X: 23/25–50/53 X: (1/2-)36/37–45–60–61
613–150–00–2	2,2'-[xxxxxxxxx-1,4-xxxxxx(xxxxxx-1,3-xxxx)]xxx(xxxxxxxxxxx[2,1-x]xxxxx[xxx][3,8]xxxxxxxxxxxx-1,3,6-xxxxx)		406–295–6	—	X53	X:53 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 H)-dion		406–360–9	104218–44–2	R53	R: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 X: 61
613–154–00–4	2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx		410–050–9	5734–64–5	Xx; R22	Xn X: 22 X: (2-)22
613–155–00-X	5-xxxxx-2,3-xxxxxxxxxxxxxx		410–090–7	89402–43–7	X10 Xx; R22 X52–53	Xx X: 10–22–52/53 X: (2-)23–36–61
613–156–00–5	2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-butyl-5-chlorimidazol-4-karbaldehyd		410–260–0	83857–96–9	R43 N; X51–53	Xx; N R: 43–51/53 S: (2-)24–37–61
613–157–00–0	2,4-xxxxxxx-5-(xxxxxxxxxxxxx)xxxxxxxxx 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx		410–330–0	54236–98–5	Xx; X22–48/22 Xx; X36	Xx X: 22–36–48/22 X: (2-)22–26–36
613–158–00–6	2,3-xxxxxxx-5-(xxxxxxxxxxxxxx)xxxxxxx		410–340–5	69045–84–7	Xx; X20/22 Xx; X41 X43 X; R51–53	Xn; X X: 20/22–41–43–51/53 X: (2-)24–26–37/39–61
613–159–00–1	4-[2-(4-xxxx-xxxxxxxxxx)xxxxxx]xxxxxxxxxx		410–580–0	120928–09–8	X; R25 Xx; X20 X; X50–53	X; X X: 20–25–50/53 X: (1/2-)37–45–60–61
613–160–00–7	2-xxxxxx-2,5-xxxxxxxxxxxx[2.2.1]xxxxxx-xxxxxxxxxxxxx		411–000–9	125224–62–6	X43	Xx X: 43 X: (2-)24-37
615–022–00–1	xxxxxx-3-(xxxxxxxxxxxxxxxxxx)xxxxxxx-2-xxxxxxxxxx		410–550–7	79277–18–2	X; X2 R14 Xn; X48/22 X42/43	X; Xx X: 2–14–42/43–48/22 S: (2-)22–30–35–36/37
615–023–00–7	xxxxxxxxxxx 2-[(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 X: 10–14–20–40–41–42–48/22 X: (2-)23–26–36/37/39
616–044–00–4	X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)-2-(3-xxxxxxxxxxxxxxxx)xxxxxxxxx		402–510–2	—	X; X51–53	X X: 51/53 X: 61
616–045–00-X	2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxxxxx		405–190–2	122371–93–1	X43 X53	Xx X: 43-53 S: (2-)22–24–37–61
616–046–00–5	X -[2-(6-xxxxx-7-xxxxxxxxxxxxxx[1,5-x][1,2,4]xxxxxxx-4-xx)xxxxxx]-2-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxxxxxx		406–390–2	—	X; X50–53	X X: 50/53 X: 60-61
616–047–00–0	Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x X, X′,X″,X′′′ - tetraalkyl(C18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx		406–640–0	—	X43	Xx X: 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 X: 61
616–050–00–7	1-[2,5-xxxxxxx-4-(1,1,2,3,3,3-xxxxxxxxxxxxxxxx)xxxxx]-3-(2,6-xxxxxxxxxxxx)xxxxxxxx		410–690–9	103055–07–8	X43 N; X50–53	Xx; X X: 43–50/53 X: (2-)24–37–60–61
616–051–00–2	Směs:3,3'-bis(4-methylfenyl)- 1,1'-(4-methyl-1,3-fenylen)dimočovina x 3,3'-xxx(4-xxxxxxxxxxx)-1,1'-(2-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx Xxxx:2,4-xxx[3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx x 2,6-xxx[(3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx		411–070–0	—	X53	X: 53 X: 61
617–015–00–9	xxx(4-xxxxxxxxxxxxx)xxxxxxx		407–950–9	895–85–2	X; X2 X; X7 N; X50–53	X; X R: 2–7–50/53 S: (2-)7–14–36/37/39–47–60–61
650–032–00-X	cyprokonazol (XXX) (2X, 3X)-, (2 X, 3 X)-, (2 R, 3 S)-, (2 X, 3 R)-2-(4-chlorfenyl)-3-cyklopropyl-1-(1H- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		—	94361–06–5	Xxxx. kat. 3; X63 Xn; X22 X; X50–53	Xx; X X: 22–50/53–63 S: (2-)36/37–60–61

PŘÍLOHA 2

XXXXXX XXXXXXXXXXXX XXXXX SPOJENÝCH X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Komise 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.

PŘÍLOHA 3X

XXXXXXXXXX POKYNY XXX XXXXXXXX XXXXXXXXX X NEBEZPEČNÝMI XXXXXXX X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.

XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES,

Úř. xxxx. X 332, 28.12.2000, x. 81.

PŘÍLOHA 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx na xxxxxxxxxxxx xxxxxxx x savců xx vitro xx xxxxxxxxxxxxx činitele, xxxxx xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx v xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Rozlišují xx xxx typy xxxxxxxxxxxx xxxxxxx: chromozomové x chromatidové. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx xxxxx rutinně používána. Xxxxxxxxxxxx xxxxxx x xxxxxxx jevy xxxx xxxxxxxx xxxxx geneticky xxxxxxxxxxx chorob x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx a s xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx změny v xxxxxxxxxx x x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx indukci xxxxxxxx u člověka x u xxxxxxxxx xxxxxx.

Xx zkoušce xx xxxxxxxxxxxx xxxxxxx in xxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx buněčné xxxxx, buněčné xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx. Xxxxxxx xxxxx xxxx xxxxxxx na xxxxxxx schopnosti růstu x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx a xxxxxxxxx xxxxxxxx chromozomových xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx obecně vyžadují xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Tento xxxxxxxxxxx xxxxxxxxx systém xxxxxx xxxxx napodobit xxxxxxxx xx xxxx x savců. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx vedly x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx x xxx xxxxx xxxxxx xX, xxxxxxxxxx nebo xxxxxxxx úrovní xxxxxxxxxxxx (4, 5).

Xxxx xxxxxxx xx xxxxxxx ke xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx pro xxxxx. Xxxxx xxxxxxxxx, xxx něž je xxxx zkouška xxxxxxxxx, xxxx pro xxxxx xxxxxxxxxxx; mezi xxxxx xxxxxxxx x karcinogenitou xxxx není xxxxxxxxx xxxxxxxx. Korelace závisí xx chemické xxxxx x xxxxxxxxx xxxxxx x tom, že xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx zjištěny xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx jinými mechanismy xxx přímým xxxxxxxxxx XXX.

Xxx xxxx Obecný xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxx nebo xxxxx a xxxxxxxx xxxxxxx chromatid.

Chromozomová xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx x xxxxxxx xxxx xxxxxxxxx v tomtéž xxxxx.

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

Xxx : xxxxxxxxxxxx xxxx xxxxx xxx xxxxx jedné xxxxxxxxxx x s xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

Xxxxxxxxx aberace : odchylka xxxxx xxxxxxxxxx od xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxx typu buněk.

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx jsou xxxxxxxxx xxxxxxxx látce, x xx s xxxxxxxxxxxx xxxxxxxx a bez xx. X předem xxxxxxxxxxx xxxxxxxxxxx po xxxxxxxx xxxxx xx xx xxxxxxxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx), xxxxxxx xx sklidí, xxxxxx x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxxxxxxx pozorováním xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Mohou být xxxxxxx xxxxx xxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxx kultury, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (xxxx. xxxxxxxxxxx xxxxxx čínského, lymfocyty xxxxxxxxx krve xxxxxxx xxxx jiných xxxxx).

1.4.1.2 Xxxxx a kultivační xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx být xxxxxxx vhodná kultivační xxxxx a xxxxxxxxx xxxxxxxx (kultivační nádoby, xxxxxxxxxxx XX2, teplota x xxxxxxx). U xxxxxxxxxxxxxxx buněčných xxxxx x xxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxxx chromozomů x mělo by xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx neměly xxx xxxxxxx. Xxx xxxxxxx xxxxx a xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx x xxxxx: xxxxx se pomnoží x xxxxxxxxx xxxxxx, xxxxxx xx xx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxxx, xxx xxxxxxxxx konfluence před xxxxxxxxx, x xxxxxxxx xx při 37 °X.

Xxxxxxxxx: xxxx xxxxxxxx xxxxxxxxxxxxxxx (xxxx. heparinem) xxxx oddělené xxxxxxxxx xxxxxxxx probandů se xxxxxxx xx kultivačního xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. xxxxxxxxxxxxxxxx) a xxxxxxxx xx při 37 °C.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx by měly xxx vystaveny zkoušené xxxxx, x xx x xxxxxxx metabolickou xxxxxxxx x xxx xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx z xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Aroclor 1254 (6, 7, 8 x 9), xxxx směs xxxxxxxxxxxxx x β-naftoflavonu (10, 11 a 12).

Postmitochondriální xxxxxx xx x xxxxxxxx testovacím xxxxx xxxxxxx používána v xxxxxxxxxxxxx 1 — 10 % obj. Xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx může záviset xx xxxxx chemické xxxxx, která xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce.

Řada xxxxxxxx xxxxxx, včetně xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, poskytuje xxxxxxxx xxx endogenní xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx linií xx xxxx xxx vědecky xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx by xxxx být xxxx xxxxxxxx na xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx rozpouštědlech xxxx vehikulech x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx mohou xxx xxxx xxxxxxxx zředěny. Xxxx xx xxx xxxxxxx čerstvě připravené xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx buněk x x xxxxxxxxx X9. Jsou-li použita xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx údaji x xxxxxx xxxxxxxxxxxxx. Doporučuje xx pokud možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx nestálých xx vodě xx xxxx být xxxxxxx xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx. Xxxx lze xxxxxxxxx přidáním molekulového xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, xxxxx mají xxx zohledněna při xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx systému x xxxxx pH xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx být xxxxxxxxx x metabolickou xxxxxxxx x xxx ní x xxxxxxx experimentu xx použití xxxxxxxx xxxxxxxxxx xxxxxxx integrity x xxxxx, xxxx xxxx stupeň xxxxxxxxxx, xxxxx životaschopných xxxxx xxxx xxxxxxxxx index. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx alespoň xxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx xxxxxxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx rozmezí dané xxxxxxxxx xx minimální xxxxxxxxx, případně xxxxxx xxxxxxxxx, což xxxxxxx xxxxxxx, xx xx xx xxxxxxxxxxx neměly xxxxx xxxx nežli xxxxxxxx 2 xx Ö10. X xxxxxxxx xxxxxxx xx xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, xxxxx xxxxx xxxx mitotického xxxxxx (xxx o xxxx xxx 50 %). Xxxxxxxxx xxxxx je xxxxx nepřímým měřítkem xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x xxxxxx xx xxxx, která xxxxxxxx od xxxxxxxx. Xxxxxxxxx xxxxx je xxxx xxxxxxxxxx u xxxxxxxxxxx xxxxxx, u xxxxx mohou xxx xxxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (AGT), xxxxx xxx xxxxxxx xxxx xxxxxxxxx xxxxxxxxx. X xxxxxxx XXX však xxx o celkovou xxxxxxxxx xxxxxxx, x xxx xxxxx usoudit xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, a x xxxx xxxxxxxxx průměrné xxxxxxxxx xxxx xxxx xxx xx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx výtěžku xxxxxxx.

X případě relativně xxxxxxxxxxxxxxx xxxxx by xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, xxxxx x xxxx xx xxxxxxxx.

X případě xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx xxxxxxx xxx xxxxxxxxxxxxx nižších, xxx xx xxxxxx xxxxxxxxxxx, xx měla být xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxx, jež xx nad xxxx xxxxxxxxxxxx v xxxxxxxx xxxxxxxxxxx xxxxx xx xxxxx doby aplikace. X xxxxxxxx xxxxxxxxx (xxxx. xxxxxxx-xx xx xxxxxxxx xxxxx při xxxxxxx koncentracích, než xx rozpustnost) xx xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, při nichž xxxxxxx xx srážení. Xxxx být xxxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx x testovacím xxxxxxx xx může x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, xxxx X9 xxx. Xxxxxxxxxxxxx xxx xxxxxxx vizuálně. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx být xxxxxxxxx x negativní xxxxxxxx (kontroly xxxxxxxxxxxx xxxx xxxxxxxx). Při xxxxxxx xxxxxxxxxxx aktivace xx měla být xxx pozitivní xxxxxxxx xxxxxxx xxxxxxxx xxxxx, xxxxx x mutagenní xxxxxx vyžaduje xxxxxxxx.

X xxxxxxxxx xxxxxxxx by xxx xxx použit xxxxx xxxxxxxxx x xxxxxxxxxxx koncentracích, které xxxxxxxx xxxxxxxxx reprodukovatelný x detekovatelný xxxxxx xxx xxxxxx, xxxx xx xxxxxxx citlivost xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx odečtu nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx	Xxxxx	Xxxxx XXX	Xxxxx xxxxx EINECS
Bez xxxxxx xxxxxxxxxxx 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 metabolickou xxxxxxxx	xxxxx[x]xxxxx	50–32–8	200–028–5
	xxxxxxxxxxxxx	50–18–0	200–015–4
	xxxxxxxxxxxxx monohydrát	6055–19–2	200–015–4

Pro xxxxxxxxx xxxxxxxx xxxxx být xxxxxxx x xxxx xxxxxx xxxxx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx xxxxx xxxxx x xxxxx použití xxxxxxxxxx xxxxx ze stejné xxxxxxxx třídy.

V okamžiku xxxxxxxx xx xxxx xxx použity xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx samotného xxxxxxxxxxxx xxxx xxxxxxxx x xxxxxxxxxxx médiu x xxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx dosud žádné xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx zkoušené xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxxxxx xxxxxxxx xxxxx xxx xx přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx bez něho. Xxxxxxxx xxxxxxxxx by xxxx xxx xxxxxxxx xxx 48 hodin xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx xxxxxx xxxxxxxxxxx xx měly xxx xxxxxxx xxxxxxx duplicitní xxxxxxx, x xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx pro xxxxxxxxx xxxxxxxx xxxx xxxxxxxx rozpouštědla. Jestliže xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), že xxxx duplicitními kulturami xx xxxxxxxxx xxxxxx, xxxx být xxxxxxxxx xxxxxxx xxxxxx xxxxxxx.

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

1.4.3.3 Doba xxxxxxx xxxxxx

X prvním xxxxxxxxxxx by xxxx xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, xxx x xxxxxxxxxxxx aktivací, xxx xxx ní, xx xxxx 3 — 6 xxxxx, x měly by xxx odebrány po xxxxxx xxxx xx xxxxxxxx aplikace, která xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx (12). Xxxxxxxx xxxxx xxxxxx xxxx negativní xxxxxxxx jak s xxxxxxxx, tak xxx xxxxxxxx, měl xx xxx xxxxxxxx xxxxxxxxx xxxxxxxxxx bez xxxxxxxx x xxxxxxxxxxxx xxxxxxxx xx xx xxxxxx x xxxx, která xxxxxxxx 1,5xxxxxxx normální xxxxx buněčného xxxxx. Xxxxxx xxxxxxxx xxxxx xxx snáze xxxxxxxxx xxx xxxxxx aplikace xxxx xxxxxx xxxxxxx xxx 1,5násobek délky xxxxx. Xxxxxxxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx xxx potvrzeny xxxxxx xx případu. X xxxxxxxxx, kdy xx nepovažuje xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, by mělo xxx podáno xxxxxxxxxx.

1.4.3.4 Xxxxxxxx preparátů pro xxxxxxx xxxxxxxxxx

Xx xxxxxxx xxxxxxx xx xxxxxxx 1-3 xxxxxx před xxxxxxxxx xxxxx Xxxxxxxx® xxxx kolchicin. Xxx xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů se xxxxx xxxxxxx kultura xxxxxx x xxxxxxxxxx xxxxxx. Příprava xxxxxxxxx xxx xxxxxxx chromozomů xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx x obarvení xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx preparátů xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx analýzou xxx xxxxxxxxxxx nezávisle kódovány. Xxxxxxxx při xxxxxx xxxxx dochází ke xxxxx části xxxxx x metafázi x xx xxxxxx xxxxxxxxxx, xxxx by xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxx xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx xxxxx. Xx xxxxxx xxxxxxxxxxx a xxxxxxxx by mělo xxx xxxxxxxxx xxxxxxx 200 dobře rozprostřených xxxxxxxx, xxxxxxxx rovnoměrně xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx.

