Group E-1

化学構造　(Chemical Structure)

● Elemental mercury and inorganic mercury compounds (水銀・無機化合物)  (See also M-3)
　　　CAS： 7439-97-6　　Industry  　MW: 200.59  
【Note】　(Cited from CICADs Documents 50,  2003)

No data are available on point mutations in bacteria after exposure to inorganic mercury compounds.    Information on other genotoxicity is available mostly on mercuric chloride. Mercuric chloride binds to the chromatin of rat fibroblasts (Rozalski & Wierzbicki 1983) and Chinese hamster ovary cells (Cantoni et al., 1984a,b). Mercuric chloride can damage DNA in rat and mouse embryo fibroblasts (Zasukhina et al., 1983), and several studies using Chinese hamster ovary cells have demonstrated that mercuric chloride induces single-strand breaks in DNA (Cantoni et al., 1982, 1984; Cantoni & Costa, 1983; Christie et al., 1984, 1986). Strand breaks have also been observed in rat and mouse embryo fibroblasts (Zasukhina et al., 1983). Howard et al. (1991) observed an increase in chromosomal aberrations and sister chromatid exchange in Chinese hamster ovary cells treated with mercuric chloride. Oberly et al. (1982) reported that doses of mercuric chloride (4.4 and 5.9 μg mercury/ml) approaching severely cytotoxic levels induced a weak mutagenic response in mouse lymphoma L5178Y cells in the presence of auxiliary metabolic activation. Mercuric chloride also induced spindle disturbances in Indian muntjak fibroblasts and human lymphocytes in vitro, cell transformation in Syrian hamster cells in vitro (Casto et al., 1979; Verschaeve et al., 1984), and sister chromatid exchanges and chromosomal aberrations in human lymphocytes in vitro (Morimoto et al., 1982; Verschaeve et al., 1985). Mercuric chloride was positive in the Bacillus subtilis rec-assay (Kanematsu et al. 1980), but failed to enhance lethality in a DNA repair-deficient strain of Escherichia coli (Brandi et al., 1990).    Mercurous chloride was also positive in the Bacillus subtilis rec-assay (Kanematsu et al., 1980).    Mercuric acetate induced chromosomal aberrations in mouse oocytes in vitro at a concentration of 35 mg/litre (Jagiello & Lin, 1973), but failed to induce anchorage-independent growth in human foreskin fibroblasts in vitro (Biedermann & Landolph, 1987).    A dose-related increase in chromosomal aberrations was observed in the bone marrow of mice administered a single oral dose of mercuric chloride at levels of at least 4.4 mg mercury/kg body weight (Ghosh et al., 1991). Chromatid breaks were the most common aberration. In contrast, no increase in chromosomal aberrations was observed in spermatogonia of mice or oocytes of Syrian hamsters after an equally large or larger parenteral dose (Poma et al., 1981; Watanabe et al., 1982).    Mercuric chloride administered orally for 12 months (0.18?1.8 mg mercury/kg body weight per day) induced a weak but dose-related increase in dominant lethal mutations (Zasukhina et al., 1983). A weakly positive result in a dominant lethal assay was also reported in an early study in mice after a single intraperitoneal dose (Suter, 1975).    Mercuric acetate failed to induce chromosomal aberrations in mouse oocytes in vivo after subcutaneous or intravenous administration (Jagiello & Lin, 1973). References ・Biedermann KA, Landolph JR (1987) Induction of anchorage independence in human diploid foreskin fibroblasts by carcinogenic metal salts. Cancer Research, 47: 3815-3823. ・Brandi G, Schiavano GF, Albano A, Cattabeni F, Cantoni O (1990) Growth delay and filamentation of Escherichia coli wild-type and rec A cells in response to hexavalent chromium and other metal compounds. Mutation