● Buformin-HCl　　（ブフォルミン）
　　CAS: 15537-73-2 　Medicine 　　 MW: 157.22 　 　

CA

CHL/IU

Max ( 0.25 mg/ml, -S9), 24h

□

1)

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

● Buprofezin (アプロード）
　 　69327-76-0 　Pesticide 　　  305.44　　　　

REC	B. subtilis	Max ( 5mg/plate,±S9)	□	1)
AM	Sal	Max ( 5mg/plate)	□	1)

1) Nihon Nohyaku Co, Ltd.: J. Pesticide Sci., 11, 655-657 (1986) (Tables in English)

● Busulfan （ブサルファン；　Myleran: ミレラン）　
　　(1,4-butanediol dimethanesulphonate)　
　 　55-98-1　      Medicine　　 246.29

AM	Sal.	Min ( 50 μg/ml, ±S9)	○	1)
CA	Barley	Min (?)	○	2)
MLA	L-5178Y	Min ( 30 μg/ml, ±S9)	○	3)
CA	CHL/IU	Min ( 2 mg/ml, -S9), 24h; D20=1.8; TR=10	○	4)
CA	Human LY	Min ( 5 μg/ml, ±S9)	○	5)
SCE	Human LY	Min ( 2μg/ml, -S9)	○	6)
MNv	Mice	Min ( 30 mg/kg)	○	7)
CAv	Mice/BM	Min ( 6 mg/kg x 5), ip	○	8)
DLv	Mice	Min ( 40 mg/kg), ip	○	9)
SPMv	Mice	Min ( 6 mg/kg x 5), ip	○	10)

1) Mortelmans K, et al: Environ. Mutagen., 8 (Suppl. 7), 1-119 (1986)
2) Nilan RA: In The cytology and Genetics of Barley, Washington State Univ., pp. 65 (1964)
3) Clive D et al : Mutation Res., 59, 61-108 (1979)
4) Sofuni T. (Ed.): Data Book of Chromosomal　Aberration Test In Vitro, LIC, Tokyo (1998)
5) Richmond, JY & Kaufmann, BN; Exp. Cell Res., 54, 377-380 (1969)
6) Honeycombe JR: Mutation Res., 84, 399-407 (1981)
7) Yamamoto, KI & Kikuchi, Y.; Mutation Res., 71, 127-131 (1980)
8) Leonard A et al: Mutation Res., 28, 137-139 (1975)
9) Generoso WM et al., Mutation Res., 28, 437-447 (1975)
10) Wyrobek AJ & Bruce WR: Pro. Natl. Acad. Sci.(USA), 72, 4425-4429 (1975)

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

Myleran is a bifunctional alkylating agent. Patients treated with this agent for chronic myeloid leukaemia were found to have increased frequencies of SCEs and CAs (in a single study) in their peripheral blood lymphocytes. 　Treatment of rodents in vivo with this agent induced DL mutations and and increased the frequency of CAs and MNs in bone marrow cells; in single studies, It induced DNA damage but not mutation. Evidence for convalent binding to DNA, RNA and protein was obtained in mice treated in vivo. It induced CAs and SCEs in human and reodent cells in vitro, and mutation in rodent cells in vitro. It induced SLRL mutations in Drosophila and was mutagenic to bacteria.

AM	Sal..	Min ( 86μg/ml, +S9)	○	１)
AM	Sal.	Min (?), +S9)	○	2)
AM	Sal.. /E. coli	Min (?), ±S9	○	10)
MLA	L5178Y	Min (?), ±S9	○	3)
SCE	CHO	Min ( 0.2/ml, +S9)	○	4)
SCE	Hum. lym.	Max ( 100% in N2 gas, +S9)	□	5)
UDSv	Rats/Mice, Liver	Max( 10000 ppm,)	□	5, 6)
CAv	Mice, BM	Min ( 1250 ppm), for 6h	○	7)
CAv	Mice, BM	Min ( 625 ppm), for 6h/d, for 10d	○	8)
SCEv	Mice, BM	Min ( 625 ppm), for 6h/d, for 10d	○	8)
SCEv	Mice, BM	Min ( 10000 ppm), 6h/d, for 2d	○	9)
MNv	Mice, BM	Min ( 625 ppm), 6h/d, for 10d	○	8)
MNv	Mice, BM	Min ( 1250 ppm), 6h/d, for 24w	○	11)
MNv	Mice, peri. lyn.	Min ( 625 ppm), 6h/d, for 13w	○	12)
MNv	Mice, BM	Min ( 500 ppm),　6h/d, for 5 days	○	13)
SMv	Mice,  Spleen	Min ( 625 ppm), 6h/d, for 2w	○	14)
SMv	Mice,  Spleen	Min ( 500 ppm), 6h/d, for 5d	○	15)
SLRLv	Drosophila	Max ( 10000 ppm),  for 27h	□	16)
DLv	Mice	Min ( 6250 ppm), 6h/d, for 10w	○	17)
DLv	Mice	Min ( 200 ppm), 6h/d, for 5d	○	18)
DLv	Mice	Min ( 200 ppm), 6h/d, for 5d	○	19)
DLv	Mice, germ.	Min ( 1300 ppm), 6h/d, for 5d	○	20, 21)

