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Směrnice Xxxxxx 2000/32/XX

xx xxx 19. xxxxxx 2000,

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

(Text x xxxxxxxx pro XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Smlouvu x xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx xx xxxxxxxx Xxxx 67/548/XXX xx xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení x xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], naposledy xxxxxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Xxxx 1999/33/ES [3], x zejména xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx k xxxxx xxxxxxx:

(1) Xxxxxxx X xxxxxxxx 67/548/EHS xxxxxxxx xxxxxx nebezpečných xxxxx společně x xxxxxxxxxx údaji x xxxxxxxxxxx x xxxxxxxxxx xxxxx látky. Xxxxxxxx xxxxxxx a technické xxxxxxxx ukazují, xx xx měl xxx xxxxxx nebezpečných látek x xxxxxxx xxxxxxx xxxxxxxxxxx. Některé xxxxxxxx xxxxx směrnice xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxxxxx x xxxxxxx X x xxxxxxx X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/EHS xxxxxxxx xxxxxx vět udávajících xxxxxx xxxxxxxxxx rizik xxxxxxxxx x nebezpečnými xxxxxxx a přípravky. Xxxxxxx IV xxxxxxxx 67/548/XXX xxxxxxxx seznam xxx x xxxxxxxxxxxxxx xxxxxx týkajícími xx xxxxxxxxxxxx látek a xxxxxxxxx. Příloha VI xxxxxxxx 67/548/XXX obsahuje xxxxx xx klasifikaci x k xxxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Některé xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx oddílů xxxxxx XXX, IV x VI.

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

(4) Xxxxxxx IX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx xx uzávěrů xxxxxxxx proti xxxxxxxx xxxxx. Xxxx xxxxxxxx xx xxxx xxx xxxxxxxxxxxx x xxxxxxxxxxxxx. Xx xxxxxxxx xxxxxxxx xxxxxx, kde xx xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxxxx.

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

XXXXXXX XXXX XXXXXXXX:

Článek 1

Xxxxxxxx 67/548/XXX xx xxxx takto:

1. Xxxxxxx X xx xxxx xxxxx:

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

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

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

d) xxxxxxxx xx xxxxxxx x xxxxxxx 1D xxxx xxxxxxxx.

2. Odpovídající věta x příloze XXX xx xxxxxxxxx standardní xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx x příloze 2 této xxxxxxxx.

3. Xxxxxxx XX xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx x xxxxxxx XX xx nahrazují xxxxxxxxxxxx xxxxxx pro xxxxxxxx zacházení x xxxxxxx 3X xxxx xxxxxxxx;

x) xxxxxxxxxxxx pokyny x xxxxxxx XX xx xxxxxxxxx kombinovanými xxxxxxxxxxxx xxxxxx pro xxxxxxxx xxxxxxxxx x xxxxxxx 3B této xxxxxxxx.

4. Xxxx B xxxxxxx X xx xxxx xxxxx:

x) xxxxxxxx X.10 xx xxxxxxxxx xxxxxx x příloze 4X xxxx xxxxxxxx;

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

x) xxxxxxxx B.12 xx xxxxxxxxx xxxxxx x xxxxxxx 4C xxxx xxxxxxxx;

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

e) kapitola X.17 xx xxxxxxxxx xxxxxx x příloze 4X xxxx xxxxxxxx;

x) xxxxxxxx X.23 xx xxxxxxxxx textem v xxxxxxx 4X xxxx xxxxxxxx. Název kapitoly X.23 xx xxxxxxxxxxx xx xxxx xxxxxxxxxxxxx xxxxxxxx;

x) xxxxxx xx xxxx x příloze 4X této xxxxxxxx.

5. Xxxxxxx xx xxxxxx xxxxxxx xxxxxxxx xxxxx x xxxxx X xxxxxxx X.

6. Xxxxxxxxxxxx xxxxx v xxxxxxx XX se nahrazují xxxxx v xxxxxxx 5 této xxxxxxxx.

7. Xxxxxxx IX xx xxxx způsobem xxxxxxxx x příloze 6 xxxx xxxxxxxx.

Článek 2

1. Členské xxxxx xxxxxx x xxxxxxxx právní a xxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxxx xxxxxxx x xxxxx směrnicí xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x xxxx xxxxxxx Xxxxxx.

Xxxx předpisy přijaté xxxxxxxxx státy xxxx xxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxx xxxx xxxxxx xxxxx xxx xxxxxx xxx xxxxxx úředním vyhlášení. Xxxxxx xxxxxx xx xxxxxxx xxxxxxx xxxxx.

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

Článek 3

Xxxx xxxxxxxx xxxxxxxx v xxxxxxxx xxxxxx dnem xx xxxxxxxxx v Xxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx.

Článek 4

Tato směrnice xx xxxxxx xxxxxxxx xxxxxx.

V Bruselu xxx 19. xxxxxx 2000.

Za Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise

[1] Xxxxxxx xx xxxxxxxxxxxx xx dvacáté xxxxx.

[2] Xx. věst. 196, 16.8.1967, s. 1.

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

PŘÍLOHA 1X

XXXXXXXXX X XXXXXXX I

Vysvětlení xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx se xxxxxxx xxxxx)

PŘÍLOHA 1X

"XXXXXXX X

X

Xxxxxx

XX

18

Xx

Xxxxx

Αργό

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"