Research, 245: 201-204. ・Cantoni O, Evans RM, Costa M (1982) Similarity in the acute cytotoxic response of mammalian cells to mercury (II) and X-rays: DNA damage and glutathione depletion. Biochemical and Biophysical Research Communications, 108 :614-619. ・Cantoni O, Costa M (1983) ・・・Correlations of DNA strand breaks and their repair with cell survival following acute exposure to mercury(II) and X-rays. Molecular Pharmacology, 24: 84-89 ・Cantoni O, Christie NT, Robison SH, Costa M (1984a) Characterization of DNA lesions produced by HgCl2 in cell culture systems. Chemico-Biological Interactions, 49: 209-224. ・Cantoni O, Christie NT, Swann A, Drath DB, Costa M (1984b) Mechanism of HgCl2 cytotoxicity in cultured mammalian cells. Molecular Pharmacology, 26: 360-368. ・Casto BC, Myers J, DiPaolo JA (1979) Enhancement of viral transformation for evaluation of the carcinogenic or mutagenic potential of inorganic metal salts. Cancer Research, 39: 193-198. ・Christie NT, Cantoni O, Evans RM, Meyn RE, Costa M (1984) Use of mammalian DNA repair-deficient mutants to assess the effects of toxic metal compounds on DNA. Biochemical Pharmacology, 33: 1661-1670 ・Christie NT, Cantoni O, Sugiyama M, Cattabeni F, Costa M (1986) Differences in the effects of Hg(II) on DNA repair induced in Chinese hamster ovary cells by ultraviolet or X-rays. Molecular Pharmacology, 29: 173-178. ・Ghosh AK, Sen S, Sharma A, Talukder G (1991) Effect of chlorophyllin on mercuric chloride-induced clastogenicity in mice. Food and Chemical Toxicology, 29(11):777?779.・Howard W, Leonard B, Moody W, Kochhar TS (1991) Induction of chromosome changes by metal compounds in cultured CHO cells. Toxicology Letters, 56(1-2): 179-186. ・Jagiello G, Lin JS (1973) An assessment of the effects of mercury on the meiosis of mouse ova. Mutation Research, 17: 93-99 ・Kanematsu N, Hara M, Kada T (1980) Rec assay and mutagenicity studies on metal compounds. Mutation Research, 77: 109-116. ・Morimoto K, Iijima S, Koizumi A (1982) Selenite prevents the induction of sister-chromatid exchanges by methyl mercury and mercuric chloride in human whole-blood cultures. Mutation Research,102: 183-192. ・Oberly TJ, Piper CE, McDonald DS (1982) Mutagenicity of metal salts in the L5178Y mouse lymphoma assay. Journal of Toxicology and Environmental Health, 9: 367-376. ・Poma K, Kirsch-Volders M, Susanne C (1981) Mutagenicity study on mice given mercuric chloride. Journal of Applied Toxicology, 1: 314-316. ・Rozalski M, Wierzbicki R (1983) Effect of mercuric chloride on cultured rat fibroblasts: Survival, protein biosynthesis and binding of mercury to chromatin. Biochemical Pharmacology, 32: 2124-2126. ・Suter KE (1975) Studies on the dominant-lethal and fertility effects of the heavy metal compounds methylmercuric hydroxide, mercuric chloride and cadmium chloride in male and female mice. Mutation Research, 30: 365-374. ・Verschaeve L, Kirsch-Volders M, Susanne C (1984) Mercury-induced segregational errors of chromosomes in human lymphocytes and in Indian muntjak cells. Toxicology Letters, 21: 247-253. ・Verschaeve L, Kirsch-Volders M, Hens L, Susanne C (1985) Comparative in vitro cytogenetic studies in mercury-exposed human lymphocytes. Mutation Research, 157:221?226. ・Watanabe T, Shimada T, Endo A (1982) Effect of mercury compounds on ovulation and meiotic and mitotic chromosomes in female golden hamsters. Teratology, 25: 381-384. ・Zasukhina GD, Vasilyeva IM, Sdirkova NI, Krasovsky GN, Vasyukovich LYa, Kenesariev UI, Butenko PG (1983) Mutagenic effect of thallium and mercury salts on rodent cells with different repair activities. Mutation Research, 124: 163-173.