1) De Meester C. et al: Toxicol. Lett., 6, 125-130 (1980)
2) De Meester C et al., Biochem. Biophis. Res. Comm., 80, 298-305 (1978)
3) McGregor JT., et al., Environ. Mol. Mutage., (?) (1991)
4) Sasiadock M., et al, Mutation Res., 263, 49-50 (1991)
5) Arce CH., et al., Envron. Health, Perspect., 86, 75-78 (1990)
6) Vincent DR et al., Environ Mutagen., 8, 235 (1986)
7) Irns RD., et al., Virology, 161,457-462 (1987)
8) Tice RR., et al., Environ. Mutagen, 9, 235-250 (1987)
9) Cunningham MJ., et al., Mutagenesis, 1, 449-452 (1986)
10) Ministry of Labour, Japan; Mutagen. Test Data of Exist. Chem. Substa., JETOC (Ed.) Suppl. 2 (2000)
11) Irons RD., et al, Toxicol. Appl. Pharmacol., 83, 95-100 (1986)
12)Jauhar PP., et al.,. Mutation Res., 209, 171-176 (1988)
13) Adler  I-D., et al., Mutation Res., 309, 307-314 (1994)
14) Cochrane JE & Skopek TR, Carcinogenesis, 15, 713-717 (1994)
15) Tates AD., et al., Mutation Res., 309, 299-306 (1994)
16) Victorian K., et al., Mutation Res., 228, 203-209 (1990)
17) Anderson D., et al., Toxicol., 113, 120-127 (1996)
18) Morrissey RE., et al., Environ. Health Perspect., 86, 79-84 (1990)
19) Adler I-D & Anderson D., Mutation Res. 309, 295-297 (1994)
20) Adler I-D., et al., Mutation Res., 347, 121-127 (1995)
21) Xiso Y & Tates AD., Environ. Mol. Mutagen., 26, 97-108 (1995)

  【Note-1】 ( Cited from IARC Monographs, Suppl., 6 ,1987)

No data were available on the genetic and related effects in humans. It induced MNs and SCEs in bone marrow cells of mice but not of rats treated in vivo. It was mutagenici to bacteria.

