Group H-4

化学構造　(Chemical Structure)

● Hydrocotarnine-HCl （ヒドロコタルニン・塩酸）
　　 CAS： 5985-55-7　 　　Medicine　　MW: 257.72　　

AM	Sal.	Max (?)	□	1)
CA	CHL/IU	Max ( 0.25 mg/ml, -S9), 24, 48h　(No data for +S9)	△	2)

1) Natl. Inst. Hygien. Sci., Tokyo (?)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

● Hydroflumethiazide （ヒドロフルメチアチド）
　　 135-09-1　Medicine 　 331.29

AM	Sal.	Max (?)	□	1)
CA	CHL/IU	Max ( 2.0 mg/ml, -S9), 24, 48h (No data for +S9)	□	2)

1) Natl. Inst. Hygien. Sci., Tokyo (?)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998)   (Tables in English)

● Hydrogenated terphenyls （水素化テルフェニール）
　　　61788-32-7　 241 (Average)

AM	Sal.	Max (?) (±S9)	□	1)
SM	CHO	Max (?) (±S9)	□	1)
UDS	Rat/hepatocytes	Max (?)	□	1)
CAv	Rat/BM	Max (?)	□	1)

1) Farr CH: Personal communication to ACGIH, Monsanto Company, St. Louis, MO (1987)

● Hydrogen cyanide　
　　　　74-90-8　Industry　 27.03 (Relative)
 
【Note】 ( Cited from CICADS Document, 61, 2004)

Sodium cyanide was not mutagenic in Salmonella typhimurium strains TA100, TA1535, TA97, or TA98 with or without exogenous metabolic activation (NTP, 1993). Potassium cyanide was not mutagenic in five strains (TA1535, TA1537, TA1538, TA98, and TA100) of S. typhimurium with or without metabolic activation (De Flora, 1981). Hydrogen cyanide induced mutations in S. typhimurium TA100 in the absence of S9 activation, but was not mutagenic to strain TA98 with or without S9 activation (Kushi et al., 1983). ACH did not induce mutations in S. typhimurium strains TA1535, TA1537, TA1538, TA100, or TA98 in a plate incorporation assay or at concentratons of 100-950 μg/ml in a CHO/HGPRT assay (Monsanto Co., 1983b,c).    DNA repair tests in Escherichia coli WP67, CM871, and WP2 with potassium cyanide were negative (De Flora et al., 1984). Potassium cyanide induced both time- and dose-dependent DNA fragmentation accompanied by cytotoxicity in rat thymocytes in vitro. Cyanide also induced DNA damage in baby hamster kidney cells (BHK-21) in vitro, where, unlike thymocytes, internucleosome DNA fragmentation was not observed (Bhattacharya & Rao, 1997). The cytotoxic mode of double strand breaks in the pathogenesis of DNA fragmentation was studied by Vock et al. (1998), employing an A549 human epithelial-like lung carcinoma cell line treated with potassium cyanide. Induction of double strand breaks by potassium cyanide was observed only after cell viability was reduced to less than 60%, indicating that double strand breaks were the consequence of extragenomic damage, as a secondary effect of high cytotoxicity in combination with cell lethality.    Sodium cyanide was a highly effective inducer of germline aneuploidy in Drosophila (Osgood & Sterling, 1991).    No statistically significant increases in the frequency of chromosomal aberrations or changes in mitotic index compared with control values were found in bone marrow cells from four groups of 24 male and 24 female Sprague-Dawley rats administered a single dose of ACH by oral gavage at levels of 0, 1.5, 5, or 15 mg/kg body weight with preparation intervals of 6, 12, and 24 h post-administration (Monsanto Co., 1984b).    No testicular DNA synthesis inhibition was detected in mice after a single oral potassium cyanide dose of 1 mg/kg body weight (Friedman & Staub, 1976). References: ・NTP, 1993 NTP (1993): Sodium cyanide administered in drinking water toF344/N rats and B6C3F1 mice. Research Triangle Park, NC, National Institutes of Health, National Toxicology Program (Toxicology Report Series No. 37; ・De Flora S (1981): Study of 106 organic and inorganic compounds in Salmonella/microsome test. Carcinogenesis, 2: 283-298. ・Kushi A, Matsumoto T, Yoshida D (1983): Mutagen from gaseous phase of protein pyrolyzate. Agricultural and Biological Chemistry, 47: 1979-1982 ・Monsanto Co. (1983b): In-vivo bone marrow chromosome study in rats. St. Louis, MO, Monsanto Co. (Report HL-83-195; US EPA/OPTS Public Files No. 878216400). ・Monsanto Co. (1983c): Salmonella typhimurium/mammalian microsome plate incorporation assay with compound (ACH). St. Louis, MO, Monsanto Co. (Report PK-83-204; US EPA/OPTS Public Files No. 878216403). ・De Flora S, Camoirano A, Zanacchi P, Bennicelli C (1984): Mutagenicity testing with TA97 and TA102 of 30 DNA-damaging compounds, negative with other Salmonella strains. Mutation Research, 134: 159-165. ・Bhattacharya R, Rao PVL (1997): Cyanide induced DNA fragmentation in mammalian cell cultures. Toxicology, 123:207?215. ・Vock EH, Lutz WK, Hormes P, Hoffmann HD, Vamvakass A (1998): Discrimination between genotoxicity and cytotoxicity in the induction of DNA double-strand breaks in cells treated with etoposide, melphalan, cisplatin, potassium cyanide, Triton X-100, and gamma-irradiation. Mutation Research, 413: 83-94. ・Osgood C, Sterling D (1991): Dichloroacetonitrile, a by-product of water chlorination, induces aneuploidy in Drosophila. Mutation Research, 261(2) 85-91. ・Friedman MA, Staub J (1976): Inhibition of mouse testicular DNA synthesis by mutagens and carcinogens as a potential mammalian assay for mutagenesis. Mutation Research, 37: 67-76.