 ● Elderberry pigment （ニワトコ色素）
　　　 Food/Natural　　　　　　　

AM	Sal	Min (?)	○	1)
CA	CHL/IU	Max ( 6.0 mg/ml, -S9), 24, 48h　(No data for + S9)	△	2)
MNv	Mice	Max (?)	□	3)

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

● Enramycin-HCl 　（エンラマイシン塩酸塩）
　　　11115-82-5　　Pesticide 　　　　

CA

CHL/IU

Max ( 1.0 mg/ml, -S9), 24-48h　(No data for +S9)

□

1)

1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test  In Vitro, LIC, Tokyo (1998) (Tables in English)

● Endosulfan （エンドスルファン）(Thiodan)
　　115-29-7 　　Pesticide　　　　 406.95

YM

Yeast

Max (?)

□

1)

1) Fahrig R.: IARC, Sci. Pub., 10, 161-181 (1974)

 US-NTP Genotoxicity Screening：
○ Ames Test：　□
○ MLA （Ｌ−5178Ｙ）:　○
○ CA Test with CHO Cells：　□
○ SCE Test with CHO Cells:：　□

● Endrin　（エンドリン)　　
　 　　72-20-8　　　Insecticide 　 　 380.93

YM	Yeast	Max (?)	□	1)
CA	Barley (オオムギ）	Max (1000 ppm)	□	2)

1) Fahrig R.: IARC, Sci. Pub., 10, 161-181 (1974)
2) Wuu KD. & Grant WF.: Cytologia, 32, 31-41 (1967)

 US-NTP Genotoxicity Screening：
 ○ Ames Test:□
 ○ MLA Test: □
 ○ CA Test with CHO Cells:　□
 ○ SCE Test with CHO Cells:　□

● Enflurane　（エンフルラン）　　
　 　 13838-16-9　　Drug/Anesthetic　　 184.50　　　　　

AM

Sal

Max （15%）

□

1

1) Waskell L.: Mutation Res., 57, 141 (1978)

  IARC Carcinogenicity Criteria：　
　Group B3　（Not calssfiable as to its carcinogenicit to humans）

【Note】 (Cited from IARC Monograph, Suppl., 6 (1987)

No adequate data were available on the genetic and related effects of this compound in humans. It did not induce DL mutations in mice in vivo or SCEs in cultured CHO cells. It was not mutagenic to bacteria. (IARC Monographs, 11, 285)

● L-Ephedrine-HCl 　（L-エフェドリン）
　　 50-98-6　　Drug/Anesthetic　　 201.70

AM	Sal	Max (?)	□	1
CA	CHL/IU	Max ( 0.25 mg/ml ), 48h	□	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)

● Epichlorohydrin　（エピクロロヒドリン）
　 　　106-89-8　　 Industry　　 92.53

AM	Sal	Min (50μg/plate, ±S9) spa=5660 (TA100)	◎	1-5)
YM	S. bombe	Min (3.2 mM, ±S9)	○	6)
YM	N. crassa	Min (?)	○	7, 8)
REC	B. subtilis	Min (?)	○	9)
DNA	E. coli	(DNA-repair)	○	10)
YM	S. cerevisiae	Min (?)	○	11)
HMA	E. coli	Min (?)	○	12)
CA	CHL/IU	Min ( 0.0625 mg/ml, -S9), 24h; D20= 0.054; TR= 890	◎	13)
CA	Hum LY	Min ( 0.019 mg/ml, -S9), 48h	○	14)
CA	CHO	Min ( 0.12 mg/ml, -S9), 1-12h	○	15)
CA	Rat/RL1	Min ( 0.005 mg/ml, -S9), 24h	○	16)
CA	C3H10T1/2	Min ( 0.25-1.0 mM)	○	17)
SCE	CHO	Min ( 0.0048 mg/ml, ±S9)	○	22)
SCE	V79	Min ( 0.023 mg/ml, -S9)	○	23)
SCE	Human lym.	Min ( 0.009 mg/ml, ±S9)	○	24)
SM	Drosophila	(Eye somatic assay) Min (?)	○	18)
SLRLv	Drosophila	Min ( 472 ppm), fed	○	25)
SLRLv	Drosophila	Max ( 0.2%), fed	□	26)
UDS	Rat/hepatocytes	Max ( 0.0046 mg/ml )	□	19)
MNv	Mice/BM	Max ( 230 mg/kg x 2, po)	□	20)
MNv	Mice/BM	Max ( 100 mg/kg x 2, ip)	□	27)
MNv	Mice/BM	Max ( 160 mg/kg x 2, ip)	□	28)
DLv	Mice	Max ( 150 mg/kg, ip)	□	29)
DLv	Mice	Max ( 20 mg/kg x 5, or)	□	30)
CAv	Mice	Min ( 1.0 mg/kg, ip)	○	31)
CAv	Mice	Max ( 200 mg/kg or)	□	30)
SCEv	Mice	Min ( 6 mg/kg, ip)	○w	32)
CT	Balb/c-3T3	Min (?)	○	21)
DNAv	Mouse organs	Min ( 0.6 mg/kg, ip)	○	33)

