Group E-4

化学構造　(Chemical Structure)

● Ethyl cyanoacrylate （シアノアクリル酸エチル；　ECA）　
　　　CAS： 7085-85-0　　Industry　　　MW: 125.12

AM	Sal.	Max (?)	□	1)
MB	Sal. (Spot test)	(Methyl-2-Cyanoacrylate) (Vapor):	○	2)

1) Andersen M., et al.: Mutation Res., 102, 373-381 (1982)
2) Rietveid EC., et al.: Mutation Res., 188, 97-104 (1987)

● Ethylene　（エチレン）　　
　 　　74-85-1　 Industry　 28.0

AM

Sal.

Max (?)

□

1)

1) Hamm TE., et al.: Fund. Appl. Toxicicol., 4, 473-478 (1984)

● Ethylene carbonate  (2-Oxo-1,3-dioxolan) (エチレンカーボナート）
　　  96-49-1　 Industry　　 88.06

AM

Sal./E. coli

Max ( 5.0 /plate, ±S9 )

□

1)

1) Ministry of Labour, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JEOC(Ed.), Suppl. 2., pp.161 (2000) (Tables in English)

● Ethylene chlorohydrin （エチレンクロロヒドリン) (2-Chloroethanol)　　
　　　107-07-3　Industry　 80.52

AM	Sal./E. coli	Min (?)	○w	1,)
AM	Sal./E. coli	Min ( 5.0 mg/plate, ±S9 ); spa= 28.6	○	5)
YM	Yeast	Max (?)	□	2)
MB	K.pneumoniae (鼻硬腫菌):	Min (?)	○	3)
CA	CHL/IU	Min ( 0.3 mg/ml, +S9), 6h D20= 0.26	○	6)
CAv	Rat/BM	Max ( 0.22 ppm), ih	□	4)

1) Rosenkranz HS. & Weodkowski TJ.: J. Agric.Food Chem., 22, 407-409 (1974)
2) Loprieno N., et al.: Cancer Res., 36, 253-257 (1977)
3) Voogd EC. & Vet P.: Experientia, 25, 85-86 (1969)
4) Semenova VN., et al.: Gig. Sanit, 1, 84-85 (1980)
5) Ministry of Labour, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JEOC(Ed.), pp. 186 (1996) (Tables in English)　
6) Ministry of Labour, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JEOC(Ed.), pp. 488 (1996) (Tables in English)　

USA-NTP Genotoxicity Screening :
○ Ames Test:　○
○ MLA: ○
○ CA Test　with CHO cells: ○
○ SCE test with CHO cells: ○
○ Drosophila SLRL Test: □

● 1,1'-Ethylene bis (1-nitrosourea)
　　　　49606-40-8　　　 Medicine　 204.15

CA

CHL/IU

Min ( 0.003 mg/ml, -S9), 24h D20= 0.0064; TR= 6400

◎

1)

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

● Ethylenediamine　（エチレンジアミン； 1,2 ジアミノエタン；1,2-エタンジアミン；　EDA）
　　　 107-15-3　　Industry　　 60.10

AM	E. coli	Min (?)	○	1)
AM	Sal.	Max (?)	□	2)
AM	Sal.	Max ( 1 mg/plate, ±S9 )	□	3)
AM	Sal.	Min ( 3 mg/plate, +S9 )	○w	4)
AM	Sal.	Min ( 6.6 mg/plate, ±S9 )	○	5)
AM	Sal.	Min ( ±S9 )	○	6)
MB	N. crassa (アカパンカビ）	Min (?)	○	7)
SM	CHO	Max ( 0.44 mg/ml, ±S9 )	□	8)
SCE	CHO	Max ( 0.44 mg/ml, ±S9 )	□	8)
UDS	Rat/hepatocytes	Max ( 0.89 mg/ml, -S9)	□	8)
SLRLv	Drosophila	Max ( 20 g/kg, fed)	□	9)
SLRLv	Rats	Max ( 0.5 g/kg, fed), for 23 w	□	4)