The genotoxicity of butadiene has been investigated in a limited range of in vitro assays and a more extensive range of in vivo tests. Butadiene was mutagenic in Salmonella typhimurium strains TA1530 and TA1535 in the presence of metabolic activation with rodent or human S9 preparations (de Meester et al., 1978, 1980; Arce et al., 1990; NTP, 1993; Araki et al., 1994), although it was generally inactive in strains TA97, TA98, and TA100 with or without exogenous activation under similar experimental conditions (Victorin & Stahlberg, 1988; Arce et al., 1990; NTP, 1993). Results of mouse lymphoma assays have been conflicting, with an increased frequency of mutations at the tk locus in one study at very high concentrations (i.e., 200 000-800 000 ppm [442400-1796 600 mg/m3]) in the presence of metabolic activation (Sernau et al., 1986), while there was no convincing activity at concen trations of up to 300 000 ppm (663 600 mg/m3) in another study (although the authors noted that the lack of a positive response may have been due to the low solubility of butadiene in the culture medium; NTP, 1993). Butadiene dissolved in ethanol induced sister chromatid exchanges in cultured mammalian cells (hamsters and humans) (Sasiadek et al., 1991a, 1991b), while in vitro exposure to gaseous butadiene did not induce this effect in preparations from rats, mice, and humans (Arce et al., 1990; Walles et al., 1995).    In general, the data are consistent with species-specific differences in sensitivity to butadiene-induced genetic damage, likely related to the quantitative differences in the formation of active metabolites, although fewer studies have been conducted in rats. Butadiene induced dominant lethal mutations in two strains of mice (CD-1 and (102/E1 × C3H/E1)F1) following short-term or subchronic exposure of males to concentrations as low as 500 ppm (1106 mg/m3) for 5 days or 65 ppm (144 mg/m3) for 4 weeks; however, exposure to 6250 ppm (13825 mg/m3) for 6 h did not induce dominant lethal mutations in CD-1 mice. The results of these studies, which depended upon the timing of mating relative to exposure, suggested that the induc tion of dominant lethal mutations in mice was likely caused by effects on mature germ cells. In the only simi lar study in rats identified, there was no evidence of dominant lethal mutations in Sprague-Dawley rats exposed to up to 1250 ppm (2765 mg/m3) butadiene for 10 weeks.    Short-term exposure to 500 or 1300 ppm (1106 or 2876 mg/m3) butadiene also induced an exposure-related increase in the incidence of heritable chromosomal changes. References ・de Meester C, Poncelet F, Roberfroid M, Mercier M (1978) Mutagenicity of butadiene and butadiene monoxide. Biochemical and biophysical research communications, 80: 298 [cited in de Meester et al., 1980]. ・de Meester C, Poncelet F, Roberfroid M, Mercier M (1980) The mutagenicity of butadiene towards Salmonella typhimurium. Toxicology letters, 6: 125-130. ・Arce GT, Vincent DR, Cunningham MJ, Choy WN, Sarrif AM (1990) In vitro and in vivo genotoxicity of 1,3-butadiene and metabolites. Environmental health perspectives, 86:75?78. ・NTP (1993) NTP technical report on the toxicology and carcino genesis studies of 1,3-butadiene (CAS No. 106-99-0) in B6C3F1 mice (inhalation studies). Research Triangle Park, NC, US Department of Health and Human Services, National Toxicology Program (Technical Report No. 434). ・Araki A, Noguchi T, Kato F, Matsushima T (1994) Improved method for mutagenicity testing of gaseous compounds by using a gas sampling bag. Mutation research, 307: 335-344 ・Victorin K, Stahlberg M (1988) A method for studying the mutagenicity of some gaseous compounds in Salmonella typhimurium. Environmental and molecular mutagenesis, 11: 65-77. ・Sernau R, Cavagnaro J, Kehn P (1986) 1,3-Butadiene as an S9 activation-dependent gaseous positive control substance in L5178Y cell mutation assays. Environmental mutagenesis, 8(Suppl.): 75 (Abstract 203). ・Sasiadek M, Jarventaus H, Sorsa M (1991a) Sister-chromatid exchanges induced by 1,3-butadiene and its epoxides in CHO cells. Mutation research, 263: 47-50. ・Sasiadek M, Norppa H, Sorsa M (1991b) 1,3-Butadiene and its epoxides induce sister-chromatid exchanges in human lymphocytes in vitro. Mutation research, 261: 117-121. ・Walles SAS, Victorin K, Lundborg M (1995) DNA damage in lung cells in vivo and in vitro by 1,3-butadiene and nitrogen dioxide and their photochemical reaction products. Mutation research, 328: 11- 19.

● 1,2-Butanediol （1，2-ブタネジオール） (1,2-Butylene glycol)　
         584-03-2    Industry     　90.12

AM	Sal.	Max ( 5.0 mg/plate, ±S9)	□	１)
CA	CHL/IU	Max ( 0.90 mg/ml, -S9), 24-48h,; (±S9), 6-18h	□	1)

1)Ministry of Health & Welfare,, Japan; Toxic. Test. Report. Environ. Chem., Vol. 1, pp.287 (1994)  (Tables in English)
       
● 1,4-Butanediol 　（1，4-ブタンジオール） (1,4-Butylene glycol)　　
    110-63-4    Industry   90.12

AM	Sal.	Max ( 5.0 mg/plate, ±S9)	□	１)
CA	CHL/IU	Max ( 0.90 mg/ml, -S9), 24-48h,; (±S9), 6-18h	□	1)

1)Ministry of Health & Welfare,, Japan; Toxic. Test. Report. Environ. Chem., Vol. 5, pp.429 (1997) (Tables in English)