1) Ishidate MJr (Ed): Data Book for Mutagenicity Tests on Chemicals  in Bacteria, LIC/ Tokyo (1991) (Tables in English)
2) Venitt B & Crofton-Sleigh C: Prog. Mutat. Res., 1, 351-360 (1981)
3) Mohn GR: Environ. Sci. Res., 24, 69-108 (1981)
4) Einestoe P & Sinsheimer J: Environ. Mol. Mutagen., 19, 16 (1992)
5) Canter DA, et al: Environ. Health Perspect., suppl. 2, 347-482 (1993)
6) Rossi AM, et al: Mutation Res., 109, 41-52 (1983)
7) Brockman HE: Environ. Sci., Res., 24, 109-138 (1981)
8) De Serres FJ, et al: Environ. Mutagen.,4..., 398-399 (1982)
9) Kada T: Environ. Sci. Res., 24, 19-26 (1981)
10) Rosenkranz HS: Environ. Sci. Res., 24, 5-18 (1981)
11) Loprieno N: Environ. Sci. Res., 24, 139-150 (1981)
12) Hellmer L & Bolosfoldi G., Mutation Res., 272, 145-160 (1992)
13) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro, LIC, Tokyo (1998)
14) Norppa H, et al,: Mutation Res., 91, 243-250 (1981)
15) Natarajan AT & Van AC: In; Progress in Mutation (Eds) FJ de Serres & Ashby J., Res., Vol. 1, Elsevier/Amsterdam, pp.551-559 (1981)
16) Dean BJ & Danford N: Mutation Res., 64, 329-337 (1979)
17) Duinsk M: Toscicol Lett., 81, 213-221 (1995)
18) Vogel EW & Nivard MJ: Mutagenesis, 8, 57-81 (1993)
19) Probst GS, et al: Environ. Mutagen., 3, 11-32 (1981)
20) Morita T, et al: Mutation Res., 389, 3-122 (1997)
21) Matthews EJ, et al: Environ. Health Perspect., 101 (Suppl.2), 397-482 (1993)
22) Evanc　EL & Michell AD. In: de Serres, FJ  & Ashby j., eds, Evaluation of Short-Term Tests for Carcinogens. Report of Intern. Collab. Prog., Prog. in Mutation Res., Vol 1, pp 538-550 (1981)
23) von der Hude et al., (1991)
24) White AD, Mutation Res., 78, 171-176 (1980)
25) Knaap A.GA.C.,et al,  Mutation Res., 101, 199-208 (1982)
26) Wurgler FE  & Graf U.,   In: de Serres, FJ  & Ashby j., eds, Evaluation of Short-Term Tests for Carcinogens. Report of Intern. Collab. Prog., Prog. in Mutation Res., Vol 1, pp 666-672 (1981)
27) Kirkhart B,  In: de Serres, FJ  & Ashby j., eds, Evaluation of Short-Term Tests for Carcinogens. Report of Intern. Collab. Prog., Prog. in Mutation Res., Vol 1, pp 698-704 (1981)
28) Salamone MF, et al  In: de Serres, FJ  & Ashby j., eds, Evaluation of Short-Term Tests for Carcinogens. Report of Intern. Collab. Prog., Prog. in Mutation Res., Vol 1, pp 686-697 (1981)
29) Epstein SS., et al Toxicol. Appl. Pharmacol., 23, 288-325 (1972)
30) Sram RJ., et al., Biol. Zbl., 95, 451-462 (1976)
31) Rossi AM., et al., Mutation Res., 118, 213-226 (1983)
32) Paika IJ., et al.,  In: de Serres, FJ  & Ashby j., eds, Evaluation of Short-Term Tests for Carcinogens. Report of Intern. Collab. Prog., Prog. in Mutation Res., Vol 1, pp 673-681(1981)
33) Prodi G., et al., Toxicol. Pathol., 14, 438-444 (1986)