1) Hulla JE., et al.: Environ. Mutagen, 3, 332 (1981)
2) McCann J, et al,: Proc. Natl. Acad. Sci. (USA), 72, 5135-5139 (1975)
3) Leung HW, Mutation Res., 320, 31-43 (1994)
4) Slesinski RS., et al., Mutation Res., 124, 299-314 (1983)
5) Haworth S., et al., Environ. Mutagen., Suppl. 1, 3-142 (1983)
6) Hedenstedt A, Mutation Res., 53, 198-199 (1978)
7) de Serres FJ & Malling HV: EMS Newsletter, 3, 36-37 (1970)
8) Slesinski RS., et al.: Mutation Res., 124, 299-314 (1983)
9) Zimmering S., et al., Environ. Mutagen., 7, 87-100 (1985)

  USA-NTP Genotoxicity Screening :
  ○　Ames Test:　○
  ○　SLRL Test in Drosophila : □

【Note】　(Cited from CICADs Documents 15  1999)

Only limited information is available on the genotoxic potential of EDA. There is some evidence that EDA may be mutagenic in bacteria with and without metabolic activation (Hedenstedt, 1978; Hulla et al., 1981; Haworth et al., 1983; Leung, 1994). Although the most recent study (Leung, 1994) appears to be negative, there was a small response in Salmonella typhimurium TA100 and a positive, but not reproducible, response in TA1535. Positive results have also been reported in these strains from the other studies, although only one of these (Haworth et al., 1983) was adequately reported. The only series of studies performed on mammalian cell systems in vitro (gene mutation and sister chromatid exchange in Chinese hamster ovary cells; unscheduled DNA synthesis in rat primary hepatocytes) were consistently negative (Slesinski et al., 1983), although there has been no assay for clastogenic activity. A sex-linked recessive lethal test in Drosophila melanogaster was negative following dosing by feeding or injection (Zimmering et al., 1985). There are no in vivo studies on somatic cells, but a dominant lethal study in rats up to doses inducing signs of toxicity (up to 500 mg EDA.2HCl/kg body weight per day in the diet) was negative (Slesinski et al., 1983).        Although there has been some evidence of mutagenicity in bacterial systems in a few limited studies, the available evidence indicates that EDA is not genotoxic, with all results in mammalian cells in vitro and in vivo (dominant lethal assay) being negative. It should be noted that the overall database is limited, with no assays available for clastogenic activity or for genotoxic potential in somatic cells in vivo. References ・Haworth S, et al., (1983) Salmonella mutagenicity test results for 250 chemicals. Environ. Mutagen.,  Suppl. 1, 3-142. (1983) ・Hedenstedt A ., Mutation Res., 53: 198-199 (1978) ・Hulla J, et al.,  Environ. Mutagen, 3: 332-333.(1981) ・Leung H-W,  Mutation Res., 320: 31-43 (1994) ・Slesinski R, et al., Mutation Res 124: 299-314. (1983) ・Zimmering S, et al., Environ. Mutagen, 7: 87-100 (1985)

● Ethylenediaminetetraacetic acid 　(Edetic acid; EDTA)
　　　 60-00-4　Industry/Laboratory　　 292.25

AM	Sal./E. coli	Max ( 5.0 mg/plate, ±S9)	□	1)
AM	Sal.	Max ( 1.0 mg/plate, +S9)	□	4)
CA	Plant/Barlay （オオムギ）	Max (?)	□	2)
SM	L5178/TK	Min ( 8.8 mg/ml,  -S9)	○	5)
CA	CHL/IU	Max ( 0.25 mg/ml, -S9), 24, 48h (No data for +S9)	□	3)
MNv	Mice, BM	Min ( 20 mg/kg, or )	○	6)
MNv	Mice, BM	Max (186 mg/kg, ip )	□	7)
SCEv	Mice, BM	Max (186 mg/kg, ip )	□	8)