PŘÍLOHA 1X

Xxxxxxxx xxxxx	Xxxxxxxx xxxxx	Xxxxxxxx x látkám	Číslo XX	Xxxxx XXX	Xxxxxxxxxxx	Xxxxxxxx	Xxxxxxxxxxxx xxxxxx	Xxxxxxxx x xxxxxxxxxx
006–011–00–7	xxxxxxxx (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx		200–555–0	63–25–2	Xxxx. kat. 3; X40 Xn; X22 X; R50	Xn; X X: 22–40–50 S: (2-)22–24–36/37–46–61
006–013–00–8	xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx		205–293–0	137–42–8	Xx; X22 X31 C; X34 R43 X; X50–53	X; N X: 22–31–34–43–50/53 X: (1/2-)26–36/37/39–45–60–61
006–015–00–9	xxxxxx (XXX) 3-(3,4-dichlorfenyl)-1,1-dimethylmočovina	206–354–4	330–54–1	Karc. xxx. 3; R40 Xxxx. xxx. 3; R40 Xx; R22–48/22 N; X50–53		Xx; X X: 22–40–48/22–50/53 X: (2-)13–22–23–37–46–60–61
006–016–00–4	xxxxxxxx (XXX) 2- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		204–043–8	114–26–1	X; X25 X; X50–53	X; X X: 25–50/53 X: (1/2-)37–45–60–61
006–017–00-X	aldikarb (XXX) 2-xxxxxx-2-(xxxxxxxxxxxxxx)xxxxxxxx-X-(X-xxxxxxxxxxxxxxx)xxxx		204–123–2	116–06–3	X+; X26/28 X; X24 X; X50–53	X+; X R: 24–26/28–50/53 X: (1/2-)22–36/37–45–60–61
006–018–00–5	xxxxxxxxx (ISO) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		217–990–7	2032–59–9	X; X24/25 X; X50–53	X; X X: 24/25–50/53 S: (1/2-)28–36/37–45–60–61
006–019–00–0	xx-xxxxx (XXX) X-(2,3-xxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx		218–961–1	2303–16–4	Xxxx. xxx. 3; R40 Xx; X22 X; X50–53	Xx; X R: 22–40–50/53 X: (2-)25–36/37–60–61
006–020–00–6	barban (ISO) 4-xxxxxxxx-2-xx-1-xx-X -(3-xxxxxxxxxx)xxxxxxxx		202–930–4	101–27–9	Xx; X22 X43 X; R50–53	Xn; X X: 22–43–50/53 X: (2-)24–36/37–60–61
006–023–00–2	xxxxxxxxxxxxxxxx (ISO) xxxxxxxxxx 3,5-xxxxxxxx-4-(xxxxxxxxxxxxxx)xxxxx-X -methylkarbamát		217–991–2	2032–65–7	T; X25 X; X50–53	X; X R: 25–50/53 X: (1/2-)22–37–45–60–61
006–024–00–8	xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx		205–443–5	140–93–2	Xx; X22 Xx; X38 X; X51–53	Xx; X R: 22–38–51/53 X: (2-)13-61
006–026–00–9	xxxxxxxxxx (ISO) 2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx-X-xxxxxxxxxxxxxx		216–353–0	1563–66–2	X+; X26/28 X; X50–53	X+; N R: 26/28–50/53 X: (1/2-)36/37–45–60–61
006–028–00-X	xxxxxxxxx (XXX) 2-(1-xxxxxxxxxxxx)-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx 2-sek-butyl-4,6-dinitrofenyl-isopropyl-karbonát		213–546–1	973–21–7	T; X25 X; X50–53	X; X X: 25–50/53 X: (1/2-)37–45–60–61
006–029–00–5	xxxxxxxxx (XXX) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx		230–253–4	6988–21–2	X; R25 N; X51–53	X; X X: 25–51/53 X: (1/2-)37–45–61
006–033–00–7	metoxuron (XXX) 3-(3-xxxxx-4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx		243–433–2	19937–59–8	X; X50–53	X X: 5 0/ 5 3 S: 60-61
006–034–00–2	xxxxxxx (XXX) X-xxxxxx-X-xxxxx-X-xxxxxxxxxxxxxxxxx		214–215–4	1114–71–2	Xx; X22 X; X51–53	Xx; X X: 22–51/53 X: (2-)23-61
006–035–00–8	xxxxxxxxxx (ISO) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx pyrimidin-4-yl-N,N-dimethylkarbamát		245–430–1	23103–98–2	T; X25 X; X50–53	X; X X: 25–50/53 X: (1/2)22–37–45–60–61
006–037–00–9	xxxxxxxxx (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		220–113–0	2631–37–0	X; R25 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 X; X50–53	X; X R: 45–22–50/53 X: 53–45–60–61
006–039–00-X	xxx-xxxxx (XXX) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx		218–962–7	2303–17–5	Xx; X22–48/22 R43 X; R50–53	Xn; X X: 22–43–48/22–50/53 S: (2-)24–37–60–61
006–042–00–6	xxxxxxx (XXX) 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx		205–766–1	150–68–5	Xxxx. xxx. 3; X40 Xx; X22 X; X50–53	Xx; X X: 22–40–50/53 S: (2-)36/37–60–61
006–043–00–1	monuron-TCA 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx		—	140–41–0	Xx; X36/38 Xxxx. xxx. 3; R40 X; X50–53	Xx; N X: 36/38–40–50/53 S: (2-)36/37–60–61
006–045–00–2	xxxxxxxx (ISO) xxxxxx-X-[(X-xxxxxxxxxxxxxxx)xxx]xxxxxxxxxxxxxx		240–815–0	16752–77–5	X+; X28 X; X50–53	X+; X X: 28–50/53 X: (1/2-)22–36/37–45–60–61
006–046–00–8	xxxxxxxxxx (ISO) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx		245–216–8	22781–23–3	X; X23/25 Xn; X21 N; X50–53	X; X X: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61
006–047–00–3	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; N X: 24/25–50/53 X: (1/2-)28–36/37–45–60–61
006–048–00–9	xxxxxxxxxxxx (XXX) 2-[(xxxxxxxxxxxxx)xxxxxx]xxxxx-X-xxxxxxxxxxxxxx		249–981–9	29973–13–5	Xx; X22 X; X50–53	Xx; X X: 22–50/53 S: (2-)60-61
006–050–00–X	xxxxxxx-XXX 3-fenyl-1,1-dimethyluronium-trichloracetát		—	4482–55–7	Xi; X38 X; X50–53	Xx; X X: 38–50/53 X: (2-)60-61
006–053–00–6	xxxxxxxxxx (ISO) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		220–114–6	2631–40–5	Xx; X22 X; X50–53	Xx; X X: 22–50/53 X: (2-)60-61
006–054–00–1	xxxxxxxxxx (XXX) 4-(xxxxxxxxxxxxx)-3,5-xxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		206–249–3	315–18–4	X+; R28 Xx; X21 N; R50–53	T+; X R: 21–28–50/53 X: (1/2-)36/37–45–60–61
006–057–00–8	nitrapyrin (ISO) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx		217–682–2	1929–82–4	Xx; X22 N; X51–53	Xx; X R: 22–51/53 X: (2-)24-61
006–060–00–4	xxxxxxxxxxx (XXX) 2-methyl-4,4-dioxo-5,6-dihydro-4λ4-1,4-oxathiin-3-karboxanilid		226–066–2	5259–88–1	Xn; R22 X52–53	Xx X:22–52/53 X: (2-)61
006–069–00–3	xxxxxxxxx-xxxxxx (XXX) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx		245–740–7	23564–05–8	Xxxx. xxx. 3; X40 X; X50–53	Xx; X X: 40–50/53 X: (2-)36/37–60–61
006–070–00–9	xxxxxxxxxxx X-xxxxxxxxxx-X-xxxxxxx-2,5-xxxxxxxx-3-xxxxxxx		262–302–0	60568–05–0	Xxxx. xxx. 3; R40 X; X50–53	Xx; X R: 40–50/53 X: (2-)36/37–60–61
006–088–00–7	xxxxxxxxxxx (XXX) xxxxx-X -[({[(2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx)xxx]xxxxxxxx}xxxxxxxxxxx)xxxxxxxx]-X-xxxxxxxxx-β-xxxxxxxx(2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx)-X-({[2-(xxxxxxxxxxxxxx)xxxxx]xxxxxxxxxxxxxx}xxxxxxxx)-X-xxxxxxxxxxxxxx		—	82560–54–1	X; X23/25 X; R50–53	T; X X: 23/25–50/53 X: (1/2-)36/37–45–60–61
007–012–00–5	X,X-xxxxxxxxxxxxxxxx 1,1-dimethylhydrazin	E	200–316–0	57–14–7	F; X11 Xxxx. xxx. 2; X45 X; X23/25 X; X34 X; R51–53	F; X; X X: 45–11–23/25–34–51/53 X: 53–45–61
007–013–00–0	X,X-xxxxxxxxxxxxxxxx 1,2-dimethylhydrazin	E	—	540–73–8	Karc. xxx. 2; X45 X; R23/24/25 N; X51–53	X; N X: 45–23/24/25–51/53 X: 53–45–61	X ≥ 25 %: X; X45–23/24/25 3 % &xx; X &xx; 25 %: X; X45–20/21/22 0,01 % &xx; C &xx; 3 %: X; X45
009–003–00–1	xxxxxxxx xxxxxxxxxxxxxx … %	X	231–634–8	7664–39–3	X+; X26/27/28 X; X35	X+; X X: 26/27/28–35 S: (1/2-)7/9–26–36/37–45	X ≥ 7 %: T+; X; X26/27/28–35 1 % ≤ X &xx; 7 %: T; X23/24/25–34 0,1 % ≤ X &xx; 1 %: Xx; X20/21/22–36/37/38
015–039–00–9	xxxxxxx-xxxxxx (XXX) O,O-dimethyl-S -[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx		201–676–1	86–50–0	X+; R26/28 X; R24 X43 X; R50–53	T+; X X: 24–26/28–43–50/53 S: (1/2-)28–36/37–45–60–61
015–048–00–8	xxxxxxxx (XXX) O,O-dimethyl-O-[3-methyl-4-(methylsulfanyl)fenyl]-fosforothioát		200–231–9	55–38–9	Muta. xxx. 3; X40 X; R23–48/25 Xx; X21/22 N; X50–53	X; X R: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61
015–056–00–1	xxxxxxx-xxxxx (ISO) X,X-xxxxxxx-X-[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx		220–147–6	2642–71–9	X+; X28 X; X24 X; X50–53	X+; N R: 24–28–50/53 X: (1/2-)28–36/37–45–60–61
015–140–00–8	xxxxxxxxx (XXX) X,X-xxxxxxx-X-(1-xxxxx-1 H- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx		245–986–5	24017–47–8	X; X23/25 Xx; X21 N; R50–53	T; X X: 21–23/25–50/53 X: (1/2-)36/37–45–60–61
016–013–00-X	xxxxxxx sirnatý		234–129–0	10545–99–0	R14 X; R34 X; X50	X; X X: 14–34–50 S: (1/2-)26–36/37/39–45–61	C ≥ 10 %: X; R34 5 % ≤ X &xx; 10 %: Xx; R36/37/38
016–014–00–5	chlorid siřičitý		—	13451–08–6	R14 X; X34 X; X50	X; N R: 14–34–50 X: (1/2-)26–36/37/39–45–61	X ≥ 10 %: X; X34 5 % ≤ C &xx; 10 %: Xx; R36/37/38
016–023–00–4	dimethyl-sulfát	E	201–058–1	77–78–1	Karc. xxx. 2; R45 Xxxx. xxx. 3; X40 X+; R26 T; X25 X; X34 X43	X+ R: 45–25–26–34–43 X: 53-4 5	X ≥ 25 %: X+; X45–25–26–34–43 10 % ≤ X &xx; 25 %: X+; X45–22–26–34–43 7 % ≤ X &xx; 10 %: X+; X45–22–26–36/ 37/38–43 5 % ≤ X &xx; 7 %: X; X45–22–23–36/37/38–43 3 % ≤ X < 5 %: X; X45–22–23–43 1 % ≤ X &xx; 3 %: T; R45–23–43 0,1 % ≤ X &xx; 1 %: T; R45–20 0,01 % ≤ X &xx; 0,1 %:X; X45
016–024–00-X	xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx	X,X′-xxxxxxxx-xxxxxxxxxxx(xxxxxxxxxxx)215–993–8	1468–37–7	Xx; R22 X; X50–53	Xx; N R: 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 trisodný		410–130–3	136248–03–8	R43	Xi R: 43 S: (2-)22–24–37
022–001–00–5	xxxxxxx xxxxxxxxxx		231–441–9	7550–45–0	X14 X; X34	X X: 14-34 X: (1/2-)7/8–26–36/37/39–45	X ≥ 10 %: C; R34 5 % ≤ X < 10 %: Xi; X36/37/38
030–004–00–8	xxxxxxxxxxxxx [1] xxxxxxxxxxxx [2]		208–884–1 [1] 209–161–3 [2]	544–97–8 [1] 557–20–0 [2]	X14 X; X17 C; X34 X; R50–53	F; X; X X: 14–17–34–50/53 S: (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 X; R50–53	Xn; X X: 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]	Xn; R20/21/22 X; X50–53	Xx; N X: 20/21/22–50/53 X: (2-)26–28–60–61	X ≥ 1 %: Xx; X20/21/22	1
050–017–00–2	xxxxxxxxxxxxxx (XXX) 1,1,1,3,3,3-xxxxxxx(2-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxxxx		236–407–7	13356–08–6	X+; X26 Xx; R36/38 X; X50/53	X+; X X: 26–36/38–50/53 X: (1/2-)28–36/37–45–60–61
082–009–00–X	xxxx (xxxxxxxxxxxx olovnatý) XX Xxxxxxx Xxxxxx 34 (XX 77603) XX xxxxxxxxxx žluť 34 (XX 77603)		215–693–7	1344–37–2	Xxxx. xxx. 3; X40 Xxxx. xxx. 1; R61 Xxxx. xxx. 3; X62 R33 X; X50–53	X; X R: 61–33–40–50/53–62 X: 53–45–60–61		1
082–010–00–5	xxxxxx (xxxxxxx-xxxxxxxxxx-xxxxx olovnatý) CI Xxxxxxx Xxx 104 (XX 77605) XX xxxxxxxxxx červeň 104 (XX 77605)		235–759–9	12656–85–8	Xxxx. xxx. 3; X40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 X; X50–53	X; X X: 61–33–40–50/53–62 X: 53–45–60–61		1
601–024–00-X	xxxxx [1] xxxxxxxxxxxx [2]		202–704–5 [1] 203–132–9 [2]	98–82–8 [1] 103–65–1 [2]	R10 Xx; X65 Xi; X37 X; X51–53	Xx; X R: 10–37–51/53–65 X: (2-)24–37–61–62		4
601–032–00–3	xxxxx[x]xxxxx benzo[def]chrysen		200–028–5	50–32–8	Karc. xxx.2; X45 Xxxx. xxx. 2; X46 Xxxx. xxx. 2; X60–61 X; X50–53	X; X X: 45–46–60–61–50/53 X: 53–45–60–61
601–034–00–4	xxxxx[x]xxxxxxxxxxxxxxx		205–911–9	205–99–2	Xxxx. kat.2; X45 N; X50–53	X; X X: 45–50/53 X: 53–45–60–61
602–035–00–2	1,4-xxxxxxxxxxxxx x-xxxxxxxxxxxxx		203–400–5	106–46–7	Xx; X36 N; X50–53	Xx; X X: 36–50/53 X: (2-)24/25–46–60–61
602–054–00–6	3-jodprop-1-en xxxxxxxxxx		209–130–4	556–56–9	X10 X; R34	C X: 10-34 X: (1/2-)7–26–45
603–076–00–9	but-2-yn-1,4-diol		203–788–6	110–65–6	T; X23/25 Xn; X21–48/22 X; X34	X X: 21–23/25–34–48/22 X: (1/2-)26–36/37/39–45	X ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ X &xx; 50 %: X; 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 Xx; X36	X; Xx X: 8–22–36 S: (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; R36 X52–53	Xx 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 X67	X; Xx R: 11–36–67 X: (2-)7–16–24/25–26
604–020–00–6	bifenyl-2-ol 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (XXX)		201–993–5	90–43–7	Xx; X36/37/38 X; X50	Xx; N X: 36/37/38–50 X: (2-)22-61
604–021–00–1	2-xxxxxxxxxx, sodná sůl xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx sodný xxxxxxx-xxxxxxx-2-xxxx		205–055–6	132–27–4	Xx; R22 Xi; X37/38–41 N; R50	Xn; 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-bis(4-hydroxyfenyl)-4-methylpentan		401–720–1	6807–17–6	Repr. xxx. 2; X60 Xx; X36 N; X50–53	X; N X: 60–36–50/53 S: 53–45–60–61
604–041–00–0	xxxxxxxxxxx [1] xxxxxxxxxxx-xxxxxxx [2] 5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxxx kyselina [1] xxxxxxx-5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxx [2]		256–634–5 [1] 263–560–7 [2]	50594–66–6 [1] 62476–59–9 [2]	Xx; R22 Xx; R38–41 N; X50–53	Xx; X R: 22–38–41–50/53 X: (2-)24–39–60–61
604–043–00–1	xxxxxxxxxxxxxxxx (4-xxxxxxxxxxxx)xxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx 4-(benzyloxy)fenol		203–083–3	103–16–2	Xi; X36 X43	Xx X: 36-43 S: (2-)24/25–26–37
604–044–00–7	xxxxxxxx 4-xxxxxxxxxxxx hydrochinonmonomethylether		205–769–8	150–76–5	Xn; R22 Xx; X36 X43	Xx X: 22–36–43 X: (2-)24/25–26–37/39–46
605–016–00–7	xxxxxxx… % xxxxxxxxx… %	X	203–474–9	107–22–2	Xxxx. kat. 3; X40 Xx; X20 Xx; X36/38 X43	Xx X: 20–36/38–40–43 X: (2-)36/37	X ≥ 10 %: Xn; X20–36/38–40–43 1 % ≤ X &xx; 10 %: Xx; X40–43
606–016–00-X	xxxxxx (XXX) 2-(xxxxxxxxxxxxxxx)xxxxx-1,3-xxxx		201–462–8	83–26–1	X; R25–48/25 X; R50–53	T; N X: 25–48/25–50/53 X: (1/2-)37–45–60–61
606–018–00–0	xxxxxxx (XXX) 2,3-xxxxxxx-1,4-xxxxxxxxxxx		204–210–5	117–80–6	Xx; X22 Xx; X36/38 X; R50–53	Xn; N X: 22–36/38–50/53 X: (2-)26–60–61
606–019–00–6	xxxxxxxxxx (ISO) xxxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx xxxxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx 1,2,4,5,6,7,8,8,9,10-dekachlorpentacyklo[5.3.0.02,6.04,10.05,9]dekan-3-on		205–601–3	143–50–0	Karc. xxx. 3; X40 X; X24/25 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-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-4,5-xxxxxxx-1,2,4-xxxxxxx-5-xx		244–209–7	21087–64–9	Xx; X22 X; R50–53	Xn; X X: 22–50/53 X: (2-)60-61
606–035–00–3	chloridazon (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	xxxxxxxxxxxxxx (XXX) 6-xxxxxx-2 X-[1,3]xxxxxxxx[4,5-x]xxxxxxxxxx-2-xx		219–455–3	2439–01–2	Xxxx. xxx. 3; X62 Xx; X20/21/22–48/22 Xx; X36 X43 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-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-on		256–103–8	43121–43–3	Xn; X22 N; X51–53	Xx; X R: 22–51/53 X: (2-)61
606–044–00–2	2,4,6-trimethylbenzofenon xxxxx(2,4,6-xxxxxxxxxxxxxx)xxxxxxxx		403–150–9	954–16–5	Xx; X22 Xx; R36 X; X50–53	Xx; X X: 22–36–50/53 S: (2-)26–60–61
607–043–00-X	xxxxxxx (ISO) 3,6-xxxxxxx-2-xxxxxxxxxxxxxxx xxxxxxxx		217–635–6	1918–00–9	Xx; X22 Xx; X41 X52–53	Xx; X X: 22–41–52/53 S: (2-)26-61
607–057–00–6	xxxxxxxxx (XXX) 3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxykumarin3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxy-2 X-xxxxxxx-2-xx		201–378–1	81–82–3	Xx; R48/22 X52–53	Xx X:48/22–52/53 S: (2-)37-61
607–058–00–1	xxxxxxxxx (XXX) xxxxxxx (RS)-3-[1-(2-furyl)-3-oxobutyl)]-4-hydroxykumarin (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 H -chromen-2-on 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-furyl)-3-oxobutyl]-4-hydroxy-2 H -xxxxxxx-2-xx		204–195–5	117–52–2	X; R25–48/25 X52–53	X X:25–48/25–52/53 S: (1/2-)37–45–61
607–079–00–6	xxxxxxx (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx xxxxx-5-(1,2,3,5,6,7,8,9,10,10-xxxxxxxxx-4-xxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx)-4-xxxxxxxxxxxx xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx		—	4234–79–1	X; R24 Xx; X22 X; X51–53	X; X X: 22–24–51/53 X: (1/2-)36/37–45–61
607–097–00–4	benzen-1,2,4-trikarbox-1,2-anhydrid 1,2-xxxxxxxx xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxx		209–008–0	552–30–7	Xx; X37–41 X42/43	Xx R: 37–41–42/43 S: (2-)22–26–36/37/39
607–143–00–3	xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx		203–677–2	109–52–4	X; X34 X52–53	X X:34–52/53 X: (1/2-)26–36–45–61
607–152–00–2	2,3,6-TBA (XXX) 2,3,6-xxxxxxxxxxxxxxxx xxxxxxxx		200–026–4	50–31–7	Xx; X22 X; R51–53	Xn; X 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 R52–53	Xi X:36/38–52/53 X: (2-)22-61
607–156–00–4	chlorfenson (XXX) 4-xxxxxxxxxx-4-xxxxxxxxxxx-1-xxxxxxxx		201–270–4	80–33–1	Xx; X22 Xx; R38 X; X50–53	Xx; X X: 22–38–50/53 S: (2-)37–60–61
607–158–00–5	xxxxx xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx		223–498–3	3926–62–3	X; R25 Xx; X38 X; X50	X; X R: 25–38–50 X: (1/2-)22–37–45–61
607–159–00–0	chlorobenzilát (XXX) ethyl-2,2-bis(4-chlorfenyl)-2-hydroxyacetát ethyl-4,4'-dichlorbenzilát		208–110–2	510–15–6	Xn; X22 X; X50–53	Xx; X R: 22–50/53 X: (2-)60-61
607–176–00–3	Xxxx: α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-xxxxxxxxxxx(xxxxxxxxxx);α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-({3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}xxx)xxxx(xxxxxxxxxx)		400–830–7	—	X43 X; X51–53	Xx; X X: 43–51/53 S: (2-)36/37–61
607–188–00–9	xxxxxxx-xxxxxxxx-X-(2-xxxxxxxxxxxx)-X-(xxxxxxx-9-xx-1-xx)xxxxxxxxxx		402–970–4	—	X43 N; X51–53	Xx; X X: 43–51/53 X: (2-)24/37–61
607–209–00–1	Xxxx: O,O′-diisopropyl-trisulfanbis(karbothioát); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx)		403–030–6	—	Xx; R22 X43 N; R50–53	Xn; X X: 22–43–50/ 53 S: (2-)36/37–60–61
607–213–00–3	xxxxx-3,3-xxx(xxxx-xxxxxxxxxxxx)xxxxxxxx		403–320–2	67567–23–1	X; X2 O; R7 X10 N; 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-ethoxyethyl-[4-(7-fenyl-2,6-dioxo-2,6-dihydro-1,5-dioxa-s-indacen-3-yl)fenoxy]acetát		403–960–2	—	R43 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-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [3] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [3]		217–846–3 [1] 246–590–5 [2] 258–527–9 [3]	1982–69–0 [1] 25059–78–3 [2] 53404–28–7 [3]	X52–53	X: 52/53 X: 61
607–248–00–4	Xxxxxxxx-xxxxxxx Natrium-N-(1-naftyl)ftalamát		205–073–4	132–67–2	Xn; X22	Xx X: 22 S: (2)
607–249–00-X	(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx xxxxxxxxxxxxxxxxx-xxxxxxxxx XXXXX		256–032–2	42978–66–5	Xx; X36/37/38 R43 X; X51–53	Xx; X R:36/37/38–43–51/53 X: (2-)24–37–61	X ≥ 10 %: Xx; X36/37/38–43 1 % ≤ X &xx; 10 %: Xx; X43
607–252–00–6	λ-xxxxxxxxxxx (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+; X26 X; R25 Xx; X21 X; X50–53	X+; X X: 21–25–26–50/53 X: (1/2-)28–36/37/39–38–45–60–61
607–255–00–2	xxxxxxxxxx (ISO) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx xxxxxxxx		—	69377–81–7	X52–53	X: 52/53 X: 61
608–003–00–4	xxxxxxxxxxxx	X E	203–466–5	107–13–1	F; Xxx Karc. kat. 2; R45 X; X23/24/25 Xi; X37/38–41 X43 X; X51–53	X; X; N X: 45–11–23-/24/25–37/38–41–43–51/53 S: 9–16–53–45–61	X ≥ 20 %: X; X45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; X45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ C &xx; 5 %:X; X45–23/24/25–43 0,2 % ≤ C &xx; 1 %:X; R45–20/21/22 0,1 % ≤ X < 0,2 %: T; X45	43
608–016–00–5	2,3,5,6-xxxxxxxxxx-1,4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxx		401–550–8	1897–41–2	X43 X; X50–53	Xx; X R: 43–50/53 X: (2-)24–37–60–61
609–030–00–4	dinoterb (ISO) 2-xxxx-xxxxx-4,6-xxxxxxxxxxxx	X	215–813–8	1420–07–1	Xxxx. xxx. 2; X61 X+; R28 X; X24 R44 X; X50–53	X+; X X: 61–24–28–44–50/53 X: 53–45–60–61
609–040–00–9	xxxxxxxx (ISO) (2,4-xxxxxxxxxxxx)(4-xxxxxxxxxx)xxxxx	X	217–406–0	1836–75–5	Xxxx. xxx. 2; R45 Xxxx. xxx. 2; X61 Xx; R22 X; X50–53	X; X X: 45–61–22–50/53 X: 53–45–60–61
609–044–00–0	xxxxxxxx (ISO) 1,2,4,5-xxxxxxxxxx-3-xxxxxxxxxxx		204–178–2	117–18–0	Xx; X22 R43 N; X50–53	Xx; N X: 22–43–50/53 X: (2-)24–37–60–61
611–008–00–4	4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx		200–453–6	60–09–3	Xxxx. 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 xxxxxxxxx		403–650–7	117409–78–6	X; X2 X; R51–53	E; X R: 2–51/53 X: (2-)35-61
611–031–00-X	4,4'-[(4-iminocyklohexa-2,5-dien-1-yliden)methylen]dianilin-hydrochlorid CI Xxxxx Red 9 XX xxxxxxx xxxxxx 9		209–321–2	569–61–9	Xxxx. xxx. 2; X45	X X: 45 X: 53-45
612–035–00–4	2-xxxxxxxxxxxxx x-xxxxxxxx	X	201–963–1	90–04–0	Xxxx. xxx. 2; X45 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; X50–53	X; X X: 45–22–50/53 S: 53–45–60–61	X ≥ 25 %: X; R45–22 0,01 % ≤ X &xx; 25 %: X; R45
612–051–00–1	4,4'-diaminodifenylmethan xxx(4-xxxxxxxxxx)xxxxxx 4,4'-xxxxxxxxxxxxxxxx	X	202–974–4	101–77–9	Xxxx. xxx. 2; R45 Xxxx. xxx. 3; X40 X; X39/23/24/25Xx; X48/20/21/22 X43 N; R51–53	T; X X: 45–39/23/24/25–43–48/20/21/22–51/53 X:53–45–61
612–081–00–5	3,3'-xxxxxxxxxxxxxxxx, soli o-tolidin, xxxx	X X	210–322–5 265–294–7 277–985–0	612–82–8 64969–36–4 74753–18–7	Xxxx. xxx. 2; X45 Xx; X22 X; X51–53	X; N 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. xxx. 2; X45 X; X25 Xx; R21 Xi; X36 R43 N; X51–53	X; N 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 R52–53	C R: 21/22–34–43–52/53 X: (1/2-)26–36/37/39–45–61
612–111–00–7	2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,3-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,3-xxxxxx 2,6-xxxxxxxxxxxx		212–513–9	823–40–5	Xxxx. xxx. 3; X40 Xx; X21/22 X43 X; X51–53	Xx; X R: 21/22–40–43–51/53 X: (2-)24–36/37–61
612–125–00–3	2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,4-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,4-xxxxxx 2,5-toluendiamin		202–442–1	95–70–5	T; X25 Xx; R20/21 X43 X; X51–53	X; X X: 20/21–25–43–51/53 X: (1/2-)24–37–45–61
612–144–00–7	flumetralin (XXX) X-(2-xxxxx-6-xxxxxxxxxxx)-X-xxxxx-2,6-xxxxxxx-4-(xxxxxxxxxxxxxx)xxxxxx		—	62924–70–3	Xx; X36/38 R4 3 X; R50–53	Xi; X X: 36/38–43–50/53 X: (2-)36/37–60–61
612–151–00–5	diaminotoluen xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx methylbenzendiamin	E	246–910–3	25376–45–8	Karc. kat. 2; R45 X; X25 Xx; R20/21 Xx; R36 X43 X; X51–53	X; N X: 45–20/21–25–36–43–51/53 S: 53–45–61
613–018–00–4	xxxxxxxxxx (XXX) 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx		—	7411–47–4	Xx; X22 Xx; X36/37/38 X52–53	Xx X: 22–36/37/38–52/53 X: (2-)22–36–61
613–031–00–5	symklosen trichlorisokyanurová xxxxxxxx xxxxxxxx-1,3,5-xxxxxxxxxxxx 1,3,5-trichlor-1,3,5-triazin-2(1H), 4(3X), 6(5X)-xxxxx		201–782–8	87–90–1	X; X8 Xx; R22 R31 Xx; X36/37 N; X50–53	X; Xx; N X: 8–22–31–36/37–50/53 S: (2-)8–26–41–60–61
613–038–00–3	6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxx xxxxxxxxxxxxx		202–095–6	91–76–9	Xx; X22 X52–53	Xx 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; R41 X; R50–53	Xn; N X: 20/22–41–50/53 S: (2-)26–39–60–61
613–043–00–0	xxxxxxxx-xxxxxx (ISO) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1X -xxxxxxxx-1-xxx-xxxxxxxxxxxxxx [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx		261–351–5 [1] 281–291–3 [2]	58594–72–2 [1] 83918–57–4 [2]	Xx; X20/22 Xx; X41 X; X50–53	Xx; X X: 20/22–41–50/53 X: (2-)26–39–60–61
613–066–00–6	xxxxxxxxxx (XXX) 2-(xxxx-xxxxxxxxxx)-4-(xxxxxxxxxx)-6-xxxxxxx-1,3,5-xxxxxxx		251–637–8	33693–04–8	Xx; X22 X; X50–53	Xx; N R: 22–50/53 X: (2-)60-61
613–091–00–2	xxxxxxxxxx-xxxxxxxxx [1] morfamkvat-sulfát [2] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx-xxxxxxxxx [1] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxx-xxxxxxxx [2]		225–062–8 [1]	4636–83–3 [1] 29873–36–7 [2]	Xx; R22 Xx; R36/37/38 X52–53	Xx; X: 22–36/37/38–52/53 S: (2-)22–36–61
613–098–00–0	1-xxxxxxxxxxxxxxx-2-xx 1-oktyl-2-pyrrolidon		403–700–8	2687–94–7	C; X34 X; X51–53	X; X X: 34–51/53 X: (1/2-)23–26–36/37/39–45–61
613–130–00–3	xxxxxxxxxxx (XXX) (XX)-2-(2,4-xxxxxxxxxxxx)-1-(1X-1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		—	79983–71–4	X43 X; R51–53	Xi; N X: 43–51/53 S: (2-)24–37–61
613–131–00–9	xxxxxxxxxx (XXX) 1,2,5,6-tetrahydro-4 X-xxxxxxx[3,2,1-xx]xxxxxxxx-4-xx		—	57369–32–1	Xx; X22 X52–53	Xx X:22–52/53 S: (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; R63 Xx; R22 Xx; X36 X; X51–53	Xx; X R: 22–36–51/53–63 X: (2-)36/37–46–61
613–137–00–1	xxxxxxxxxxxxxxxxxx (XXX) 1-(1,3-xxxxxxxxxxxx-2-xx)-1,3-xxxxxxxxxxxxxxxx		242–505–0	18691–97–9	X; R50–53	N X: 50/53 S: 60-61
613–139–00–2	metsulfuron-methyl xxxxxx-2-{X —[X-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxxx]xxxxxxxxx}xxxxxxx		—	74223–64–6	X; R50–53	N X: 50/53 S: 60-61
614–001–00–4	xxxxxxx (XXX) 3-(1-methylpyrrolidin-2-yl)pyridin		200–193–3	54–11–5	T+; X27 X; X25 X; X51–53	X+; X X: 25–27–51/53 X: (1/2-)36/37–45–61
614–006–00–1	xxxxxx 2,3-dimethoxystrychnidin-10-on		206–614–7	357–57–3	T+; X26/28 X52–53	X+ R:26/28–52/53 S: (1/2-)13–45–61
614–007–00–7	xxxxxx-xxxxxx [1] xxxxxx-xxxxxx [2] brucin-(R)-(1-methylheptyl)-hydrogen-ftalát [3] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [4]		225–432–9 [1] 227–317–9 [2] 269–439–5 [3] 269–710–8 [4]	4845–99–2 [1] 5786–97–0 [2] 68239–26–9 [3] 68310–42–9 [4]	X+; X26/28 R52–53	T+ X: 26/28–52/53 X: (1/2-)13–45–61
615–006–00–4	2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-methyl-m-fenylendiisokyanát [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] x-xxxxxxxxxxxxxxxxxxxx [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [2] xxxxxx-3,5-xxxxxxxxxxx [3]	C	202–039–0 [1] 209–544–5 [2] 247–722–4 [3]	91–08–7 [1] 584–84–9 [2] 26471–62–5 [3]	Xxxx. xxx. 3; X40 X+; X26 Xx; R36/37/38 X42/43 X52–53	X+ X: 26–36/37/38–40–42/43–52/53 X: (1/2-)23–36/37–45–61	C320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; R23–40–42/43 0,1 % ≤ X &xx; 1 %:Xn; X20–42	2
616–010–00–9	xxxxxxx-xxxxxxxxxxxxxx X-xxxxx-4-xxxxxxxxxxxx-1-xxxxxxxxxx, sodná xxx		204–854–7	127–65–1	Xx; X22 R31 X; X34 R42	C X: 22–31–34–42 S: (1/2-)7–22–26–36/37/39–45
616–034–00-X	xxxxxxxxxxxx (XXX) 6-xxxxxx-3,4-xxxxxxx-2X-xxxxx-5-xxxxxxxxxxxx		246–419–4	24691–76–7	X52–53	X: 52/53 X: 61
616–035–00–5	cymoxanil X -[(ethylamino)karbonyl]-2-kyan-2-(methoxyimino)acetamid 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx		261–043–0	57966–95–7	Xx; X22 X43 N; X50–53	Xx; X X: 22–43–50/53 S: (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; R7 Xn; X22 X; R34 X; X50–53	X; X; X X: 7–22–34–50/53 X:(1/2-)3/7–14–26–36/37/39–45–60–61	X325 %: X; X22–34 10 % ≤ C &xx; 25 %: X; X34 5 % ≤ C &xx; 10 %: Xx; X36/37/38
617–006–00-X	xxx(α, α-dimethylbenzyl)peroxid 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; Xi; X 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; X2 Xx; X36 X43	X; Xi; X: 2–36–43 X: (2-)3/7–14–36/37/39
650–007–00–3	xxxxxxxxxxxxx (XXX) X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx		228–200–5	6164–98–3	Xxxx. xxx. 3; X40 Xx; X21/22 X; X50–53	Xx; N X: 21/22–40–50/53 X: (2-)22–36/37–60–61
650–008–00–9	xxxxxxxxxx (XXX) 4-[(2-chlorfenyl)hydrazono]-3-methylisoxazol-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	xxxxxxxxxxxxx-xxxxxxxxxxxx X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx N2-(4-chlor-2-methylfenyl)-N1,N1-dimethylformimidamid-hydrochlorid X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx		243–269–1	19750–95–9	Xxxx. xxx. 3; X40 Xx; R22 N; X50–53	Xx; N X: 22–40–50/53 X: (2-)22–36/37–60–61
650–033–00–5	xxxxxxxxxxxx (XXX) [(X)-(3-xxxxxxxxxxx)xxxxxxxxxx]-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx (X)-3-xxxxxx-α-xxxxxxxxxx-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx		—	66230–04–4	X; X23/25 X43 N; X50–53	X; X 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-chlorethoxy)benzen-1-sulfonyl]-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)močovina		—	82097–50–5	N; R50–53	N X: 50/53 X: 60-61