【Review】
 1) IARC Monogr. (Suppl. 6), Lyon, France (1987)

  US-NTP Genotoxicity Screening：
 ○　Ames Test ：　○
 ○　MLA (L-5178Y)：　□

 IARC Carcinogenicity Criteria：
 Group 2A　（Probably carcinogenic to humans）

【Note】 (Cited from IARC Monograph, Suppl., 6 (1987)

Epichlorohydrin is a bifunctional alkylating agent. CAs have been observed in workers exposed to this compound , although the studies are difficult to interpret. 　　It induced SCEs in bone-marrow cells but not MNs or DL mutation in mice treated in vivo; equivocal findings were found for CAs. It induced CAs, SCEs and UDS in human cells in vitro. Weakly positive results were obtained in a cell transformation assays in C3H 10T1/2 cells. It induced CAs, SCEs, mutation and DNA strand breaks in rodent cells in vitro. It induced SLRL mutation in Drosophila; aneuploidy, mutation, recombination, gene conversion and DNA damage in fungi;; and mutation and DNA damage in bacteria. (IARC Monographs, 11, 131)

● 2,3-Epoxy-1-propanol （See also G-3）

● Epoxy resin intermediate (Products of metylene bisphenol and chloromethyloxirane)
     58421-55-9　Industry　　 MW: average: 330

AM	Sal/E. coli	Min ( 19.5 μg/plate, -S9); spa= 5 x 103 (TA100, +S9)	◎	1)
CA	CHL/IU	Min ( 0.04 mg/ml, -S9), 24h; D20= 0.0095; TR= 2000	◎	2)

1) Ministry of Labour, Japan: Mutagenicity Test Data on Exist. Chem. Subst., JETOC (Ed.), pp. 328 (1996) (Tables in English)
2) Ministry of Labour, Japan: Mutagenicity Test Data on Exist. Chem. Subst., JETOC (Ed.), pp. 557 (1996) (Tables in English)

● 2,3-Epoxypropyl methacrylate　（2,3-エポキシメタクリレート）(Glycilmethacrylate)
　 （メタクリル酸2,3-エポｐキシプロピル）
　　　106-91-2　Industry　　 142.17

AM	Sal.	Min ( 0.8 mg/plate, ±S9)	○	1)
AM	Sal.	Min ( 10.7 mg/plate ±S9)	○	2)
AM	Sal.	Min ( 1.0 mg/plate, ±S9)	○	3)
AM	Sal.	Min ( 1.0 mg/plate, ±S9)	○	4)
AM	Sal.	Min ( 12.5 mg/plate, ±S9)	○	5)
AM	Sal.	Min ( 0.89 mg/plate, ±S9)	○	6)
MB	K.. pneumomiae	Min ( 0.095 mg/ml, -S9)	○	7)
CA	CHL/IU	Min ( 0.025 mg/ml, -S9), 24h	○	14)
SM	CHO	Min ( 0.35 mg/ml, +S9)	○	8)
SM	V79	Min ( 0.028 mg/ml, -S9)	○	5)
CA	CHL/IU	Min ( 0.05 mg/ml, ±S9)	○	9)
DNA	E. coli	Min ( 0.095 mg/ml, -S9)	○	10)
UDS	Human lym.	Min ( 2.2 mg/ml, -S9)	○	11)
SCE	V79	Min ( 0.044 mg/ml, -S9), for 2h	○	12)
CT	Syr. hamster	Min ( 0.0036 mg/ml, -S9)	○	13)
MNv	Mice, BM	Min ( 1.0 g/kg, or )	○	14)
MNv	Mice, BM	Max ( 300 mg/kg, ip )	□	15)
UDSv	Mice/germ cells	Min ( 100 mg/kg, ip ), for 16d	○	11)