● Hydrogen peroxide 　（過酸化水素）
　　　　7722-84-1　Industry/Medicine 　 34.02

AM	Sal.	Max (0.1 mg/plate, -S9)	□	1,2)
YM	N. crassa	Min ( 20 mM, -S9	○	3)
YM	S. cerev.	Min ( 0.1 mg/ml, -S9	○	4)
CA	CHL/IU	Min ( 0.063 mg/ml, -S9), 24, 48h　(No data for +S9); D20=0.12; TR=230	◎	5)

1) Ishidate MJr. et al.; Mutagens & Toxicity, 4, 10-19 (1981) (in Japanese)
2) Kawachi T., et al.: Montesano R et al. (Eds), IARC Sci. Pub., Lyon, pp. 323-330 (1980)
3) Auerbach C & Ramsey D: Mol. Gen. Genet., 117, 1-13 (1972)
4) Thacker J: Mutation Res., 33, 147-156 (1975)
5) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

● Hydrogen sulfide （硫化水素）
　　　　7783-06-4　 34.08

AM

Sal.

Min (?) (-S9)

○w

1)

1) Gocke E, et al,: Mutation Res., 90, 91-109 (1981)

【Note】 ( Cited from CICADS Document, 61, 2004)

The genotoxicity of hydrogen sulfide has been inadequately investigated. No mutagenicity was observed in the only available study, an Ames test with Salmonella typhimurium TA97, TA98, and TA100 strains with hydrogen sulfide at 17, 57, 175, 582, and 1750 μg/plate, either with or without S9 liver fractions from male Syrian Golden hamsters or Sprague-Dawley rats that had been induced with 500 mg Aroclor 1254/kg body weight (US EPA, 1984). The toxic potential of hydrogen sulfide was not tested in this study. References ・US EPA (1984) Validation of chemical and biological techniques for evaluation of vapors in ambient air/mutagenicity testing of twelve (12) vapor-phase compounds. Report to the Health Effects Research Labouratory, US Environmental Protection Agency, Research Triangle Park, NC, by Hughes TJ, Sparacino C, Frazier S, Research Triangle Institute, Research Triangle Park, NC (EPA-600/1-84-005; NTIS Publication No. PB84-164219