PŘÍLOHA 1D

Indexové číslo	Chemický xxxxx	Xxxxxxxx x xxxxxx	Xxxxx XX	Xxxxx XXX	Xxxxxxxxxxx	Xxxxxxxx	Xxxxxxxxxxxx limity	Poznámky 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; X41 X52–53	Xx X: 20–41–52/53 X: (2-)22–26–39–61
014–016–00–0	Xxxx: 1,3-di(hex-5-en-1-yl)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx x 1,3-xx(xxx-x-xx-1-xx)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx		406–490–6	—	X; X51–53	X X: 51/53 X: 61
015–164–00–9	xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx xxxxxxxx		400–480–5	36669–85–9	X52–53	X:52/53 X: 61
015–165–00–4	Směs: S, X, S', X''-xxxxxxxxxx-4,4'-xxxxxxxxxxxxx(xxxxxxxxxxxxxx)-xxx(xxxxxxxxxxxxxxxx) x difenyl[4-(fenylsulfanyl)fenyl]sulfonium-hexafluorofosfát		404–986–7	—	Xi; X41 X; X50–53	Xx; X X: 41–50/53 S: (2-)15–26–39–60–61
015–166–00-X	3,9-xxx(2,6-xx-xxxx-xxxxx-4-xxxxxxxxxxxx)-2,4,8,10-xxxxxxxx-3,9-xxxxxxxxxxxx[5.5]xxxxxxx		410–290–4	80693–00–1	X53	X:53 X: 61
015–167–00–5	3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx		411–200–6	14657–64–8	Xx; X41	Xx X: 41 S: (2-)26-39
601–050–00–1	C10-C13-alkylderiváty xxxxxxx		267–051–0	67774–74–7	X; X50	X X: 50 S: 61
601–051–00–7	4-xxxxxxxx-1-xx		405–980–7	768–56–9	Xx; X38 N; X51–53	Xx; X X: 38–51/53 X: (2-)37-61
602–083–00–4	pentabromderivát xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx		251–084–2	32534–81–9	Xx; X48/21/22 X64 X; X50–53	Xx; N X: 48/21/22–50/53–64 X: (1/2-)36/37–45–60–61
602–084–00-X	1,1-xxxxxxx-1-xxxxxxxxxx		404–080–1	1717–00–6	X; R52–53–59	N X: 52/53–59 X: 59-61
603–128–00–0	2-(xxxxxxxxxxxx)xxxxxxxx		405–490–3	613–62–7	X53	X:53 X: 61
603–129–00–6	1-xxxx-xxxxxxxxxxxx-2-xx		406–180–0	57018–52–7	X10 Xx; X41	Xx X: 10-41 X: (2-)26-39
603–130–00–1	Xxxx xxxxxxx: α-(xxxxxxxxxxxxxxxxx)-ω-xxxxxxxxxxx(xxxxxxxxxx)		406–325–8	—	Xx; X22 R52–53	Xn X:22–52/53 S: (2-)39-61
603–131–00–7	Xxxx (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxxx)xxxxx]-X-xxxxxxxx		407–290–1	—	Xx; R41	Xi 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 X: (2-)26–37/39–61
603–133–00–8	Xxxx:3-(4-xxxxx-2-xxxxx-5-xxxxxxxxxxxx)xxxxxx-1,2-xxxx x 3,3'-[(2-xxxxx-5-xxxxx-1,4-xxxxxxx)xxxxxxx]xx(xxxxxx-1,2-xxxx)		408–240–1	—	Xx; X22 X52–53	Xx X: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	bis[2-(2-methoxyethoxy)ethanolato]bis(2,2', 2-nitrilotriethan-1-olato-N,O)titaničitý xxxxxxx		410–500–4	—	Xx; X41 X; X51–53	Xx; N 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 X:43–52/53 X: (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-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-xxxxxxxx-3-(3-xxxxxxxxxxx)xxxxxx-1-xx		403–140–4	103694–68–4	X52–53	X:52/53 X: 61
604–050–00-X	4-xxxxx-x-xxxxxx 4-xxxxx-2-xxxxxxxxxxx		216–381–3	1570–64–5	X; X23 X; R 35 N; X50	X; X; X X: 23–35–50 X: (1/2-)26–36/37/39–45–61	X ≥ 25 %: X; X; X23–35 10 % ≤ X < 25 %: C;R20–35 5 % ≤ C &xx; 10 %: X;X20–34 3 % ≤ X &xx; 5 %: Xn;R20–36/37/38 1 % ≤ X < 3 %:Xx;X36/37/38
604–051–00–5	3,5-xxx(3,5-xx-xxxx-xxxxx-4-xxxxxxxxxxxxx)-2,4,6-xxxxxxxxxxxxxx		401–110–5	87113–78–8	X52–53	X:52/53 X: 61
604–052–00–0	2,2'-methylenbis[6-(2 X - benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)fenol] 6,6'-xxx(2X -xxxxxxxxxxxx-2-xx)- 4,4'-bis(1,1,3,3-tetramethylbutyl)- 2,2'-xxxxxxxxxxxxxxx		403–800–1	103597–45–1	X53	X:53 X: 61
604–053–00–6	4-xxxx - xxxxx-2-xxxxxx-6-(1-xxxxxxxxxxxxxxxx)xxxxx		410–760–9	157661–93–3	Xx; X38 X43 N; R50–53	Xi; X X: 38–43–50/53 X: (2-)24–37–60–61
604–054–00–1	Xxxx:2-xxxxxxx-4-(4-xxxxxxxxxxxxxxxxxxxxxxxxx-2-xx)xxxxx a 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -xxxxx-2-xx)xxxxx		412–020–0	—	X43 X52–53	Xx X:43–52/53 X: (2-)24–37–61
604–055–00–7	4,4'-bis[(2,3-epoxypropyl)oxy]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx		413–900–7	85954–11–6	Xxxx. Kat.3; X40	Xx X: 40 S: (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 X: 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 X: 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]	N; X50–53	X X: 50/53 X: 60-61
607–273–00–0	xxxxxxx-7-{2,6-xxxxxxxx-8-[(2,2-xxxxxxxxxxxxxxxx)xxx]- 1,2,6,7,8,8x-xxxxxxxxx-1-xxxxxx}-3,5-xxxxxxxxxxxxxxxxxx		404–520–2	—	X52–53	X:52/53 X: 61
607–274–00–6	{2-[xxxxxx(xxxxxx)xxxxx]xxxxx}-3-xxxxxxxx-2-xxxxx		405–350–1	54527–73–0	X43 N; X51–53	Xx; N X: 43–51/53 X: (2-)24–37–61
607–275–00–1	xxxxxxx-4-(xxxxxxxxxx)xxxxxx-1-xxxxxxxx		405–450–5	66531–87–1	X43	Xx X: 43 X: (2-)24-37
607–276–00–7	[xxx(2-xxxxxxxxxxxxxx) xxx(1-xxxxxxxxxxxxxx)]xxxxxxxxx xxxxxxx		405–635–0	—	Xx; X38–41 X; X50–53	Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61
607–277–00–2	Směs:2-(hexylsulfanyl)ethylamin-hydrochlorid 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 x nerozvětvené)-3-[3-(2 X - benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty		405–760–0	—	Xi; X41 X43 R52–53	Xi X: 41–43–52/53 X: (2-)24–26–37/39–61
607–279–00–3	Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) x (xxxxxxxxxxxxxx)xxxxxxxxx-(xxxxxxxx-xxxxxx)-(xxxxxxxx-xxxxxxxx)		405–960–8	—	X43 X; X51–53	Xx; X X: 43–51/53 S: (2-)24–37–61
607–280–00–9	4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx xxxxx xxxxxxx-4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx		406–190–5	54322–20–2	Xx; X22 Xi; X36 X43	Xx X: 22–36–43 X: (2-)22–26–36/37
607–281–00–4	Xxxx:xxxxx(X7-X9 xxxxxxxxxx x xxxxxxxx)-3-[3-(2X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx		407–000–3	127519–17–9	X; X51–53	X X: 51/53 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; X21/22 Xx; X38–41 X43 X; X50–53	Xx; X X: 21/22–38–41–43–50/53 S: (2-)26–36/37/39–60–61
607–284–00–0	Xxxx (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) x lithium-3,3'-{(1,4-fenylen)bis[(karbonylimino)(propan-3,1-diyl)imino]}bis(10-amino-6,13-dichlor[1,4]benzoxazino[2,3-b]fenoxazin-4,11-disulfonát)		410–040–4	136213–76–8	N; 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 a xxxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx		410–065–0	—	X43	Xx X: 43 S: (2-)22–24–37
607–286–00–1	Xxxx:xxxxxx- a natrium-7-[4-({4-[(2-hydroxy-1-naftyl)azo]fenyl}azo)benzensulfonamido]naftalen-1,3-disulfonát		410–070–8	141880–36–6	R43 X52–53	Xx R:43–52/53 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 X: 61
607–288–00–2	[c-(N -{3-[(1-{3-[(2,6(4,6)-xxxxxxx-5-xxxxxxxxxxxxx-4(2)-xx)xxxxxxxxxxx]xxxxxx}-2-xxxxxxx-4-xxxxxx-6-xxx-1,6-xxxxxxx-3-xxxxxxx)xxx]-4-xxxxxxxxxxxxxx}xxxxxxxxx)-x,x,x -xxxxxxxxxxxxxxxxxxxxxxx]xxxxxxxxx xxxxxxx, xxxxxxxxxx xxx; x = 15, 16, 17 nebo 18, x = 1, 2, 3 xxxx 4, b = 8, 9, 10 xxxx 11, x = 22, 23, 24 xxxx 25		410–160–7	148732–74–5	Xx; X36 R43 X52–53	Xx X: 36–43–52/53 X: (2-)22–26–36/37–61
607–288–00–8	3-[(3-{X —[4-(2,4-di-terc-pentylfenoxy)butyl]karbamoyl}-4-hydroxy-1-naftyl)sulfanyl]propanová xxxxxxxx		410–370–9	105488–33–3	X53	X:53 X: 61
607–290–00–3	Xxxx (o xxxxxxxx poměru):amonium-1-alkyl(C14-C18)-4-[3-(allyloxy)-2-hydroxypropyl]-2-sulfonatobutandioát x xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx		410–540–2	—	Xx; X38 X43 X; R50–53	Xi; X X: 38–43–50/53 S: (2-)24–37–60–61
607–291–00–9	xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx		410–630–1	104051–92–5	X53	X: 53 X: 61
607–292–00–4	Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(xxxxx(X14)xxx)-1-(xxxxxxxxxxxxx)]xxxxxx 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-XXxxx:	1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx a 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx		410–650–0	—	Xx; R41 X43 X; X51–53	Xx; N X: 41–43–51/53 S: (2-)26–36/37/39–61
607–294–00–5	xxxxxxx-2-(xxxxxxxxxx)-1-xxxxxxxxxxxx-1-xxxxxxxx		410–680–4	—	X43	Xx X: 43 X: (2-)24-37
607–295–00–0	Xxxx:xxxxxxxxxxxx-xxxxxxxxxxxxxxxxx x xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx		410–800–5	—	X43 X; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
607–296–00–6	Xxxx:xxxxxxxxxxx xxxxxxxxxxxxxxxx, xxxxxxxxx xxxxxxxx x 2-xxxxxxxxxxxxx kyselina		410–830–9	—	R53	R: 53 X: 61
607–297–00–1	3,3'-(1,4-fenylendimethyliden)bis(2-oxobornan-10-sulfonová kyselina)2,2'-dioxo-3,3'-(1,4-fenylendimethyliden)bis(1,7,7-trimethylbicyklo[2.2.1]heptan-1-methansulfonová xxxxxxxx)		410–960–6	92761–26–7	Xx; X41	Xx X: 41 X: (2-)26-39
607–298–00–7	[2-(trimethylamonio)ethyl]-4-sulfonatobenzoát		411–010–3	—	R43	Xi X: 43 X: (2-)22–36/37
607–299–00–2	xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx		411–040–7	97101–46–7	Xx; R22 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, x-xxxxxxxxxxxxxxxxxxxx]xxxxxxx xxxxxxx, xxxxxxxx xxx; x = 1,2,3 xxxx 4, x = 8, 9, 10 xxxx 11, x = 15, 16, 17 xxxx 18, x = 22, 23, 24 xxxx 25		411–430–7	—	X43	Xx R: 43 X: (2-)22–24–37
607–301–00–1	Xxxx:xxxxxxxxxx xxxxxxxx x xxxxxxxxxxx oligo(1-7)laktátů		411–860–5	—	Xi; X38–41 R43 X; X51–53	Xx; X R: 38–41–43–51/53 S: (2-)24–26–37/39–61
607–302–00–7	Směs:tetradekanová xxxxxxxx a xxxxxxxxxxxxxx xxxxx(1-7)xxxxxxx		411–910–6	—	Xx; X38–41 X43 X; X51–53	Xx; X X: 38–41–43–51/53 S: (2-)24–26–37/39–61
607–303–00–2	1-xxxxxxxxxxx-6,7-xxxxxxx-4-xxx-1,4-xxxxxxxxxxxxxxx-3-xxxxxxxxxxx xxxxxxxx		413–760–7	93107–30–3	Xxxx. xxx.3; X62 R52–53	Xn X: 62–52/53 X: (2-)22–36/37–61
608–023–00–3	4-(4-xxxxxxxxxx)-2-xxxxx-2-[(1X- 1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx		406–140–2	114369–43–6	X; R50–53	N X: 50/53 X: 60-61
608–024–00–9	2-{4-[xxxxx(xxxxxxxx)xxxxx]xxxxx}xxxxx-1,1,2-xxxxxxxxxxxxxx		407–650–8	97460–76–9	X53	X:53 X: 61
608–025–00–4	[2-xxxxx-4,5-xxx(xxxxxxxxx)xxxxx]xxxxxxxxxxx		410–970–0	117568–27–1	X53	X:53 S: 61
609–053–00-X	xxxxxxxxxxx-xxxxxxxxxxxxxxxx		414–850–9	—	X; R3 O; X8 Karc. xxx. 2; X45 X; X23/25 X43	X; X X: 45–3–8–23/25–43 X: 53-45
610–010–00–2	1-xxxx-2-(2-xxxxx)-1-xxxxxxxxxx		406–110–9	35950–52–8	Xx; X22–48/22 X; X34 X43 N; X50–53	X; N R: 22–34–43–48/22–50/53 X: (1/2-)22–26–36/37/39–45–60–61
611–043–00–5	Xxxx (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx trisodný, [xxx{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx xxxxxxxx x[{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx trisodný		402–850–1			Xi X: 41–52/53 X: (2-)26–39–61
611–044–00–0	Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx x[(4(5)-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx) (3-nitro-5-pentylbenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx		403–720–7	117527–94–3	X; X51–53	Xx; X41 X52–53
611–045–00–6	2-({4-[(4-xxxxxxxxxxxx)xxxxxxxxxx]-2-xxxxxxxxxxx}xxx)-3-xxxxxx-5-xxxxxxxxxxxx		404–830–8	—	X53	X:53 X: 61	X X: 51/53 S: 61
611–046–00–1	4,4'-xxxxxxx-2-xxxxxxxxxxxxxxx2-xxxxxxxxxxxxxxx-4,4'-xxxxxx		407–590–2	43151–99–1	X; R25 Xx; X48/22 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	Směs (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx	407–900–6	111381–12–5	X53	X: 53 S: 61
611–049–00–8	Xxxx (2:1:1)7-[(4-{[3-(xxxxxxxxxxxx)xxxxxx]xxxxx}-6-{[3-(xxxxxxxxxxxxx)xxxxxx]xxxxx}-1,3,5-xxxxxxx-2-xx)xxxxx]-3-{[4-(xxxxxxxx)xxxxx]xxx}-4-xxxxxxxxxxxxxxx-2-xxxxxxxx, xxxxxxxx xxxxxx x mléčná kyselina (2:1:1)	408–000–6	118658–98–3	Xx; R48/22 R43 X52–53	Xx R: 43–48/22–52/53 X: (2-(22–36/37–61
611–051–00–9	2-({4-[xxxxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxx}xxx)-6-xxxxxxx-3-xxxxxxxxxxxxxxxxxxxxx-xxxxxxx		411–110–7	136213–74–6	X; R50–53	N X: 50/53 S: 60-61
611–052–00–4	[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) azo]-6-[(6-sulfonato-1-naftyl)azo]benzen-1,3-diolato}]železnatý xxxxxxx, xxxxx xxx		400–720–9	—	X52–53	X: 52/53 X: 61
612–156–00–2	Xxxx:xxxxxxxxxxxx(xxxxxx)xxxxxxx-xxxxxxx a xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx		405–620–9	—	Xx; X41 N; X50–53	Xx; X X: 41–50/53 X: (2-)26–39–60–61
612–157–00–8	(X)-1-(1-xxxxxxxxxxxx-2-xx)xxxxx-1-xx-xxxx-xxxxxxxxxxxx		410–780–8	—	Xx; X22–48/22 Xx; R41 X43 N; R51–53	Xn; X R: 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 S: 61
612–159–00–9	xxxxxxx xxxxxxxx xxxxx 2,2,4-xxxxxxxxx- x 2,4,4-trimethylhexan-1,6-diaminu (x seznamu XXXXXX), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Epoxid 8) a 4-methylbenzen-1-sulfonové xxxxxxxx		410–880–1	—	Xx; R22 C; X34 X; X50–53	X; X X: 22–34–50/53 X: (1/2-)23–26–36/37/39–45–60–61
613–149–00–7	2-terc-butyl-5-[(4-terc-butylbenzyl)sulfanyl]-4-chlorpyridazin-3(2H)-on		405–700–3	96489–71–3	T; R23/25 X; R50–53	T; X X: 23/25–50/53 S: (1/2-)36/37–45–60–61
613–150–00–2	2,2'-[xxxxxxxxx-1,4-xxxxxx(xxxxxx-1,3-xxxx)]xxx(xxxxxxxxxxx[2,1-x]xxxxx[xxx][3,8]xxxxxxxxxxxx-1,3,6-xxxxx)		406–295–6	—	X53	X:53 S: 61
613–151–00–8	1-(2-deoxy-3-O-mesyl-5-O-trityl-β-D-threo-pentofuranosyl)-5-methylpyrimidin-2(1H), 4(3 H)-dion		406–360–9	104218–44–2	R53	R:53 S: 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-trichlorpyridin		407–270–2	16063–70–0	R52–53	R:52/53 X: 61
613–154–00–4	2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx		410–050–9	5734–64–5	Xx; R22	Xn X: 22 X: (2-)22
613–155–00-X	5-xxxxx-2,3-xxxxxxxxxxxxxx		410–090–7	89402–43–7	X10 Xx; X22 R52–53	Xn X: 10–22–52/53 S: (2-)23–36–61
613–156–00–5	2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-xxxxx-5-xxxxxxxxxxxxx-4-xxxxxxxxxxx		410–260–0	83857–96–9	X43 N; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
613–157–00–0	2,4-xxxxxxx-5-(xxxxxxxxxxxxx)xxxxxxxxx 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx		410–330–0	54236–98–5	Xx; X22–48/22 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; X51–53	Xx; N 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 Xn; 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 R: 43 S: (2-)24-37
615–022–00–1	xxxxxx-3-(xxxxxxxxxxxxxxxxxx)xxxxxxx-2-xxxxxxxxxx		410–550–7	79277–18–2	X; X2 X14 Xx; X48/22 X42/43	X; Xn 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 Xn; 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; R51–53	N X: 51/53 S: 61
616–045–00-X	2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(diethylamino)-2-methoxyacetanilid		405–190–2	122371–93–1	R43 X53	Xx X: 43-53 X: (2-)22–24–37–61
616–046–00–5	X -[2-(6-xxxxx-7-xxxxxxxxxxxxxx[1,5-x][1,2,4]xxxxxxx-4-xx)xxxxxx]-2-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxxxxxx		406–390–2	—	X; R50–53	N X: 50/53 X: 60-61
616–047–00–0	Xxxx:X,X′,X″,X′′′ - tetraalkyl(C16)-2,2′, 2″, 2′′′ (xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx x X, N′,N″,N′′′ - tetraalkyl(C18)- 2,2′, 2′′, 2′′′-(ethylendinitrilo)tetraacetamid		406–640–0	—	R43	Xi R: 43 S: (2-)24-37
616–048–00–6	3'-(trifluormethyl)isobutyranilid		406–740–4	1939–27–1	Xn; X48/22 N; R51–53	Xn; X X: 48/22–51/53 X: (2-)22–36–61
616–049–00–1	2-(2,4-xx-xxxx-xxxxxxxxxxx)-X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxx		408–150–2	99141–89–6	X53	X:53 X: 61
616–050–00–7	1-[2,5-xxxxxxx-4-(1,1,2,3,3,3-xxxxxxxxxxxxxxxx)xxxxx]-3-(2,6-xxxxxxxxxxxx)xxxxxxxx		410–690–9	103055–07–8	X43 X; X50–53	Xx; X R: 43–50/53 X: (2-)24–37–60–61
616–051–00–2	Směs:3,3'-bis(4-methylfenyl)- 1,1'-(4-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx x 3,3'-bis(4-methylfenyl)-1,1'-(2-methyl-1,3-fenylen)dimočovina 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 X; X50–53	X; N X: 2–7–50/53 X: (2-)7–14–36/37/39–47–60–61
650–032–00-X	xxxxxxxxxxxx (XXX) (2R, 3R)-, (2 X, 3 X)-, (2 X, 3 X)-, (2 X, 3 X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxx-1-(1X- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		—	94361–06–5	Xxxx. kat. 3; X63 Xx; X22 X; R50–53	Xn; X X: 22–50/53–63 X: (2-)36/37–60–61

PŘÍLOHA 2

XXXXXX SPECIFICKÝCH XXXXX XXXXXXXXX S XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx směrnice Komise 2001/59/XX,

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

XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/ES,

Úř. xxxx. X 332, 28.12.2000, x. 81.

XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX BEZPEČNÉ XXXXXXXXX X NEBEZPEČNÝMI XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.

XXXXXXX 4X

"X.10 XXXXXXXXXX — XXXXXXX NA XXXXXXXXXXXX XXXXXXX U XXXXX XX XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx chromozomové xxxxxxx x xxxxx xx xxxxx má xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: chromozomové x chromatidové. U xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx typu, avšak xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Nárůst xxxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx indukovat xxxxxxxxx aberace. Xxxx xxxxxx však xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx k xxxxxx xxxxx xxxxxxx používána. Xxxxxxxxxxxx xxxxxx a xxxxxxx jevy jsou xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx důkazů x xxx, že xxxxxxxxxxxx xxxxxx x s xxxx související jevy xxxxxxxxxxx xxxxx v xxxxxxxxxx x x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx xxxxxx, mají xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx buněčné xxxxx, xxxxxxx xxxxx xxxx primární buněčné xxxxxxx. Xxxxxxx xxxxx xxxx xxxxxxx xx xxxxxxx schopnosti růstu x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx chromozomů x xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx in xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx zdroje xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační xxxxxx xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx vivo x savců. Xx xxxxx xx zcela xxxxxxxxx xxxxxxxx, které xx xxxxx k xxxxxxxxxx xxxxxxxxx, jež xxxxxxxxxx xxxxxxx mutagenitu x xxxx x xxx dojít změnou xX, osmolality xxxx xxxxxxxx úrovní xxxxxxxxxxxx (4, 5).

Xxxx xxxxxxx xx používá xx xxxxxxxx xxxxxxx xxxxxxxx x karcinogenů xxx xxxxx. Mnoho sloučenin, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx xxx xxxxx xxxxxxxxxxx; xxxx xxxxx xxxxxxxx x karcinogenitou xxxx xxxx xxxxxxxxx xxxxxxxx. Korelace závisí xx xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx karcinogeny, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx mechanismy xxx přímým xxxxxxxxxx XXX.

Xxx také Obecný xxxx, xxxx X.

1.2 XXXXXXXX

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

Chromozomová aberace : strukturní xxxxxxxxx xxxxxxxxxx v xxxxxx xxxxx nebo zlomu x spojení xxxx xxxxxxxxx x xxxxxx xxxxx.

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

Xxx : xxxxxxxxxxxx léze menší xxx xxxxx xxxxx xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

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

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, a xx x metabolickou xxxxxxxx a xxx xx. V xxxxxx xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx látce xx xx xxxxxxxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx), xxxxxxx xx sklidí, obarví x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxxxxxxx pozorováním xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx být xxxxxxx xxxxx xxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (xxxx. xxxxxxxxxxx xxxxxx xxxxxxxx, xxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx x kultivační xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx měla xxx xxxxxxx vhodná kultivační xxxxx a inkubační xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). X xxxxxxxxxxxxxxx buněčných linií x xxxxx xx xxxx xxx rutinně xxxxxxxxxxxx xxxxxxxxx modální xxxxxxx xxxxx chromozomů x xxxx by xxx kontrolováno, zda xxxxxx kontaminovány xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Xxx použité xxxxx a xxxxxxxxx xxxxxxxx xx měla xxx známa normální xxxxx buněčného xxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

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

Xxxxxxxxx: xxxx xxxxxxxx xxxxxxxxxxxxxxx (např. xxxxxxxxx) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx probandů se xxxxxxx do xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. xxxxxxxxxxxxxxxx) a xxxxxxxx se xxx 37 °X.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx zkoušené xxxxx, x to x vhodnou metabolickou xxxxxxxx x xxx xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx enzymy, xxxx xx Xxxxxxx 1254 (6, 7, 8 x 9), xxxx xxxx fenobarbitonu x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx je x xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % obj. Xxxx xxxxxxxxxxxxx aktivačního xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. V některých xxxxxxxxx xxxx xxx xxxxxx použít více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx výsledků xxxxxx, včetně xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx specifické xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx endogenní xxxxxxxx. Xxxxx použitých xxxxxxxxx xxxxx by xxxx xxx vědecky xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx metabolismus xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx rozpouštědlech xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou xxx xxxxxxx xxxxx x testovacím systémům x/xxxx xxxxx být xxxx aplikací xxxxxxx. Xxxx by být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx být xxxx podezření, že xxxxxxx se xxxxxxxxx xxxxxx, x mělo xx xxx xxxxxxxxxx x přežitím xxxxx x x xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx údaji x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx použita xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx nejvyšší koncentrace, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x změny pH xxxx osmolality.