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

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx jednotkou je xxxxx x xxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx buněk xx strukturní xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx a experimentální xxxxxxx xx xxxx xxx xxxxxxx různé xxxx strukturních xxxxxxxxxxxxxx xxxxxxx x jejich xxxxxx x xxxxxxxx. Xxxx se xxxxxxxxxxxxx xxxxxxxx a xxxxxxx xx, xxx nezahrnují xx do xxxxxxx xxxxxxxx xxxxxxx.

Xxxx xx xxx také xxxxxxxxxxx xxxxxxxx, která xxxx xxxxxxxxx xxx stanovení xxxxxxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxxxxxxxxxx s xxxxxxxxx.

Xxxx xx být xxxxxxx xxxxx pro xxxxxxxxxx kultury. Dále xx měly být xxxxxxx údaje xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx odpovědi xx xxxxxxxxxx. Dvojznačné xxxxxxxx by xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx byla diskutována x xxxx 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x xxxxx rozšířit xxxxxx posuzovaných xxxxxxxx xx xxxx xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x závislosti xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx xxxxxx xxxxx. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx pomocný prostředek xxxxxxxxxxx metody (3, 13). Xxxxxxxxxxx významnost xx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx odpověď.

Nárůst xxxxx xxxxxxxxxxx xxxxx xxxx znamenat, xx xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxx mitotické xxxxxxx x xxxxxxxxx xxxxxxxxx chromozomové xxxxxxx. Xxxxxx xxxxx buněk x endoreduplikovanými xxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (17, 18).

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx xxxx sporné xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx výsledky xx zkoušky na xxxxxxxxxxxx xxxxxxx xx xxxxx znamenají, že xxxxxxxx látka xxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx aberace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxxxxxxx karyotypu a xxxxxxxx použitého xxxx xxxxx,

- popřípadě nepřítomnost xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx xxxxx,

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

- případně xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxx hodnota xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

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

- xxxxxxx xxxxx, případně xxxxxxxxxxx XX₂,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx vehikula x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- případně xxxxxxx xxxxx při nasazení,

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

- xxxxxxxxx a xxxxxxxxx kontroly,

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxx, xxxxx x xxxxxxxx xxxxx, počty buněk, xxxxxxxxx index,

- xxxxxx xxxxxxx,

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

- xxxxxxxx xxxxxxx, xxxxxx xxxx,

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

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

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

2) Xxxxxxxx, X. Xx., Xxxxxx, X. (1985), Xxx Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Xxxxx Chinese Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Xxxxx xx Xxxxxxx, xx: Progress xx Xxxxxxxxxx Research, Xxx. 5, Xxxxx, X. xx xx., (xxx) Xxxxxxxx Science Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Galloway, S. X., Armstrong, M. X., Xxxxxx, X., Xxxxxx, S., Xxxxx, X., Cannon, X., Xxxxx, X. X., Xxxxxxxx, X., Xxxxx, X., Xxx, S., Xxxxx, X., Margolin, X. X., Xxxxxxx, X. X., Anderson, X., Zeiger E. (1978), Xxxxxxxxxx xxxxxxxxxx xxx xxxxxx chromatic xxxxxxxxx in Chinese xxxxxxx xxxxx xxxxx: Xxxxxxxxxx xx 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Xxxxx, X., Xxxxxxxx, S. X., Xxxxxxxx, R. X., Xxxxxxxx, X. Xx., Xxxxxxx, X., Xxxxx, X., Myhr, X. X. (1991), Xxxxxxxxxxxx under Xxxxxxx Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx ICPEMC Xxxx Group 9, Xxxxxxxxxx Res., 257, 147-204.

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

6) Xxxx, X. N., McCann, X., Xxxxxxxx, E. (1975), Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx with the Xxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxx Res., 31, 347-364.

7) Xxxxx, X. X., Ames, X. N. (1983), Xxxxxxx Xxxxxxx xxx xxx Salmonella Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 113, 173-215.

8) Xxxxxxxxx, X. T., Xxxxx, X. X., xxx Xxxx, P. X. X., Xxxxxxx, X., xx Xxxxx, X. (1976), Xxxxxxxxxxx Xxxxxxx xx Mutagen/Carcinogens xxxxx Xxxxxxxxxx in x Xxxxxxxxxxx Xxxxxx In xxxxx, I. Xxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xxx Sister Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Dimethylnitrosamine (XXX) xx XXX Xxxxx xx xxx Xxxxxxxx xx Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

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

10) Xxxxxx, X. X., Xxxxxx, X. D., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. G., Xxxxxx, X. X., Wolf, X. C. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 in In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Sawamura, X., Hara, X., Xxxxxxxx, X. (1976), X. Xxxx Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Systems, in: xx Xxxxxx, X. X., Xxxxx, X. X. Xxxx, J. X., Xxxxxxx, X. X. (xxx), In xxxxx Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Testing, Xxxxxxxx, North-Holland, 85-88.

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

13) Xxxxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, J. X., Xxxxxxxx, X., Chanter, X. X., Xxxxxxxx, X. (1989), Analysis xx Xxxx from Xx xxxxx Xxxxxxxxxxx Xxxxxx, in: Statistical Xxxxxxxxxx of Mutagenicity Xxxx Xxxx, Kirkland, X. X., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

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

15) Xxxxx, X. F., Xxxxxx, X. X., XxXxxxx, K. T. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. M. (eds), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, X. X., Xxxxxx, J. X., Xx, X. P., Xxxxxx, X. X. (1983), Evaluation xx xx Xxxxxxxx Xxxxxx Xxxxx Cells Xxxxx xx Xxxxxxxx Gels xxx Xxxxxxxxx Highly Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Xxxxxxxx Xxxxx, Environmental Xxxxxxx., 5, 795-801.

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

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

XXXXXXX 4X

"X.11 MUTAGENITA–ZKOUŠKA XX XXXXXXXXXXXX ABERACE X XXXXXXX XXXXXX XXXXX XXXXX XX XXXX

1. XXXXXX

Xxxx xxxxxx xx replikou xxxxxx XXXX XX 475 — Xxxxxxx na xxxxxxxxxxxx xxxxxxx x xxxxxxx kostní dřeně xxxxx (1997).

1.1 XXXX

Xxxxxxx xx chromozomové xxxxxxx x xxxxx in xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx aberací indukovaných xxxxxxxxx xxxxxx x xxxxxxx xxxxxx dřeně xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Rozlišují xx xxx xxxx strukturních xxxxxxx — chromozomové x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx může xxxxxxxx, xx chemická xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. V xxxxxxx většiny xxxxxxxxxx xxxxxxxx jsou indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx rovněž xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob u xxxxxxx a xxxxxxxx xxxxx důkazů x xxx, xx xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxxxxxxxxx změny x onkogenech a x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Cílovou xxxxx xx x xxxx zkoušce kostní xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx x xxxxxxx xxxxxx, které xx xxxxxx xxxxxxx a xxxxxxxxxxxx. Xxxx xxxxx x cílové xxxxx xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx je xxxxxxx určená x xxxxxxxxx nebezpečí xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, farmakokinetiku x xxxxxxx xxxxxxxx DNA, xxxxxxx se xxxxx x xxxxxxx xxxxx x xxxxx měnit. Xxxxxxx in xxxx xx xxxxxx užitečná xxx další xxxxxx xxxxxxxxxxx xxxxxx zjištěných xxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx důkaz x xxx, xx se xxxxxxxx látka xxxx xxxxxxxxx metabolity nedostanou xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : strukturní xxxxxxxxx xxxxxxxxxx v podobě xxxxx jednotlivých xxxxxxxxx xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx nebo xxxxx x spojení xxxx xxxxxxxxx x xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : xxxxxx, xxx kterém x xxxxx xx X-xxxx xxxxxxxxx XXX xxxxxxx x xxxxxx, xxxxx xxxxxxxxx xxxxx X-xxxx. Výsledkem jsou xxxxxxxxxx xx 4, 8, 16,… xxxxxxxxxxxx.

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

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

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

Xxxxxxxxxx aberace : mikroskopicky xxxxxxxxxxxxx xxxxx struktury xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx metafáze; xxxx xx jako xxxxxx x fragmenty, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxxxx jsou vystavena xxxxxxxx látce vhodným xxxxxxxx x ve xxxxxxx xxxxxxxx po xxxxxxxx se xxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx podá látka xxxxxxxxxxx metafázi (např. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx xxxxxx xxxxx xx xxxx xxxxxxxx preparáty chromozomů, xxxxxx xx a xxxxxxxxx se chromozomové xxxxxxx buněk v xxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx je xxxxxxxx potkan, myš x křeček xxxxxx, xxxxxx xxx použít xxxxxxxx xxxxxx xxxxx xxxx. Měly by xxx xxxxxxx xxxxx xxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx studie xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx x xxxx pohlaví překročit ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx skupinu x skupinu, xxxxx xx vystaví xxxxxxxx xxxxx. Klece xx xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata se xxxxxxxxxxx identifikují. Xxxxxxx xx x laboratorních xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxx

Xxxxx xxxxxxxx látky xx měly xxx xxxx aplikací xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx mohou xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx při xxxxxxxxx xxxxxxxx dávek toxické xxxxxx x mělo xx xxx xxxxxxxxx xxxxxxxxx, xx reaguje xx zkoušenou xxxxxx. Xxxx-xx použita xxxx xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje se xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí každého xxxxxxxxxxx xx měly xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx obě xxxxxxx. X výjimkou xxxxxxxx xxxxxxxx látky xx xxxx zvířata xxxxxxxxx xxxxxxx podstoupit identický xxxxxx xxxx xxxxxxx xx skupinách, x xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx kontroly xx xxxx xxxxxxxxxx strukturní xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, xx poskytnou xxxxxxxxxxxxx nárůst xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx by měly xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, xxx aby xxx xxxxxx nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx byla xxxxxxxxx kontrola podávána xxxxx xxxxxxxx než xxxxxxxx látka x xxx byl xxxxx x xxxxx případě xxxxxxxx xxx jednou. Xxx pozitivní xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

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

X xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxxxxxx xxxxxxx, jimž xx xxxxxxxxxx xxxxx rozpouštědlo xxxx xxxxxxxxx x xxx xxxxx xxxxxxxxxx xxxxxx proces jako xxxxxxxxxx xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x četnosti buněk x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx prvního xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx x xxxxxxx zvířat

Každá xxxxxxxxxx x kontrolní xxxxxxx xx skládá x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx. Xxxxxxxx xxxx v době xxxxxx k xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx druhem x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx zkoušení xxxxxxx xxxxxxx. Xx-xx xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx pohlaví, xxxx je xxxx xxxxxxxxx u některých xxxxxxxxxxxxxxx xxxxx, měla xx xxx zkouška xxxxxxxxx se xxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx by xxxx být xxxxx xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx mohou xxx xxxxxxxx také xx xxxx xxxxxxx, xxx. dvě xxxxx x xxx xxx x xxxxxxx ne xxxx než xxxxxxxx xxxxx, aby xxxx xxxxxxxxx xxxxxxxx velkých xxxxxx materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx xxx vědecky xxxxxxxxxx.

Xxxxxx xx měly xxx xxxxxxxx ve xxxx různých intervalech xx aplikace xxxxxx x jednom xxx. X xxxxxxxx se xxxxx provádí xx xxxxxx době xx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu (jenž xxxx xxxxxxx 12 — 18 x). Xxxxxxxx doba nezbytná xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx pro xxxxxx na xxxxxxxx xxxxxxxxx xxxxx může xxx xxxx xx xxxxxxxxx okamžik pro xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx xx provést xxxxx odběr po 24 h xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx xx xxxx než xxxxxxx xxx, xxx xx xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky buněčného xxxxx.

Xxxx xxxxxxxxx se xxxxxxxx intraperitoneálně xxxx xxxxxx dávka xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx po xxxxxx době xxxxxxx x zvířat xxxxx. X xxxx je xxxx xxxx přibližně 3 — 5 x; x xxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 x. X xxxxxx dřeně xx odeberou xxxxx x analyzují xx xx xxxxxxxxxxxx xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx studie xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx stejným xxxxxx, kmenem, pohlavím x za stejného xxxxxx xxxxxxxx, jež xx xxxxxxx x xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx xxx první xxxxx xxxxxxx tři xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx stejném režimu xxxxxxxxx podle očekávání x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx vyhovovat x xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší xxxxx xxxx xxx také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx některé známky xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x jednou dávkou xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx toxické xxxxxx x xxxx-xx xx základě údajů x látkách, xxxxx xxxx xxxxxxxx strukturu, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx xx xxxxx úrovněmi xxxxx xx xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx delší než 14xxxxx xxxxxxxx xx xxxxxxx xxxxxx 1000 xx/xx xxxxxxx hmotnosti/den. Xxxxxxxxx expozice xxxxxxx xxxx znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx se xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo vhodnou xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Maximální objem xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, xxxxx obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx xxxxxxxxxx objem při xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů pro xxxxxxx xxxxxxxxxx

Xxxxx po xxxxxxxx se odebere xxxxxx xxxx, hypotonizuje xx x fixuje. Xxxxx se nanesou xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx xxxxxxx cytotoxicity xx xxx xxx x xxxxx xxxxxxxxxxxx xxxxxx (včetně xxxxxxxxxxx xxxxxxx) x x xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx, a xx xxxxxxx u 1000 buněk xx xxxxx zvíře.

U xxxxxxx xxxxxxx xx mělo xxx xxxxxxxxxxx xxxxxxx 100 buněk. Tento xxxxx xxx xxxxxx, xx-xx pozorován xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxx xxxxxxxxxxxxxx analýzou xxxxxxxxx xxxxxxxx. Xxxxxxx při xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xx xxxxxx xxxxxxxxxx x xxxxx xxxxx v xxxxxxxx, xxxx by vyšetřované xxxxx xxxxxxxxx centromery x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx zvířata xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Pro xxxxx xxxxx by měl xxx vyhodnocen xxxxx xxxxx, xxxxx aberací xx buňku a xxxxx xxxxx s xxxxxxxxxxxxx xxxxxxx (chromozomovými xxxxxxxxx) xxxxxxxxx v xxxxxxxxxx. Pro xxxxxxxxxx x kontrolní xxxxxxx xx xxxx být xxxxxxx xxxxx typy xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich počtem x xxxxxxxx. Gapy xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx obecně xx xxxxxxxxxx xx celkové xxxxxxxx aberací. Neexistuje-li xxxxx x xxxxxxx x odpovědi xxxx xxxxxxxxx, mohou být xxx xxxxxxxxxxxx analýzu xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx na xxxxx xxxx xxxxx nárůst xxxxx buněk x xxxxxxxxx pro skupinu x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Statistická xxxxxxxxxx xx neměla xxx xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx polyploidie xxxx xxxxxxxx, xx xxxxxxxx látka má xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx progresi buněčného xxxxx (7, 8).

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, v ojedinělých xxxxxxxxx neumožní soubor xxxxx xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx sporné xxx xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

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

Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx zkoušená xxxxx xxxx její xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, stáří x pohlaví zvířat,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

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

Xxxxxxxx podmínky:

- xxxxxxxxx a negativní (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- xxxxx xx studie xxx xxxxxxxx rozsahu, pokud xxxx xxxxxxxxx,

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- popřípadě metody xxxxxxx, xxx se xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx do cílové xxxxx,

- xxxxxxxx xxxxxxxx xxxx koncentrací xxxxxxxx xxxxx v krmivu xxxx xxxx (xxx) xx odpovídající xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx o xxxxxxx xxxxxx x xxxx,

- podrobný xxxxx xxxxxxx expozice x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- metody přípravy xxxxxxxxx,

- kritéria xxxxxxxxx xxxxxxx,

- xxxxx analyzovaných xxxxx xx xxxxx xxxxx,

- xxxxxxxx klasifikace xxxxxx xx pozitivní, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- typ x xxxxx xxxxxxx uvedený xxxxxxxxxx xxx každé xxxxx,

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

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

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx pozitivní xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

3) Richold, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxxxxx, X. X., Bootman, X., Xxxxxxxxx, L. (1990), In xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Kirkland (xx.), Xxxxx Mutagenicity Xxxxx, XXXXX Recommended Xxxxxxxxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx X xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. R., Xxxxxxx, X., XxxXxxxxxx, X. X., Xxxxxxxx, X., Xxxxxx, X. X., Xxxxxx, X. E., Xxxxxx-Xxxxxxx, M., Xxxxxx Xx., F. X., Xxxxxxxxxxxx, F., Xxxxxxx, X. X., Romagna, X., Xxxxxxx, H., Xxxxx, X., Vannier, X. (1994), Xxxxxx xxxx the Working Xxxxx xx xxx xx xxxx Mammalian Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, R. J., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, P. A., Xxx, X., Esdaile, X. J., Gatehouse, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Richold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx: Dose Xxxxxxx xx In xxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Amphlett, X. X., Xxxxx, G., Xxxxxxxx, X., Xxxxxxx, X., Papworth, D. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxxx Analysis of Xx xxxx Xxxxxxxxxxx Xxxxxx, in: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxx, X. X. Xxxxxxxx (xx.) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 184-232.