1) Ministry of Labor, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JEOC(Ed.), Suppl. 2, pp.34 (2000) (Tables in English)　
2) Nilan RA: In : The Cytology and Genetics of Barley, Washington State Unv., pp.65 (1964)
3) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)
4) Ito Y & Hamaguchi A.,  Suishitsuosen-kenkyu, 4, 97-101 (1981) (in Japanese)
5) Carberg P., et al., Mutation Res., 203, 155-176 (1988)
6) Muralidhara & Narsimhamurthy K, Food Chem. Toxcol., 29, 845-849 (1991)
7) Russo A & Levis AG, Environ Mol. Mutagen., 19, 125-131 (1992)
8) Zordan M et al., Environ. Mutagen.., 15,205-213 (1990)

● Ethylenediaminetetraacetic acid disodium salt dihydrate (EDTA・2Na）
　　　 139-33-3　Laboratory　　 372.24

AM	Sal.	Max ( 10 mg/plate, +S9 )	□	2)
CA	CHL/IU	Min ( 0.4 mg/ml, -S9), 24, 48h D20= 0.43;	○w	1)
UDS	Syr. ham	Min ( 37.2 mg/L, -S9)	○	3)

1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)　
2) McCann J., et al., Proc. Natl Acad. Sci. (USA)72, 5135-5139 (1975)
3) Fukuda S.,  Shigaku, 74, 1365-1384 (1987)

● Ethylene dibromide　（二臭化エイチレン) ( 1,2-Dibromoethane）　
　　　 106-93-4　　Industry　 187.88

AM	E. coli	Min ( 1.0 mg/plate, ±S9 )	○	1)
YM	Yeast	Min ( 0.17 mM )	○	2)
CA	CHL/IU	Min ( 0.4 mg/ml, -S9), 24h D20= 0.16	○	3)
PLNv	Tradescantia （ムラサキツユクサ）	Min ( 3.6 ppm )	○	3)
MLA	L5178Y/TK-	Min ( 30 μｇ/ml )	○	4)

1) Blum A. & Ames BN.: Science, 195, 17-23 (1977)
2) Fahrig R.: IARC, Sci. Pub.10, 161-181 (1974)
3) Ministry of Labour, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JEOC(Ed.), (1996) (Tables in English)　
3) Sparrow AH., et al.: Mutation Res., 26, 265-276 (1974)
4) Clive D., et al.: Mutation Res.., 59, 61-108 (1979)
　 　
 USA-NTP Genotoxicity Screening :
 ○ Ames Test:　○
  ○ MLA (L5178Y):　○
  ○ SCE Test with CHO cells: 　○
  ○ SLRL Test in Drosophila: 　○
　
 IARC　Criteria for Carcinogenicity:　
  Group 2A （Probably carcinogenic to humans)

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

Ethylene dibromide did not induce CAs or SCEs in exposed pine-tree sprayers and fruit packers. 　　It did not induce DL mutations in mice or rats or CAs or MNs in bone-marrow cells of mice treated in vivo; however, a weak SCE response was observed. It bound covalently to DNA in rat hepatocytes and induced DNA strand breaks in mouse and rat hepatocytes and in rat testicular cells in studies of rodents treated in vivo. SCEs, mutation and UDS were induced in human cells in vitro, and CAs, SCEs, mutation, DNA strand breaks and UDS in rodent cells in vitro. It induced SLRL mutations in Drosophila and CAs and mutation in plants. It was mutagenic to fungi and bacteria and produced DNA damage in bacteria. It bound covalently to isolated DNA. (IARC Monographs, 15, 195)

● Ethylen dichloride　（二塩化エチレン) ( 1,2-Dichloroethane）  (See also D-4)　
　　　 　107-06-2　 Industry　 98.96