Cytotoxicita by xxxx být xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx ní x hlavním xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, jako xxxx xxxxxx xxxxxxxxxx, xxxxx xxxxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx. Xxxx xxx xxxxxxx xxxxxxxx cytotoxicitu x xxxxxxxxxxx v předběžném xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx tři xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx až xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, což xxxxxxx xxxxxxx, že xx xx koncentrace xxxxxx xxxxx více nežli xxxxxxxx 2 až Ö10. X xxxxxxxx xxxxxxx xx xxxx xxxxxxxx xxxxxxxxxxx vykazovat xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, xxxxx xxxxx xxxx xxxxxxxxxxx indexu (xxx x více xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx nepřímým xxxxxxxx xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x xxxxxx xx xxxx, která xxxxxxxx xx xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx xxxxxxxxxx x xxxxxxxxxxx xxxxxx, x xxxxx xxxxx být xxxx xxxxxx xxxxxxxxx xxxxxxxx obtížné x xxxxxxxxxxx. Informace x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (XXX), xxxxx xxx použity xxxx xxxxxxxxx xxxxxxxxx. X xxxxxxx XXX xxxx xxx o celkovou xxxxxxxxx hodnotu, x xxx nelze usoudit xx existenci zpožděných xxxxxxxxxxx, x x xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx může xxx xx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx optimálního xxxxxxx xxxxxxx.

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

X případě relativně xxxxxxxxxxxxx látek, které xxxxxx xxxxxxx xxx xxxxxxxxxxxxx xxxxxxx, xxx xx jejich rozpustnost, xx xxxx xxx xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxx, xxx xx xxx mezí xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxx aplikace. X xxxxxxxx xxxxxxxxx (xxxx. xxxxxxx-xx xx xxxxxxxx pouze xxx xxxxxxx xxxxxxxxxxxxx, xxx xx xxxxxxxxxxx) se xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, xxx xxxxx xxxxxxx ke srážení. Xxxx xxx užitečné xxxxxxxx xxxxxxxxxxx xx xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx v xxxxxxxxxx xxxxxxx xx xxxx x průběhu expozice xxxxx v xxxxxxxx xxxxxxxxxxx xxxxx, xxxx X9 xxx. Xxxxxxxxxxxxx xxx zjistit xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx experimentu xx měly xxx xxxxxxxxx x negativní xxxxxxxx (xxxxxxxx rozpouštědla xxxx xxxxxxxx). Xxx xxxxxxx metabolické xxxxxxxx xx měla xxx xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx látka, xxxxx x xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx.

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

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxx, xxx byl účinek xxxxxxxx, xxx xxx xxx xxxxxx nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx:

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

Xxx xxxxxxxxx xxxxxxxx mohou xxx xxxxxxx x jiné xxxxxx xxxxx. Xxx xxxxxxxxx kontrolu by xxxx xxx pokud xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx.

X okamžiku xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula x xxxxxxxxxxx médiu a xxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx žádné xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx rozpouštědlo xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx se xxxxxxx xxxxxxxx xxxxx xxx za xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému, xxx xxx xxxx. Xxxxxxxx xxxxxxxxx xx xxxx xxx zahájena xxx 48 xxxxx xx xxxxxxxxx stimulaci.

1.4.3.2 Xxx xxxxxx koncentraci xx měly být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, a totéž xx xxxxxxx xxxxxxxxxx x kultur xxx xxxxxxxxx xxxxxxxx nebo xxxxxxxx xxxxxxxxxxxx. Xxxxxxxx xxx xx základě xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxx rozdíl, xxxx xxx xxxxxxxxx xxxxxxx xxxxxx xxxxxxx.

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

1.4.3.3 Doba xxxxxxx xxxxxx

X xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, xxx x xxxxxxxxxxxx aktivací, xxx bez ní, xx dobu 3 — 6 xxxxx, x xxxx xx xxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu (12). Xxxxxxxx xxxxx xxxxxx dává xxxxxxxxx xxxxxxxx xxx x xxxxxxxx, tak xxx xxxxxxxx, měl xx xxx xxxxxxxx dodatečný xxxxxxxxxx bez xxxxxxxx x xxxxxxxxxxxx expozicí xx xx xxxxxx x xxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx xxxxx xxx xxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxx xxx 1,5xxxxxxx xxxxx xxxxx. Negativní xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx být xxxxxxxxx xxxxxx xx případu. X případech, xxx xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx za xxxxxxxx, xx mělo xxx xxxxxx zdůvodnění.

1.4.3.4 Xxxxxxxx preparátů xxx xxxxxxx chromozomů

Do xxxxxxx xxxxxxx xx obvykle 1-3 xxxxxx xxxx xxxxxxxxx přidá Xxxxxxxx® xxxx xxxxxxxxx. Xxx xxxxxxxx preparátů pro xxxxxxx chromozomů xx xxxxx xxxxxxx xxxxxxx xxxxxx x xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx analýzu xxxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx a obarvení xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx kontrol, xx xxxx být xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx dochází ke xxxxx části xxxxx x xxxxxxxx x xx ztrátě chromozomů, xxxx by vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxx xxxxxxx xxxxxxx ± 2 xxx xxxxxxx xxxx xxxxx. Na xxxxxx xxxxxxxxxxx x xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxx 200 dobře xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Tento xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx počet xxxxxxx.

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

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx x xxxx xx xxxx xxx xxxxxxxxxxx množství xxxxx xx strukturní xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx strukturních xxxxxxxxxxxxxx xxxxxxx s xxxxxx xxxxxx x četností. Xxxx xx zaznamenávají xxxxxxxx x xxxxxxx xx, xxx nezahrnují xx xx xxxxxxx xxxxxxxx aberací.

Měla by xxx xxxx xxxxxxxxxxx xxxxxxxx, xxxxx byla xxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxx u xxxxx xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx kultur x xxxxxxxx experimentech x xxxxxxxxx.

Xxxx xx být xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxx. Xxxx xx měly být xxxxxxx xxxxx shrnuty xx xxxxx tabulky.

Ověření xxxxx xxxxxxxxx xxxxxxxx xx nepožaduje. Xxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxx negativní xxxxxxxx xxxx xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x cílem rozšířit xxxxxx posuzovaných podmínek xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X parametrům xxxxxx, xxxxx by xxxxx xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx x podmínky metabolické xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro stanovení xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx aberacemi x závislosti xx xxxxxxxxxxx, nebo reprodukovatelný xxxxxx tohoto xxxxx. Xxxxxxxx xx xxxx xxx uvážena biologická xxxxxxxxx výsledků. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx být použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx pozitivní odpověď.

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

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

Xxxxxx xxxxxxx xxxxxxxxxxx poskytne xxxxx pozitivní nebo xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu na xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx in xxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx x kultivovaných xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx znamenají, xx xxxxxxxx látka xx xxxxxxxx zkoušky neindukuje x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx strukturní xxxxxxxxxxxx aberace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx 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 xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxx xxxxx,

- xxxxxxxxx nepřítomnost xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx xxxxx,

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

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx buněčné xxxxxxx,

- xxxxxxx hodnota xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

- identifikace xxxxx xxxxxxxxxxx xxxxxxxx, xxxx xxxxxxxxxxx x xxxxx xxxxxxxx buněk,

- xxxxxxxxxx xxxxxx koncentrací x xxxxx xxxxxx, xxxxxx např. xxxxx x xxxxxxxxxxxx x xxxxxx rozpustnosti, xxxx-xx x dispozici,

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX₂,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx vehikula x xxxxxxx xxxxxxxx xxxxx,

- inkubační xxxxxxx,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- případně xxxxxxx xxxxx xxx xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx metafází,

- xxxxxx xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxxxx studie na xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxxx xxxxxxx,

- údaje x xX a xxxxxxxxxx xxxxxxxxxxx média, pokud xxxx xxxxxxxxx,

- xxxxxxxx xxxxxxx, xxxxxx xxxx,

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

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx analýzy,

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

- dosavadní údaje x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx kontrole x xxxxxxxxx, středními xxxxxxxxx x směrodatnými xxxxxxxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, H. J. (1976), Xxxxxxxxxxx Xxxxxxx xxx Detecting Xxxxxxxx Xxxxxxxx, xx: Chemical Xxxxxxxx, Xxxxxxxxxx and Xxxxxxx for their Xxxxxxxxx, Vol. 4, Xxxxxxxxxx, X. (xx) Xxxxxx Xxxxx, New Xxxx and London, 1-29.

2) Xxxxxxxx, M. Xx., Sofumi, X. (1985), Xxx In xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Xxxxx Xxxxxxx Xxxxxxx Xxxx (CHL) Xxxxxxxxxx Xxxxx xx Xxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Xxxxx, X. xx xx., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Galloway, X. X., Xxxxxxxxx, M. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxx, A. D., Xxxxxxxx, X., Xxxxx, X., Xxx, S., Xxxxx, X., Xxxxxxxx, X. X., Resnick, X. A., Xxxxxxxx, X., Zeiger E. (1978), Xxxxxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxxx in Chinese xxxxxxx xxxxx cells: Xxxxxxxxxx xx 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.

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

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

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

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

8) Natarajan, X. X., Xxxxx, X. D., xxx Xxxx, X. X. X., Xxxxxxx, X., xx Vogel, N. (1976), Cytogenetic Effects xx Xxxxxxx/Xxxxxxxxxxx after Xxxxxxxxxx in x Xxxxxxxxxxx Xxxxxx Xx xxxxx, X. Xxxxxxxxx xx Chromozome Xxxxxxxxxxx xxx Sister Chromatid Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) and Xxxxxxxxxxxxxxxxxxx (XXX) xx XXX Xxxxx in the Xxxxxxxx of Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

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

10) Xxxxxx, X. X., Xxxxxx, X. X., Elcombe, X. X., Gatehouse, X. G., Xxxxxx, X. X., Xxxxxx, X. M., Wolf, X. X. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Mutagen Society Xxxxxxx Party. Alternative xx Xxxxxxx 1254-xxxxxxx X9 xx In xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, T., Xxxxxxxx, X., Hara, K., Xxxxxxxx, X. (1976), X. Safe Substitute xxx Polychlorinated Biphenyls x. s. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: xx Serres, F. X., Xxxxx, X. X. Xxxx, X. X., Philpot, R. X. (xxx), Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Testing, Xxxxxxxx, North-Holland, 85-88.

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

13) Xxxxxxxxxx, X., Xxxxxxxx, D. X., Xxxxx, X. X., Xxxxxxxx, X., Chanter, X. O., Phillips, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx vitro Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Xxxxxxxx, X. J., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

14) Soper, X. X., Xxxxxxxx, X. X. (1994), Xxxxxxxxx Xxxxxx are xxx Xxxxxxxxx xxx Xx vitro Xxxxxxxxxx Xxxxxxxxxx Xxxxxx in XXX Xxxxx, Mutatation Xxx., 312, 139-149.

15) Xxxxx, D. X., Xxxxxx, X. X., XxXxxxx, X. T. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Evaluation xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Tice, X. X., Xxxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Effects xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.

16) Xxxxxx, P. X., Xxxxxx, X. X., Xx, X. P., Xxxxxx, A. X. (1983), Xxxxxxxxxx of xx Exposure System Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Highly Xxxxxxxx Xxxxxxxx in xxx XXX/XXXXX Mutation Xxxxx, Environmental Mutagen., 5, 795-801.

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

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

XXXXXXX 4X

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

1. METODA

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

1.1 ÚVOD

Zkouška xx chromozomové xxxxxxx x xxxxx xx xxxx je xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx x xxxxxxx xxxxxx dřeně xxxxx, xxxxxxx hlodavců (1, 2, 3, 4). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx — xxxxxxxxxxxx x chromatidové. Xxxxxx xxxxxxxxxxx může znamenat, xx chemická xxxxx xx xxxxxxxxx indukovat xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx chemických xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx chromozomové xxxxxxx xx xxxxxx vyskytují. Xxxxxxxxxxxx mutace x xxxxxxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxx způsobující xxxxx x onkogenech x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx podíl xx xxxxxxx rakoviny x xxxxxxx a x xxxxxxxxxxxxxxxx systémech.

Při xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx hlodavci. Xxxxxxx xxxxx je x xxxx xxxxxxx xxxxxx xxxx, xxxxxxxx xx xxxxxx vaskularizovanou tkání x obsahuje xxxxxxxx xxxxx x xxxxxxx xxxxxx, které xx xxxxxx izolují a xxxxxxxxxxxx. Xxxx xxxxx x xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx x xxxxxxx druhů x xxxxx xxxxx. Xxxxxxx in xxxx xx rovněž xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx xxxxxx zjištěných xxxxxxxx in xxxxx.

Xxxxxxxx xxxxxxxx důkaz o xxx, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx metabolity xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx úvod, část X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x podobě xxxxx jednotlivých xxxxxxxxx xxxx xxxxx x xxxxxxxx spojení xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx a xxxxxxx xxxx chromatid x xxxxxx xxxxx.

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

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

Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx xxxxxxxxxx xx xxxxxxxx hodnoty xxxxxxx u xxxxxxxxx xxxxx.

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

Xxxxxxxxxx xxxxxxx : mikroskopicky xxxxxxxxxxxxx xxxxx struktury chromozomů xxx buněčném dělení xx xxxxxx metafáze; xxxx se xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx jsou xxxxxxxxx xxxxxxxx látce xxxxxxx xxxxxxxx x ve xxxxxxx okamžiku xx xxxxxxxx xx xxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx nebo Xxxxxxxx®). X xxxxx kostní xxxxx xx xxxx xxxxxxxx preparáty xxxxxxxxxx, xxxxxx se x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx buněk x xxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xx xxxxxxxx xxxxxx, xxx x křeček xxxxxx, xxxxxx lze xxxxxx xxxxxxxx vhodný xxxxx xxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx a xxxxxx xx x xxxx pohlaví překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, xxxxx xx xxxxxxx xxxxxxxx xxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, xxx byl xxxx xxxxxx polohy xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x laboratorních xxxxxxxxxx alespoň pět xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx nebo suspendovány xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx být xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx při xxxxxxxxx xxxxxxxx dávek xxxxxxx xxxxxx a xxxx xx být vyloučeno xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx obě xxxxxxx. X xxxxxxxx aplikace xxxxxxxx látky xx xxxx xxxxxxx xxxxxxxxx xxxxxxx podstoupit xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx kontroly xx xxxx xxxxxxxxxx strukturní xxxxxxx xx vivo xxx xxxxxxxxxxx úrovních, x xxxxx se xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst nad xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx by měly xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Je xxxxxxxxxx, aby xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx xxxxx x xxx xxx odběr x jejím xxxxxxx xxxxxxxx jen jednou. Xxx xxxxxxxxx xxxxxxxx xxxxx být xxxxxxx xxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx:

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

V xxxxxxxx xxxxxxx odběru xx xxx xxx proveden xxxxx x negativních xxxxxxx, xxxx je xxxxxxxxxx pouze xxxxxxxxxxxx xxxx xxxxxxxxx a xxx xxxxx xxxxxxxxxx xxxxxx proces jako xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx údajů k xxxxxxxxx xxxxxxxxxx xxxxx x variabilitě xxxxxx x četnosti xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Kromě toho xx xxxx být xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, neexistují-li xxxxx kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává žádné xxxxxxx xxxx mutagenní xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx xx skládá x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx. Xxxxxxxx xxxx v xxxx xxxxxx k dispozici xxxxx xx xxxxxx xx stejným druhem x xx použití xxxxxxxx xxxxxxx xxxxxxxx, xxx prokazují, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx pohlaví, xxxx xx xxxx xxxxxxxxx u některých xxxxxxxxxxxxxxx xxxxx, měla xx být zkouška xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx by xxxx xxx pokud xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx mohou xxx podávány xxxx xx xxxx dávkách, xxx. xxx xxxxx x xxx xxx x xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, aby bylo xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxxxxxx by xxxx být vědecky xxxxxxxxxx.

Xxxxxx xx měly xxx xxxxxxxx ve xxxx různých xxxxxxxxxxx xx xxxxxxxx podané x jednom xxx. X xxxxxxxx xx xxxxx provádí xx xxxxxx xxxx xx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx normální xxxxx xxxxxxxxx cyklu (xxxx xxxx obvykle 12 — 18 h). Xxxxxxxx xxxx nezbytná xxx xxxxxx a xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx pro xxxxxx na xxxxxxxx xxxxxxxxx xxxxx xxxx xxx vliv xx xxxxxxxxx okamžik xxx xxxxxxxxx chromozomových xxxxxxx, xxxxxxxxxx se xxxxxxx xxxxx odběr po 24 h xx xxxxxxx odběru. Xx-xx xxxxxxxx xxxxxxxxx xx xxxx než xxxxxxx xxx, měl by xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx odpovídá 1,5násobku xxxxxxxx délky buněčného xxxxx.

Xxxx xxxxxxxxx se xxxxxxxx xxxxxxxxxxxxxxxxx podá xxxxxx xxxxx látky xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® nebo xxxxxxxxx). Xxxx xx po xxxxxx době xxxxxxx x zvířat xxxxx. X xxxx xx xxxx doba xxxxxxxxx 3 — 5 x; x xxxxxx xxxxxxxx xx tato xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xx xx chromozomové xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx dávek, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, pohlavím x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx v xxxxxx studii (5). X xxxxxxx xxxxxxxx xx xxx první xxxxx xxxxxxx tři xxxxxx dávky. Xxxx xxxxxx xxxxx by xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru xxxxx, xxxx xxxx použita xxxxx nejvyšší xxxxx. Xxxxxxxx xxxxx je xxxxxxxxxx jako dávka xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx xxxxx xxxxx xx vedly xxx stejném režimu xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Látky xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx dávkách (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx vyhovovat x xxxx by být xxxxxxxxx případ xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x xxxxxx xxxxx některé známky xxxxxxxx (např. více xxx 50 % xxxxxxx mitotického xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx ve xxxx dávkách x xxxxxx xxx nevykazuje xxxxx xxxxxxxxxxxxx toxické xxxxxx a xxxx-xx xx základě xxxxx x xxxxxxx, které xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, nepovažuje xx úplná xxxxxx xx třemi xxxxxxxx xxxxx xx nezbytnou. X xxxx xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx a xxx delší xxx 14xxxxx aplikaci xx xxxxxxx dávkou 1000 xx/xx xxxxxxx hmotnosti/den. Xxxxxxxxx expozice člověka xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx se xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Maximální objem xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl překročit 2 ml/100 x xxxxxxx hmotnosti. Použití xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx být xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx látky, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx zajišťující xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů pro xxxxxxx chromozomů

Ihned po xxxxxxxx xx xxxxxxx xxxxxx xxxx, hypotonizuje xx x fixuje. Xxxxx xx xxxxxxx xx podložní sklíčka x xxxxxx se.

1.5.7 Xxxxxxx

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

U každého xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 buněk. Xxxxx xxxxx xxx xxxxxx, xx-xx pozorován xxxxx xxxxx xxxxxxx. Všechny xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx kontrol by xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxx xxx xxxxxx často xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xx xxxxxx xxxxxxxxxx u xxxxx xxxxx x xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx odpovídajícímu xxxxx 2 n ± 2.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx xxxxxxxxxx xxxxxxx xx xxxx xxx zpracovány xx xxxxx tabulky. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Xxx každé xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx, xxxxx xxxxxxx xx xxxxx x xxxxx xxxxx x xxxxxxxxxxxxx xxxxxxx (xxxxxxxxxxxxxx xxxxxxxxx) vyjádřený x xxxxxxxxxx. Pro exponované x xxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx různé typy xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich xxxxxx x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx obecně xx xxxxxxxxxx do xxxxxxx xxxxxxxx aberací. Xxxxxxxxxx-xx xxxxx o rozdílu x odpovědi mezi xxxxxxxxx, xxxxx xxx xxx statistickou analýzu xxxxx pro obě xxxxxxx zkombinovány.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx pozitivního výsledku xxxxxxxx xxxxxxx kritérií, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx pro xxxxxxx x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx odběru. Nejdříve xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx použity xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx jediným určujícím xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, že xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Nárůst xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx progresi xxxxxxxxx xxxxx (7, 8).

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx konečný xxxxx o xxxxxxxx xxxxxxxx látky. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx xx, xxxxxxxx je experiment xxxxxxxx.

Xxxxxxxxx výsledky xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx vivo znamenají, xx xxxxxxxx látka xxxxxxxx v xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx xxxxx chromozomové xxxxxxx.

Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx se zkoušená xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx do xxxxxxxx xxxxx, xxxx xxxxxxxxxx xx cílové xxxxx (např. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- použitý xxxx/xxxx,

- počet, xxxxx x xxxxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

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

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

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

- zdůvodnění xxxxxxxxx úrovní dávek,

- xxxxx x přípravě xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- popřípadě xxxxxx xxxxxxx, xxx xx xxxxxxxx látka dostala xx xxxxxxxx xxxxx xxxx xx cílové xxxxx,

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

- xxxxxxxx údaje o xxxxxxx krmiva x xxxx,

- xxxxxxxx popis xxxxxxx expozice x xxxxxx,

- metody stanovení xxxxxxxx,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx hodnocení xxxxxxx,

- počet xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- typ a xxxxx aberací xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

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

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

- xxxxx ploidie, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

- dosavadní údaje x xxxxxxxxx xxxxxxxx x rozpětími, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx,

- údaje o xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Adler, X. D. (1984), Xxxxxxxxxxx Tests in Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, X. Xxxxxx, X. X. Xxxxx (xxx), XXX Xxxxx, Xxxxxx, Washington X. X., 275-306.

2) Xxxxxxx, X. J., Xxxx, X. J., Galloway, X., Holden, X., XxXxx, X. X., Xxxxxx, M. (1987), Xxxxxxxxx Xx vivo Xxxxxxxxxxx Xxxxxx: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xx Bone Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 157-165.

3) Xxxxxxx, X., Chandley, X., Xxxxx, X., Xxxxxxxxx, X. G., Bootman, X., Henderson, X. (1990), Xx vivo Xxxxxxxxxxx Xxxxxx, xx: X. X. Kirkland (xx.), Xxxxx Mutagenicity Xxxxx, XXXXX Recommended Xxxxxxxxxx. UKEMS Xxx-Xxxxxxxxx xx Guidelines for Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx I xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

4) Tice, X. X., Xxxxxxx, X., XxxXxxxxxx, X. X., Anderson, X., Xxxxxx, X. H., Xxxxxx, H. X., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., X. B., Xxxxxxxxxxxx, X., Xxxxxxx, X. J., Romagna, X., Xxxxxxx, X., Xxxxx, S., Vannier, X. (1994), Xxxxxx xxxx xxx Xxxxxxx Xxxxx xx xxx xx xxxx Mammalian Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Test, Mutatation Xxx., 312, 305-312.

5) Xxxxxxx, X. X., Xxxxx, J. A., Xxxxxx, X. X., Xxxxxx, X. A., Xxx, X., Esdaile, X. X., Xxxxxxxxx, X. X., Hodson-Walker, X., Morton, D. X., Xxxxxxxx, D. X., Richold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Society/UK Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, D. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxx, X., Papworth, X. X., Xxxxxx, X. X. X. (1989), Xxxxxxxxxxx Analysis xx Xx vivo Xxxxxxxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, X. X. Xxxxxxxx (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, 184-232.

7) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx in Xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx-xxxxxxxxx-xxxxxxx G2 arrest, Xxxxxxxxxx Xxx., 119, 403-413.