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

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

XXXXXXX 4X

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

1. METODA

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

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx in vivo xx xxxxxxxx pro xxxxxxx poškození chromozomů xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx zkoušenou xxxxxx, x to xxxxxx xxxxxxx erytrocytů xxxxxxxxxx x kostní dřeně x/xxxx xxxxx xxxxxxxxx xxxx, obvykle xxxxxxxx.

Xxxxxx xxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx je xxxxxxxxxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, jehož xxxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxx xxxxxxxxx xxxx xxxx xxxxxxxxxx.

Xxxx xx xxxxxxxxxxx xxxxxx dřeně xxxx xx xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxx xxxxx xx xxxxxxxx x xxxxxxxxxx, xxxxx xxx xxx xxxxx vzniknout, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx mikrojader je x těchto xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx hlavní xxxxx. Xxxxxx xxxxxxx polychromatických xxxxxxxxxx s mikrojádry x exponovaných zvířatech xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X tomto xxxxx xx xxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, poněvadž xxxx xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) erytrocytů x xxxxxxxxxx x xxxxxxxxx xxxx xx rovnocenně xxxxxxxxxx u xxxxxxxxxxx xxxxx, x xxxxx xxxx prokázána xxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, nebo xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx nebo numerické xxxxxxxxxxxx xxxxxxx. Xxxxxxxxxx xxx rozlišit řadou xxxxxxxx. Xx zahrnují xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx centromerní (xxxxxxxxxxxx) XXX x xxxxxxxxxx. Xxxxxxxxx se xxxxxxx xxxxxxx xxxxxxxxx (polychromatických) xxxxxxxxxx x mikrojádry. Xxxxx zralých (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxx xxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxxxxxxxx xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx xxxx konečný xxxxxxxx zkoušky, xxxxxxxx xxxx zvířata exponována xxxxx xxxxx xxxx xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx je zvláště xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, třebaže xx xxxxx lišit x xxxxxxx xxxxx x xxxxx, xxxxx x z xxxxxxxxxxx xxxxxxxx. Xxxxxxx in xxxx je rovněž xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx x xxxxxxxxx xx xxxxx.

Xxxxxxxx existuje xxxxx x xxx, xx se xxxxxxxx xxxxx xxxx reaktivní xxxxxxxxxx xxxxxxxxxx xx xxxxxx tkáně, xxxx xxxxxx xxxx zkoušku xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

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

Xxxxxxxxxx : xxxx xxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx x xxxxx xxxx, xxxxxxxxx xxxxx xxxxxxxx mitosy (xxxxxx) xxxxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxxxx fragmenty xxxx xxxxxx chromozomy.

Normochromatický xxxxxxxxx : zralý xxxxxxxxx xxxxxxxxxxxx xxxxxxxx, xxxxx xxx xxxxxxxx od xxxxxxxxx xxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

Xxxxxxxxxxxxxxx erytrocyt : xxxxxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxxx, který xxxxx xxxxxxxx ribozomy, x xxxx xxx xxxx xxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxxxx se xxxxxxx xxxxxxxx vystaví zkoušené xxxxx. Při xxxxxxx xxxxxx dřeně xx xxxxxxx xx xxxxxxx xxxxxxxx xx xxxxxxxx xxxxxx, xxxxxxx xx xxxxxx xxxx, xxxxxxxx xx xxxxxxxxx a xxxxxx se (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx xxxxxxxxx xxxx xx xxxx xx xxxxxxx xxxxxxxx xx xxxxxxxx odebere, xxxxxxxxxx xx připraví xxxxxxxx x xxxxxx xx (4, 8, 9, 10). Xxx xxxxxxxx s xxxxxxxxx xxxx xx měla xxxx xxxxxxxx xxxxxxxx x xxxxxxxxx buněk xxxxxxxx xx xxxxxxxxx xxxx. Xxxxxxxxx jsou xxxxxxxxxxx xx xxxxxxxxxx xxxxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxx použití xxxxxx dřeně se xxxx xxxxxxxxx zvíře xxxxxxxxxx xxx xxxx xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxxx xxxx. Xxx xxxxxxx xxxxxxxxx xxxx xx xxxxxxxxxx xxx. Xxx xxxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx za xxxxxxxxxxx, xx jde x xxxx, u xxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, nebo xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx způsobují xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxx xx xxx použity xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx zvířat. X xxxxxxxx zahájení studie xx měla být xxxxxxxx v xxxxxxxxx xxxxxx minimální x xxxxxx by x xxxx xxxxxxx překročit ± 20 % xxxxxxx hodnoty hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

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

1.4.1.4 Xxxxxxxx dávek

Pevné zkoušené xxxxx by měly xxx před xxxxxxxx xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx zkoušené xxxxx xxxxx být xxxxxxxx xxxxx nebo mohou xxx xxxx xxxxxxx xxxxxxx. Měly xx xxx použity xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxx xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých xxxxxxxx xxxxx toxické účinky x mělo xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Jsou-li xxxxxxx jiná xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Xxxxxxxxxx se pokud xxxxx nejdříve xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx xxx xxxxxxx. S xxxxxxxx aplikace xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx identický xxxxxx xxxx zvířata xx xxxxxxxxx, v nichž xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xx xxxx při xxxxxxxxxxx xxxxxxxx, x xxxxx xx očekává, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, aby byl xxxxxx zřetelný, xxx xxx při xxxxxx xxxxxxx ihned xxxxxx xxxxxxxx identifikace preparátu. Xx přijatelné, xxx xxxxxxxxx xxxxxxxx byla xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka x aby xxx xxxxx x tomto xxxxxxx xxxxxxxx jen xxxxxx. Pro pozitivní xxxxxxxx xxxxx xxxx xxx vzato x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx, xxxx-xx x dispozici. Xxxxxxxx xxxxx xxx pozitivní xxxxxxxx:

Xxxxx	Xxxxx CAS	Číslo podle 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-xxxxxxx	51–18–3	200–083–5

X xxxxxxxx odběru xx xxx xxx xxxxxxxx odběr x xxxxxxx xxxxxxxxx kontroly, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x která xxxxx xxxxxxxxxx stejný xxxxxx xxxx exponované xxxxxxx, pokud nejsou x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx s xxxxxxxxxx. Provádí-li xx xxx negativní kontrolu xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx nebo xxxxxx-xx publikovány xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx xxxx xxxx xxx jako negativní xxxxxxxx xxxxxxxxxx xxxx xxxxxx krve xxxxxxxx xxxx expozicí, xxxxx xxxx x xxxxxxxx xxxxxx s periferní xxxx (xxxx. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, xx xxxxxxxx xxxxx budou x xxxxxxx, xxxxx xx xx xxxxxxx xxxxxxxxxxx xxxxxxx očekává.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx zvířat

Každá xxxxxxxxxx x kontrolní skupina xx musí xxxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx (11). Xxxxxxxx xxxx x xxxx xxxxxx k xxxxxxxxx xxxxx ze xxxxxx xx stejným xxxxxx a xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, jež xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx v xxxxxxxx, xxxx postačující xxxxxxxx xxxxxxx xxxxxxx. Xx-xx expozice xxxxxxx xxxxxxxxxx pro určité xxxxxxx, xxxx xx xxxx například x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx xx xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx aplikace

Nelze xxxxxxxxx xxxxx xxxxxxxxxx plán (xx. jednu, dvě xxxx tři xxxxxxxx x xxxxxxxxx 24 xxxxx). Xxxxxx xx xxxxxx x xxxxxxxxxxxx xxxxxxx podávání jsou xxxxxxxxxx, pokud xx x xxxxxx xxxxxx xxxxxxx xxxxxxxxx výsledky, xxxx –x xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx byla xxxxxxxxx xxxxxxxx xxxx xxxx xxxxxxxxx limitní dávka x podávání xxxxxxxxx xx xx okamžiku xxxxxx. Xxxxxxxx xxxxx xxxxx xxx podávány xxxx xx dvou xxxxxxx, tzn. xxx xxxxx x xxx xxx v xxxxxxx xx více než xxxxxxxx xxxxx, aby xxxx usnadněno xxxxxxxx xxxxxxx xxxxxx materiálu.

Test xxxx xxx xxxxxxxx xxxxx xxxxxxx:

x) zkoušená xxxxx xx aplikuje xxxxxxxx xxxxxx. Vzorky xxxxxx xxxxx xx xxxxxxxx alespoň xxxxxxx, xxxxxxx první xxxxx xx xxxxxxx xxxxxxxx 24 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx xxxxxxxx a x přiměřeným xxxxxxxx xxxx odběry. Xxxxx xxxxx než 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx xxxxxxxxx xxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx se xxxxxxx xxxxxxxx 36 hodin xx aplikaci x xxxxxxxx xxxxxxxxxx 72 xxxxx xx xxxxxxxx x xx xxxxxxxxxxxx xx dodrží xxxxxxxxxxxx xxxxxx. Xx-xx xx xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx odběr nutný;

b) xxxx-xx xxxxxxxx xxx xxxx xxxx dávek xxxxx (např. xxx xxxx xxxx dávek x intervalu 24 xxxxx), měly xx xxx xxxxxx xxx xxxxxxx xxxxxx dřeně xxxxxxxx jednou xx 18 xx 24 xxxxxxxx xx xxxxxxxx xxxxxxxx a xxx xxxxxxx periferní xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).

Xxxxx xxxxxxx xxxxx xxx navíc xxxxxxx xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx studie xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx xxx xxxxxxxxx ve stejné xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, xxxxxxxx x za xxxxxxxx xxxxxx expozice, xxx xx použijí v xxxxxx xxxxxx (13). X případě xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx xxxxx by xxxx pokrývat rozpětí xxxx maximální xx xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru xxxxx, xxxx bude xxxxxxx xxxxx nejvyšší dávka. Xxxxxxxx dávka je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové známky xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx stejném xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx dávkách (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx v xxxxxx xxxxx některé xxxxxx xxxxxxxx (např. snížení xxxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx x xxxxxxxxx xxxx).

1.5.4 Limitní xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx o xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx v xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx toxické xxxxxx a xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx podobnou strukturu, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx úplná xxxxxx xx xxxxx xxxxxxxx xxxxx xx nezbytnou. X déle xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx xxx 14xxxxx xxxxxxxx je xxxxxxx dávkou 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx znamenat xxxxxxx xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx injekcí. Jiné xxxxxxx podávání jsou xxxxxxxxxx x odůvodnitelných xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx je uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, které obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx kostní xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx získávají z xxxxxx xxxx xxxxx xxxxx xx xxxxxxxx. Xxxxx xx xxxxxxxx x xxxxxx xxxx xxxxx x xxxxxxxxxx xxxxxxxx xx preparují x obarví. Xxxxxxxxx xxxx se xxxxxxx x xxxxxx žíly xxxx jiné vhodné xxxxxx cévy. Xxxxxx xxxxx xx xxxxx xxxxxxxxxxxx obarví (8, 9, 10), nebo xx připraví xxxxxxxxx xxxxxxxx x xxxx xx obarví. Xxxxxxxx xxxxxxx xxxxxxxxxxxx xxx XXX (xxxx. akridinová xxxxx (14) nebo Xxxxxxx 33258 x xxxxxxx-X (15)) se xxx vyhnout některým xxxxxxxxxx xxxxxxxx x xxxxxxxx xxxxxxx nespecifického xxx DNA. Xxxx xxxxxx nebrání použití xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Přídavné xxxxxxx (xxxx. xxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, že se xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx pro xxxxxxxxx mikrojader v xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx xx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x celkového (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx xx x xxxxxxx xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 xxxxxxxxxx x v xxxxxxx xxxxxxxxx xxxx alespoň 1000 xxxxxxxxxx (17). Xxxxxxx preparáty xxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx, by xxxx být xxxx xxxxxxxx pod mikroskopem xxxxxxxxx xxxxxxxx. U xxxxxxx xxxxxxx se xxxxxxx alespoň 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx mikrojader x xxxxxxxxxxxxxxxxxxxxx. Xxxxx informace xxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxx erytrocytů xx xxxxxx xxxxxxxxxx. Xxx mikroskopické xxxxxxx xx xxxxx xxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx než 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx nebo xxxx, xxx xxxx xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx erytrocytů na xxxxx xxxxx. Xxxxxxx xxx automatickou analýzu (xxxxxxx xxxxxx x xxxxxxxxx cytometrická xxxxxxx xxxxxxx xxxxxxxx) jsou xx xxxxxxxxxxxxx xxxxxxxxxx x validaci xxxxxxxxxxxx xxxxxxxxxxxxx manuálního hodnocení.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx jednotlivá zvířata xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Xxx xxxxx xxxxxxxxxxx xxxxx xx měl být xxxxxx xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx a xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství erytrocytů. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx nepřetržitě xxxxx xxxxx xxxx xxxx, xxxx xx xxx xxxx uvedeny xxxxx x zralých erytrocytech, xxxx-xx shromažďovány. Pro xxxxx xxxxx xx xxxxx xxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx a xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, xxxxx xxx xxx statistickou xxxxxxx xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx počtu xxxxx x mikrojádry x xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxxx pro xxxxxxx s xxxxxxx xxxxxx x x xxxxxxxx okamžiku odběru. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Xxxxxxxxxxx významnost xx xxxxxx být xxxxxxx určujícím faktorem xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx vyjasněny xxxxxx zkoušením, nejlépe x úpravou xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech neumožní xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu na xx, kolikrát je xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxx xx mikrojádra xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx xxxxxxxxxx, xxx xxxx důsledkem xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxx aparátu xxxxxxxxxxxx testovacího xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx zkoušená xxxxx xx xxxxxxxx zkoušky xxxxxxxxxxx xxxxxxxxxx v xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx.

Xxxx xx být xxxxxxxxxxx pravděpodobnost, s xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx dostanou xx xxxxxxxx xxxxx, nebo xxxxxxxxxx do cílové xxxxx (např. systémová xxxxxxxx).

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx atd.,

- individuální xxxxxxxx xxxxxx na xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné hmotnosti, xxxxxxx xxxxxxx x xxxxxxxxxx odchylka xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

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

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

- zdůvodnění zvolených xxxxxx xxxxx,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- údaje o xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx podávání,

- xxxxxxxxx xxxxxx xxxxxxx, xxx se xxxxxxxx xxxxx dostala do xxxxxxxx oběhu nebo xx xxxxxx tkáně,

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

- xxxxxxxx xxxxx x kvalitě xxxxxx a vody,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x odběru,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx stanovení xxxxxxxx,

- xxxxxxxx xxxxxxxxx mikrojader x xxxxxxxxx erytrocytech,

- xxxxx analyzovaných xxxxx xx jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx z celkového xxxxxxxx xxxxxxxxxx,

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

- xxxxxxx xxxxxxx ± xxxxxxxxxx odchylka xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx ve skupině,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx statistické analýzy x xxxxxx,

- údaje x xxxxxxxx x xxxxxxxxx xxxxxxxxx kontrole,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

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

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

3) Xxxxxx, J. X., Xxxxxxxx, M. X., Xxxx, M., Xxxxxxxx, X., Mavournin, X., XxxXxxxxx, X. X., Xxxxxx, X. X. (1983), Xxx Xxxxxxxxx xx Xxxxxxxxxxx a. x. x Xxxxxxx xx Xxxxxxxxxxxx, Mutatation Xxx. 123, 61-118.

4) Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxx, X. A. (1990), The Xx xxxx Xxxxxxxxxxxx Assay xx Xxxxxxxxx Xxxx Xxxxxx xxx Xxxxxxxxxx Xxxxx. X xxxxxx xx the X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) XxxXxxxxx, X. X., Schlegel, X., Xxxx, W. X., Xxxx, C. M. (1983), Micronuclei xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Screen xxx Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Xxxxxxxx Testing xx Mice, in: Xxxxxxxxxxxx xx Science xxx Xxxxxxxx of Xxxxxxxxxx, xx. A. X. Xxxxx, R. X. Schnell, X. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) MacGregor, X. X., Xxxxxx, X. A. Hite, X., Margolin, X. X., Xxxxx, C., Xxxxxxxx, X. X., Xxxx, X. R., Xxxx, D. (1987), Xxxxxxxxxx for the Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx xx Mammalian Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) XxxXxxxxx, X. X., Wehr, C. X., Xxxxxx, X. X., Xxxxxx, X. X. (1990), Xxx xx vivo Xxxxxxxxxxx Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Xxxxxx Xxxxx Xxxxxxxxx Xxxxx Xxxxxxxxxx xxx Permits Xxxxxxxxxxx xxxx Xxxxxxxx Studies, Xxxxxx. Xxxx. Xxxxxxx. 14, 513-522.

8) Xxxxxxx, X., Xxxxxx, T., Xxxxxx, X., Sofumi, X., Xxxxxxxx, M. Xx. (1990), The Xxxxxxxxxxxx Xxxxx xxxx Xxxxx Xxxxxxxxxx Blood Xxxxxxxxxxxxx Xxxxx Acridine Xxxxxx-Xxxxxx Xxxxxx, Mutatation Xxx., 245, 245-249.

9) Xxx Collaborative Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Test (1992). Xxxxxxxxxxxx Xxxx xxxx Xxxxx Xxxxxxxxxx Blood Xxxxxxxxxxxx by Xxxxxxxx Xxxxxx Xxxxxxxxxx Xxxxxxxx: Xxx Xxxxxxx Xxxxxx xx xxx 5xx Xxxxxxxxxxxxx Xxxxx xx XXXXX/XXXXX, XXX, Xxxxxxxxxx Xxx., 278, 83-98.

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx for xxx Xxxxxxxxxxxx Test (XXXXX/XXXXX, XXX: Xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxx Xxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx of Xxxxx) (1995), Protocol xxxxxxxxxxx for the xxxxx-xxxx mouse peripheral xxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 53-159.

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

12) Xxxxxxxxxxx, N., Xxxxx, S. (1995), Xx xxxxxxx, xxxxxxxxxxx xxxxxxxx time xx 30 ± 6 x xxxxx xxxxxx xxxxxx xx the xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 313-319.

13) Fielder, R. X., Xxxxx, J. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, D. X., Xxxxxx-Xxxxxx, X., Morton, X. B., Kirkland, X. J., Rochold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Environmental Xxxxxxx Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

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

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

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

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

18) Xxxxxxx, X., Xxxxx, J., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Henderson, L. (1990), Xx xxxx Xxxxxxxxxxxx Assay, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Testing. Report, Xxxx 1, xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx York, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Ferguson X., Richold, M., Xxxxxxxx, D. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx of Mutagenicity Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Mutagenicity Xxxxxxx. Xxxxxx, Part XXX, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, New York, Xxxx Chester, Melbourne, Xxxxxx, 184-232."

XXXXXXX 4X

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

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX XX 471 — Zkouška na xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx xx xxxxxxxx xxxxxx s bakteriemi xx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Xxxxxxxxxx typhimurium x Escherichia xxxx, x xxxxxxx bodových xxxxxx, které xxxxxxxx xxxxxxxxxx, xxxxx x xxxxxx xxxxxxx nebo xxxxxxxx xxxx xxxx XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xxxxxxx v detekci xxxxxx, xxxxx xxxxxxxxx xxxxxx xxxxxxxx v xxxxxxxxxxx xxxxxxx x xxxxxxxx tak funkční xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Bakterie xx reverzi jsou xxxxxxxxxx xxxx xxx xxxxxxxxxx xxxx v xxxxxxxxxxxxx xxxxxxxxxxxx, které xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx kmenem.

Bodové xxxxxx x podobné jevy xxxx příčinou xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x xxxxxxxx xxxxx xxxxxx x tom, xx xxxxxx xxxxxx v xxxxxxxxxx x v xxxxxx somatických xxxxx xxxxxxxxx xxxxxx xxxx xxxxx xx tvorbě xxxxxxxx x člověka x x xxxxxxxxx xxxxxx. Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxx, xxxxxxxxxx x xxxxxxxxx xxxxxx. Mnoho testovacích xxxxx xx xxxx xxxxxxxxxx, xxxx nimž xxxx citlivější xx xxxxxxx xxxxxx, včetně xxxxxxxxxxxxx sekvencí XXX xx xxxxxxxxxx místech, xxxxxxx permeability xxxxx xxx xxxxx molekuly x eliminaci xxxxxxxxxxx xxxxxxx DNA xxxx xxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxxxxxxxx x xxxxxx. Specifičnost xxxxxxxxxxx xxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxx informace x xxxxxx mutací, xxx jsou indukovány xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx na xxxxxxxx xxxxxx x bakteriemi xx k xxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxx xxxxx xxxxxxxx x xxxx xxxx xxxxxxxx xxxxx xxxxxxxxxx metody xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx xxxxxxxx xxxxxxxxx, x různými fyzikálně-chemickými xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx xxxxxx x xxxxxxx mutací x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (xxxxxxxx resp. xxxxxxxxx), xxxxxxx xxxxxx xxxx nezávislý xx xxxxxxx xxxxxxx xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx bází xxxx činitele, jež xxxxxxxxx xxxxx x xxxxxx XXX. Xxx xxxxxxx xxxxxxxxxx mutací xx xxxxx tyto xxxxx xxxxxxxxxx xx xxxxx xxxxxxx xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx mutageny xxxx xxxxxxxx, jež xxxxxxxxx xxxxx nebo xxxxxx xxxxxxx xxxx xxxx párů xxxx XXX x posunují xxx xxxxx xxxxx XXX.

1.3 VÝCHOZÍ XXXXX

Xxx xxxxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx využívají prokaryotické xxxxx, xxxxx xx xxxx od buněk xxxxx xxxxxxx, jako xxxx příjem, xxxxxxxxxxxx, xxxxxxxxxxxx struktura a xxxxxxxxx xxxxxxx XXX. Xxxxxxx xxxxxxxxx in xxxxx obecně vyžadují xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx aktivace. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx a xxxxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx xxxxxxxxx využívána xxx počáteční xxxxxxxxx xxxxxxxxxxx xxxxxxxx, x xxxxxxx aktivity vyvolávající xxxxxx xxxxxx. Z xxxxxxxx xxxxxxxx xxxxxxx, xx xxxxx xxxxxxxxxx xxxxx, které jsou x xxxx xxxxxxx xxxxxxxxx, vykazuje mutagenní xxxxxxxx x v xxxxxx xxxxxxxxx. Existují xxxxxxxx mutagenních xxxxxxxx, xxxxx nejsou detekovány xxxxx xxxxxxxx. Xxxxxxx xxxxxx skutečností lze xxxxxxxxx ve specifické xxxxxx xxxxxxxxxxxxxxxxxxxxx jevu, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx xxxx x rozdílech v xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx citlivost xxxxxxx xx xxxxxxxx xxxxxx na bakteriích, xxxxx vést k xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx xxxxxxxx mutace x bakteriemi xxxxxx xxx xxxxxx xxx xxxxxx třídy xxxxxxxxxx xxxxx, například vysoce xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx xxxxxxxxxxx) x xxx xxxxxxxx látky, x nichž se xxxxxxxxxxx (xxxx x xxxxx se xx), xx xxxxxxxxxx xxxxxxxx xx replikačního systému xxxxx xxxxx (xxxx. xxxxxxx inhibitory xxxxxxxxxxxxx x některé xxxxxxx xxxxxxxxxx). X takových xxxxxxxxx mohou xxx xxxxxxxxx xxxxxxx mutagenity x xxxxx.

Xxxxxxxx xxxxx xxxxxxxxx, xxx xxx xx tato xxxxxxx xxxxxxxxx, xx xxxxxxxxxxxx xxx xxxxx, není xxxxxxxx absolutní. Xxxxxx xx chemické xxxxx x xxxxxxxx xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx touto xxxxxxxx, xxxxx působí xxxxxx, xxxxxxxxxxxxxxx mechanismy, xxxx xxxxxxxxxx, xxxxx v xxxxxxxxxxxxx xxxxxxx neexistují.

1.4 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxxx xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx zkoušené xxxxx, x to xx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému x xxx xxxx. Ve xxxxxxxxxxx xxxxxxxx testu xx xxxxxxxx smíchají x vrchním agarem x xxxxx xx xxxxxxx xx xxxxxxxxx xxxx. X xxxxxxxxxxxx xxxxxx xx zkoušená xxxx inkubuje x xxxx se xxxx xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx s xxxxxxx agarem. Xxx xxxx technikách se xx xxxx xxxx xxxxx dnech xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxx xx xxxxxxxx s xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxx misce x xxxxxxxxxxxxx.

Xx xxxxxxx xxxxxxx postupů provedení xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx. Xxxx xxxxx používané xxxxx xxxxxxxxxx xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx xxxx (9, 10) x xxxxxxxxx xxxxxx (11). Xxxxxx xxx xxxxxxxx xxxxx a par xxxx xxxxxxx (12).

Xxx xxxxxxx xxxxxxx xx xxxxxx hlavně xxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Xxxxx x nich xx xxxxxxxxxx xxx provádění xxxxxxxxxxx jak x xxxxxxxxxxxx xxxxxxxx, xxx xxx ní. Některé xxxxx xxx xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxx xxxxx xxxxx xx xxxxxxxxxx tříd, do xxxxx xxxxx mezi xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx kovy, xxxxxxxx, azobarviva x xxxxxxxxxx sloučeniny, xxxxxxxxxxxxxxx xxxxxxxxx, allylové xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx xxxxxxxxx, xx xxxxxx xxxxx xxxxxxxx nelze xxxx xxxxxxxxx xxxxxxxxxxxx postupy, xxxx je xxxxxxxxxx xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Xxxx xx xxx považovány xx "xxxxxxxx xxxxxxx" x x xxxxxx xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx tyto "xxxxxxxx xxxxxxx" (xxxxxxxx x xxxxxxxx xxxxxxx xxxxxx xxxxxxx): xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxx xxx vědecky zdůvodněna.

1.5 XXXXX ZKUŠEBNÍ XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx měly xxx xxxxxxxxxxx do xxxxxx xxxxxxxxxxxxx xxxx xxxx do časné xxxxxxxxxxx xxxx xxxxx (xxxxxxxxx 109 xxxxx xx xx). Buňky x xxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxxx. Xx xxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx xxxx xxx xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x růstové xxxxxx, xxxx xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx xxxxx xx miskách.

Doporučená xxxxxxxxx xxxxxxx xx 37 °X.

Xxxx xx xxx xxxxxxx alespoň xxx xxxxx bakterií. Mezi xxxx xx xxxx xxx xxxxx xxxxx X. xxxxxxxxxxx (XX1535; XX1537 nebo TA97a xxxx TA97; TA98 x XX100), xxxxxxx xxxxxxx xx xxxxxxx x xxxxxxx laboratořích xxxx spolehlivá x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx X. typhimurium xxxx pár xxxx XX xx primárním xxxxxxxxx xxxxx x xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx nelze xxxxxxxxx určité oxidační xxxxxxxx, xxxxxxxx způsobující xxxxxxxxxx xxxxxx DNA x xxxxxxxxx. Xxxx xxxxx mohou xxx xxxxxxxxxx xxxxx X. xxxx WP2 xxxx X. typhimurium TA102 (19), xxxxx xxxx xx xxxxxxxxx xxxxxxxxx xxxxx xxx bází XX. Xxxxxxxxxx xxxxxxxxx xxxxx xx xxxx xxxx:

- X. typhimurium XX1535 x

- X. xxxxxxxxxxx XX1537 xxxx XX97x x

- S. xxxxxxxxxxx XX98 a

- X. xxxxxxxxxxx XX100 x

- X. coli XX2 xxxX, xxxx X. coli WP2 xxxX (xXX101), nebo X. typhimurium XX102.

Xxx xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx XXX xxxx xxx xxxxxxxxx xxxxxxx TA102 xxxx xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx xxxxxxxx DNA, (xxxx. X. xxxx XX2 (xXX101)).

Xxxx xx xxx xxxxxxx xxxxxxxx xxxxxxx přípravy kmenové xxxxxxx, xxxxxxxxxx xxxxxxx x skladování. Xxxxxxx xxxxxxxxxxxxx xxx xxxx xx měla xxx xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx pro xxxxx X. xxxxxxxxxxx a xxxxxxxxx xxx X. xxxx). Xxxxxxx xx xxxx xxx xxxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxxxx xxxxx potřeby xxxxxxxxxx nebo xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, XX100 x XX97x nebo XX97, WP2 xxxX x WP2 xxxX (xXX101) x xxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxx x xxxxx XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx mutací (xx. xxx xxxxxx x S. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx xxxxxx a xxxX xxxxxx x X. xxxx nebo xxxX xxxxxx x S. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxxx) (2, 3). Xxxxx xx xxxx rovněž dávat xxxxx kolonií spontánních xxxxxxxxxx xx xxxxx x xxxxxxx xxxxxxxx xxxxxxxxxxx na základě xxxxxxxxxxx xxxxx laboratorních xxxxxxx x xxxxxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx minimální xxxx (xxxx. obsahující xxxxxxxxx xxxx E (Xxxxx-Xxxxxx) x glukosu) x xxxxxx xxxx xxxxxxxxxx xxxxxxxx x xxxxxx xxxx tryptofan xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx xxxxxxxx

Xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx látce, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x bez xxxx. Nejčastěji používaným xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx ošetřených xxxxxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (1, 2) xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (18, 20, 21). Postmitochondriální frakce xx xxxxxxx xxxxxxxxx x koncentracích x xxxxxxx 5 xx 30 % obj. xx xxxxx X9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx xxxx záviset xx xxxxx zkoušené xxxxxxxx xxxxx. V některých xxxxxxxxx xxxx xxx xxxxxx použít xxxx xxx xxxxx koncentraci xxxxxxxxxxxxxxxxxxx frakce. X xxxxxxxxx x diazoniových xxxxxxxxx xxxx být xxxxxxxxx xxxxxxx redukčního xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx přípravek

Pevné xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx na bakterie xxxxxxxxxx nebo suspendovány xx xxxxxxxx rozpouštědlech xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx přidány přímo x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být xxxx aplikací xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx mimo xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou, a xxxx by xxx xxxxxxxxxx s přežitím xxxxxxxx x x xxxxxxxxx S9 (22). Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx použita organická xxxxxxxxxxxx xxxxxxxxxxxx vodu.

1.5.2 Xxxxxxxx podmínky

1.5.2.1 Xxxxxxxx xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, xxxxx mají být xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx patří xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x předběžných xxxxxxxxxxxxx. Xxxxxxxxxxxx xxxx xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx stupně přežití xxxxxxxxxxxx xxxxxx. Cytotoxicita xxxxx xx xxxx xxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx aktivačních systémů. Xxxxxxxxxxxxx by xxxx xxx posouzena na xxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxxx xxxxx xx skutečných xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx pro rozpustné xxxxxxxxxxxxx xxxxx xx 5 mg/misku xxxx 5 μx/xxxxx. U xxxxxxxxxxxxxxx xxxxx nerozpustných xxx koncentracích 5 xx/xxxxx nebo 5 μx/xxxxx xx xxxx xxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, aby xxxxx xxxx v konečné xxxxx xxx aplikaci xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, by xxxx xxx zkoušeny až xx xxxxxxxxxxx koncentrace. Xxxxxxxxx xx neměla xxxxx při xxxxxxxxxxx.

Xxxx xx xxx použito xxxxxxx pět xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, přičemž při xxxxxx xxxxxxxxxxx by xxxx xxx intervaly xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxx polovině xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx xxxx vhodné x případě, kdy xx xxxxxxxxx křivka xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Zkoušení xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx xxxx xxx xxxxxxx při xxxxxxxxx xxxxx obsahujících xxxxxxxx xxxxxxxx xxxxxxxxxxx mutagenních xxxxxxxx.

1.5.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxx specifické xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx xxxx vehikulum) xxxxxxxx x xxxxxxxxxxxx xxxxxxxx a xxx xx. Pro pozitivní xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx účinnost xxxxx xxxxxxx.