1) Haskell Lab. EPA Doc., ID 878220444. OTSO215042 (1982)
2) Litton Bionetics, EPA DOC., ID 98-90009251 (1992)
3)The Goodyear Tire & Rubber, Lab. Rep., 81-4-5.ＥＰＡ DOC., No. 878210412, NTIS OTSO206047 (1981)
4) Canter DA et al., Mutation Res., 172, 105-138 (1986)
5) Schweikl H., et al., Mutation Res.,  415, 119-130 (1998)
6) Ou-Yang GS., et al., J.Hyg. Res., 17, 1-5 (1981)
7) Voogd CE., et al., Mutation Res., 89, 269-282 (1981)
8) E I. Du Pont, Haskell Lab. ,EPA DOC., ID. 878220444, OTSO215042 (1992)
9) Kusakabe M., et al, Mutation Res., 517, 187-198 (1997)
10) von der Hude W., et al., Mutation Res., 231, 205-218 (1990)
11) Xie D-Y., et al., Biomed. Environ. Sci., 3, 281-289 (1990)
12) von der Hude W., et al., Mutation Res., 249, 55-70 (1991)
13) Xie D-Y., et al., J. Helth. Toxicol. 6, 91-93 (1992) (in Chinese)
14) Ministry of Health, Labor & Welfare, Japan (Ed): Toxicity Testing Reports of Environ. Chemicals, Vol. 5 (1997) (Tables in English)
15) GMA Insustry Group, Dow Chemi. Co., EPA, DOC., ID 44620, OTSO558846, (1990)

● Ergometrine maleate （エルゴメトリン　マレイン酸）
　　　129-51-1 　Medicine 　　 441.48

AM	Sal	Min (?)	○	1)
CA	CHL/IU	Min ( 0.5 mg/ml, ±S9), 3-21h　D20= 0.27; TR= 80	○	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)

● Erwinia mitsuensis gum
　　　　　　 Food/Natural

CA

CHL/IU

Max ( 2.0 mg/ml, -S9), 24h

△

1)

1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test i In Vitro, LIC, Tokyo (1998) (Tables in English)

● Erythorbic acid (Isoascorbic acid)
　　　　89-65-6　　 Food 176.13

AM	Sal	Max ( 20.0 mg/ml, ±S9), spa=8.1	○w	1)
MNv	Mice	Max ( 1500 mg/kg, ip)	□	2)

1) Ishidate MJr (Ed.), Data Book of Mutagenicity Tests on Chemicals in Bacteria. LIC/Tokyo (1991) (Tables in English)
2) Ishidate MJr, et al.,, Mutagenicity & Toxicity, 5 (6), 579-587 (1982)
 
● Esprocarb 　（フジグラス）　
　　85785-20-2　　Pesticide 　 265.45

REC	B. subtilis	Max ( 26 mg/disk)	□	1)
AM	Sal	Max ( 5 mg/plate ±S9)	□	1)
CA	CHL/IU	Max ( 0.072 mg/ml, ±S9)	□	1)

1) ICI Japan Co. Ltd.: J. Pesticide Sci., 15, 117-120 (1990) (in Japanese)

● Erythorbic acid 　(Isoascorbic acid) （エリソルビン酸）
　　89-65-6 　Food/Insustry　 176.12

AM	Sal	Max (10 mg/plate, ±S9)	△	1
CA	CHL/IU	Max ( 0.25 mg/plate -S9), 24, 48h (No data for +S9)	□	2
MNv	Mice	Max (?)	□	3

1) Ishidate MJr (Ed): Data Book for Mutagenicity Tests on Chemicals  in Bacteria, LIC/ Tokyo (1991) (Tables in English)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro, LIC, Tokyo (1998)  (Tables in English)
3) (?)