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

XXXXXXX 4X

"X.12 XXXXXXXXXX–XXXX XXXXXXX ERYTROCYTÁRNÍCH MIKROJADER XX XXXX

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX XX 474 — Test xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx (1997).

1.1 XXXX

Xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx in xxxx xx používán xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx mitotického aparátu xxxxxxxxxxxx, xxxxx je xxxxxxxxxx zkoušenou xxxxxx, x to xxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxx x xxxxxx dřeně x/xxxx xxxxx periferní xxxx, obvykle xxxxxxxx.

Xxxxxx xxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx identifikovat xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxxxxxxx nereplikující xx (xxxxxxx) xxxxxxxxxxxx xxxxxxxxx xxxx xxxx xxxxxxxxxx.

Xxxx se xxxxxxxxxxx xxxxxx xxxxx xxxx xx polychromatický xxxxxxxxx, xxxxxx jádro je xxxxxxxx x xxxxxxxxxx, xxxxx xxx xxx xxxxx xxxxxxxxx, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx xx x xxxxxx buňkách xxxxxxxxx xxx, že xxxxxxxxxx xxxxxx xxxxx. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x exponovaných xxxxxxxxx xx xxxxxxx indukovaného xxxxxxxxxxxxxx xxxxxxxxx.

X tomto xxxxx je rutinně xxxxxxxxx xxxxxx xxxx xxxxxxxx, poněvadž tato xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Stanovení xxxxxxxxx (xxxxxxxxxxxxxxxxx) erytrocytů s xxxxxxxxxx v periferní xxxx je rovnocenně xxxxxxxxxx x xxxxxxxxxxx xxxxx, u xxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx odstraňovat xxxxxxxxxx x xxxxxxxxxx, xxxx xxxxxxxxxx citlivost xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx nebo xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxxxxx xxx rozlišit řadou xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx nebo xxxxxxxxxxxxx centromerní (xxxxxxxxxxxx) XXX v mikrojádře. Xxxxxxxxx xx xxxxxxx xxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx v periferní xxxx, xxxxx obsahují xxxxxxxxxx, připadající na xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx jako xxxxxxx xxxxxxxx xxxxxxx, jestliže xxxx xxxxxxx xxxxxxxxxx xxxxx týdny nebo xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx x procesy xxxxxxxx DNA, xxxxxxx xx mohou lišit x xxxxxxx xxxxx x tkání, xxxxx x x genetického xxxxxxxx. Xxxxxxx xx xxxx xx xxxxxx xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx v xxxxxxxxx xx vitro.

Jestliže existuje xxxxx x xxx, xx se zkoušená xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx zkoušku xxxxxx.

Xxx také Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (kinetochor) : xxxxxx (xxxxxxx) chromozomu, x xxx (x xxxx) xx xxxxx xxxxxx buněk xxxxxxx xxxxxx vřeténko umožňující xxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx k xxxxx xxxxxxxxx xxxxx.

Xxxxxxxxxx : xxxx xxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx x vedle xxxx, xxxxxxxxx xxxxx xxxxxxxx xxxxxx (meiosy) xxxxxxxxxxxxxxx se (xxxxxxx) xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx xxxxxxxxx : xxxxx xxxxxxxxx xxxxxxxxxxxx ribozomy, který xxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx pro xxxxxxxx.

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx xxxxx se xxxxxxx ve xxxxxxx xxxxxxxx xx expozici xxxxxx, odebere xx xxxxxx dřeň, připraví xx xxxxxxxxx x xxxxxx se (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx periferní xxxx se xxxx xx vhodném xxxxxxxx xx xxxxxxxx xxxxxxx, xxxxxxxxxx se xxxxxxxx xxxxxxxx a obarví xx (4, 8, 9, 10). Při xxxxxxxx x periferní xxxx xx xxxx xxxx poslední xxxxxxxx x sklizením buněk xxxxxxxx xx xxxxxxxxx xxxx. Preparáty xxxx xxxxxxxxxxx na xxxxxxxxxx xxxxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Při použití xxxxxx dřeně xx xxxx xxxxxxxxx xxxxx xxxxxxxxxx myš xxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx vhodný xxxxx xxxx. Při xxxxxxx xxxxxxxxx krve xx xxxxxxxxxx xxx. Xxx však xxxxxx xxxxxxxx vhodný xxxx xxxxx xx xxxxxxxxxxx, xx jde x xxxx, u xxxxx xxxxxxx neodstraňuje erytrocyty x mikrojádry, xxxx xxxx xxxxxxxxxx dostatečnou xxxxxxxxx xxxxxxxxx činitele, xxxxx způsobují xxxxxxxxxx xxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxx by xxx použity xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx xxxxxx xx měla být xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx a xxxxxx xx u xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, u xxx xx xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Nechají xx v xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx. Xxxxx xx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx minimalizován.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx xxxx aplikací xxxxxxxx rozpuštěny xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx být xxxxxxxx xxxxx xxxx mohou xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx použity čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxx stálosti xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých úrovních xxxxx xxxxxxx xxxxxx x xxxx by xxx xxxxxxxxx xxxxxxxxx, xx reaguje xx xxxxxxxxx látkou. Jsou-li xxxxxxx xxxx než xxxxx rozpouštědla/vehikula, mělo xx xxx xxxxxx xxxxxxxx podloženo údaji x xxxxxx kompatibilitě. Xxxxxxxxxx se pokud xxxxx xxxxxxxx xxxxxx xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) kontroly pro xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by měla xxxxxxx kontrolní xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx k expozici.

Pozitivní xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx in xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx ihned xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby xxxxxxxxx xxxxxxxx xxxx xxxxxxxx jiným xxxxxxxx xxx zkoušená látka x xxx xxx xxxxx v xxxxx xxxxxxx prováděn xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxxx xxxx xxx vzato v xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx pozitivní xxxxxxxx:

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

X okamžiku odběru xx měl xxx xxxxxxxx odběr x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx aplikováno xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako exponované xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx údaje o xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx x xxxxxxxxxx. Provádí-li se xxx negativní xxxxxxxx xxxxx odběr, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud xxxx xxxxxx-xx publikovány xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx rozpouštědlo/vehikulum xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx krve xxxx xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxx xxxx xxxxxxxx xxxx expozicí, xxxxx xxxx x xxxxxxxx xxxxxx s xxxxxxxxx xxxx (xxxx. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, xx xxxxxxxx xxxxx xxxxx x xxxxxxx, xxxxx xx xx základě xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx xxxxxxx x xxxxxxx pěti xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx (11). Xxxxxxxx xxxx x xxxx xxxxxx k xxxxxxxxx údaje xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx prokazují, xx neexistuje xxxx xxxxxxxxx rozdíl v xxxxxxxx, xxxx postačující xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, jako je xxxx například x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx být xxxxxxx xxxxxxxxx se xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx aplikace

Nelze xxxxxxxxx xxxxx xxxxxxxxxx plán (xx. jednu, xxx xxxx tři xxxxxxxx x intervalu 24 xxxxx). Xxxxxx xx xxxxxx x xxxxxxxxxxxx xxxxxxx podávání jsou xxxxxxxxxx, pokud xx x xxxxxx xxxxxx xxxxxxx xxxxxxxxx výsledky, xxxx –v xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx xxxx prokázána xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxx dávka x podávání xxxxxxxxx xx do xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. dvě xxxxx v xxx xxx x xxxxxxx xx xxxx xxx xxxxxxxx hodin, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx objemů xxxxxxxxx.

Xxxx xxxx xxx proveden xxxxx xxxxxxx:

x) zkoušená xxxxx xx aplikuje xxxxxxxx xxxxxx. Xxxxxx xxxxxx xxxxx se xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx první odběr xx xxxxxxx xxxxxxxx 24 xxxxx po xxxxxxxx x poslední xxxxxxxxxx 48 xxxxx xx xxxxxxxx a x xxxxxxxxxx odstupem xxxx odběry. Xxxxx xxxxx xxx 24 xxxxx xx aplikaci xxxx xxx zdůvodněn. Xxxxxx xxxxxxxxx xxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx provede xxxxxxxx 36 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx po xxxxxxxx x xx prvnímodběru xx dodrží xxxxxxxxxxxx xxxxxx. Je-li po xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx xxxxx xxxxx;

x) xxxx-xx xxxxxxxx xxx xxxx xxxx dávek xxxxx (xxxx. xxx xxxx xxxx dávek x intervalu 24 xxxxx), xxxx xx xxx xxxxxx xxx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx xx 18 xx 24 xxxxxxxx po xxxxxxxx xxxxxxxx x při xxxxxxx periferní xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).

Xxxxx xxxxxxx xxxxx xxx xxxxx xxxxxxx xxxx xxxx odběru.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se kvůli xxxxxxxxxxx vhodných dostupných xxxxx studie xxx xxxxxxxx rozsahu dávek, xxxx xx xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx stejným xxxxxx, xxxxxx, xxxxxxxx x xx stejného xxxxxx xxxxxxxx, xxx xx použijí x xxxxxx xxxxxx (13). X xxxxxxx toxicity xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Tyto xxxxxx dávky xx xxxx pokrývat rozpětí xxxx maximální xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx je xxxxxxxxxx jako xxxxx xxxxxxxxxxxx takové známky xxxxxxxx, že vyšší xxxxx xx xxxxx xxx xxxxxxx režimu xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx být xxxxxxxxx případ xx xxxxxxx. Nejvyšší dávka xxxx xxx xxxx xxxxxxxxxx jako dávka xxxxxxxxxxxx x xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx nezralých xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx x xxxxxx xxxxx xxxx v xxxxxxxxx krvi).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx o xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo ve xxxx dávkách v xxxxxx dni nevykazuje xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxx xxxxxxxxxx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx než 14xxxxx xxxxxxxx je xxxxxxx dávkou 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x limitní xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx jsou xxxxxxxxxx v xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx podán xxxxxxxxx sondou xxxx xxxxxxxx, závisí xx xxxxxxxxx testovacího xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, musí xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx vyšších koncentracích xxxxxxxx zesílené xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava kostní xxxxx xxxx xxxx

Xxxxx xxxxxx dřeně se xxxxxxx získávají z xxxxxx nebo xxxxx xxxxx po xxxxxxxx. Xxxxx xx xxxxxxxx x xxxxxx nebo xxxxx x zavedenými xxxxxxxx xx xxxxxxxxx x xxxxxx. Xxxxxxxxx xxxx xx xxxxxxx x ocasní žíly xxxx xxxx vhodné xxxxxx cévy. Xxxxxx xxxxx se xxxxx xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx připraví xxxxxxxxx xxxxxxxx x xxxx xx xxxxxx. Xxxxxxxx xxxxxxx xxxxxxxxxxxx pro XXX (xxxx. akridinová xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) se xxx xxxxxxx xxxxxxxx xxxxxxxxxx spojeným s xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxx XXX. Tato xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. celulosová xxxxxx x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, xx xx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx systémů pro xxxxxxxxx xxxxxxxxxx v xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx každé xxxxx se xxxxxxx xxxxx xxxxxxxxx erytrocytů x celkového (xxxxxxx + xxxxx) množství xxxxxxxxxx, xxxxxxx xx x xxxxxxx xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 xxxxxxxxxx x x případě xxxxxxxxx krve xxxxxxx 1000 xxxxxxxxxx (17). Xxxxxxx preparáty xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx kontrol, by xxxx být před xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx zvířete xx xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Xxxxx informace xxxxx být xxxxxxx xxxxxxxxxx xxxxxxx erytrocytů xx xxxxxx xxxxxxxxxx. Xxx mikroskopické xxxxxxx xx xxxxx xxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxx 20 % kontrolní xxxxxxx. Xxxxxxxx jsou xxxxxxx exponována xxxxxxxxxxx xxxxx xxxxx nebo xxxx, lze xxxx xxxxxxxx xx výskyt xxxxxxxxxx alespoň 2000 xxxxxxx xxxxxxxxxx na xxxxx xxxxx. Systémy xxx automatickou xxxxxxx (xxxxxxx xxxxxx x xxxxxxxxx cytometrická analýza xxxxxxx suspenze) jsou xx xxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx být xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Xxx xxxxx xxxxxxxxxxx xxxxx xx měl být xxxxxx počet vyšetřených xxxxxxxxx xxxxxxxxxx, počet xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx xxxx xxxx, xxxx xx být xxxx xxxxxxx údaje x zralých xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx xxxxx xx xxxxx xxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x procentech. Xxxxxxxxxx-xx xxxxx o xxxxxxx x odpovědi xxxx xxxxxxxxx, mohou xxx xxx statistickou xxxxxxx xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxx x závislosti xx xxxxx xxxx xxxxx xxxxxx počtu xxxxx x mikrojádry xxx xxxxxxx x určitou xxxxxx a x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (18, 19). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, jejíž xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, se xxxxxxxx x tomto xxxxxxx za xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo sporné xxx xxxxxx na xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx mikrojádra, xxx jsou xxxxxxxxx xxxxxxxxxxxxxx poškození nebo xxxxxxxxx xxxxxxxxxxx aparátu xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx zkoušená látka xx podmínek xxxxxxx xxxxxxxxxxx xxxxxxxxxx v xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx.

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

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx o zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- rozpustnost a xxxxxxx xxxxxxxx xxxxx x rozpouštědle/vehikulu, xx-xx xxxxx.

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, stáří x pohlaví xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx na xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx odchylka xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

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

- xxxxxxxxxx zvolených xxxxxx dávek,

- xxxxx x přípravě xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx způsobu xxxxxxxx,

- xxxxxxxxx xxxxxx ověření, xxx xx zkoušená xxxxx dostala xx xxxxxxxx oběhu nebo xx cílové xxxxx,

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

- xxxxxxxx xxxxx x kvalitě xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx xxxxxxxx preparátů,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx hodnocení mikrojader x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx buněk xx jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx,

- počet xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx xxxxxxx samostatně xxx xxxxx xxxxx,

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxx,

- xxxxx x xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx o souběžné xxxxxxxxx xxxxxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxxx, X. X. (1973), A Xxxxx In xxxx Xxxx xxx Chromozomal Xxxxxx, Xxxxxxxxxx Xxx., 18, 187-190.

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

3) Xxxxxx, X. X., Xxxxxxxx, M. X., Xxxx, X., Kirkhart, X., Xxxxxxxxx, K., XxxXxxxxx, J. X., Xxxxxx, G. W. (1983), Xxx Induction xx Micronuclei x. x. a Measure xx Xxxxxxxxxxxx, Mutatation Xxx. 123, 61-118.

4) Xxxxxxxxx, X. H., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxxxx, M. F., Xxxxxx, X. A. (1990), Xxx Xx xxxx Xxxxxxxxxxxx Assay xx Mammalian Xxxx Xxxxxx xxx Peripheral Xxxxx. X report xx the X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Gene-Tox Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) MacGregor, J. X., Xxxxxxxx, X., Xxxx, X. X., Xxxx, C. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Xxxxxx for Xxxxxxxxxxx Damage Xxxxxx Xxxxxxx Xxxxxxxx Xxxxxxx xx Mice, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx xx Xxxxxxxxxx, ed. X. X. Xxxxx, X. X. Schnell, X. X. Xxxx. Elsevier, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. T., Xxxxxx, X. A. Xxxx, X., Xxxxxxxx, X. X., Ramel, X., Xxxxxxxx, X. F., Xxxx, X. X., Xxxx, X. (1987), Xxxxxxxxxx for xxx Xxxxxxx of Xxxxxxxxxxxx Xxxxxx in Xxxxxxxxx Xxxx Marrow Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) MacGregor, X. X., Wehr, X. X., Henika, P. X., Shelby, X. X. (1990), Xxx xx vivo Xxxxxxxxxxx Xxxxxxxxxxxx Test: Xxxxxxxxxxx xx Steady Xxxxx Xxxxxxxxx Xxxxx Xxxxxxxxxx xxx Xxxxxxx Xxxxxxxxxxx xxxx Xxxxxxxx Xxxxxxx, Xxxxxx. Xxxx. Xxxxxxx. 14, 513-522.

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

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

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: The Xxxxxxxxx Xxxxxxxxxxx Study Xxxxx xx the Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx of Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx for xxx xxxxx-xxxx xxxxx xxxxxxxxxx xxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Xxxx, X. X., XxxXxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, X. X., Kirsch-Volders, X., Xxxxxx, Jr. F. X., Xxxxxxxxxxxx, F., Xxxxxxx, X., Xxxxxxx, X., Sutou, S., Xxxxxxx, X. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Micronucleus Assay, Xxxxx. Xxx., 312, 293-304.

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

13) Xxxxxxx, X. X., Xxxxx, J. X., Boobis, X. X., Xxxxxx, P. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, D. G., Xxxxxx-Xxxxxx, G., Xxxxxx, X. B., Xxxxxxxx, X. X., Rochold, X. (1992), Xxxxxx xx British Xxxxxxxxxx Xxxxxxx/XX Environmental Xxxxxxx Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx in Xx vivo Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

14) Hayashi, X., Xxxxxx, T., Xxxxxxxx, X. Xx. (1983), Xx Xxxxxxxxxxx xx Xxxxxxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxx xx the Xxxxxxxxxxxx Test, Xxxxxxxx Xxx., 120, 241-247.

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

16) Xxxxxxx, F., Xxxxxxxxxx, C. D. (1989), Xxx automated xxxx xxxxxx micronucleus xxxx, Mutatation Res., 213, 91-104.

17) Xxxxxxxxx, X., XxXxxxxx, X. X. (1995), Xxxxxx Xxxx xxx the Xxxxxxxxxx xx Xxxxxxxxxxxxx xx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxx xx xxx Xxxx Xxxxxx Micronucleus Xxxx, Xxxxxxxxxx Res., 347, 97-99.

18) Richold, X., Xxxxx, J., Xxxxxxx, X., Chandley, X., Gatehouse, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxxx Xxxxx, xx: X. X. Kirkland (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx 1, revised, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Lovell, X. P., Xxxxxxxx, X., Albanese, X., Xxxxxxxx, G. E., Xxxxx, X., Ferguson X., Richold, X., Xxxxxxxx, X. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Data. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx XXX, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."

XXXXXXX 4D

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

1. XXXXXX

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

1.1 XXXX

Xxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx používají xxxxxxxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Salmonella xxxxxxxxxxx x Escherichia xxxx, x detekci bodových xxxxxx, xxxxx zahrnují xxxxxxxxxx, xxxxx x xxxxxx jednoho xxxx xxxxxxxx párů xxxx XXX (1, 2, 3). Xxxxxxxx této xxxxxxx na xxxxxxxx xxxxxx x bakteriemi xxxxxxx x xxxxxxx xxxxxx, xxxxx xxxxxxxxx xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxx x xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx jsou xxxxxxxxxx xxxx xxx xxxxxxxxxx xxxx v xxxxxxxxxxxxx xxxxxxxxxxxx, xxxxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx mutace x xxxxxxx xxxx xxxx příčinou xxxxx xxxxxxxxx xxxxxxxxxxx chorob x člověka a xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxx xxxxxx x xxxxxxxxxx x v xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx nádory mají xxxxx na tvorbě xxxxxxxx x člověka x u xxxxxxxxx xxxxxx. Xxxxxxx xx xxxxxxxx mutace x xxxxxxxxxx xx rychlá, xxxxxxxxxx a xxxxxxxxx xxxxxx. Xxxxx testovacích xxxxx má řadu xxxxxxxxxx, díky nimž xxxx citlivější na xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx xxxxxxxx DNA xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx buněk xxx xxxxx molekuly x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxxxxxxxx x xxxxxx. Xxxxxxxxxxxx xxxxxxxxxxx xxxxx může xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxx x xxxxxx mutací, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx reverzní xxxxxx s bakteriemi xx k xxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxxxx pro xxxxxxx xxxxx xxxxxxxx a xxxx xxxx vyvinuty xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx látek, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx fyzikálně-chemickými xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx xxxxxx x xxxxxxx mutací x kmeni vyžadujícím xxxxxxxxxxxxx (histidin xxxx. xxxxxxxxx), přičemž vzniká xxxx nezávislý na xxxxxxx xxxxxxx xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx bází xxxx činitele, xxx xxxxxxxxx xxxxx x xxxxxx XXX. Při xxxxxxx reverzních xxxxxx xx mohou xxxx xxxxx xxxxxxxxxx na xxxxx původní xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx genomu.

Posunové mutageny xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx xxxx xxxxxx jednoho xxxx xxxx xxxx xxxx XXX x xxxxxxxx xxx čtecí rámec XXX.

1.3 VÝCHOZÍ XXXXX

Xxx xxxxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, které se xxxx xx buněk xxxxx xxxxxxx, jako xxxx příjem, metabolismus, xxxxxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxx XXX. Xxxxxxx xxxxxxxxx in xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx xxxxx xxxxxxxxx podmínky in xxxx x savců. Xxxxxxx tedy xxxxxxxxxxx xxxxxx informaci x xxxxxxxxxx a karcinogenním xxxxxxxxxx xxxxx pro xxxxx.

Xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx xx xxxxxxxxx využívána xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx, x xxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxxx, xx xxxxx chemických xxxxx, které xxxx x xxxx zkoušce xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx x v xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx činitelů, xxxxx nejsou xxxxxxxxxx xxxxx zkouškou. Xxxxxxx xxxxxx skutečností xxx xxxxxxxxx xx xxxxxxxxxx xxxxxx detekovanéhokonečného xxxx, x rozdílech v xxxxxxxxxxx xxxxxxxx xxxx x rozdílech v xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx faktory, xxxxx xxxxxxx xxxxxxxxx xxxxxxx na xxxxxxxx xxxxxx na xxxxxxxxxx, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxx xxx xxxxxx xxx xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx vysoce xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx xxxxxxxxxxx) a xxx xxxxxxxx látky, x nichž se xxxxxxxxxxx (xxxx o xxxxx xx xx), xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx systému xxxxx xxxxx (xxxx. xxxxxxx xxxxxxxxxx topoisomerasy x některé xxxxxxx xxxxxxxxxx). V xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxxx zkoušky xxxxxxxxxx x savců.

Přestože xxxxx xxxxxxxxx, pro xxx xx xxxx xxxxxxx xxxxxxxxx, je xxxxxxxxxxxx xxx savce, xxxx xxxxxxxx xxxxxxxxx. Závisí xx xxxxxxxx xxxxx x existuje xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx, xxxxx působí xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, nebo xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx neexistují.

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx xxxxx jsou xxxxxxxxx zkoušené xxxxx, x xx xx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx x xxx něho. Xx xxxxxxxxxxx miskovém xxxxx xx suspenze smíchají x vrchním xxxxxx x xxxxx xx xxxxxxx na minimální xxxx. V preinkubační xxxxxx xx xxxxxxxx xxxx xxxxxxxx x xxxx xx před xxxxxxxxx na minimální xxxx xxxxxx s xxxxxxx xxxxxx. Xxx xxxx technikách xx xx xxxx nebo xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx x provede xx xxxxxxxx x počtem xxxxxxx spontánních xxxxxxxxxx xx xxxxxxxxx xxxxx x rozpouštědlem.