●α-Hydro-ω-hydroxypoly(oxy-1,4-butanediyl
　　　　 25190-06-1　Industry 　 (av,) 600-710

AM

Sal/E. coli

Max( 10.0 mg/plate, ±S9)

□

1)

1) Ministry of Labour, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JETOC (Ed.) Suppl. 2 (2000) (Tables in English)

● Hydroquinone 　(1,4-Dihydroxybenzene)（ハイドロキノン）
　　　　123-31-9　Industry 　 110.11

AM	Sal.	Max ( 0.25 mg/plate,±S9)	□	1, 2, 3)
AM	Sal.	Min ( 500 nmol/plate, -S9)	○	4)
AM	Sal.	Max ( 0.01 mg/plate,±S9)	□	5)
AM	Sal.	Max ( 1.0 mg/plate,±S9)	□	6, 7)
MLA	L5178Y	Min ( 0.01 mg/ml, -S9)	○	8, 9)
CA	A. mudulans	Min ( 0.39 mg/ml, -S9)	○	10)
CA	CHO	Min (?),  + S9	○	11)
CA	CHL/IU	Min ( 0.002 mg/ml, -S9), 24h; D20= 0.0012; TR= 14000	◎	12)
CA	Hum. lym.	Min ( 8.25 mg/L, -S9)	○	13-16)
SCE	Hum. lym.	Min ( 110 mg/L, +S9)	○	17)
SCE	Hum. lym.	Min ( 33 mg/L, -S9)	○	15)
SCE	V79	Min ( 22 mg/L, -S9)	○	7)
SCE	CHO	Min (?), ±S9	○	11)
DNA	E. coli	Min (?), -S9	○	18)
DNA	Sal.	Min (?), -S9	○	19)
SLRLv	Drosophila	Max ( 50-100 ppm)	□	5)
SMv	Mice/Spot test	Max ( 110 mg/kg, ip )	□	20)
CAv	Mice, BM	Min ( 100 mg/kg, ip )	○	21, 22)
MNv	Mice, BM	Min ( 200 mg/kg , or )	○	23)
MNv	Mice/BM	Min ( 100 mg/kg, ip )	○	24, 25)
MNv	Mice/BM	Min ( 100 mg/kg, sc )	○	26)
DNAv	Rats	Min ( 200 mg/kg, or ), for 7w	○	27)
DNAv	Mice	Max ( 75 mg/kg, ip )	□	28)