AM	Sal.	Min (?)	○	1)
AM	Sal.	Min ( 0.23 mmol/plate, ±S9)	○	2)
AM	Sal.	Min ( 0.01 mmol,  -S9)	○	3)
AM	Sal.	Min ( 60 mol/plate, ±S9)	○	4)
DNA	E. coli	Min ( 10 μｌ, -S9)	○	3)
MB	A. nidulans P1	Min ( 0.2%,  -S9)	○	5)
SM	CHO/HGPRT)	Min (1.3 mM, -S9), for 5h	○	6)
SM	Hum. lym.	Min ( 1.0 mg., -S9), for 20, 28h	○	7)
SM	Hum. EUE cells	Min ( 10-2 M, -S9),  for 24h	○	8)
CT	Balb/c-3T3	Max (250 μg/ml, -S9)	□	9)
CT	C3H/10T1/2	Min ( 0.6 mg/ml, -S9),  for 48h	○	10)
MN	Hum. lym.	Min ( 20 mM, -S9),  for 72h	○	11)
SCG	Hum. lym.	Min ( 20 mM, -S9),  for 3h	○	12)
UDS	Hum. lym.	Min ( 10 μL/ml, +S9),  for 4h	○	12)
MNv	Mice	Max ( 360 mg/kg, ip)	□	13)
MNv	Mice	Max ( 4 mmol/kg x 2, ip), 24h	□	14)
MNv	Mice	Max ( 300 mg/kg, or), for 41w	□	15)
SCEv	Mice	Min ( 16 mg/kg, ip)	○	16)
SCGv	Mice, organs	Min ( 200 mg/kg, ip)	○	17)
DNAv	Mice	Min ( 400 mg/kg, or)	○	18)
DNAv	Mice/rats	Min (8.7  μmol/kg, ip)	○	19)
SMv	Drosophila	Min (400 ppm, ih), for 17h	○	20)
SLRLv	Drosophila	Min (800 mg/m3, ih), for 6h	○	21)

1) McCann J., et al.: Proc. Nat. Acad Sci. (USA), 72, 5135-5139 (1975)
2) Barber ED., et al., Mutation Res., 90, 31-48 (1981)
3) Brem H., et al., Cancer Res., 34, 2576-2579 (1974)
4) Rannug U., et al. Chem-Biol. Interactions. 10, 1-16 (1978)
5) Crebelli R & Carere A., Cancer Res., 34, 2576-2579 (1988)
6) Tan EL& Hsie AW., Mutation Res., 90, 183-191 (1981)
7) Crespi CL.,et al. Mutation Res., 142, 133-140 (1983)
8) Ferreri AM., et al., J. Cancer Res. Clin. Oncol., 105, 111-112 (1983)
9) Arthur D., Lttle Inc., EPA Doc. No. 40+8324457, NTIS No. 0509392 (1983)
10) Schultz K., et al., In Vitro Cell Dev. Biol., 28A, 267-272 (1992)
11) Tafazoli M., et al., Mutagenesis, 13, 115-126 (1998)
12) Perocco P., & Prodi, G., Cancer Lett., 13, 213-218 (1981)
13) Sasaki YF., et al., MMS Com., Japan, 2, 87-93 (1994)
14) King MT., et al.,  Mutation Res., 252-17-33 (1979)
15) Armstrong MJ & Galloway SM,  Mutation Res., 302, 61-70) (1993)
16) Giri AK & Que Hee SS Environ. Mol. Mutagene., 12, 331-334 (1988)
17) Sasaki YF., et al., Mutation Res., 419, 13-20 (1998)
18) Storer RD & Colony RB., Toxicol. Appl. Pharmacol.. 77, 36-46 (1985)
19) Arfellini G., et al., J. Cancer Res. Clin. Oncol., 108,204-213 (1984)
20) Vogel EW., & Nivard MJM., Mutagenisis, 8, 57-81 (1993)
21) Kramers PGN., et al., Mutation Res., 252-17-33 (1991)
　
USA-NTP Genotoxicity Screening :
○　Ames Test:　□
○　CA Test with CHO cells: 　□

IARC Criteria for Carcinogenicity:　
Group 2B 　(Possiblly carcinogenic in humans)

● N,N'-Ethylenedi  (Stearamide)　
　　　 110-30-5　Industry　 593.03

AM

Sal./E. coli

Max ( 5.0 mg/plate ±S9)

□

1)

1) Ministry of Labour, Japan, Mutagenicity Test Data of Exist. Chem. Subst., JEOC(Ed.), Suppl. 2,  pp. 113 (2000) (Tables in English)　