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

Xxx xxxxxxx xxxxxxx xx xxxxxx hlavně xxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Xxxxx x nich xx xxxxxxxxxx xxx provádění xxxxxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx ní. Některé xxxxx xxx xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxx xxxxx xxxxx xx xxxxxxxxxx tříd, xx xxxxx patří xxxx xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx xxxx, xxxxxxxx, xxxxxxxxxx a xxxxxxxxxx xxxxxxxxxx, pyrrolizidinové xxxxxxxxx, allylové xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx xxxxxxxxx, xx určité třídy xxxxxxxx xxxxx xxxx xxxxxxxxx standardními xxxxxxx, xxxx xx xxxxxxxxxx xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Měly xx xxx xxxxxxxxxx xx "xxxxxxxx případy" x k jejich xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (xxxxxxxx x xxxxxxxx postupů xxxxxx xxxxxxx): xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx a těkavé xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx od xxxxxxxxxxxx postupu musí xxx vědecky zdůvodněna.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Bakterie

Čerstvé xxxxxxx xxxxxxxx xx xxxx xxx kultivovány xx xxxxxx xxxxxxxxxxxxx fáze xxxx do časné xxxxxxxxxxx xxxx xxxxx (xxxxxxxxx 109 buněk xx ml). Xxxxx x xxxxxx xxxxxxxxxxx xxxx by neměly xxx xxxxxxx. Je xxxxxxxx, aby xxxx xxxxxxx bakterie xxxxxx xxxx životaschopných xxxxxxxx. Xxxx xxxx xxx xxxxxxxx buď xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxx pro xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx buněk xx xxxxxxx.

Xxxxxxxxxx inkubační xxxxxxx xx 37 °X.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxx xxxxxxxx. Xxxx xxxx by měly xxx xxxxx xxxxx X. xxxxxxxxxxx (TA1535; XX1537 xxxx XX97x xxxx TA97; TA98 x XX100), xxxxxxx xxxxxxx xx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx S. xxxxxxxxxxx xxxx xxx xxxx XX xx primárním xxxxxxxxx xxxxx a xx xxxxx, že xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, xxxxxxxx způsobující xxxxxxxxxx xxxxxx DNA x xxxxxxxxx. Tyto xxxxx xxxxx být xxxxxxxxxx kmeny X. xxxx WP2 nebo X. typhimurium TA102 (19), xxxxx xxxx xx xxxxxxxxx reverzním xxxxx pár bází XX. Xxxxxxxxxx xxxxxxxxx xxxxx xx xxxx xxxx:

- X. xxxxxxxxxxx XX1535 x

- X. xxxxxxxxxxx TA1537 xxxx XX97x x

- S. xxxxxxxxxxx XX98 a

- X. typhimurium XX100 x

- X. coli XX2 uvrA, xxxx X. xxxx WP2 xxxX (xXX101), xxxx X. typhimurium TA102.

Pro xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx XXX xxxx být vhodnější xxxxxxx XX102 xxxx xxxxxx xxxx E. xxxx x vysokou xxxxxxxxxx reparace XXX, (xxxx. X. xxxx XX2 (xXX101)).

Xxxx xx xxx použity xxxxxxxx xxxxxxx xxxxxxxx kmenové xxxxxxx, xxxxxxxxxx xxxxxxx x skladování. Potřeba xxxxxxxxxxxxx pro xxxx xx xxxx xxx xxxxxxxxx xxx každou xxxxxxxxx kmenovou xxxxxxx (xxxxxxxx xxx kmeny X. xxxxxxxxxxx x xxxxxxxxx xxx X. xxxx). Xxxxxxx by xxxx xxx xxxxxxxxxxxx xxxx fenotypové charakteristiky, xxxxxxxxx xxxxx potřeby xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx rezistence u xxxxx TA98, XX100 x XX97x nebo XX97, XX2 xxxX x XX2 xxxX (xXX101) a ampicilinová x tetracyklinová rezistence x xxxxx TA102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. rfa xxxxxx x S. typhimurium xxxxxxxxxx xx krystalovou xxxxxx x uvrA xxxxxx u X. xxxx xxxx uvrB xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx světlo) (2, 3). Xxxxx xx xxxx xxxxxx dávat xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx na misce x xxxxxxx četností xxxxxxxxxxx xx základě xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx a xxxxxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx xxxxxxxxx xxxx (xxxx. xxxxxxxxxx xxxxxxxxx půdu X (Xxxxx-Xxxxxx) x glukosu) x vrchní xxxx xxxxxxxxxx histidin a xxxxxx nebo xxxxxxxxx xxxxxxxxxx několik buněčných xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx xxxxxxxx

Xxxxxxxx xx xxxx být xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx a xxx xxxx. Nejčastěji používaným xxxxxxxx je kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx ošetřených xxxxxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (1, 2) xxxx fenobarbitonu a β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx xxxxxx xx xxxxxxx xxxxxxxxx x koncentracích x xxxxxxx 5 xx 30 % obj. xx směsi X9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx chemické xxxxx. X xxxxxxxxx xxxxxxxxx může být xxxxxx použít více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. X xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xxxx být xxxxxxxxx xxxxxxx redukčního xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx před xxxxxxxx xx bakterie xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky mohou xxx xxxxxxx xxxxx x xxxxxxxxxx systémům x/xxxx xxxxx být xxxx aplikací zředěny. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx podezření, xx xxxxxxx xx xxxxxxxxx látkou, a xxxx xx xxx xxxxxxxxxx s xxxxxxxx xxxxxxxx x x xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno nejdříve xxxxxx xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx. Xxx zkoušení xxxxx xxxxxxxxx xx xxxx by měla xxx xxxxxxx organická xxxxxxxxxxxx neobsahující vodu.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Xxxxxxxx xxxxx (viz 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx kritéria, xxxxx mají být xxxxxxxxxx při xxxxxxxxx xxxxxxxxxx množství xxxxxxxx xxxxx xxxxx xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxx směsi xxx xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx může xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx xx může xxxxxx x přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx xx měla xxx posouzena xx xxxxxxx viditelného srážení x xxxxxxx směsi xx skutečných xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx je 5 xx/xxxxx xxxx 5 μx/xxxxx. U xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx by xxxx xxx xxxxx xxxx xxxx xxxxxxxxxx koncentrací xxxxxxxx, xxx látky xxxx v konečné xxxxx xxx xxxxxxxx xxxxxxxxxxx. Zkoušené xxxxx, xxxxx xxxx xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx, xx xxxx xxx xxxxxxxx až xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx koncentrací xxxxxxxx xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx xx xxxx být intervaly xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxx polovině xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Menší xxxxxxxxx xxxx xxxxxx x případě, xxx xx xxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx xxxx xxx xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx kontroly

Součástí xxxxxxx xxxxxxxxx xx měly xxx xxxxxxx specifické xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx x xxxxxxxxxxxx xxxxxxxx x bez xx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X xxxxxxx xxxxxxx x xxxxxxxx metabolického xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxx (xxxxx) xxx pozitivní xxxxxxxx xxxxxxx (xxxxxxx) xx xxxxxxx typu xxxxxxxxx xxxxx xxxxxxxx.

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

Xxxxx	Xxxxx CAS	Číslo xxxxx EINECS
9,10-dimethylanthracen	781–43–1	212–308–4
7,12-dimethylbenzo[a]anthracen	57–97–6	200–359–5
benzo[a]pyren	50–32–8	200–028–5
2-aminoanthracen	613–13–8	210–330–9
Cyklofosfamid	50–18–0	200–015–4
cyklofosfamid xxxxxxxxxx	6055–19–2	200–015–4

Xxxx xxxxx je vhodnou xxxxxxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx metabolické xxxxxxxx:

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

2-xxxxxxxxxxxxxx by neměl xxx použit xxxx xxxxxx xxxxxxxxx xxxxxxxxx xxxxx X9. Při xxxxxxx 2-xxxxxxxxxxxxxxx by xxxx xxx xxxxx xxxxx S9 xxxxxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx aktivaci xxxxxxxxxxxxxx xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

Xxxxxxxxx kmenověspecifické xxxxxxxxx xxxxxxxx u xxxxxxx xxx xxxxxx xxxxxxxxxxx aktivace xxxx xxxx xxxxx:

Xxxxx	Xxxxx 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, XX97 x XX97x
XXX 191	17070–45–0	241–129–4	XX1537, XX97 a XX97x
Xxxxxxxxxxxxxxxxx	80–15–9	201–254–7	XX102
xxxxxxxxx X	50–07–7	200–008–6	XX2xxxX x TA102
1-methyl-3-nitro-1-nitrosoguanidin	70–25–7	200–730–1	WP2, XX2 xxxX x XX2 xxxX (xXX101)
4-xxxxxxxxxxxxx-1-xxxx	56–57–5	200–281–1	XX2, XX2 xxxX x XX2 xxxX (xXX101)
α-[(5-xxxxx-2-xxxxx)xxxxxxxxxx]xxxxx-2-xxxxxxxx (XX2)	3688–53–7		xxxxx obsahující xxxxxxxx

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

Xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxxx skládající se xx samotného xxxxxxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, zpracované xxxxx stejným způsobem xxxx exponované xxxxxxx. Xxxxx toho xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity také xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx mutagenní účinky.

1.5.3 Xxxxxx

X xxxxxxxxxx miskové xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,05 xx xxxx 0,1 xx xxxxxxxxxx roztoků, 0,1 ml xxxxxxx xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx xxxxxxxxxx pufru x 2,0 xx xxxxxxxx xxxxx. X xxxxxxx zkoušky x xxxxxxxxxxxx aktivací xx xxxxxxx smíchá 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx obsahující xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx frakce (x rozmezí 5 xx 30 % xxx. v xxxxxxxxxxx xxxxxxxxx směsi) x xxxxxxx xxxxxx (2,0 xx) x zároveň x xxxxxxxxxx x xxxxxxxxx látkou xxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxx xxxxxxxx xx xxxxxxxx a xxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx xxxxx. Xxxx xxxxxxxx xx xxxxx xxxxxx xxxx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx xxxxxxxx xxxxxx xxxx xxxxxxxxx x vrchním agarem x přelitím xxxx xxxxxx minimálního xxxxx xx xxxxx xxxxxxx 20 xxxxx nebo xxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxx (obsahujícím xxxxxxxxx 108 životaschopných xxxxx) x sterilním xxxxxx xxxx metabolickým xxxxxxxxxx systémem (0,5 xx) xxx 30 — 37 °X. Xxxxxxx xx xxxxxx 0,05 xxxx 0,1 xx xxxxxxxx látky xxxx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxxx x 0,5 xx xxxxx S9 xxxx xxxxxxxxxx pufru x 2,0 ml xxxxxxxx xxxxx. Zkumavky xx xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.

X dostatečnému odhadu xxxxxxxx xx xxxx xxx xxx každé xxxxxx xxxxx xxxxxxx 3 xxxxx. Xxxxxxx xxxx xxxxx je xxxxxxxxxx xx vědeckém xxxxxxxxxx. Xxxxxxxx ztráta xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx zkoušky.

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

1.5.4 Xxxxxxxx

Xxxxxxx xxxxx v xxxx zkoušce xx xxxx být inkubovány xxx 37 °X xx 48 –72 xxxxxxxx. Po xxxxxxxx xxxxxxxxx xxxx se xxxxxx xxxxx kolonií xxxxxxxxxx xx misku.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx na xxxxx. Xxx xx xxx xxxxxx xxxxxx xxxxx xxxxxxx revertantů xxx xx xxxxxxx x xxxxxxxxx xxxxxxxxx (xxxxxxxx rozpouštědla x xxxxxxxx xxxxxxxxxxxx kontrola), xxx xx xxxxxxx x pozitivní kontrolou. Xxxxx xx xxxxxxxxxxxx xxxxxxx, střední xxxxxxx xxxxx kolonií xxxxxxxxxx xx xxxxx a xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxx x xxxxxxxxx x xxxxxxxxx kontrolu (neexponovanou xxxxxxxx a/nebo xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx jasně pozitivní xxxxxxxx xx nepožaduje. Xxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx být xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx výsledků xxxxxxxxxx xx xxxxxxxx, xxxx xx být xxxxxx xxxxxxxxxx. Změna parametrů xxxxxx x xxxxx xxxxxxxx rozsah posuzovaných xxxxxxxx by měla xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx xx mohly být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx xxxxxxx metoda xxxx preinkubace v xxxxxxxx xxxxx) a xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx stanovení pozitivního xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx xxx xxxxxxxxx rozsah x xxxxxxx xxxxxxx kmene x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxx xxxx, x xx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx xxxxx xxx xxxxx nebo xxxx xxxxxxxxxxx (23). Xxxxxxxx by měla xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (24). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx nesplňují xxxx xxxxxxx xxxxxxxx, xx xxxxxxxx v xxxxx xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx výsledky, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Výsledky mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx experiment opakován.

Pozitivní xxxxxxxx xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x genomu xxxxx Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx bodové xxxxxx xxxxxxxxxx bází xxxx posunem xxxxxxx xxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxx za xxxxxxxx xxxxxxx xxx xxxxxxxxx druhy xxxxxxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx volby xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx kmeny,

- xxxxx xxxxx x xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxx zkoušené látky xx xxxxx (xx/xxxxx xxxx μl/misku) x xxxxxxxxxxx výběru xxxxx x xxxxx misek xx xxxxxxxxxxx,

- xxxxxxx xxxxx,

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

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- známky xxxxxxx,

- počty xx xxxxxxxxxxxx xxxxxxx,

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

- xxxxx xxxxxxxx závislost xxxxxxxx na xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxx, X. N., XxXxxx, X., Yamasaki X. (1975), Methods of Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Res., 31, 347-364.

2) Xxxxx, X. X., Ames, X. X. (1983), Revised Xxxxxxx xxx the Xxxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx., 113, 173-215.

3) Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxx, X., Gocke, X., Xxxx, X., Xxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, E. (1994), Xxxxxxxxxxxxxxx xxx xxx Performance of Xxxxxxxxx Xxxxxxxx Assays, Xxxxxxxxxx Xxx., 312, 217-233.

4) Xxxx, X. X., Xxxxxxx X. X., Auletta, A. X., Von Xxxxx, X. S., Brown, X. X., Simmon, X. X., Xxxxxx, X., XxXxxx, X., Xxxxxxxxxx, K., Xxxxxx, X., Xxx, X. X., Ray V. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Xxxxxx of xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, X., Degawa, X., Seino, Y. X., Xxxxxxxxxx, T., Xxxxx, M., Sugimura, X., Xxxxxxxxx, X. (1975), Xxxxxxxxxxxx of Xxxxxxxxxx Xxx Xxxx xxx xxxxx Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

6) Matsushima, X., Xxxxxxxx, T., Xxxxx, X., Yahagi, X., Xxxxxx, X., Xxxxxxxx, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Microbial Xxxxx, xx: Xxxxx-xxxx Xxxx Systems for Xxxxxxxxx Carcinogens, xx. Xxxxxxx X. X., Xxxxxx, X. X., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

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

8) Xxxxxxxxxx, X. X., Wolleb, X., Xxxxxxx, L. (1987), Xxxxxx Preincubation Xxxxxxxxxxxx Xxxx for Foods, X. Xxxx Xxxxxx., 8, 167-177.

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

10) Hubbard, X. A., Xxxxx, X. X. X., Xxxxxxxxx, D., Bridges, X. W. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, xx: Xxxxxxxx xx Mutagenicity Xxxx Procedures, 2. xxx., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (xxx.), Elsevier, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

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

12) Araki, X., Xxxxxxx, X., Kato, X., Xxxxxxxxxx, X. (1994), Xxxxxxxx Xxxxxx xxx Mutagenicity Xxxxxxx xx Gaseous Compounds xx Xxxxx a Xxx Sampling Bag, Xxxxxxxxxx Res., 307, 335-344.

13) Prival, X. X., Bell, X. X., Xxxxxxxx, V. X., Reipert, X. X., Vaughan, X. X. (1984), Xxxxxxxxxxxx xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Monoazo Xxxx xx a Xxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 136, 33-47.

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

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

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

17) Xxxxxxxxxx, T., Xxxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx xxx Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx, Cancer Xxx., 39, 3780-3782.

18) Xxxxxx, G., Gold, X., Xxxxx-Xxxxx, X., Xxxx, X. X. (1980), Fecalase: X Xxxxx for Activation xx Dietary Xxxxxxxxxx xx Mutagens xx Xxxxxxxxxx Xxxxx, Proc. Xxxx. Acad. Sci. X. S. X, 77, 4961-4965.

19) Xxxxxx, X., Xxxxxx, X., Xxxx, X. J., Xxxxxxxxx, X. X. (1990), Xxxxxxxxxx xx Xxxxxxxxxx typhimurium XX 102 xxxx Xxxxxxxxxxx xxxx WP2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Matsushima, X., Xxxxxxxx, M., Hara, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. s. xx Inducer or Xxxxxxxxx Xxxxxxxxxx Systems, xx: Xx vitro Xxxxxxxxx Activation in Xxxxxxxxxxx Testing, eds. X. X. xx Xxxxxx et xx. Xxxxxxxx, North Xxxxxxx, 85-88.

21) Elliot, X. X., Xxxxxx, X. X., Elcombe, X. X., Xxxxxxxxx, X. X., Gibson, G. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 xx xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, X., Xxxxxxxxxxxxxxxx, X., Ames, X. X. (1981), Xxxxxxxxxxxxx xx Xxxxxxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 88, 343-350.

23) Claxton, X. D., Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, K., Xxxxxxxx, X., Xxxxxx, X. (1987), Xxxxx xxx xxx Xxxxxxxxxx typhimurium/Mammalian Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Mutagenicity, Mutatation Xxx., 189, 83-91.

24) Xxxxx, X. X. X., Xxxxx, M. X. X., Xxxxxxxxx, X., Mitchel, X., Xxxxxxxx, X. X., Xxxxxx, X. X. (1989), Xxxxxxxx xx Xxxx xxxx Xxxxxxxxx Xxxxxx Xxxxxx, in: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Xxxx II. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Xxxx Xxxx, xx. Kirkland, X. X., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 28-65."

XXXXXXX 4X

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

1. XXXXXX

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

1.1 ÚVOD

Zkoušku xx xxxxxx mutace x xxxxxxx xxxxx xx vitro xxx xxxxxx pro detekci xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx látkami. Xxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxx xxxxxxx X5178X xxxx, xxxxxxx xxxxx CHO, XXX-XX52 x X79 xxxxxx xxxxxxxx a lymfoblastoidní xxxxx XX6 xxxxxxx (1). X xxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx xxxxxx genů xxx xxxxxxxxxxxxxx (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x transgen xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx xx xxxxxx XX, XXXX x XPRT xxxxxxxx xxxxx xxxxxxxx genetických xxxxxxxx. Xxxxxxxxxxx lokace XX x XPRT xxxx umožnit xxxxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx delece), které xxxxx detekovat v XXXX xxxxxx na X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx in xxxxx lze použít xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxx buněčné xxxxx. Buňky se xxxxxxxx xxxxx schopnosti xxxxx v xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx mutací.

Zkoušky xxxxxxxxx xx vitro xxxxxx xxxxxxxx použití xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx metabolický aktivační xxxxxx xxxxxx zcela xxxxxxxxx xxxxxxxx in xxxx x xxxxx. Xx xxxxx xx xxxxx vyvarovat xxxxxxxx, xxxxx by xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X pozitivním xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx, xxxx xxxxx xxxxxx xX, xxxxxxxxxx xxxx vysokých xxxxxx cytotoxicity (7).

Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x karcinogenů xxxxx. Xxxxx xxxxxxxxx, xxx xxx je xxxx xxxxxxx xxxxxxxxx, xxxx karcinogeny savců; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx důkazy o xxx, že existují xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx zkouškou, xxxxx zřejmě xxxxxx xxxxxx, negenotoxickými mechanismy, xxxx mechanismy, xxxxx x bakteriálních xxxxxxx xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Přímá xxxxxx : xxxxxx xxxxxx xxxxxxxxx typu xxxxxxxx xxxxx, která xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxxxxxx xxxxxxxx kódovaných xxxxxxxx.

Xxxxxxxx xxxxxxxxxx párů xxxx : látky, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxx více xxxx xxxx x XXX.

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

Xxxx exprese xxxxxxxx : xxxx, xxxxx xxx xxxxxx x nově xxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxxxxxx.

Xxxxxxx xxxxxxx : xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxx počtem xxxxxxxxxxxxxxx buněk.

Relativní xxxxxxx xxxx : nárůst xxxxx buněk v xxxx xx srovnání x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx se xxxx součin xxxxxx xxxxxxxxx xxxxx x xxxxxxxx x x xxxxxxxxx kontrole a xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx x negativní xxxxxxxx.

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

Životaschopnost : xxxxxxxx xxxxxxxxx xxxxx v xxxxxxxx xxxxxxxx xx xxxxx xx xxxxxxxxxxxx xxxxxxxx xx expresi.

Přežití : xxxxxxxx klonování xxxxx xxx xxxxxxxx xx xxxxx xx xxxxx xxxxxx xxxxxxxx; přežití xx xxxxxxx vyjádřeno x poměru k xxxxxxx kontrolní populace xxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxx, které x xxxxxxxx xxxxxx TK+/-® XX— /- neobsahují xxxxxxxxxxxxxx (XX) jsou xxxxxxxxxxx k xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxxxxxx (TFT). Xxxxx xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx xx XXX, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxx xxxxx xxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxx xxxx schopny xxxxxxxxxxx xx xxxxxxxxxxx XXX, zatímco normální xxxxx, které xxxxxxxx xxxxxxxxxxxxxx xxxx schopnost xxxxxx. Xxxxxxx lze x buněk x xxxxxxxxxxxx XXXX nebo XXXX provést xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx x 6-xxxxxxxxxxx (XX) nebo 8-xxxxxxxxxx (XX). Vlastnosti xxxxxxxx látky by xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx xx xx zkoušce xx xxxxxx xxxxxx x xxxxxxx savců xxxxxxx xxxxxx xxxx nebo xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx na xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxx mutantní xxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxx chemických xxxxx, které xxxx xxxxxxxx xxxxxxxxx jako xxxxxxxx xxxxxxx, xxxx xxxx xxx potvrzena xxxxxxxx xxxxxxx nebo xxxxxxx xxx xxxxxxx (8).

Xxxxx x xxxxxxxxx xxxx xxxxxxxxxxxxx kultuře xxxx vhodnou xxxx xxxxxxxxx zkoušené xxxxx xxx s xxxxxxxxxxxx xxxxxxxx, tak bez xx, x xxxxxxxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxxxxxxx a xx xxxxxx xxxxxxx xxxxxxxx xxxx selekcí xxxxxxx (9, 10, 11, 12, 13). Cytotoxicita xx xxxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxxx doby expozice. Xxxxxxxxxx xxxxxxx xx xxxxxxx x xxxxxxxx xxxxx xx xxxxxxx xxxx xxxxxxxxxxxxxxxxx pro xxxxx xxxxxxx xxxxx x typ xxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx se stanoví xxx, xx se xxxxxx xxxxx xxxxx xxxxx xx média xxxxxxxxxxxx selekční xxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxx x xx xxxxx bez selekčního xxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx klonování (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx se xxxxxxxxx kolonie. Xxxxxxx xxxxxxx xx xxxxxxx x xxxxx mutantních xxxxxxx x xxxxxxxxx xxxxx x xxxxx xxxxxxx v xxxxx xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Pro použití x xxxx xxxxxxx xxxx k xxxxxxxxx xxxxx typy xxxxx, xxxxxx xxxxxxxx xxxxx X5171X, XXX, XXX-XX52, X79 xxxx XX6. Xxxx buněk x xxxx zkoušce by xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx být xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx mykoplasmaty, x x xxxxxxx xxxxxxxxxxx xx xxxxxx být xxxxxxx.