1) NTP Technical Report: TR 366; NIH, Pub. No. 90-2821, Research Triangle Park, NC (1989)
2) Sakai M, et al,: Mutation Res., 156, 61-67 (1985)
3) Haworth S., et al., Environ. Mutagen., 5, 3-142 (1983)
4) Hakura A., et al., Mutation Res., 371, 293-299 (1996)
5) Gocke E., et al., Mutation Res., 90, 91-109 (1981)
6) Florin I., et al., Toxicol. 18, 219-232 (1980)
7) Glatt H., et al., Environ. Health Perspect., 82, 81-89 (1989)
8) McGregor DB., Environ. Mol. Mutagen., 11, 91-118 (1988)
9) Pellack-Waker P. & Blumer., Mol Pharm., 30, 42-47 (1991)
10) Crebelli R., et al., Mutagenesis, 6, 131-136 (1987)
11) Galloway SM, et al,: Environ. Molec. Mutagen., 10 (Suppl. 10), 1-175 (1987)
12) Ministry of Labour, Japan; Japan Bioassay Res. Center, Ann. Rep. (2005)(Tables in English)
13) Yager JW., et al., Cancer Res., 50, 383-399 (1990)
14) Robertson MC et al., Mutation Res., 249, 201-209 (1991)
15) Erexson GL., et al., Cancer Res., 45, 2471-2477 (1985)
16) Morimoto K & Wolff S., Cancer Res., 40, 1189-1193 (1983)
17) Morimoto K., et al., Mutation  Res., 119, 355-360 (1983)
18) Bilimoria MH., Mutation Res., 31, 328 (1975)
19) Nakamura S., et al., Mutation Res., 192, 239-246 (1987)
20) Gocke E, et al,: Mutation Res., 17, 201-212 (1983)
21) Xu W & Adler ID Mutagenesis, 5, 371-374 (1990)
22) Pacchierotti F., et al., Mutagenesis, 6, 307-311 (1991)
23) Gad-El-Karim MM., et al., Am. J. Indust. Med., 7, 475-484 (1985)
24) Adler ID & Kliesch U., Mutation Res., 234, 115-123 (1990)
25) Barale R et al., Mutation Res., 244, 15-20 (1990)
25) Ciranni R., et al., Mutation Res., 208, 61-67 (1988)
26) Tunek K, et al,: Chem. Biol. Interact., 39, 129-138 (1982)
27) Stenius U., et al., Cacrinogenesis, 10, 593-599 (1989)
28) Kolchana P., et al., Cancer Res., 53, 1023-1026 (1993)

● 3-Hydroxyanthranilic acid （３−オキシアントラニル酸）
　　　　548-93-6 　Labouratory　　 153.14

AM	Sal.	Max (?)	□	1)
CA	CHL/IU	Max (0.25 mg/ml, -S9), 24, 48h　(No data for +S9)；	□	2)

1) Natl. Inst. Hygien. Sci., Tokyo, Japan (?)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

● 4-Hydroxybenzoid acid (p-Hydroxybenzoic acid)
　　　　99-96-7 　Industry　　 138.12

AM

Sal/E. coli

Max( 5.0 mg/plate, ±S9)

□

1)

1) Ministry of Labour, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JETOC (Ed.) Suppl. 2 (2000) (Tables in English)

● (2-Hydroxyethyl) trimethylammonium chloride (Choline chloride)
　　　　67-48--1　Industry　　 139.63

AM

Sal./E. coli

Max ( 5.0 mg/plate, ±S9)

□

1)

1) Ministry of Labour, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JETOC (Ed.) Suppl. (1997) (Tables in English)

● 2-Hydroxyethyl acrylate　（アクリル酸＝２−ヒドロキシエチル）
　　 818-61-1　Industry　　 116.12

AM	SalE. coli	Min ( 1,250 mg/plate ±S9） spa= 113 (E.coli)	○	1)
CA	CHL/IU	Min ( 0.01 mg/ml, -S9), 24; D20=　0.0082;  TR=　3500	◎	2)

1) Ministry of Labour, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JETOC (Ed.) Suppl. 3, pp. 181 (2005) (Tables in English)
1) Ministry of Labour, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JETOC (Ed.) Suppl. 3, pp. 220 (2005) (Tables in English)

● L-Hydroxy-kynurenine （L-オキシキヌレニン）
　　 606-14-4　Labouratory　　 224.24

AM	Sal.	Max (?)	□	1)
CA	CHL/IU	Max ( 0.125 mg/ml, -S9), 24, 48h 　(No data for +S9)；	□	2)

1) Natl. Inst. Hygien. Sci., Tokyo ?
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

●N-Hydroxymethyl dimethyl phosphonopropionamide　(Pyrovatex CP)
　　　 20120-33-6　　 Industry　　 226.17

AM	Sal	Max (?)	□	1)
CA	CHL/IU	Min (1.0 mg/ml, -S9), 24h(No data for +S9)； D20=1.9; TR=8.	○w	2)

1) Natl. Inst. Hygien. Sci., Tokyo, Japan (?)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)