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

Xxxxxxxxx xxxxxx pozitivní kontroly x xxxxxxx x xxxxxxxxxxxx aktivací xxxx xxxx xxxxx:

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

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

Xxxxx	Xxxxx XXX	Xxxxx xxxxx XXXXXX
XX Xxxxxx Red 28	573–58–0	209–358–4

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

Xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx u xxxxxxx xxx xxxxxx xxxxxxxxxxx xxxxxxxx xxxx xxxx látky:

Látka	Číslo CAS	Číslo xxxxx EINECS	Kmen
azid xxxxx	26628–22–8	247–852–1	XX1535 x XX100
2-xxxxxxxxxxxx	607–57–8	210–138–5	XX98
9-xxxxxxxxxxxx	90–45–9	201–995–6	XX1537, TA97 x XX97x
XXX 191	17070–45–0	241–129–4	XX1537, XX97 x XX97x
Xxxxxxxxxxxxxxxxx	80–15–9	201–254–7	XX102
xxxxxxxxx X	50–07–7	200–008–6	XX2xxxX x XX102
1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx	70–25–7	200–730–1	XX2, XX2 xxxX x XX2 uvrA (xXX101)
4-xxxxxxxxxxxxx-1-xxxx	56–57–5	200–281–1	XX2, XX2 xxxX a XX2 uvrA (pKM101)
α-[(5-nitro-2-furyl)methyliden]furan-2-acetamid (XX2)	3688–53–7		xxxxx xxxxxxxxxx plasmidy

Pro xxxxxxxxx xxxxxxxx mohou xxx xxxxxxx xxxx xxxxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxxx kontrolu xx xxxx xxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné chemické xxxxx, xxxx li x xxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, zpracované xxxxx xxxxxxx způsobem xxxx exponované xxxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní xxxxxx.

1.5.3 Xxxxxx

X standardní miskové xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx aktivace xx xxxxxxx xxxxxx 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 ml xxxxxxx xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) x 0,5 xx sterilního pufru x 2,0 ml xxxxxxxx xxxxx. V xxxxxxx xxxxxxx x xxxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,5 xx xxxxxxxxxxx aktivační xxxxx obsahující xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x xxxxxxx 5 xx 30 % xxx. x metabolické xxxxxxxxx xxxxx) s xxxxxxx xxxxxx (2,0 xx) x zároveň x bakteriemi x xxxxxxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx. Obsah xxxxx zkumavky se xxxxxxxx a xxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx misce. Xxxx xxxxxxxx xx xxxxx vrchní xxxx xxxxxxxx.

X xxxxxxxxxxxx metody (2, 3, 5, 6) xx zkoušená xxxxx nebo xxxxxxxx xxxxxx před smícháním x xxxxxxx xxxxxx x přelitím xxxx xxxxxx minimálního xxxxx xx xxxxx obvykle 20 xxxxx nebo xxxx preinkubuje x xxxxxxxxxx xxxxxx (xxxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x xxxxxxxxx xxxxxx xxxx metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) xxx 30 — 37 °X. Xxxxxxx xx xxxxxx 0,05 nebo 0,1 xx xxxxxxxx xxxxx xxxx xxxxxxxxxx roztoku, 0,1 xx xxxxxxxx x 0,5 ml xxxxx S9 xxxx xxxxxxxxxx xxxxx x 2,0 xx vrchního xxxxx. Zkumavky by xxxx být xxxxx xxxxxxxx provzdušňovány na xxxxxxxx.

X dostatečnému xxxxxx xxxxxxxx by xxxx xxx při každé xxxxxx xxxxx xxxxxxx 3 xxxxx. Xxxxxxx xxxx misek je xxxxxxxxxx xx vědeckém xxxxxxxxxx. Případná ztráta xxxxx xxxxxx znamenat xxxxxxxxxxxx zkoušky.

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

1.5.4 Xxxxxxxx

Xxxxxxx xxxxx x xxxx xxxxxxx xx xxxx xxx inkubovány xxx 37 °C xx 48 –72 xxxxxxxx. Po uplynutí xxxxxxxxx doby xx xxxxxx počet xxxxxxx xxxxxxxxxx na xxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxx xxxxx xx xxxx xxx počty xxxxxxx xxxxxxxxxx připadající na xxxxx. Xxx by xxx rovněž xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx na xxxxxxx x negativní kontrolou (xxxxxxxx xxxxxxxxxxxx a xxxxxxxx xxxxxxxxxxxx kontrola), xxx na xxxxxxx x pozitivní kontrolou. Xxxxx na jednotlivých xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx revertantů xx misku x xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxx x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx jasně pozitivní xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx být xxxxxxxxx xxxxxx xx případu. Xxxxxxxx xx potvrzení xxxxxxxxxxx výsledků xxxxxxxxxx xx xxxxxxxx, mělo xx být xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx s xxxxx xxxxxxxx rozsah xxxxxxxxxxxx xxxxxxxx by xxxx xxx zvážena v xxxxxxxxxx experimentech. X xxxxxxxxxx studie, xxxxx xx xxxxx xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx, metoda zpracování (xxxxxxxxxx xxxxxxx metoda xxxx preinkubace v xxxxxxxx xxxxx) x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx xxx xxxxxxxxx rozsah x xxxxxxx xxxxxxx xxxxx x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx nebo bez xxxx, x xx x závislosti xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx xxxxx xxx jednu xxxx xxxx xxxxxxxxxxx (23). Xxxxxxxx xx měla xxx xxxxxxx biologická xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx významnost by xxxxxx xxx xxxxxxx xxxxxxxxx faktorem pro xxxxxxxxx xxxxxxx.

Xxxxxxxx látka, xxxxx xxxxxxxx xxxxxxxxx xxxx uvedená xxxxxxxx, xx xxxxxxxx x xxxxx systému xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx negativní výsledky, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx bez ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky na xxxxxxxx xxxxxx x xxxxxxxxxx znamenají, že xxxxxxxx xxxxx xxxxxxxx x genomu xxxxx Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx xxxxxx xxxxxx substitucí bází xxxx posunem xxxxxxx xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, že xxxxxxxx xxxxx xxxx za xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxx mutagenní.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x zkoušce musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

- xxxxxxxxxxx a stálost xxxxxxxx látky x xxxxxxxxxxxx/xxxxxxxx, je-li xxxxx.

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx v xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxx xxxxx,

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

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

- xxxxxxxxx údaje x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

3) Xxxxxxxxx, D., Xxxxxxx, S., Xxxxxx, X., Xxxxx, X., Xxxx, X., Matsushima, X., Melcion, C., Xxxxx, T., Xxxxxx, X., Xxxxxx, X. (1994), Recommendations xxx xxx Performance xx Xxxxxxxxx Xxxxxxxx Xxxxxx, Xxxxxxxxxx Res., 312, 217-233.

4) Xxxx, X. X., Brusick D. X., Auletta, A. X., Xxx Halle, X. X., Brown, X. X., Xxxxxx, X. X., Xxxxxx, X., XxXxxx, J., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, X. X., Xxx X. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Xxxxxx xx xxx U. S. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 168, 69-240.

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

6) Matsushima, X., Xxxxxxxx, T., Nagao, X., Xxxxxx, X., Xxxxxx, A., Xxxxxxxx, X. (1980), Factors Xxxxxxxxxx Xxxxxxxxxxxx Microbial Xxxxx, in: Xxxxx-xxxx Xxxx Xxxxxxx for Xxxxxxxxx Carcinogens, xx. Xxxxxxx X. H., Xxxxxx, X. X., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

7) Gatehouse, X. X., Rowland, X. X., Wilcox, X., Xxxxxxxxx, X. X., Xxxxxx, R. (1980), Xxxxxxxxx Xxxxxxxx Xxxxxx, xx: Xxxxx Mutagenicity Xxxxx: UKEMS Xxxx 1 Revised, ed. X. J. Xxxxxxxx, Xxxxxxxxx University Xxxxx, 13-61.

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

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

10) Xxxxxxx, X. A., Xxxxx, X. X. X., Xxxxxxxxx, D., Xxxxxxx, X. X. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, xx: Xxxxxxxx of Mutagenicity Xxxx Xxxxxxxxxx, 2. xxx., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, W., Xxxxx, X. (eds.), Elsevier, Xxxxxxxxx-Xxx York-Oxford, 141-161.

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

12) Xxxxx, X., Xxxxxxx, X., Xxxx, X., Matsushima, X. (1994), Xxxxxxxx Method xxx Xxxxxxxxxxxx Xxxxxxx xx Xxxxxxx Xxxxxxxxx xx Xxxxx a Xxx Xxxxxxxx Xxx, Xxxxxxxxxx Res., 307, 335-344.

13) Prival, X. X., Xxxx, X. X., Xxxxxxxx, X. X., Reipert, X. X., Xxxxxxx, V. X. (1984), Mutagenicity xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Xxxx xx a Xxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, X., Anderson, X. E., Haworth, X., Xxxxxx, T., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Tests. X. Xxxxxxx xxxx xxx Testing of 311 Chemicals, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

15) Xxxxxx, X., Xxxxxxxx, X., Xxxxxxx, X. X. (1977), Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxx Xxxxx, xx Xxxxxxxx in Xxxxxxx Xxxxxxxxxx, X. Scott, X. Xxxxxxx, F. Xxxxxx (xxx.) Xxxxxxxx, Xxxxxxxxx, 249-258.

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

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

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

19) Wilcox, X., Naidoo, X., Xxxx, X. X., Xxxxxxxxx, X. X. (1990), Comparison of Xxxxxxxxxx typhimurium TA 102 xxxx Xxxxxxxxxxx xxxx WP2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

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

21) Xxxxxx, X. X., Combes, X. X., Elcombe, X. X., Gatehouse, X. X., Xxxxxx, G. X., Mackay, J. X., Wolf, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx xx xxxxx Genotoxicity Assays, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, D., Xxxxxxxxxxxxxxxx, X., Xxxx, X. X. (1981), Compatibility xx Organic Solvents xxxx the Xxxxxxxxxx/Xxxxxxxxx Xxxx, Xxxxxxxxxx Res., 88, 343-350.

23) Xxxxxxx, X. X., Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Nestmann, X., Zeiger, E. (1987), Xxxxx xxx xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Tests for Xxxxxxxxx Xxxxxxxxxxxx, Mutatation Xxx., 189, 83-91.

24) Xxxxx, G. X. X., Green, X. X. X., Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, W. X., Xxxxxx, D. X. (1989), Xxxxxxxx of Xxxx xxxx Microbial Xxxxxx Xxxxxx, xx: XXXXX Sub-Committee on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Part XX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, xx. Xxxxxxxx, X. X., Cambridge Xxxxxxxxxx Xxxxx, 28-65."

XXXXXXX 4X

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

1. METODA

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

1.1 XXXX

Xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx xx vitro xxx xxxxxx xxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx látkami. Xxxx xxxxxx xxxxxxx linie xxxxx xxxxx xxxxxxx X5178X xxxx, xxxxxxx xxxxx XXX, XXX-XX52 x X79 křečka xxxxxxxx a lymfoblastoidní xxxxx TK6 člověka (1). X xxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx mutace xxxx xxx xxxxxxxxxxxxxx (XX) x hypoxanthin-guaninfosforibosyltransferasu (HPRT) x xxxxxxxx xanthin-guaninfosforibosyltransferasy (XXXX). Xxxxxxx xx xxxxxx TK, XXXX x XXXX detekují xxxxx spektrum xxxxxxxxxxx xxxxxxxx. Autosomální lokace XX x XXXX xxxx umožnit xxxxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx delece), xxxxx xxxxx detekovat x XXXX lokusu na X chromozomech (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx lze použít xxxxxxx zavedených xxxxx xxxxx nebo xxxxxxx xxxxx. Buňky se xxxxxxxx xxxxx xxxxxxxxxx xxxxx x xxxxxxx x xxxxxxxx četnosti xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx použití vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx nemůže xxxxx xxxxxxxxx podmínky xx xxxx x savců. Xx třeba xx xxxxx vyvarovat xxxxxxxx, xxxxx by xxxxx x xxxxxxxxxx xxxxxxxxx, xxx neodrážejí xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx mutagenitu, může xxxxx xxxxxx pH, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Tato xxxxxxx se používá xx xxxxxxxx možných xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx zkouška pozitivní, xxxx karcinogeny xxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx závisí xx xxxxxxxx xxxxx a xxxxxxxxx xxxxxx o xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxx xxxxxx : xxxxxx mutace xxxxxxxxx typu xxxxxxxx xxxxx, která způsobuje xxxxx xxxx xxxxxx xxxxxxxxxxx aktivity kódovaných xxxxxxxx.

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

Xxxxxxxx xxxxxxxx : xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxx nebo xxxx xxxx xxxx x xxxxxxxx DNA.

Doba xxxxxxx xxxxxxxx : doba, xxxxx níž xxxxxx x nově xxxxxxxxxx xxxxx xxxxxxxxx genové xxxxxxxx.

Xxxxxxx mutantů : xxxxx pozorovaných mutantních xxxxx xxxxxx xxxxxx xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxx celkový xxxx : xxxxxx xxxxx buněk x xxxx ve xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx xx xxxx xxxxxx poměru xxxxxxxxx xxxxx x xxxxxxxx x x xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx klonování xxxxxxxx k negativní xxxxxxxx.

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

Životaschopnost : účinnost xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx na xxxxx xx xxxxxxxxxxxx podmínek xx xxxxxxx.

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

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) jsou xxxxxxxxxxx k xxxxxxxxxxxx xxxxxxx analogu pyrimidinu xxxxxxxxxxxxxxxxx (XXX). Xxxxx xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx na TFT, xxx způsobuje inhibici xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxx xxxxxxx xxxxxx. Xxxxxxxx buňky xxxx xxxx schopny xxxxxxxxxxx za xxxxxxxxxxx XXX, xxxxxxx xxxxxxxx xxxxx, které xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Podobně xxx x xxxxx x xxxxxxxxxxxx XXXX xxxx XXXX provést xxxxxxx xxxxxxxxxxxxxxx rezistence x 6-xxxxxxxxxxx (XX) nebo 8-xxxxxxxxxx (XX). Vlastnosti xxxxxxxx xxxxx xx xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx xx xx zkoušce xx xxxxxx xxxxxx x xxxxxxx xxxxx zkoušen xxxxxx báze nebo xxxxxxxxxx xxxxxxx selekčnímu xxxxxxx. Mělo by xxx například xxxxxxxxx xxxxxxxx podezření xx xxxxxxxxxx toxicitu zkoušené xxxxx xxx mutantní xxxx xxxxxxxxxx buňky. Xxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx strukturu xxxx xxxxxxxx xxxxxxx, xxxx xxxx být xxxxxxxxx xxxxxxxx systému xxxx xxxxxxx xxx selekci (8).

Xxxxx x suspenzní xxxx jednovrstevné xxxxxxx xxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxx x metabolickou xxxxxxxx, tak xxx xx, a subkultivovány xx xxxxxx stanovení xxxxxxxxxxxx a xx xxxxxx exprese fenotypu xxxx selekcí xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxx relativního celkového xxxxx kultur xx xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx se xxxxxxx x růstovém xxxxx xx xxxxxxx xxxx charakteristickou xxx xxxxx xxxxxxx xxxxx x xxx xxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx fenotypová exprese xxxxxxxxxxxx mutací. Četnost xxxxxxx se stanoví xxx, xx xx xxxxxx xxxxx xxxxx xxxxx do média xxxxxxxxxxxx xxxxxxxx činidlo xxx xxxxxxx mutantních xxxxx x xx xxxxx bez xxxxxxxxxx xxxxxxx, xxx byla xxxxxxxxx xxxxxxxx klonování (xxxxxxxxxxxxxxx). Po vhodné xxxxxxxxx xxxx xx xxxxxxxxx xxxxxxx. Četnost xxxxxxx xx vypočte x xxxxx xxxxxxxxxx xxxxxxx x xxxxxxxxx xxxxx a xxxxx xxxxxxx x xxxxx xxx xxxxxxxxxx činidla.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Pro xxxxxxx x této zkoušce xxxx x xxxxxxxxx xxxxx typy buněk, xxxxxx xxxxxxxx xxxxx X5171X, XXX, XXX-XX52, X79 nebo XX6. Xxxx xxxxx v xxxx xxxxxxx by xxxx xxxxxxxxx xxxxxxxxx x chemickým xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxxxxxxxx mutací. Buňky xx xxxx xxx xxxxxxxxxxxx, zda nejsou xxxxxxxxxxxxx xxxxxxxxxxxx, x x xxxxxxx kontaminace xx xxxxxx xxx xxxxxxx.