Xxxxxxx xx xxxx xxx xxxxxxxx xxx, xxx měly předem xxxxxxxxxx xxxxxxxxx a xxxx. Xxxxx xxxxxxxxx xxxxx, kultur x xxxxxxxxxxx zkoušené xxxxx xx xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxx (14). Minimální xxxxx xxxxx, které xxxxxxx xxxxxxxx x které xxxxx xxxxxxx x xxxxxx xxxxxx zkoušky, xx xxx být xxxxxxx xx četnosti xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx xx, aby xxx xxxxxx xxxxx xxxxx, xxxxx je xxxxxxxxxxxxxx xxxxxxxxxx hodnoty xxxxxxxx xxxxxxxxxxx xxxxxx. Xx xxxx xxxxxxxxxx, xxx xxxx použito xxxxxxx 106 xxxxx. Xxxx xx xxx x dispozici dostatečné xxxxxxxxx xxxxx o xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxxx výpovědní hodnota xxxxxxx.

1.4.1.2 Média x xxxxxxxxxx podmínky

Pro xxxxxxxxx xxxxxx by xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx média x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, koncentrace CO₂, xxxxxxx a xxxxxxx). Xxxxx by xxxx xxx zvolena xxxxx xxxxxxxxxx systémů x xxxx buněk xxxxxxxxx xxx xxxxxxx. Xx xxxxxxx důležité, xxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxx xxx, aby xxxx xxxxxxxxx xxxxxxxxx xxxx buněk xxxxx xxxxxx xxxxxxx a xxxxxxxxx xxx mutovaných, xxx xxxxxxxxxxxx xxxxx xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxx, xxxxxxxx xx xxxxxxxxxxxx média x xxxxxxxxxx při 37 °X. Před xxxxxxxx x xxxx xxxxxxx xxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxx xxx přítomné xxxxxxxx xxxxx.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

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

Xxxxxxxxxxxxxxxxxxx xxxxxx xx v konečném xxxxxxxxxx xxxxx obvykle xxxxxxxxx x koncentracích 1 — 10 % obj. Volba x xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx může xxxxxxx na xxxxx xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx případech xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx postmitochondriální xxxxxx.

Xxxx xxxxxxxx vývoje, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx enzymy, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx buněčných xxxxx xx xxxx být xxxxxxx zdůvodněna (xxxx. xxxxxxxxxxx isoenzymu cytochromu X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Příprava xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx xxxx xxxxxxxx xx buňky rozpuštěny xxxx suspendovány ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou být xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být xxxx xxxxxxxx xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx mělo být xxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx, x xxxx xx být xxxxxxxxxx x přežitím xxxxx x x aktivitou X9. Xxxx-xx použita xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud možno xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Cytotoxicita xx xxxx být stanovena x xxxxxxxxxxxx xxxxxxxx x bez ní x hlavním experimentu xx použití xxxxxxxx xxxxxxxxxx xxxxxxx integrity x xxxxx, jako xxxx relativní účinnost xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxx celkový xxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx koncentrace. V xxxxxxx xxxxxxxx by xxxx tyto koncentrace xxxxxxxx xxxxxxx dané xxxxxxxxx x minimální xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, což xxxx xxxxxxx xxxxxxxx, xx xx se koncentrace xxxx lišit xxxxxxxx 2 xx Ö10. Xx-xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx, xxxx xx být xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx nejméně 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx by xxxx být xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, která x xxxx xx xxxxxxxx.

Xxxxxxxxx nerozpustné xxxxx xx měly xxx xxxxxxxx xx x xxxx rozpustnosti za xxxxxxxxxxxx xxxxxxxx, nebo xx za tuto xxx. Xxxx xx xxx xxxxxxxxx případná xxxxxxxxxxxxx v xxxxxxxx xxxxx, ve kterému xxxx xxxxx xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx x na xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx xx xxxx x xxxxxxx expozice x xxxxxxxxxx xxxxxxx xxxxx x důsledku xxxxxxxxxxx buněk, X9 xxxx, xxx. Nerozpustnost xxx xxxxxxx xxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx měly xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx xxxx vehikulum) xxxxxxxx jak x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Xxx xxxxxxx xxxxxxxxxxx aktivace xx xxxx být xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, která k xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxx xxxxx:

Xxxx metabolické xxxxxxxx	Xxxxx	Xxxxx	Xxxxx XXX	Xxxxx xxxxx Xxxxxx
Xxx xxxxxx xxxxxxxxxxx aktivace	HPRT	ethyl-methansulfonát	62–50–0	200–536–7
	HPRT	1-ethyl-1-nitrosomočovina	759–73–9	212–072–2
	TK (xxxx a xxxxx xxxxxxx)	xxxxxx-xxxxxxxxxxxxxx	66–27–3	200–625–0
	XXXX	xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
	XXXX	1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
X vnější metabolickou xxxxxxxx	XXXX	3-xxxxxxxxxxxxxxxxx	56–49–5	200–276–4
		X-xxxxxxxxxxxxxxxxxxx	62–75–9	200–549–8
		7,12-xxxxxxxxxxxxxxxxxxxxxx	57–97–6	200–359–5
	XX (malé x xxxxx xxxxxxx)	xxxxxxxxxxxxx	50–18–0	200–015–4
		xxxxxxxxxxxxx monohydrát	6055–19–2
		benzo[a]pyren	50–32–8	200–028–5
		3-methylcholanthren	56–49–5	200–276–5
	XPRT	N-nitrosodimethylamin (xxx vysoké xxxxxx X9)	62–75–9	200–549–8
	XPRT	xxxxx[x]xxxxx	50–32–8	200–028–5

Xxxxx xxx použity xxxx jiné referenční xxxxx pro xxxxxxxxx xxxxxxxx, xxxx. má-li xxxxxxxxx databázi dosavadních xxxxx x 5-brom-2′-deoxyuridinu (XXX 59–14–3, XXXXXX 200–415–9), xxxx xxx xxxx referenční xxxxx xxxxxx xxxxxxx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx x xxxxx použití xxxxxxxxxx xxxxx xxxxx xxxxx xx xxxxxx xxxxxxxx třídy.

Měly xx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx samotné rozpouštědlo xxxx xxxxxxxxx x xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx jako xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx nevyvolává žádné xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx látce

Proliferující xxxxx xx měly xxx xxxxxxxxx zkoušené látce xxx xx přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx by xxxx xxxxx xxxxxxx xxxx (xxxxxxx je xxxxxx xxxx 3 xx 6 xxxxx). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx xx xxxxx xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxx xxx xxxxxxx duplicitní xxxxxxx xxxx xxxxx xxxxxxxxxx xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, xxx xx být počet xxxxxxxxxxx xxxxxx tak, xxx xxx xxxxxxxx xxxxxxxxxxxx xxxxx xxxxxx xxx analýzu (např. xxxxxxx xxx analyzovatelných xxxxxxxxxxx). Xxxx xx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx kultury (xxxxxxxx xxxxxxxxxxxx).

Xxxxxx xxxx xxxxxx xxxxx xx xxxx xxx zkoušeny xxxxxxxx metodami, xxxx. x těsně xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Stanovení přežití, xxxxxxxxxxxxxxxx a xxxxxxxx xxxxxx

Xx konci xxxxxxxxx xxxx se xxxxx xxxxxxx x kultivují xx účelem xxxxxxxxx xxxxxxx x xx xxxxxx umožnění xxxxxxx xxxxxxxx xxxxxxx. Xx xxxxxxxxxx cytotoxicity xxxxxxxxxxxxxxx xxxxxxxxx relativní xxxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx se započne xxxxxxx po xxxxxxxxx xxxx.

Xxxxx xxxxx xx xxxxxxxxxx minimální xxxxxx xxxxxx, xxx xxxxxxx xxxxxxxxx optimální xxxxxxxxxxx xxxxxxx nově indukovaných xxxxxxx (XXXX a XXXX vyžadují alespoň 6 až 8 xxx, XX xxxxxxx xxx xxx). Buňky xxxx xxxxxxxxxxx x xxxxx xx selekčním xxxxxxxx (xxxxxxxxxx xxxxxxx) x xxx něho (xxx xxxx) za xxxxxx xxxxxxxxx xxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx pro xxxxxxx četnosti xxxxxxx) xx xxxxxxx xx xxxxx doby xxxxxxx xxxxxxxxx xx misku xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx látka pozitivní xx xxxxxxx L5178Y XX+/-, mělo xx xxx provedeno xxxxxxx xx xxxxx xx xxxxxxxxxx xxxxxx (x xxxxxxxx pozitivní xxxxxxxxxxx) x xx xxxxxxxxxxx x pozitivních xxxxxxxxxx xxxxxxxxx xxxxxxx podle xxxxxxxxx kolonií. Je-li xxxxxxxx xxxxx xx xxxxxxx L5178Y TK+/- xxxxxxxxx, mělo by xxx xxxxxxxxx xxxxxxx xxxxx velikosti xxxxxxx xxxxxxxxx xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx XX6 XX+/- xxxx xxx xxxx xxxxxxxxx rozdělení xxxxxxx xxxxx xxxxxxxxx xxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xx měly xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x xxxxxxxx mutantů xxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx odpovědi xx xxxxxxx X5178X XX+/- se kolonie xxxxxxxxx xxxxxxx u xxxxx xxxxxxxxxxx zkoušené xxxxx (nejvyšší pozitivní xxxxxxxxxxx) a x xxxxxxxxx x pozitivní xxxxxxxx xx xxxxxxx xxxxxxxx xxxx xxxxxxx — xxxxx kolonie. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx jak xxxxxxx xxxxxxxxx velké xxxxxxx, xxx mutantů xxxxxxxxx xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Xx xxxxxxx XX+/- xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx kolonie x xxxxxxxxx xxxxxx (velká) x xxxxxxx s xxxxxxx xxxxxx (xxxx) (25). X xxxxxxxxxx xxxxx, xxxxx utrpěly xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx doby xxxxxxxx, x tvoří xxxx xxxx xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx xx ztrát xxxxxx xxxx xx xx xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxx xxxxxxx xxxxxxxxx xxxx xxxxxxx xx spojuje x xxxxxxxxxx látkami, xxxxx indukují xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx postižené xxxxx mutantů xxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxx xxxxx x xxxxx xxxxx kolonie.

Mělo xx být xxxxx xxxxxxx (xxxxxxxxx účinnost xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx růst. Xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxx jako xxxxx xxxxxxx x xxxxx xxxxxxxxxx xxxxx.

Xxxx xx být xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxx. Xxxx xx xxxx xxx všechny xxxxx xxxxxxx xx xxxxx tabulky.

Ověření jasně xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxx, kde xxxx potvrzení xxxxxxxxxxx xxxxxxxx xxxxxxxxxx za xxxxx, xx třeba xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx rozšířit rozsah xxxxxxxxxxxx xxxxxxxx by xxxx být xxxxxxx x následných experimentech xxx xxx dvojznačné xxxxxxxx, xxx pro xxxxxxxxx xxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx xx mohly být xxxxxxx, xxxxx rozmezí xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx několik xxxxxxxx, xxxx. nárůst četností xxxxxxx v xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx této xxxxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých případech xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na xxxxxx mutace x xxxxxxx savců xx xxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx x použitých kultivovaných xxxxxxx xxxxx genové xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx na xxxxxxxxxxx xx velmi xxxxxxxx. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx za podmínek xxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx genové mutace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby rozpouštědla/vehikula,

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

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx kultury,

- xxxxxxxxxxxx mykoplasmat.

Zkušební xxxxxxxx:

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

- xxxxxxx xxxxx, případně koncentrace XX₂,

- koncentrace xxxxxxxx xxxxx,

- objem xxxxxxxx x přidané xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- xxxxxxxx hustota xxxxx během expozice,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- délka xxxx xxxxxxx (případně xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx x xxxxxx xxxxx),

- xxxxxxxx xxxxxxx,

- kritéria xxxxxxxxxxx xxxxxxx xx pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx buněk,

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

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- xxxxx x xX x xxxxxxxxxx xxxxx expozice xxxxxxxx xxxxx, pokud xxxx stanoveny,

- xxxxxxxx xxxxxxx, xxxx-xx vyšetřována, xxxxxxx xxx negativní x xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxxxxxxx laboratoře xxxxxxxxx mutanty xxxxxxx xxxx xxxxxxx systémem X5178X XX+/-,

- xxxxx xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

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

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

- xxxxxxx xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Moore, X. X., XxXxxxxx, X. X., XxXxxxxx, X. J., Tindal, X. X. (xxx.) (1987), Xxxxxxx Xxxxxx 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Cold Spring Xxxxxx Xxxxxxxxxx, New Xxxx.

2) Xxx, X. X. Y., Xxxxxxx X. X. (1968), Xxxxxxxxx Xxxx Genetics. XX. Chemical Xxxxxxxxx xx Specific Locus Xxxxxxxxx xx Xxxxxxx Xxxxxxx Cells Xx xxxxx, Xxxx. Xxxx. Xxxx. Xxx. X. X. X, 61, 1306-1312.

3) Liber, X. X., Thilly, W. X. (1982), Xxxxxxxx Xxxxx xx xxx Xxxxxxxxx Kinase Xxxxx xx Diploid Xxxxx Xxxxxxxxxxxx, Xxxxxxxx Xxx. 94, 467-485.

4) Xxxxx, X. M., Harington-Brock, X., Xxxxx, X. X., Dearfield, K. X. (1989), Differential Xxxxxx Xxxxxxxxxxxx xx xxx Xxxxx Xxxxxxxx XX and XXX XXXXX Xxxx, Mutagenesis, 4, 394-403.

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

6) Xxxxx, X. X., Xxxxxxxxxx, X., Xxxxx, X. R., Moore, X., Nishi, X., Xxxxxxxxxx, Xx. L. X., Xxxxxx, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Xxxx Xxxxxxxx Xxxxxx Working Xxxxx Xxxxxx. Xxxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxxx xx Standardisation xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Mutation Xxx. 312, 235-239.

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

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

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20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, K., Xxxxxxxx, X. (1976), X Xxxx Substitute xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, X: Xx vitro Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xx Xxxxxx, X. X., Fouts, X. X., Xxxx, X. X., Philpot, X. X. (xxx), Xxxxxxxx, North-Holland, 85-88.

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

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

23) Xxxxxxxxx, X. X., Moore, X. X., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxx, J. X. (1990), Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Locus xx Mouse Xxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Sci. X. X. X, 87, 51-55.

24) Xxxxx, M. X., Clive, X., Xxxxxx, X. C., Xxxxxx, X. X., Xxxxxx, A. G., Xxxxxx, X. X., Xxxxxx, X. (1985), Xxxxxxxx of Trifluorothymidine, Xxxxxxxxx (XXX+) Xxxxxxx xx X5178X/XX+/--Xxxxx Lymphoma Xxxxx, Mutatation Xxx. 151, 161-174.

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

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

XXXXXXX 4X

"X.23 XXXXXXX XX XXXXXXXXXXXX ABERACE XX XXXXXXXXXXXXXXX XXXXX

1. XXXXXX

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

1.1 ÚVOD

Účelem xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx spermatogoniích xxxxx xx vivo xx xxxxxxxxxxxxx xxxxxx xxxxx, které způsobují xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx dva xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Tato xxxxxx xxxx určena xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x není x xxxxxx xxxxx xxxxxxx používána. Chromozomové xxxxxx a xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx podmíněných xxxxxx x člověka.

Touto xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx změny ve xxxxxxxxxxxxxxx x předpokládá xx xxxx, xx xxxx zkouška poskytne xxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx x xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx in xxxx xx xxxxxxxx xxxxxxxxxxxx xxxxxxx xxx xxxxxx xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx xxxxxxxxxxxxxx typu xx spermatogoniích by xxxx xxx — xxxxx xxx xxxxx xx ztrátě xxxx — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx po xxxxxxxx. Další informace x exponovaných xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx lze xxxxxx xxxxxxxxxx chromozomovou xxxxxxxx xxxxxxx chromozomového xxxx x xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx in xxxx je xxxxxxxx xxx xxxxxxxxx, xxx xxxx mutageny xxxxxxxxxxx xxxxx aktivní také x xxxxxxxxxxxx buňkách. Xxxxx xx xxxx xxxxxxx se xxxxxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX.

Xx xxxxxxxxx xx xxxxxxxx řada xxxxxxxx spermatogonií x xxxxxx citlivostí na xxxxxxxx chemické látce. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx populace spermatogonií x xxxxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X xxxxxxxxxx xx své poloze xx xxxxxxxxx, xxxxx xxxx xxxxxx být xxxxx xxxxxxxx spermatogonií xxxxxxxxxx celkovému xxxxxxxx xxxxx x důsledku xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx buněk x xxxxxxx xxxx xxxxxxx xxxxxx a xxxxxxx.

Xxxxxxxx xxxxxxxx důkaz x tom, že xx zkoušená xxxxx xxxx reaktivní xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx vhodné xxxx xxxxxxx xxxxxx.

Xxx xxxx xxxxxx úvod, xxxx B.

1.2 DEFINICE

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

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

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

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

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx změny xxxxxxxxx chromozomů při xxxxxxxx dělení ve xxxxxx metafáze xxx xxxxxxxxxxx, xxxx xx xxxx delece a xxxxxxxxx, xxxxxxxxxxxxxxxxxx nebo xxxxxxxxxxxxxxxxxx xxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx jsou xxxxxxx xxxxxxxx exponována xxxxxxxx látce x xx xxxxxx době xx expozici xxxxxxxx. Xxxx usmrcením xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx x xxxx; xxx xxxx xxxxxx xxxxx xxxxxxxxxx xxxxxx vhodného druhu xxxxx. Xxxx xx xxx použity běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx zvířat. X xxxxxxxx zahájení studie xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx by překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx mladí xxxxxxxx xxxxxxx xxxxx se xxxxxxxx xxxxxxx rozdělí xx kontrolní skupinu x xxxxxxx, xxxxx xx xxxxxxxx. Xxxxx xx xxxx být xxxxxxxxxx xxx, xxx xxx vliv xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx započetím studie xx nechají v xxxxxxxxxxxxx xxxxxxxxxx alespoň xxx dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx aplikací xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Měly xx xxx xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, pokud údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxxxx xxx při xxxxxxxxx xxxxxxxxx xxxxx xxxxxxx xxxxxx a xxxx xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx jejich zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx souběžné xxxxxxxxx a negativní (xxxxxxxxxxxx/xxxxxxxxx) kontroly. S xxxxxxxx aplikace zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx spermatogoniích xx xxxx xxx expozičních xxxxxxxx, x nichž xx předpokládá, xx xxxxxxxxx detekovatelný nárůst xxx pozadí.

Dávky xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx xxx, xxx xxx účinek xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Je xxxxxxxxxx, aby xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxx xxx navíc xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx chemické xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx látek xxx xxxxxxxxx kontrolu:

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

V xxxxxxxx xxxxxxx xxxxxx xx měl být xxxxxxxx odběr x xxxxxxx negativní xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x která xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx exponované xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx zvířat a xxxxxxxx xxxxx x xxxxxxxxxxxxxx aberacemi. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx také tehdy, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx xxxxxx

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

1.5.2 Xxxx expozice

Zkoušené xxxxx xx měly být xxxxx možno xxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxx (xx. při xxxxx xxxxxxxx nebo dvou xxxxxxxxxx). Xxxxxxxx látky xxxxx xxx xxxxxxxx xxxx ve xxxx xxxxxxx, xxx. xxx xxxxx x týž xxx x xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx režimy podávání xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x xxxxxxxx xxxxxx xx xxxx být xx expozici xxxxxxxxx xxx xxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx xxxx xxx zkoušenou xxxxxx ovlivněna, xxxxxxx xx xxxxx časný xxxxx x xxxxx xxxxxxxx odběr přibližně 24 x 48 xxxxx xx expozici. X případě jiné xxx nejvyšší xxxxx xx xxx xxx xxxxx xxxxxxxx xx 24 hodin xxxx xx xxxxxx xxxx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxx buněčného xxxxx, xxxxx xxxx xxxxx xxxx xxxxxxxxx xxxx xxx xxxxxxx xxxxxx (6).

Xxxxx mohou xxx odběry xxxxxxxxx xxxx v jiné xxxx. Například v xxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (lagging) xxxxxxxxxx nebo mohou xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx být xxxxxxxxx xxxxxxxx xxxxx (1).

Vhodnost xxxxx xxxxxxxxx expozice xxxx xxx určena xxxxxx xx xxxxxxx. X případě plánu x xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx délky xxxxx) xx poslední xxxxxxxx. Xxxxx potřeby xxxxx xxx prováděny xxxxx xxxxxx x xxxx xxxx.

Xxxx usmrcením xx zvířatům xxxxxxxxxxxxxxxxx xxxx xxxxxx dávka xxxxx zastavující metafázi (xxxx. Colcemid® xxxx xxxxxxxxx). Xxxx se xx xxxxxx xxxx xxxxxxx x zvířat xxxxx. X xxxx xx tato xxxx xxxxxxxxx 3 — 5 xxxxx; u xxxxxx xxxxxxxx xx xxxx doba xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx rozsahu, xxxx by být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx x kmenem x xx xxxxxxxx xxxxxx xxxxxxxx, který xx použije x xxxxxx xxxxxx (7). X xxxxxxx toxicity xx pro první xxxxx xxxxxxx tři xxxxxx xxxxx. Tyto xxxxxx dávky xx xxxx xxxxxxxx rozmezí xxxx maximální x xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx stačí, xxxx xxxx xxxxxxx xxxxx nejvyšší dávka. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xx xxxxx xxxxx vedly xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx dávka xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx vyvolávající xx spermatogoniích xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx počtu spermatogonií x mitose xxxxxxxx x první x xxxxx xxxxxxxxx xxxxxxxx; xxxx snížení xx xxxxxx xxxxxxxxx 50 %).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx s jednou xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx žádné xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx základě xxxxx x látkách, xxxxx mají xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx se xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. Očekávaná xxxxxxxx xxxxxxx může xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx intubační xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, musí xxx xxxxxxxxxx. Až na xxxxxxxx x xxxxxx xxxxx, které xxxxxxx xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx zkoušeného objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů xx xxxxxxx xxxxxxxxxx

Xxxxx xx usmrcení se x xxxxxxx xxxx xxxx xxxxxx xxxxx xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx a fixuje. Xxxx xx xxxxxx xx xxxxxxxx sklíčka x obarví se.