● Ethylene glycol　（エチレングリコ−ル）　(1, 2-Ethanediol)　(1,2-ヒドロキシエタン；　1,2-エタンジオールエチレンジヒドラート）
　　　 107-21-1　　Industry　 62.07

AM	Sal.	Max ( 10.0 mg/plate, ±S9)	□	1-3)
AM	Sal./E. coli	Max (5.0 mg/plate, ±S9)	□	9)
YM	Yeast	(Mutation & Aneuploidy)  Max (?)	□	4, 5)
MLA	L5178Y	Max (?), ±S9	□	6)
MLA	L5178Y	Min (?)	○	7)
CA	Human/fetus fibroblasts	Max (?)	□	8)
CA	CHL/IU	Max ( 20 mg/ml, +S9), 6-18h	□	9, 18)
CA	CHO	Max (?), ±S9	□	10)
SCE	CHO	Max (?), ±S9	□	10)
DNA	Rat hepatocytes	Max (?)	□	11)
DNA	E. coli	Max (?)	□	12)
DNA	E. coli	Max (?)	□	13)
CAv	Rats, BM	Min ( 1.2 g/kg, po ), 50h	○	14)
CAv	Mice, BM	Max (?), ip)	□	15)
CAv	Drosophila	Max (?)	□	16)
DLv	Rats	Min ( 1.2 g/kg, po )	○	14)
DLv	Rats	Max (?), po	□	17)
MNv	Mice	Max (?), ip/po	□	15)

1) NTP: TR 413, NIEHS, NTP, Research Triangle Park, NC (1991)
2) McCann J., et al.: Proc. Nat. Acad Sci. (USA), 72, 5135-5139 (1975)
3) Zeiger E., et al.: Environ. Mutagen., 9 (Supp.9), 1-109 (1987)
4) Griffiths AJF.: Short-Term Test for Chemical Carcinogens, pp.187-199, Springer-Verlag, New York (1981)
5) Abbondandolo A., et al.: Mutation Res., 79, 141-150 (1980)
6) McGregor DB., et al., Environ. Mol. Mutagen.,17, 196-219  (1991)
7) Brown AM., et al., Z. Wasser Abwasser Forsch., 13, 170-173 (1980)
8) Oya Y., et al.: Mutation Res., 172, 245-253 (1986)
9) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998)
10) US-NTP., Tech. Rep. , CNTP TR 413 (1993)
11) Storer RD., et al., Mutation Res. 368, 59-101 (1996)
12) McCarroll NE., et al., Environ. Mutagen., 3, 429-444 (1981
13) von der Hude W., et al.,  Mutation Res., 203, 81-94 (1988)
14) Barilyak IR. & Kozachuk SI.: Titol Genet. 19, 436-442 (1985) (Russian)
15) Conan L., et al., Ann. Falsif. Expert. Chim., 72, 141-151 (1979)
16) Bhattacharya S., Proc Roy. Soc., 630,b 242-248  (1949)
17) De Pass LR., et al., Fund. Appl. Toxicol., 7,  566-572 (1986)
18) Ministry of Labour, Japan Mutagenicity Test Data of Exist. Chem. Subst., JEOC (Ed.), pp. 191 (1996) (Tables in English)

USA-NTP Genotoxicity Screening :
 ○ Ames Test:　□
 ○ MLA: (L5178Y/TK^-) : 　□
 ○ ＣＡ Test with CHO cells: 　□
 ○ SCE Test with CHO cells: 　□

 IARC Criteria for Carcinogenicity:　
　Group 2B 　(Possiblly carcinogenic in humans)

【Note】　(Cited from CICADs Documents 22  2000)

In vitro studies       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, 1984a,b; 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). In vivo studies  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)

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●Abbreviation 　（省略記号）

●Mutagenicity Testing　（変異原性試験）

●Test Systems　(試験法の種類）

●Technical Problems　（技術的問題点）

●List of　Compounds（化合物リスト）

●Evaluation of Results　（試験結果の評価）