Xxxxxxx by xxxx xxx xxxxxxxx tak, xxx měly xxxxxx xxxxxxxxxx xxxxxxxxx x xxxx. Xxxxx xxxxxxxxx xxxxx, xxxxxx a xxxxxxxxxxx xxxxxxxx látky xx xxx xxxx xxxxxxxxxx xxxxxxxxx odrážet (14). Xxxxxxxxx xxxxx xxxxx, xxxxx xxxxxxx xxxxxxxx x xxxxx xxxxx xxxxxxx v xxxxxx xxxxxx xxxxxxx, xx xxx být xxxxxxx na xxxxxxxx xxxxxxxxxxx mutací. Obecným xxxxxxxxx xx, xxx xxx použit xxxxx xxxxx, který je xxxxxxxxxxxxxx převrácené hodnoty xxxxxxxx spontánních xxxxxx. Xx však doporučeno, xxx xxxx xxxxxxx xxxxxxx 106 xxxxx. Xxxx xx být x dispozici dostatečné xxxxxxxxx údaje x xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx doložena xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.

1.4.1.2 Média x xxxxxxxxxx podmínky

Pro xxxxxxxxx xxxxxx xx měla xxx použita vhodná xxxxxxxxxx xxxxx x xxxxxxxxx podmínky (kultivační xxxxxx, xxxxxxxxxxx CO₂, xxxxxxx a xxxxxxx). Xxxxx by xxxx xxx xxxxxxx xxxxx xxxxxxxxxx systémů a xxxx buněk použitých xxx zkoušce. Xx xxxxxxx xxxxxxxx, xxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxx tak, xxx xxxx zajištěny xxxxxxxxx xxxx xxxxx během xxxxxx exprese a xxxxxxxxx xxx xxxxxxxxxx, xxx xxxxxxxxxxxx xxxxx xxxxxx kolonie.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx xx xxxx xxx získávány x xxxxxxxxx xxxxxx, xxxxxxxx xx kultivačního xxxxx x xxxxxxxxxx xxx 37 °X. Xxxx xxxxxxxx v xxxx xxxxxxx xxxx být xxxxxxxx xxxxxxxxx x xxxxxxx xxx přítomné xxxxxxxx buňky.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

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

Postmitochondriální xxxxxx xx v xxxxxxxx xxxxxxxxxx médiu obvykle xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % obj. Volba x xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx třídě xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. V xxxxxxxxx případech může xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx exprimujících xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx xxxxx xx xxxx být xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx isoenzymu xxxxxxxxxx X450 pro metabolismus xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx aplikací xx xxxxx rozpuštěny xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a popřípadě xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx být xxxxxxx přímo x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx zředěny. Xxxx xx xxx použity xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx xxxxxxxxxxx možnost skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx podezření, že xxxxxxx xx xxxxxxxxx xxxxxx, a mělo xx xxx xxxxxxxxxx x xxxxxxxx xxxxx x x xxxxxxxxx X9. Jsou-li použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx použitá xxxxxxxxx rozpouštědla neobsahující xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

Xxxx xxxxxxxx, která xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxx koncentrace, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x testovacím xxxxxxx x xxxxx xX xxxx osmolality.

Cytotoxicita xx xxxx být xxxxxxxxx x xxxxxxxxxxxx aktivací x xxx ní x xxxxxxx xxxxxxxxxxx xx použití vhodných xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, xxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxx celkový xxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx alespoň xxxxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx toxicity by xxxx tyto koncentrace xxxxxxxx rozmezí xxxx xxxxxxxxx x minimální xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, což bude xxxxxxx xxxxxxxx, xx xx xx koncentrace xxxx xxxxx faktorem 2 až Ö10. Xx-xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx, xxxx by xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx nejméně 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx klonování) xxxx xxxxxxxxx xxxxxxx xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 M, xxxxx xxxx, xxxxx x xxxx xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxx xx x xxxx rozpustnosti xx xxxxxxxxxxxx xxxxxxxx, xxxx xx za tuto xxx. Xxxx xx xxx xxxxxxxxx případná xxxxxxxxxxxxx v xxxxxxxx xxxxx, xx kterému xxxx buňky exponovány. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx a xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx xx může x xxxxxxx xxxxxxxx x testovacím xxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, S9 xxxx, xxx. Nerozpustnost xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při vyšetřování.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly být xxxxxxxxx x negativní (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx jak s xxxxxxxxxxxx xxxxxxxx, xxx xxx ní. Xxx xxxxxxx xxxxxxxxxxx aktivace xx xxxx být xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxxxx vyžaduje xxxxxxxx.

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxx xxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx	Xxxxx	Xxxxx	Xxxxx XXX	Xxxxx podle Einecs
Bez 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 velké xxxxxxx)	xxxxxx-xxxxxxxxxxxxxx	66–27–3	200–625–0
	XXXX	xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
	XXXX	1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
X xxxxxx xxxxxxxxxxxx xxxxxxxx	XXXX	3-xxxxxxxxxxxxxxxxx	56–49–5	200–276–4
		X-xxxxxxxxxxxxxxxxxxx	62–75–9	200–549–8
		7,12-xxxxxxxxxxxxxxxxxxxxxx	57–97–6	200–359–5
	XX (xxxx x xxxxx 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 úrovně X9)	62–75–9	200–549–8
	XXXX	xxxxx[x]xxxxx	50–32–8	200–028–5

Xxxxx xxx použity xxxx xxxx xxxxxxxxxx xxxxx pro pozitivní xxxxxxxx, xxxx. má-li xxxxxxxxx databázi dosavadních xxxxx o 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, XXXXXX 200–415–9), může xxx xxxx referenční látka xxxxxx použita. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx x úvahu xxxxxxx xxxxxxxxxx xxxxx pokud xxxxx ze stejné xxxxxxxx xxxxx.

Xxxx xx xxx použity xxxxxxxxx xxxxxxxx tvořené médiem xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxxxxxxx jinak xxxxxxx xxxxxxxx xxxx exponované xxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky xx xxxx xxx xxxxxxxxx xxxxxxxx látce xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému, xxx bez xxxx. Xxxxxxxx by xxxx xxxxx vhodnou dobu (xxxxxxx xx účinná xxxx 3 xx 6 xxxxx). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx na xxxxx xxxx více xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx mohou xxx xxxxxxx xxxxxxxxxx kultury xxxx jedna xxxxxxxxxx xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, xxx xx xxx xxxxx xxxxxxxxxxx xxxxxx xxx, xxx byl xxxxxxxx xxxxxxxxxxxx xxxxx kultur xxx xxxxxxx (xxxx. xxxxxxx osm xxxxxxxxxxxxxxxx xxxxxxxxxxx). Měly xx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx rozpouštědla).

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

1.4.3.2 Xxxxxxxxx xxxxxxx, xxxxxxxxxxxxxxxx a četnosti xxxxxx

Xx xxxxx xxxxxxxxx xxxx xx xxxxx xxxxxxx a xxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxx x za xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Se xxxxxxxxxx cytotoxicity prostřednictvím xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxxx celkového xxxxx xxxxxx xx xxxxxxx xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx lokus xx xxxxxxxxxx minimální časové xxxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (XXXX a XXXX xxxxxxxx xxxxxxx 6 až 8 xxx, TK xxxxxxx xxx dny). Xxxxx xxxx xxxxxxxxxxx v xxxxx se selekčním xxxxxxxx (xxxxxxxxxx činidly) x bez něho (xxx xxxx) xx xxxxxx stanovení počtu xxxxxxx x xxxxxxxxx xxxxxxxxx. Se stanovením xxxxxxxxxxxxxxxx (použité pro xxxxxxx xxxxxxxx mutantů) xx xxxxxxx xx xxxxx xxxx xxxxxxx xxxxxxxxx xx xxxxx xxx selekčního činidla.

Je-li xxxxxxxx xxxxx xxxxxxxxx xx xxxxxxx L5178Y XX+/-, xxxx xx xxx xxxxxxxxx alespoň xx xxxxx ze xxxxxxxxxx kultur (x xxxxxxxx xxxxxxxxx koncentrací) x na xxxxxxxxxxx x xxxxxxxxxxx kontrolách xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií. Xx-xx xxxxxxxx látka xx xxxxxxx X5178X XX+/- xxxxxxxxx, xxxx xx xxx xxxxxxxxx kultury xxxxx xxxxxxxxx xxxxxxx xxxxxxxxx na negativních x pozitivních kontrolách. Xxx studiích xx xxxxxxx XX6 XX+/- xxxx xxx xxxx xxxxxxxxx xxxxxxxxx kultury xxxxx xxxxxxxxx xxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xx xxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxxxxxxx, xxxxx kolonií x xxxxxxxx mutantů xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. V xxxxxxx pozitivní odpovědi xx xxxxxxx X5178X XX+/- se kolonie xxxxxxxxx alespoň u xxxxx xxxxxxxxxxx xxxxxxxx xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x u xxxxxxxxx x xxxxxxxxx xxxxxxxx xx použití xxxxxxxx xxxx xxxxxxx — xxxxx kolonie. Xxxxxxxxxxx a cytogenetická xxxxxx xxx mutantů xxxxxxxxx xxxxx xxxxxxx, xxx mutantů xxxxxxxxx xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Xx xxxxxxx XX+/- xxxx kolonie xxxxxxxxxxx za použití xxxxxxxx kolonie x xxxxxxxxx růstem (xxxxx) x xxxxxxx s xxxxxxx růstem (malá) (25). X xxxxxxxxxx xxxxx, xxxxx utrpěly xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx doby xxxxxxxx, x xxxxx xxxx xxxx kolonie. Xxxxxxxxx xx obvykle xxxxxx xx ztrát xxxxxx xxxx xx xx karyotypické xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxx xxxxxxx xxxxxxxxx xxxx xxxxxxx xx spojuje x xxxxxxxxxx látkami, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx xxxxxxxxx xxxxx mutantů xxxxxx xxxxxxxx tempem xxxx xxxxxxxx xxxxx x xxxxx xxxxx xxxxxxx.

Xxxx xx xxx xxxxx xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. Četnost xxxxxxx xx xxxx xxx xxxxxxxxx xxxx xxxxx mutantů x xxxxx přeživších xxxxx.

Xxxx xx být uvedeny xxxxx xxx xxxxxxxxxx xxxxxxx. Xxxx xx xxxx být všechny xxxxx shrnuty ve xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx být xxxxxxxxx xxxxxx xx xxxxxxx. Tam, xxx xxxx potvrzení xxxxxxxxxxx xxxxxxxx považováno za xxxxx, je třeba xxxxx xxxxxxxxxx. Změna xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx podmínek xx xxxx xxx zvážena x následných experimentech xxx xxx dvojznačné xxxxxxxx, tak pro xxxxxxxxx xxxxxxxx. X xxxxxxxxxx studie, xxxxx xx xxxxx xxx xxxxxxx, patří rozmezí xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, xxxx. nárůst xxxxxxxx xxxxxxx v závislosti xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx této xxxxxxxx. Xxxxxxxx by xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx xxxxxxx xxxxxxxxx faktorem pro xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx negativní výsledky, x xxxxxxxxxxx případech xxxxxxxx soubor údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky na xxxxxx xxxxxx x xxxxxxx savců xx xxxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx kultivovaných xxxxxxx xxxxx genové xxxxxx. Reprodukovatelná xxxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx je xxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx neindukuje v xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx genové xxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Buňky:

- xxx x zdroj xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- případně xxxxx xxxxxx,

- případně metody xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxx xxxxx, případně xxxxxxxxxxx XX₂,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- případně xxxxxxx xxxxx xxxxx xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

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

- xxxxxxxx xxxxxxx,

- xxxxxxxx klasifikace xxxxxxx xx pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx buněk,

- xxxxxxxx xxxxxxx podle xxxxxxxxx x xxxx (xxxxxxxx xxxxxx xxxxxxxx xxx "xxxx" x "velké" xxxxxxx).

Xxxxxxxx:

- známky toxicity,

- xxxxxx xxxxxxx,

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

- velikost xxxxxxx, xxxx-xx vyšetřována, xxxxxxx pro negativní x pozitivní xxxxxxxx,

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

- xxxxxxxxx xxxxx x negativní (rozpouštědlo/vehikulum) x pozitivní xxxxxxxx x rozmezími, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx,

- xxxxxxx xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., XxXxxxxx, X. M., DeSerres, X. X., Xxxxxx, X. X. (xxx.) (1987), Xxxxxxx Xxxxxx 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Xxxx Spring Xxxxxx Xxxxxxxxxx, Xxx Xxxx.

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

3) Liber, X. X., Xxxxxx, W. X. (1982), Xxxxxxxx Xxxxx xx the Xxxxxxxxx Kinase Xxxxx xx Xxxxxxx Xxxxx Xxxxxxxxxxxx, Xxxxxxxx Res. 94, 467-485.

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

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

6) Xxxxx, C. X., Xxxxxxxxxx, X., Xxxxx, X. X., Xxxxx, X., Nishi, X., Xxxxxxxxxx, Xx. X. X., Xxxxxx, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Working Xxxxx Xxxxxx. Report xx the International Xxxxxxxx xx Standardisation xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxxx Res. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, D., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. X report xxxx ICPEMC Xxxx Xxxxx 9, Mutation Xxx. 257, 147-204.

8) Xxxxx, X., XxXxxx, X., Xxxxxxx, J. X. X., Xxxxx, X., Xxxxxxxxx, K. X. (1983), Specific Xxxx Xxxxxxxxx in X5178X Cells xx Xxxxxxx. X Xxxxxx xx xxx X. X. Environmental Xxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Res., 115, 225-251.

9) Li, A. X., Xxxxx, X. X., Xxxxxxx, R. X., Xxxxxx, X. X. (1988), A Xxxxxx xxx Xxxxxxxx xx the Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Transferase System xx Determine xxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx: X Xxxxxx xx Phase III xx the U. X. Xxxxxxxxxxxxx Protections Xxxxxx Gene-Tox Program, Xxxxxxxxxx Res., 196, 17-36.

10) Xx, X. X., Xxxxxx, X. X., Xxxx, W. X., Hsie, X. X., Xxxxx, R. X., Xxxxxxx, X. X., X'Νxxxx, X. X., Xxxxxx, J. X., Stankowski, X. X. Jr., Xxxx, X. X. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx of xxx Xxxxxxx Xxxxxxx Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

11) Xxxxx, X. L., Xxxxxxx, X. X., Xxxxxx, X. X. (1989), X Xxxxxxxxxx of Xxxxxxxx Induction xx xxx XX and XXXX Xxxx xx Xxxxx Xxxxxxxxxxxxxx Xxxxx: Xxxxxxxxxxxx Xxxxxxxxxxx are Xxx to xx Xxxxxxxxxx Class xx Xxxxxxxxx xx xxx Xxxxxxxxx XX Locus, Xxxxxxxxxx Xxx., 216, 9-17.

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

13) Xxxxxx, N. X., Xxxxxx, A. X., Xxxxx, D. (1984), Xxxxxxxxx for xxx X5178X/XX+/--XX+/- Xxxxx Lymphoma Xxxx Xxxxxxxxxxxx Xxxxx, xx: Xxxxxx, X. X. xx al (xxx.) Xxxxxxxx of Xxxxxxxxxxxx Test Xxxxxxxxxx, Xxxxxxxx Science Xxxxxxxxxx, Xxx York, 239-268.

14) Xxxxxx, X. F., Xxxxx, X. M., Xxxxxx, X. M., Xxxxx, M. X. X., Xxxx, X., XxXxxxxx, X. X., Xxxxxxx X. X. (1989), Mammalian Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxx xxxx Colony Xxxxxxxxx, xx: Statistical Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, Kirkland, X. X., ed., Xxxxxxxxx University Press, 66-101.

15) Abbondandolo, A., Xxxxxxx, S., Corti, X., Xxxxxx, R., Xxxxxxxx, N., Xxxxxxxxxx, X. (1977), Induction xx 6-Thioguanine-Resistant Xxxxxxx xx X79 Chinese Xxxxxxx Cells xx Xxxxx-Xxxxx Microsome-Activated Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Res. 46, 365-373.

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

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

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

19) Xxxxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, C. X., Xxxxxxxxx, X. X., Gibson, X. X., Mackay, X. X., Xxxx, R. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-Xxxxxxx X9 xx: Xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Sawamura, X., Hara, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Biphenyls x. x. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, X: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xx Xxxxxx, X. J., Xxxxx, X. X., Bend, X. X., Xxxxxxx, X. M. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, X. X. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Xxxxxxxxxx of Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Ticc, X. X., Xxxxx, X. L., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Agents, Xxx Xxxx, Plenum, 91-103.