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx mělo xxx xxxxxxxxxxx xxxxxxx 100 xxxxx x xxxxx xxxxxxxxxxxx xxxxxxxx (tj. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Tento xxxxx xxx snížit, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx včetně preparátů xxxxxxxxxxx x negativních xxxxxxx, by xxxx xxx xxxx mikroskopickou xxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx při fixaci xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx xxxxxxxxxx x xxxxx xxxxxxxx, měly xx xxxxxxxxxxx buňky xxxxxxxxx centromery v xxxxx xxxxxxxxxxxxxx číslu 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx by xxxx xxx zpracovány ve xxxxx xxxxxxx. Experimentální xxxxxxxxx je xxxxx. Xxx xxxxx xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx různé xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx aberací x jejich xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx odděleně x xxxxxxx xx, xxx obecně se xxxxxxxxxx xx xxxxxxx xxxxxxxx aberací.

Je-li xxxxxxxxxx xxxxxx x xxxx xxxxxx, xxx xx xxx xxx xxxxxxxxx xxxxxxx cytotoxických xxxxxx xxxx míra xxxxxxxxxxxx xxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx a xxxxxx sloužících xxxx xxxxxxxxx xxxxxxxx poměr xxxxxxxxxxxxx v xxxxxx xxxxxxxx x xxxxx x druhé xxxxxxxxx xxxxxxxx, x xx x xxxxxxxx xxxxxx 100 xxxxxxxx se xxxxx xx xxxxx xxxxx. Xxxxx xx xxxxxxxxx pouze xxxxxx, xxxxxxx v 1000 xxxxxxx xx xxxxx xx měl být xxxxxxxx xxxxxxxxx xxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx buněk s xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx xx dávce xxxx xxxxx xxxxxx xxxxx xxxxx s xxxxxxxxx xxx skupinu x xxxxxxx dávkou x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek statistické xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx podmínek.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx konečný výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx ve xxxxxxxxxxxxxxx savců in xxxx xxxxxxxxx, že xxxxxxxx látka indukuje x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx strukturní xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx látka xx xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxx buňkách xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx x stáří xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx na xxxxxxx xxxxxxx, včetně xxxxxxx tělesné xxxxxxxxx, xxxxxxx hodnoty a xxxxxxxxxx odchylky xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

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

- xxxxxxxxxx zvolených úrovní xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxx xxxxxxxx,

- xxxxxxxx xxxxxxxx mezi xxxxxxxxxxx xxxxxxxx látky x xxxxxx nebo vodě (xxx) xx odpovídající xxxxx (xx/xx tělesné xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx krmiva x vody,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx toxicity,

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

- xxxxxx xxxxxxxx preparátů,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxx na xxxxx xxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx index,

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

- xxx x xxxxx xxxxxxx uvedený xxxxxxxxxx xxx každé xxxxx,

- xxxxxxx xxxxx xxxxxxx xx xxxxxxx,

- xxxxx xxxxx s xxxxxxxxx ve skupině,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Potential in Xxxxx Xxxxxxxxxxxxx of Xxxxxxxx Xxxxxxxx Xxxxxxx xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Genetic Xxxxxxxxxx xx Xxxxxxxxxxxxx Xxxxxxxxx, Xxxx X: Xxxxxxx Effects xxx Xxxxxxx Xxxxxxxxxxx, Ramel, X., Xxxxxxx, X., Xxxxxxxxx, X. (eds) Xxxx, Xxx York, 477-484.

2) Xxxxx, X. X., (1984), Cytogenetic xxxxx xx Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Approach, (xx.) X. Venitt, X. X. Parry, XXX Xxxxx, Xxxxxx, Xxxxxxxxxx DC, 275-306.

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

4) Xxxxxxx, X., Ashby, J., Xxxxxxxx, X., Gatehouse, X. G., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxx Xxxxxx, xx: D. X. Xxxxxxxx (ed.), Basic Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Sydney, 115-141.

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

6) Xxxxx, X. X., Xxxxxx X. X., Xxxxxxx, J., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx N. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Standardisation of Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxx Xxxxxx of xxx Xxxxxxx Xxxxx xx Xxxxxxxxx Germ Xxxx Xxxxx, Mutatation Xxx., 312, 313-318.

7) Xxxxxxx, R. X., Xxxxx, J. X., Xxxxxx, X. R., Xxxxxx, X. A., Xxx, X., Xxxxxxx, X. X., Gatehouse, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, D. X., Xxxxxxx, X. (1992), Report of Xxxxxxx Toxicology Society/UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Dose Xxxxxxx xx In xxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. X., Xxxxxxxx, D., Xxxxxxxx, X., Amphlett, G. X., Clarc, X., Xxxxxxxx, X., Xxxxxxx, X., Papworth, X. X., Savage X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx vivo Xxxxxxxxxxx Xxxxxx, in: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxx. XXXXX Subcommittee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Report, Xxxx XXX. Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Chester, Xxxxxxxxx, Sydney, 184-232."

PŘÍLOHA 4X

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

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX XX 486 — Xxxxxxx xx xxxxxxxxxxxx syntézu XXX (UDS) x xxxxxxxxx buňkách savců xx xxxx (1997).

1.1 XXXX

Xxxxxx zkoušky xx xxxxxxxxxxxx syntézu XXX (XXX) v xxxxxxxxx xxxxxxx xxxxx in xxxx xx xxxxxxxxxxxxx xxxxxxxx xxxxx, které xxxxxxxx reparace XXX x xxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).

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

Jestliže xxxxxxxx důkaz x xxx, že xx xxxxxxxx xxxxx xxxxxxxxx xx xxxxxx xxxxx, xxxx vhodné xxxx xxxxxxx použít.

Rozsah neplánované xxxxxxx XXX (UDS) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx nukleosidů xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxxxxxxxxxx xxxxxxxxx inkorporace xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx zkoušky xx XXX xx vivo xx xxxxxxxxxx používají xxxxx potkana. Xxxx xxxxx než xxxxx xxxxx xxx xxxxxx xxxxxxx, nejsou však xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx XXX závisí xx počtu xxxx XXX xxxxxxxxxxx x xxxxxxxxxxx x místě xxxxxxxxx. Xxxxxxx na XXX je tedy xxxxxx xxxxxxx pro xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 bází) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("short-patch repair") (xxxxx xx xxx xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx s xxxxxx menší xxxxxxxxxx. Xxxxx může důsledkem xxxxxxxxxxxxx reparace, xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxxxx lézí XXX xxxxx x xxxxxxxxxx xxxxxxxxx. Xxxxxx odpovědi XXX xxxxxxxxxxx žádnou xxxxxxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, xx xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxx, xxxxx xxxx xxxxxxx xxxxxxxxx x mutagenní aktivitě, xx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxx, xxxxx xx xxxxxxxxxx x xxxxx xxxxxx.

Xxx xxxx obecný úvod, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx jádrům (XXX), xxxxx než xxxxxxxxxx xxxxxxx stanovená laboratoří xxxxxxxxxxx zkoušku.

Čistý xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx xxxxx x xxxxxxxxxxxxxxxxx zkoušce na XXX, vypočtená odečtením xxxxxxxxxx xxxxx zrn x xxxxxxxxxxxxxxxxx xxxxxxxxx (XX) odpovídajících xxxxxx xx počtu xxx xxxxxxxxxxxxxx buněčným xxxxxx (XX): XXX = XX — CG. Xxxxxxx NNG xx xxxxxxx xxx xxxxxxxxxx xxxxx, poté společně xxx xxxxx x xxxxxxx, x xxxxxxxxxxx xxxxxxxxx atd.

Neplánovaná xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx chemickými xxxxxxx nebo fyzikálními xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx XXX x xxxxxxxxx xxxxxxx xxxxx xx vivo xxxxxxxx xxxxxxx xxxxxxxx XXX xx vyštěpení x odstranění úseku XXX xxxxxxxxxxxx xxxxxx x poškozením xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx xxxxxxxx xx inkorporaci 3H-TdR xx DNA xxxxxxxxx xxxxx, xxx je xxxx xxxxxxx xxxxx x X-xxxx xxxxxxxxx xxxxx. Xxxxxxxxxxx 3X-XxX xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx tato xxxxxxxx není xxx xxxxxxx xx xxxx X-xxxx xxxxx jako xxxx. xxxxxxx scintilační xxxxxxxxxxxxx.

1.4 XXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx používané laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx by xxxx xxx odchylka v xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx xxx obě xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx obecné xxxxxxxx xxxxx obecného xxxxx k části X, přičemž by xxxx xxx dosaženo xxxxxxxx xxxxxxx 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

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

1.4.1.4 Příprava zkoušené xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx zvířatům xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx zředěny. Xxxx xx být xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou látkou. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx zařazení xxxxxxxxx xxxxx o jejich xxxxxxxxxxxxx. Doporučuje se xxxxxxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxx části xxxxxxxxxxx by xxxx xxx xxxxxxxx pozitivní x negativní (rozpouštědlo/vehikulum) xxxxxxxx. X výjimkou xxxxxxxx zkoušené xxxxx xx měla xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxx ve xxxxxxxxx, x xxxxx dojde x expozici.

Pozitivními kontrolami xx xxxx být xxxxx, x xxxxx xx xxxxx, xx xxxxxx podávání v xxxxxxxxxxx xxxxxxxxxxx koncentracích xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx nad xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx v xxxxxxx xxxxxxxxxxxx mírnou xxxxxxx (4). Xxxxx xxxxx xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx odečtu nevyšla xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxx pro xxxxxxxxx xxxxxxxx:

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

Mohou xxx použity xxxx xxxx xxxxx xxx xxxxxxxxx kontrolu. Je xxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxx jiným xxxxxxxx, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Počet a xxxxxxx xxxxxx

Xxx xx xxx xxxxxx dostatečný xxxxx xxxxxx, aby xxxx zohledněno přirozené xxxxxxxxxx xxxxxxxx odpovědi xx zkoušku. Xxxxx xxxxxxx xx xx xxxx xxxxxxx xxxxxxx xx tří xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxxxx dosavadní xxxxx, je pro xxxxxxxxx a pozitivní xxxxxxxxx xxxxxxx nezbytné xxxxx jedno až xxx xxxxxxx.

Xxxxxxxx jsou x xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx neexistuje xxxx pohlavími xxxxxx x xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx samců. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx určité xxxxxxx, xxxx xx xxxx například x xxxxxxxxx farmaceutických xxxxx, xxxx by xxx xxxxxxx xxxxxxxxx se xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx expozice

Zkoušené látky xxxx zpravidla xxxxxxxx xxxxxxxxxxx.

1.5.3 Dávkování

Za xxxxxxxxxx xxxxxxxx xx používají xxxxxxx dvě xxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx vyvolávající takové xxxxxx toxicity, xx xxxxx xxxxx by xxxxx xxxxx očekávání xxx stejném xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx xx xxxx být xxxxxxxxx 50 % xx 25 % xxxxx xxxxx.

Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx dávkách (xxxx. xxxxxxx a xxxxxxxx) nemusí xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x měly xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Provádí-li xx kvůli xxxxxxxxxxx xxxxxxxx dostupných údajů xxxxxx pro zjištění xxxxxxx, měla xx xxx xxxxxxxxx xx xxxxxx laboratoři, xx xxxxxxx xxxxxx, kmenem, xxxxxxxx x za xxxxxxxx xxxxxx xxxxxxxx, xxx se xxxxxxx x hlavní studii.

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

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x jednou dávkou x xxxxxxx 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx dvou dávkách x jednom xxx xxxxxxxxxx žádné pozorovatelné xxxxxxx účinky x xxxx-xx xx základě xxxxx x látkách, xxxxx mají podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxx xxx úplná xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx může xxxxxxxx potřebu použít x limitní zkoušce xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx látka xx xxxxxxx podává xxxxxxxxxxxxxx, xxxxxxxxx sondou xxxx vhodnou intubační xxxxxxx. Jiné xxxxxxx xxxxxxxx xxxx xxxxx, xxx-xx xx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxxxxxxxx xx xxxx xxxxxxxxxxxx, xxxxx xx xxxxx mohla xxx xxxxxxxxxx xxxxxxxx xxxxx přímo x xxxxxx xxxxxxxxxxxxxxx oběhového xxxxxxx. Xxxxxxxxx objem xxxxxxxx, který může xxx xxxxxxxx podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx testovacího xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Až na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx účinky, xx měla xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx konstantní xxxxx xxx xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx jaterních xxxxx

Xxxxxxx xxxxx se xxxxxxxxxx x xxxxxxxxxxxx xxxxxx zpravidla 12 xx 16 xxxxx xx xxxxxx dávky. Xxxxxxxxxx dřívější xxxxxxxx xxxxxx (xxxxxx xxx xx xxxxx xxxxxx xx xxxxxxxx) xx xxxxxxxx, xxxx-xx po 12 xx 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Mohou však xxx xxxxxxx xxxx xxxx xxxxxx, jsou-li xxxxxxxxxx na základě xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxxx xx zpravidla zakládají xxxxxxx jater xxxxxxxxxxx xx xxxx x xxxxxx se, aby xx xxxxxxx disociované xxxxxxx buňky zachytily xx xxxxxxx xxxxxxx. Xxxxxxx xxxxx x xxxxxxxxx kontroly xx xxxx vykazovat xxxxxxxxxxxxxxx (5) alespoň 50 %.

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxx xxxx, xxxx. xxx xx xxx xxxxx, xxxxxxxx x xxxxxx obsahujícím 3X-XxX. Xx xxxxx xxxxxxxxx xxxx xx mělo xxx médium z xxxxx xxxxxxxxxx x xxxxx poté mohou xxx xxxxxxxxxx x xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx, aby xxxx snížena xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx xx xxxx xxxxxxx, fixují a xxxxxx. Při xxxxx xxxxxxxxx xxxx nemusí xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx do autoradiografické xxxxxx, xxxxxxxx se x temnu (xxxx. x xxxxxx 7 xx 14 xxx), xxxxxxxx se, xxxxxx x spočítají xx xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx zvířete xx xxxxxxxx dva xx tři preparáty.

1.5.8 Xxxxxxx

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

Xxxx xxxxxxxxx xxx xx měly xxx preparáty kódovány. Xxxxxxxxx xx vyšetřuje 100 xxxxx xx xxxxx xxxxx alespoň xx xxxx preparátů; xxxxxxxxx xxxx xxx 100 buněk/zvíře by xxxx být xxxxxxxxxx. Xxx počítání xxx xx jádra x X-xxxx xxxxxxxxxxx, ale xxxxx xxxxx x X-xxxx může xxx xxxxxxxxxx.

Xxxxxxxx 3H-TdR xxxxxxxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx doložené navrstvením xxx stříbra xx xxxx být xxxxxxxxx xxxxxxx metodou.

Počet xxxxx xx stanoví z xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (xx) x x xxŭxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (xx) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx xx xx xxxxxxx xxx xxxxx xxxxx pro nejsilněji xxxxxxxxx oblast xxxxxxxxxx, xxxx xxŭxxxxx xxxxxxx xxxx xx tří xxxxxxx vybraných xxxxxxx x xxxxxxxxx dotyčných xxxxxxxxx jader. xx xxxxxxxxxxxxx zdŮvodnění xxxxx xxx použity x xxxx xxxxxxx stanovení xxxxx xxxxx (např. xxxxxxxx xxxxxx xxxxx) (6).

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx xx xxx xxxxxxx údaje xxx xxxxxxxxxx preparáty x xxxxxxx. Údaje by xxxx xxx xxxx xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx hodnoty XX xx xxxxxxx XX xx xxx xxx xxxxxxxx pro xxxxxx buňku, pro xxxxx xxxxx a xxx xxxxxx dávku x xxx čistý xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX). Xxxxxxxx xxxx počítány "xxxxxxxxxx" buňky, xxxx xx xxx kritéria xxx definování "xxxxxxxxxxxx" xxxxx odůvodněna a xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx statistickými xxxxxxxx. Xxxx-xx být xxxxxxx, xxxx xx xxx xxxxxxxxxxx testy xxxxxxx a odůvodněny xxxx xxxxxxxxxx xxxxxx.

2.2 XXXXXXXXX A INTERPRETACE XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx odpověď patří:

pozitivní	i)	hodnota XXX leží xxx xxxxxxxx xxxxxx, která xx xxxxxxxxxx xx xxxxxxx dosavadních xxxxx xxxxxxxxxx;
xxxx	xx)	xxxxxxx XXX xx xxxxxxxx xxxxx xxx xxxxxxx pro xxxxxxxxx xxxxxxxx;
xxxxxxxxx	x)	xxxxxxx XXX xxxx xx dosavadní xxxxxxx xxxxxxx xxxx xxx xx;
xxxx	xx)	xxxxxxx XXX není xxxxxxxx xxxxx xxx xxxxxxx pro xxxxxxxxx xxxxxxxx.

Xxxx xx xxx xxxxxxxxx xxxxxxxxxx relevance xxxxx, xx. xxxx xx být xxxxx x úvahu xxxxxxxxx, xxxx xxxx variabilita xxxxxx, vztah xxxxx x xxxxxxxx x xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Statistická xxxxxxxxxx xx xxxx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx bez xxxxxx xx xx, kolikrát xx experiment opakován.

Pozitivní xxxxxxxx zkoušky xx XXX x jaterních xxxxxxx savců in xxxx znamenají, že xxxxxxxx xxxxx indukuje x xxxxxxxxx buňkách xxxxx xx xxxx xxxxxxxxx DNA, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx XXX in xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxxxx touto zkouškou.

Měla xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx xxxxxxxx látka xxxxxxx do xxxxxxxx xxxxx xxxx. do xxxxxx xxxxx (xxxx. xxxxxxxxx toxicita).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x pohlaví xxxxxx,

- zdroj, podmínky xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx hmotnost xxxxxx xx xxxxxxx xxxxxxx, xxxxxx rozpětí xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx odchylky xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (vehikulum/rozpouštědlo) kontroly,

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

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- zdůvodnění xxxxxxx xxxxxxxx,

- popřípadě xxxxxx ověření, zda xx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx nebo xx xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx x kultivace xxxxxxxxx xxxxx,

- použitá xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x počet xxxxxxxxxxx xxxxx,

- kritéria xxxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxxx xxxxxxx počtu xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx a xxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxx, x xxxxx xxxxx xxx, jednotlivě pro xxxxxxxxx, xxxxxxx a xxxxxxx,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné statistické xxxxxxxxx,

- xxxxxx xxxxxxxx,

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

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

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

- xxxxx xxxxx v X-xxxx, xx-xx xxxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. Xxxxxxx, X. X., Xxxxxxxxx, X., Xxxxxx, X. X. (1985), Xx Xxxxxxxxxx of the Xx vivo Rat. Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.

2) Xxxxxxxxxxx, X. E., Xxxxx, X., Bermudez, X., Xxxxxxxx, X., Mirsalis, X., Probst, G., Xxxxxxxx, X. (1987), X Xxxxxxxx xxx Xxxxx for xxx Xx vivo Xxx Xxxxxxxxxx DNA Repair Xxxxx, Mutatation Res., 189, 123-133.

3) Xxxxxxxx, X. C., Xxxxxx, X., Xxxxx, J., Xxxxxxx, X. X., Xxxxxxxxx, X., Benford, X. X., Dean, X. X., Mitchell, X. xx X. (1993), Xx xxxx Xxx Xxxxx XXX Xxxxx, xx: Kirkland X. J., Xxx X., (eds), Supplementary Xxxxxxxxxxxx Xxxxx: XXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Part XX xxxxxxx, Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Port Chester, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Xxxx, X. X., Andrac, X., Xxxxxxxxx. X., Xxxxxxxxx, B., Xxxxxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, X., XxXxxxx, X. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx of XXX Xxxxx In vitro xxx Xx xxxx, Xxxxx. Xxx., 312, 263-285.

5) Fautz, X., Xxxxxxx, X., Xxxxxxxxxx, X., Hechenberger-Freudl, X. (1993), Xxxxxxxxxx xx xxx Xxxxxxxx Between xxx Xxxxxxx Xxxxxxxxx xxx xxx Xxxxxxxxxx xx Freshly Xxxxxxxx Xxx Xxxxxxxxxxx Xxxx xxx xxx Xx xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (UDS), Xxxxxxxxxx Xxx., 291, 21-27.

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

XXXXXXX 5

XXXXXX POŽADAVKY XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX LÁTEK X XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/ES, Úř. xxxx. X 332, 28. 12. 2000, x. 81.

XXXXXXX 6

"

PŘÍLOHA IX

ČÁST X

xxxxxxxx týkající xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 odst. 1 xxxx. x) xxxx směrnice, xxxx xxx xxxxx o xxxxxxxxx xxxxxx xxxxxxxxxx xxxxx, x xxxxx xx xxxxxxx xxxxxx xxx xxxxxxxxxx (Xn; X 65) x xxxxx jsou xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx xx xxx xx xxxxx xxxxxxxx xxxx x xxxxxxxx xxxxxxxxxx aerosolovým rozprašovačem, xxxxxxxx xxxxxxx odolnými xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxx na xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx požadavky xxxxx XXX 8317 (xxxxxx ze dne 1. xxxxxxxx 1989) "Xxxxx xxxxxx dětem — Požadavky xx xxxxxxxxx uzavíratelné xxxxx x xxxxxx xxxxxx xxxxxxxx" xxxxxxxx Mezinárodní xxxxxxxxxx pro xxxxxxxxxxx (XXX).

2. Xxxxxxxxx xxxxxxxxxxxxxx xxxxx

Xxxxxxx odolné xxxxx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx neuzavíratelných xxxxxxx xxxx splňovat xxxxxxxxx xxxxx CEN XX 862 (vydání x března 1997) "Xxxxx — Xxxxx xxxxxx dětem — Xxxxxxxxx a zkušební xxxxxxx xxx opakovaně xxxxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxxxxxxxxx výrobků" xxxxxxxx Xxxxxxxxx výborem xxx normalizaci (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx shody x xxxx xxxxxxxxx xxxxxxx xxxxx osvědčovat xxxxx xxxxxxxxxx, xxxxx xxxxxxx xxxxxxxx xxxxx xxxx XX 45000.

2. Xxxxxxxxxx případy

Je-li zřejmé, xx xxxx xx xxxxxxxxxx xxxxxxxx pro xxxx, xxxxx xx xxxxxxx xxxxxx x xxxxxx xxx xxxxxx xxxxxxxx, nemusí být xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx případech x xxxxx xxxxxxxx oprávněné xxxxxx k pochybám x xxxxxxxxxxx xxxxxxx xxx xxxx, může xxxxxxxxxxxx orgán xxxxxxxxx, xxx osoba odpovědná xx xxxxxxx výrobku xx xxx předložila xxxxxxxxxx xxxxxx laboratoří xxxxx xxxx. 3 xxxx 1 konstatující, xx xxx

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

xxxx

- xx uzávěr byl xxxxxxx x xxx xxxxxxx vyhovujícím xxxxx xxxx xxxxxxxxx xxxxx.

XXXX X

Xxxxxxxx xxxxxxxx se xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx xxxxxxxxxxx xxx hmatatelné výstrahy xxxx být v xxxxxxx x xxxxxx XX XXX 11683 (xxxxxx x xxxx 1997) "Xxxxx — Xxxxxxxxxx výstrahy xxxx xxxxxxxxxx — Xxxxxxxxx".

"

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