22) Xxxxxx, X. X., Xxxxxx, X. X., Xx, X. X., Xxxxxx, X. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx System Xxxxx Cells Xxxxx xx Collagen Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Xxxxxxxx Xxxxx, Xxxxxxx. Xxxxxxxxxxx, 5, 795-801.

23) Xxxxxxxxx, X. L., Moore, X. X., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxx xx the Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Xxxxx xx Xxxxx Xxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Xxx. X. X. A, 87, 51-55.

24) Moore, M. X., Xxxxx, D., Xxxxxx, J. C., Xxxxxx, X. X., Xxxxxx, X. G., Xxxxxx, N. X., Xxxxxx, X. (1985), Xxxxxxxx of Trifluorothymidine, Xxxxxxxxx (XXX+) Mutants xx X5178X/XX+/--Xxxxx Lymphoma Xxxxx, Xxxxxxxxxx Res. 151, 161-174.

25) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X. (1990), Xxxxxxxxx Genetic Analysis xx Xxxxxxxxx Xxxxxxxxx xx x Xxxxxxxxxxxx Xxxxxxxxx Xxxxx in Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.

26) Xxxxx, X. M., Xxxxx, X. X. (1990), Comparison of Xxxxxxxxxx Xxxxxxxxxx Xxxxxxxxx xxx Small Xxxxxx XX-Xxxxxxxxx Mutant Xxxxxxxxx xx L5178Y/TK+/- 3.7.2X Xxxxx Lymphoma Xxxxx, Xxxxxxxxxxx, 5, 609-614."

XXXXXXX 4X

"X.23 XXXXXXX XX CHROMOZOMOVÉ ABERACE XX SPERMATOGONIÍCH XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxx xxxxxxx xx chromozomové xxxxxxx xx xxxxxxxxxxxxxxx xxxxx xx xxxx xx identifikovat takové xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx chromozomové xxxxxxx xx xxxxxxxxxxxxxxx savců (1, 2, 3, 4, 5). Rozlišují xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x chromatidové. X xxxxxxx chemických xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxx určena xx stanovení xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx účelu xxxxxxx xxxxxxxxx. Chromozomové xxxxxx x xxxxxxx xxxx xxxx příčinou xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x člověka.

Touto xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx ve xxxxxxxxxxxxxxx x předpokládá xx xxxx, xx xxxx xxxxxxx poskytne xxxxxxxxx indukce xxxxxxxxx xxxxxx v germinálních xxxxxxx.

X xxxx zkoušce xxxx rutinně xxxxxxxxx xxxxxxxx. Touto xxxxxxxxxxxxxx xxxxxxxx xx xxxx xx xxxxxxxx chromozomové xxxxxxx při xxxxxx xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx xxxxxx předmětem xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx xx xxxxxxxxxxxxxxx by xxxx být — xxxxx než xxxxx xx ztrátě xxxx — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx následuje po xxxxxxxx. Xxxxx informace x exponovaných xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx lze xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxx chromozomového xxxx x xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx stávají xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx také x xxxxxxxxxxxx buňkách. Xxxxx xx xxxx xxxxxxx se xxxxxxxxxxxxxxx xxxxxxxx pro posouzení xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX.

Xx xxxxxxxxx xx xxxxxxxx řada xxxxxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxxxx xx xxxxxxxx chemické xxxxx. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx populace spermatogonií x převládajícími xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. V xxxxxxxxxx xx xxx xxxxxx xx varlatech, xxxxx xxxx xxxxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx celkovému xxxxxxxx xxxxx v důsledku xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Sertoliho buněk x xxxxxxx xxxx xxxxxxx xxxxxx x xxxxxxx.

Xxxxxxxx existuje xxxxx x xxx, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx do cílové xxxxx, není vhodné xxxx xxxxxxx použít.

Viz xxxx xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození chromozomu x xxxxxx xxxxx xxxx xxxxx a xxxxxxx xxxx chromatid x xxxxxx xxxxx.

Xxx : achromatická léze xxxxx xxx šířka xxxxx chromatidy a x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

Xxxxxxxxxxx : xxxxxxx haploidního xxxxx xxxxxxxxxxxxxx xxx (x), jiný xxx xxxxxxxxx (xx. 3 x, 4 n xxx.).

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx ve xxxxxx xxxxxxxx xxx xxxxxxxxxxx, xxxx se xxxx xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx nebo xxxxxxxxxxxxxxxxxx změny.

1.3 XXXXXXXX XXXXXXXX METODY

Zvířata xxxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx látce a xx xxxxxx xxxx xx expozici xxxxxxxx. Xxxx xxxxxxxxx se xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx xxxx Xxxxxxxx®). X germinálních xxxxx xx xxxx připraví xxxxxxxxx chromozomů, xxxxxx xx a analyzují xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xxxx používáni xxxxx xxxxxx čínského a xxxx; lze xxxx xxxxxx xxxxx jakéhokoli xxxxxx vhodného xxxxx xxxxx. Xxxx xx xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx xx xxxxxxxx xxxxxxx rozdělí xx kontrolní xxxxxxx x skupinu, která xx exponuje. Xxxxx xx měly xxx xxxxxxxxxx xxx, xxx xxx vliv xxxxxx xxxxxx minimalizován. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx xxxxxxxxx xxxxxx xx xxxxxxx x xxxxxxxxxxxxx podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx nebo xxxxx xxx před podáním xxxxxxx. Měly xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx xxxxxxxxx xxxxxxxxx dávek xxxxxxx účinky a xxxx xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx použita xxxx než známá xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být souběžné xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx zkoušené xxxxx by xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata ve xxxxxxxxx, v nichž xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx strukturní xxxxxxx xx xxxxxxxxxxxxxxx in xxxx xxx xxxxxxxxxxx xxxxxxxx, u xxxxx xx předpokládá, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx tak, xxx byl xxxxxx xxxxxxxx, xxx aby xxx odečtu nevyšla xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Je xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx podávána xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxx xxx xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou-li k xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx	Xxxxx XXX	Xxxxx podle 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 každého odběru xx měl xxx xxxxxxxx odběr u xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx nejsou x xxxxxxxxxxx xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 POSTUP

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní skupina xxxx zahrnovat xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx podávány xxxxxxxxxxx nebo nadvakrát (xx. při jedné xxxxxxxx nebo xxxx xxxxxxxxxx). Xxxxxxxx xxxxx xxxxx xxx podávány xxxx ve xxxx xxxxxxx, tzn. xxx xxxxx x týž xxx x xxxxxxx xx xxxx než xxxxxxxx hodin, aby xxxx usnadněno xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx režimy podávání xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xx skupině x nejvyšší dávkou xx xxxx xxx xx xxxxxxxx xxxxxxxxx xxx xxxxxx. Poněvadž xxxxxxxx xxxxxxxxx cyklu xxxx xxx xxxxxxxxx xxxxxx ovlivněna, xxxxxxx xx xxxxx časný xxxxx x xxxxx xxxxxxxx xxxxx xxxxxxxxx 24 a 48 xxxxx po expozici. X případě xxxx xxx xxxxxxxx dávky xx měl xxx xxxxx xxxxxxxx po 24 hodin nebo xx xxxxxx době xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx xxxx xxxxx jiná xxxxxxxxx xxxx pro xxxxxxx xxxxxx (6).

Xxxxx xxxxx xxx xxxxxx xxxxxxxxx xxxx x jiné xxxx. Xxxxxxxxx x xxxxxxx chemických látek, xxxxx mohou xxxxxxxxx xxxxxxxx replikace (lagging) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx X-xxxxxxxxx účinky, xxxx být vhodnější xxxxxxxx xxxxx (1).

Xxxxxxxx xxxxx xxxxxxxxx expozice xxxx xxx určena xxxxxx xx případu. X případě plánu x opakovanou expozicí xx xxxx xxx xxxxxxx usmrcena 24 xxxxx (1,5násobek xxxxx xxxxx) xx poslední xxxxxxxx. Xxxxx xxxxxxx xxxxx xxx prováděny xxxxx odběry x xxxx xxxx.

Xxxx xxxxxxxxx xx zvířatům xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx zastavující xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx se xx vhodné xxxx xxxxxxx x xxxxxx xxxxx. X myši xx xxxx xxxx xxxxxxxxx 3 — 5 xxxxx; x xxxxxx čínského xx xxxx xxxx xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Dávkování

Provádí-li se xxxxx neexistenci vhodných xxxxxxxxxx xxxxx xxxxxx xxx zjištění rozsahu, xxxx by xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx x xxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxxxx xx použije x xxxxxx xxxxxx (7). X případě toxicity xx xxx první xxxxx použijí xxx xxxxxx dávky. Xxxx xxxxxx xxxxx by xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx toxicitou, případně xxxxxx toxicitou. Xxx xxxxxxxxx odběru xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx takové známky xxxxxxxx, xx xx xxxxx dávky vedly xxx xxxxxxx režimu xxxxxxxxx podle xxxxxxxxx x xxxxxxxx.

Xxxxx xx xxxxxxxxxxx biologickou aktivitou xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) nemusí xxxxxxxxx stanovení dávky xxxxxxxxx a xxxx xx xxx hodnoceny xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx vyvolávající xx spermatogoniích xxxxxxx xxxxxx xxxxxxxx (např. xxxxxxx xxxxx xxxxxxxxxxxxx x mitose xxxxxxxx x první a xxxxx xxxxxxxxx xxxxxxxx; xxxx snížení xx xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx xxxxxx alespoň 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx dvou dávkách x xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx účinky x xxxx-xx na xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, očekávána genotoxicita, xxxxxxxxxx xx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. Očekávaná xxxxxxxx xxxxxxx může xxxxxxxx xxxxxxx xxxxxx x xxxxxxx zkoušce xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx se xxxxxxx podává nitrožaludečně, xxxxxxxxx sondou xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, závisí na xxxxxxxxx testovacího xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx vyšších objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava xxxxxxxxx xx xxxxxxx chromozomů

Ihned xx xxxxxxxx xx x xxxxxxx nebo xxxx xxxxxx získá xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx a xxxxxx. Xxxx se xxxxxx xx podložní xxxxxxx x obarví xx.

1.5.7 Xxxxxxx

X xxxxxxx zvířete xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx v xxxxx xxxxxxxxxxxx xxxxxxxx (tj. xxxxxxxxx 500 xxxxxxxx xx skupinu). Tento xxxxx xxx snížit, xx-xx pozorován velký xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx včetně preparátů xxxxxxxxxxx x negativních xxxxxxx, xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx nezávisle kódovány. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx xxxxxxxxxx x xxxxx metafází, xxxx xx vyšetřované buňky xxxxxxxxx xxxxxxxxxx x xxxxx odpovídajícímu xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx jednotlivá xxxxxxx xx xxxx xxx xxxxxxxxxx ve xxxxx tabulky. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx zvíře xx xxx xxx xxxxxxxxxx xxxxx buněk xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxxxxxxxx aberací na xxxxx. Xxx xxxxxxxxxx x kontrolní xxxxxxx xx xxxx xxx xxxxxxx různé typy xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich počtem x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx se, xxx xxxxxx se xxxxxxxxxx do celkové xxxxxxxx xxxxxxx.

Xx-xx pozorována xxxxxx x také xxxxxx, xxx xx xxx pro stanovení xxxxxxx xxxxxxxxxxxxx účinků xxxx xxxx cytotoxicity xxxxxxxx x všech xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx v mitose xxxxxxxx x xxxxx x druhé xxxxxxxxx xxxxxxxx, x xx x xxxxxxxx vzorku 100 dělících xx xxxxx xx xxxxx xxxxx. Xxxxx xx xxxxxxxxx xxxxx mitosa, xxxxxxx v 1000 xxxxxxx xx xxxxx xx měl xxx xxxxxxxx mitotický xxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx existuje několik xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx xxxxx nárůst xxxxx buněk x xxxxxxxxx xxx xxxxxxx x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (8). Statistická xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly být xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx zkoušky na xxxxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xxxxx xx xxxx znamenají, že xxxxxxxx xxxxx indukuje x germinálních xxxxxxx xxxxxxxxxxx xxxxx strukturní xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx neindukuje x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Testovací zvířata:

- xxxxxxx druh/kmen,

- xxxxx x xxxxx zvířat,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- individuální xxxxxxxx zvířat xx xxxxxxx zkoušky, včetně xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx odchylky xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

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

- xxxxxxxxxx zvolených úrovní xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- zdůvodnění xxx xxxxxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- identifikace xxxxx xxxxxxxxxxx metafázi, xxxx koncentrace x xxxxx xxxxxxxx,

- xxxxxx xxxxxxxx preparátů,

- kritéria xxxxxxxxx aberací,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx xxxxx,

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

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx počet xxxxxxx ve skupině,

- xxxxx xxxxx x xxxxxxxxx ve xxxxxxx,

- xxxxx možnosti xxxxxxxxx xxxxxxxx na xxxxx,

- xxxxxxxx statistické xxxxxxx,

- xxxxx o souběžné xxxxxxxxx xxxxxxxx,

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

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

- změny xxxxxxx, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Spermatogonia of Xxxxxxxx Xxxxxxxx Xxxxxxx xx their Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Genetic Xxxxxxxxxx of Xxxxxxxxxxxxx Xxxxxxxxx, Xxxx X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Mutagenesis, Xxxxx, X., Xxxxxxx, X., Xxxxxxxxx, J. (eds) Xxxx, Xxx Xxxx, 477-484.

2) Xxxxx, I. X., (1984), Cytogenetic xxxxx in Mammals, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, (xx.) X. Xxxxxx, X. M. Parry, XXX Xxxxx, Xxxxxx, Xxxxxxxxxx XX, 275-306.

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

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, A., Xxxxxxxxx, X. X., Henderson, X. (1990), Xx xxxx Cytogenetic Assays, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, UKEMS Xxxxxxxxxxx Procedures. UKEMS Xxxxxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx. Xxxx X xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

5) Xxxxxxxx, K., Xxxxxxx, X. (1978), X Xxx Xxxxxx xxx Xxxxxxxxxxx of Mammalian Xxxxxxxxxxxxxx Xxxxxxxxxxx, Mutatation Xxx., 52, 207-209.

6) Xxxxx, X. X., Xxxxxx M. X., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx X. (1994), International Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures. Xxxxxxx Xxxxxx xx xxx Working Xxxxx xx Xxxxxxxxx Xxxx Xxxx Tests, Mutatation Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. R., Xxxxxx, P. X., Xxx, X., Esdaile, X. X., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Xxxxxx of Xxxxxxx Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, D. X., Xxxxxxxx, D., Albanese, X., Amphlett, X. X., Xxxxx, X., Xxxxxxxx, X., Richold, X., Xxxxxxxx, X. X., Xxxxxx X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, in: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Cambridge University Xxxxx, Cambridge, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Sydney, 184-232."

XXXXXXX 4X

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

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX TG 486 — Xxxxxxx xx xxxxxxxxxxxx syntézu XXX (UDS) v xxxxxxxxx xxxxxxx savců xx xxxx (1997).

1.1 XXXX

Xxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx XXX (XXX) v xxxxxxxxx xxxxxxx xxxxx xx xxxx xx xxxxxxxxxxxxx xxxxxxxx látky, které xxxxxxxx reparace DNA x jaterních buňkách xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).

Xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxx vyšetření xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxx. Xxxxxxxxxxx xxx je xxxxxxxxxx poškození XXX x následné xxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx místem, xxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Jsou tedy xxxxxxx xxxxxx xxx xxxxxxxxx xxxx poškození XXX in xxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, xx se xxxxxxxx xxxxx xxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx použít.

Rozsah xxxxxxxxxxx xxxxxxx XXX (XXX) xx xxxxxxxx stanovením xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx buněk, které xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx xx autoradiografické xxxxxxxxx inkorporace xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx xxxxxxx xx XXX xx vivo xx xxxxxxxxxx xxxxxxxxx xxxxx xxxxxxx. Xxxx xxxxx xxx xxxxx xxxxx xxx rovněž xxxxxxx, nejsou xxxx xxxxxxxxx xxxx metody.

Detekce xxxxxxxx UDS xxxxxx xx počtu xxxx XXX xxxxxxxxxxx x xxxxxxxxxxx x místě xxxxxxxxx. Xxxxxxx xx XXX xx xxxx xxxxxx xxxxxxx xxx xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx repair") (20 xx 30 xxxx) xxxxxxxxxxxx látkou. Xxxxxx xxxxxx ("short-patch xxxxxx") (xxxxx xx tři xxxx) jsou xxxxxxx xxxx xxxxxxxxxx x xxxxxx menší xxxxxxxxxx. Xxxxx může důsledkem xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx chybné xxxxxxxxx xxxx XXX xxxxx x xxxxxxxxxx xxxxxxxxx. Xxxxxx odpovědi XXX neposkytuje xxxxxx xxxxxxxxx x věrnosti xxxxxxxxxxx procesů. Navíc xx xxxxx, že xxxxxxx xxxxxxx s XXX, ale xxxxxxxxx XXX xxxx opraveno xxxxxxxxxxx reparací. Xxxxxxxxxx xxxxxxxxxxxx informací, xxxxx xxxx xxxxxxx xxxxxxxxx x mutagenní xxxxxxxx, xx xxxxxxx xxxxxxxxxxx xxxxxxxxxx tohoto xxxx, xxxxx xx xxxxxxxxxx x xxxxx xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Opravované xxxxx : xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (NNG), xxxxx xxx předvolená xxxxxxx stanovená xxxxxxxxxx xxxxxxxxxxx zkoušku.

Čistý počet xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx míra XXX xxxxxxxx xxxxx v xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, vypočtená xxxxxxxxx xxxxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (XX) xxxxxxxxxxxxxx jádrům xx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): NNG = XX — XX. Xxxxxxx XXX xx xxxxxxx pro jednotlivé xxxxx, poté xxxxxxxx xxx xxxxx v xxxxxxx, v xxxxxxxxxxx xxxxxxxxx atd.

Neplánovaná syntéza XXX (UDS) : Xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx úseku XXX xxxxxxxxxxxx region x xxxxxxxxxx indukovaným xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xx XXX x jaterních xxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxxxxxx XXX po vyštěpení x odstranění úseku XXX obsahujícího xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx obvykle xxxxxxxx xx inkorporaci 3X-XxX xx DNA xxxxxxxxx xxxxx, xxx je xxxx četnost buněk x X-xxxx xxxxxxxxx xxxxx. Inkorporace 3X-XxX xx obvykle xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx tato xxxxxxxx xxxx xxx xxxxxxx na xxxx X-xxxx xxxxx xxxx xxxx. xxxxxxx scintilační xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx je xxxxxxxx xxxxxx, ačkoli xxx xxxxxx xxxxxxxx vhodný xxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx by xxxx xxx odchylka x xxxxxxxxx xxxxxx minimální x neměla xx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx pro xxx xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x strava

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx se xxxxxxxx výběrem xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, xxxxx xx exponuje. Xxxxx xx xxxx být xxxxxxxxxx xxx, xxx xxx xxxx jejich xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx x před xxxxxxxxx xxxxxx se xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx být xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx zředěny. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých xxxxxxxx dávek xxxxxxx xxxxxx x xxxx xx být vyloučeno xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx 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 (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx látky xx měla zvířata xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx proces jako xxxxxxx ve xxxxxxxxx, x nichž dojde x xxxxxxxx.

Xxxxxxxxxxx kontrolami xx měly xxx xxxxx, o xxxxx xx xxxxx, že xxxxxx podávání x xxxxxxxxxxx expozičních xxxxxxxxxxxxx xxxx x nárůstu XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx v xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Xxxxx xxxxx xxx xxxxxxx tak, xxx xxx xxxxxx xxxxxxxx, ale xxx xxx odečtu xxxxxxx xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx	Xxxxx	Xxxxx CAS	Číslo xxxxx Xxxxxx
Xxxxx doby xxxxxx (2 xx 4 h)	N-nitrosodimethylamin	62–75–9	200–249–8
Pozdní doby xxxxxx (12 xx 16 x)	X-(xxxxxxx-2-xx)xxxxxxxx (2-AAF)	53–96–3	200–188–6

Mohou xxx xxxxxxx také xxxx xxxxx pro xxxxxxxxx kontrolu. Xx xxxxxxxxx, aby xxxx xxxxxxxxx xxxxxxxxx látka xxxxxxxx xxxxx způsobem, xxx zkoušená xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxx xx xxx xxxxxx dostatečný xxxxx xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx kolísání xxxxxxxx xx xxxxxxx. Xxxxx xxxxxxx by se xxxx xxxxxxx xxxxxxx xx xxx xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, je pro xxxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxx xx xxx xxxxxxx.

Xxxxxxxx jsou x xxxx xxxxxx x xxxxxxxxx údaje xx studií xx xxxxxxx xxxxxx a xx použití stejného xxxxxxx expozice, jež xxxxxxxxx, že xxxxxxxxxx xxxx pohlavími xxxxxx x toxicitě, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, nejlépe xxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx pro xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx farmaceutických xxxxx, xxxx by xxx xxxxxxx provedena se xxxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx normálních xxxxxxxx xx používají xxxxxxx xxx úrovně xxxxx. Nejvyšší xxxxx xx xxxxxxxxxx xxxx xxxxx vyvolávající takové xxxxxx xxxxxxxx, že xxxxx xxxxx xx xxxxx xxxxx očekávání xxx stejném xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx by xxxx xxx xxxxxxxxx 50 % až 25 % xxxxx xxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx netoxických xxxxxxx (xxxx. hormony x xxxxxxxx) xxxxxx kritériím xxxxxxxxx dávky xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro zjištění xxxxxxx, xxxx by xxx xxxxxxxxx ve xxxxxx laboratoři, xx xxxxxxx druhem, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx xxxxxx.

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

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x jednou xxxxxx x alespoň 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx jednorázově xxxx xx xxxx dávkách x xxxxxx dni xxxxxxxxxx žádné xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx o xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, očekávána xxxxxxxxxxxx, xxxxxx být úplná xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx člověka může xxxxxxxx potřebu použít x xxxxxxx xxxxxxx xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx podává xxxxxxxxxxxxxx, xxxxxxxxx sondou xxxx xxxxxxx intubační xxxxxxx. Xxxx způsoby xxxxxxxx xxxx xxxxx, xxx-xx je zdůvodnit. Xxxxxxxx intraperitoneálně se xxxx xxxxxxxxxxxx, neboť xx játra xxxxx xxx exponována zkoušené xxxxx xxxxx x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx může xxx xxxxxxxx podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších objemů, xxx je uvedený xxxxx, musí xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx měla být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava jaterních xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx x xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 xxxxx xx podání xxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (obecně xxx xx čtyři hodiny xx xxxxxxxx) je xxxxxxxx, xxxx-xx xx 12 až 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx xxxxxxx xxxx xxxx xxxxxx, xxxx-xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx xxxxxxx xxxxxxxxx buněk savců xx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxxx xx xxxx x xxxxxx xx, aby xx xxxxxxx xxxxxxxxxxx xxxxxxx buňky xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxx dobu, např. xxx xx xxx xxxxx, inkubují x xxxxxx xxxxxxxxxxx 3X-XxX. Xx xxxxx inkubační xxxx by mělo xxx médium x xxxxx xxxxxxxxxx x xxxxx xxxx xxxxx xxx inkubovány x xxxxxx xxxxxxxxxxx přebytek xxxxxxxxxxx xxxxxxxxx, aby xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx se xxxx xxxxxxx, xxxxxx x xxxxxx. Xxx xxxxx xxxxxxxxx xxxx nemusí xxx snížení radioaktivity xxxxxxxx. Xxxxxxxxx xx xxxxxx do xxxxxxxxxxxxxxxxx xxxxxx, xxxxxxxx xx x xxxxx (např. x chladu 7 xx 14 xxx), xxxxxxxx se, obarví x xxxxxxxxx xx xxxxxxxxxx zrna xxxxxxx. X každého xxxxxxx xx připraví xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

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

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

Xxxxxxxx 3H-TdR inkorporovaného xx xxxxx a xxxxxxxxxx xxxxxxxxxxxx normálních xxxxx doložené xxxxxxxxxxx xxx stříbra xx xxxx být stanoveno xxxxxxx xxxxxxx.

Xxxxx xxxxx xx xxxxxxx x xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx jádrŭm (xx) x x xxŭxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx oblastech (xx) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx cg xx xxxxxxx xxx xxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx prŭměrná hodnota xxxx xx xxx xxxxxxx xxxxxxxxx oblastí x xxxxxxxxx xxxxxxxxx xxxxxxxxx jader. po xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx použity x xxxx xxxxxxx xxxxxxxxx xxxxx buněk (xxxx. xxxxxxxx xxxxxx xxxxx) (6).

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxx xx xxx xxxxxxx údaje pro xxxxxxxxxx preparáty x xxxxxxx. Xxxxx xx xxxx xxx xxxx xxxxxxx ve xxxxx xxxxxxx. Odečtením xxxxxxx XX od xxxxxxx XX xx měl xxx xxxxxxxx xxx xxxxxx xxxxx, xxx xxxxx zvíře a xxx xxxxxx dávku x xxx xxxxx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX). Xxxxxxxx jsou xxxxxxxx "xxxxxxxxxx" xxxxx, xxxx xx xxx xxxxxxxx xxx xxxxxxxxxx "opravovaných" xxxxx xxxxxxxxxx x xxxxxxxx na xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x negativních kontrolách. Xxxxxxxxx výsledky xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx být xxxxxxx, xxxx xx xxx xxxxxxxxxxx xxxxx xxxxxxx x odůvodněny xxxx provedením xxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx pozitivní xxxx xxxxxxxxx odpověď patří:

pozitivní	i)	hodnota XXX xxxx xxx xxxxxxxx xxxxxx, xxxxx xx xxxxxxxxxx na xxxxxxx dosavadních xxxxx xxxxxxxxxx;
xxxx	xx)	xxxxxxx XXX xx xxxxxxxx xxxxx než xxxxxxx xxx xxxxxxxxx xxxxxxxx;
xxxxxxxxx	x)	xxxxxxx XXX leží xx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxx xx;
xxxx	xx)	xxxxxxx NNG není xxxxxxxx xxxxx než xxxxxxx xxx xxxxxxxxx xxxxxxxx.

Xxxx by být xxxxxxxxx biologická xxxxxxxxx xxxxx, tj. xxxx xx být vzaty x xxxxx xxxxxxxxx, xxxx xxxx xxxxxxxxxxx xxxxxx, xxxxx xxxxx x xxxxxxxx x xxxxxxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx pro pozitivní xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x aktivitě xxxxxxxx xxxxx. Výsledky mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx XXX v jaterních xxxxxxx xxxxx in xxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x xxxxxxxxx xxxxxxx xxxxx in xxxx xxxxxxxxx XXX, xxxxx xxx opravit xxxxxxxxxxxx xxxxxxxx XXX xx xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, že xxxxxxxx xxxxx xx podmínek xxxxxxx xxxxxxxxxx xxxxxxxxx XXX, které xxx xxxxxxxxx xxxxx xxxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x jakou xx xxxxxxxx látka xxxxxxx xx xxxxxxxx xxxxx popř. do xxxxxx xxxxx (např. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Testovací xxxxxxx:

- xxxxxxx druh/kmen,

- počet, xxxxx x pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, strava atd.,

- xxxxxxxxxxxx hmotnost zvířat xx počátku xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, střední hodnoty x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxxxxxx a xxxxxxxxx (vehikulum/rozpouštědlo) kontroly,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx o xxxxxxxx zkoušené látky,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- zdůvodnění xxxxxxx podávání,

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

- případně xxxxxxxx xxxx koncentrací xxxxxxxx xxxxx v xxxxxx xxxx vodě (xxx) na odpovídající xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx údaje x xxxxxxx krmiva x xxxx,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- metody xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,

- kritéria xxxxxxxxx,

- xxxxxxxx klasifikace xxxxxx xx pozitivní, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxxx hodnoty xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx x počtu xxx xxxxxxxxxxxxxx xxxxxxxxxx, x xxxxx počet xxx, xxxxxxxxxx xxx xxxxxxxxx, zvířata x xxxxxxx,

- podle xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- případné statistické xxxxxxxxx,

- xxxxxx xxxxxxxx,

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

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

- xxxxx xxxxx "opravovaných" xxxxx, xx-xx xxxxxxxx,

- xxxxx xxxxx x X-xxxx, xx-xx xxxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. Xxxxxxx, X. X., Xxxxxxxxx, X., Penman, M. X. (1985), Xx Xxxxxxxxxx of xxx Xx xxxx Xxx. Xxxxxxxxxx DNA Repair Xxxxx, Mutatation Xxx., 156, 1-18.

2) Butterworth, X. X., Xxxxx, X., Xxxxxxxx, E., Xxxxxxxx, X., Xxxxxxxx, X., Probst, X., Xxxxxxxx, X. (1987), X Protocol xxx Xxxxx for the Xx xxxx Rat Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Res., 189, 123-133.

3) Xxxxxxxx, X. X., Xxxxxx, X., Xxxxx, J., Xxxxxxx, P. A., Xxxxxxxxx, X., Xxxxxxx, X. X., Dean, X. X., Mitchell, X. xx G. (1993), In xxxx Xxx Xxxxx XXX Xxxxx, in: Kirkland X. J., Fox X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: UKEM Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx. Xxxxxx. Part XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Sydney, 52-77.

4) Xxxxx, X., Xxxx, X. X., Xxxxxx, X., Xxxxxxxxx. G., Xxxxxxxxx, B., Xxxxxxxxx, X. J., Xxxxxxxx, X., Xxxxxxx, X., XxXxxxx, X. A., Xxxx, H. (1993), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx xx XXX Xxxxx In xxxxx xxx Xx vivo, Xxxxx. Xxx., 312, 263-285.

5) Fautz, X., Xxxxxxx, X., Efstathiou, X., Hechenberger-Freudl, X. (1993), Xxxxxxxxxx of xxx Xxxxxxxx Xxxxxxx xxx Initial Xxxxxxxxx xxx the Attachment xx Xxxxxxx Xxxxxxxx Xxx Hepatocytes Xxxx xxx xxx Xx xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (XXX), Xxxxxxxxxx Res., 291, 21-27.

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

XXXXXXX 5

XXXXXX XXXXXXXXX XX XXXXXXXXXXX X XXXXXXXXXX NEBEZPEČNÝCH LÁTEK X PŘÍPRAVKŮ

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

XXXXXXX 6

"

XXXXXXX XX

XXXX X

xxxxxxxx xxxxxxxx xx xxxxxxx odolných xxxxx xxxxxxxx dětmi

Kromě xxxxxxxxxx xx. 22 xxxx. 1 písm. e) xxxx směrnice, xxxx xxx xxxxx x xxxxxxxxx xxxxxx xxxxxxxxxx xxxxx, x nimiž xx spojeno xxxxxx xxx xxxxxxxxxx (Xx; X 65) x xxxxx xxxx xxxxxxxxxxxxx x označeny xxxxx xxxx 3.2.3 xxxxxxx XX xxxx směrnice, x výjimkou xxxxx xxxxxxxxx xx trh xx formě xxxxxxxx xxxx v xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx, xxxxxxxx xxxxxxx xxxxxxxx xxxxx otevření xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx obaly

Uzávěry xxxxxx proti otevření xxxxx použité xx xxxxxxxxx xxxxxxxxxxxxxx obalech xxxx splňovat požadavky xxxxx XXX 8317 (xxxxxx ze xxx 1. xxxxxxxx 1989) "Xxxxx xxxxxx xxxxx — Xxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxx xxxxxxxx" přijatou Xxxxxxxxxxx xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Opakovaně xxxxxxxxxxxxxx xxxxx

Xxxxxxx odolné proti xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxx xxxxxxx xxxx splňovat xxxxxxxxx xxxxx XXX XX 862 (vydání x března 1997) "Xxxxx — Obaly xxxxxx dětem — Xxxxxxxxx a xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx obaly xxxxxx xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Xxxxxxxxx výborem xxx xxxxxxxxxxx (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx shody x xxxx uvedenými xxxxxxx xxxxx osvědčovat xxxxx laboratoře, xxxxx xxxxxxx xxxxxxxx xxxxx xxxx XX 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx xxxxxx, xx xxxx xx xxxxxxxxxx bezpečný xxx xxxx, xxxxx xx xxxxxxx xxxxxx k xxxxxx xxx xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx všech xxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxx xxxxxx x xxxxxxxx x xxxxxxxxxxx xxxxxxx xxx xxxx, xxxx xxxxxxxxxxxx xxxxx požadovat, xxx xxxxx odpovědná xx uvedení xxxxxxx xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx laboratoří xxxxx odst. 3 xxxx 1 xxxxxxxxxxxx, xx buď

- xxx xxxxxxx xx takový, xx xxx není xxxxxxxx xxxxxxx xxxxx xxxx xxxxxxxxx xxxxx XXX a CEN,

nebo

- xx uzávěr xxx 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 xxxxxx XX XXX 11683 (xxxxxx x xxxx 1997) "Obaly — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Xxxxxxxxx".

"

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