● tert-Butanol （tert-ブタノール）
　　  75-65-0 　Industry 　 74.1　

AM	Sal.	Max (?)	□	１)
MB	N crassa	Max (?)	□	2)
SM	V79	Max (?)	□	3)
MLA	L-5178Y	Max (?)	□	4)
CA	CHO/Hybrid	Min (?)	○	5)
CAv	Mice/Rats	Min ( 6.25 ppm), ih	○	6)

1) Mortelmans K., et al.: Environ. Mutagen., 8 (Suppl. 7), 1-119 (1986)
2) Dickey FH., et al.: Proc. Natl. Acad. Xci. (USA) 35, 581-586 (1949)
3) Abbondandolo A., et al.: Mutation Res.,79, 141-150 (1980)
4) McGregor DB., et al.: Environ. Molec. Mutagen., 11, 91-118 (1988)
5) Waldren C.: Mutation Res. 97, 234 (1982)

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

tert-Butanol showed some protective effects on radiation-induced genotoxicities. This effect has been attributed to the hydroxyl radical scavenging properties of the compound.

 ● 1-Butene （1-ブテン）　(1-Butylene)
　　　　　　　106-98-9　　Industry　 56.10

AM

Sal./E. coli

(gas) Max (42%, ±S9)

□

１)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exist. Chem. Substa., JEYOC (Ed.) Suppl. 2 (2000)  (Tables in English)

● 2-Butene (2-ブテン)　(2-Butylene)
　　107-01-7　　Natural/Solvent　 116.16

AM

Sal./E. coli

(gas) Max (48%, ±S9)

□

１)

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

● 2-Butoxyethanol (EGBE) 　（2-ブトキシエタノール）
　　123-86-4　　Industry  118.17

AM	Sal.	Max (?)	□	１)
CA	CHO	Max (?)	□	2)
SCE	CHO	Max (?)	□	2)

1) Zeiger E. et al.: Environ. Mutagen., １9 (Suppl. 21), 2-141 (1992)
2) NTP Technical Rep., NIH Publication 93-3349 (1993)

【Note】 ( Cited from CICADS Document, 30, 2001)

2-Butoxyethanol has been tested for genotoxicity in a range of in vitro and in vivo assays (see Elliott & Ashby, 1997, for a recent review). In standard tests in bacteria, 2-butoxyethanol was not mutagenic in Salmonella typhimurium strains TA1535, TA1537, TA97, TA98, TA100, and TA102 (Zeiger et al., 1992; Hoflack et al., 1995; Gollapudi et al., 1996). However, the results for strain TA98a were inconsistent, with one report of mutagenicity observed in both the presence and absence of metabolic activation (Hoflack et al., 1995) and another report of no mutagenicity (Gollapudi et al., 1996). 2-Butoxyethanol was not mutagenic at the HPRT locus in Chinese hamster ovary cells in either the presence or absence of metabolic activation (McGregor, 1984; Chiewchanwit & Au, 1995). However, there was evidence that it caused gene mutations at the HPRT locus in Chinese hamster lung (V79) cells (Elias et al., 1996). An in vitro assay for unscheduled DNA synthesis in rat hepatocytes yielded equivocal results (Elliott & Ashby, 1997). 2-Butoxyethanol produced sister chromatid exchanges in human peripheral lymphocytes but not in Chinese hamster lung (V79) or ovary cells. In vitro cytogenetic assays conducted with human peripheral lymphocytes, Chinese hamster lung (V79) cells, and Chinese hamster ovary cells revealed no induction of chromosomal aberrations. An in vitro micronucleus assay in Chinese hamster lung (V79) cells, which incorporated a test for aneuploidy, yielded equivocal results (Elliott & Ashby, 1997).     In vivo mutagenicity tests have yielded uniformly negative results for 2-butoxyethanol. These assays have included three bone marrow micronucleus tests utilizing intraperitoneal injection in rats and mice (Elias et al., 1996; Elliott & Ashby, 1997); a [32P]post-labelling assay for DNA adducts in the brain, kidney, liver, spleen, and testes of orally dosed rats (Keith et al., 1996); an assay for DNA methylation in the brain, kidney, liver, spleen, and testes of rats and in FVB/N transgenic mice carrying the v-Ha- ras. Results of a US National Toxicology Program 2-year carcinogenesis bioassay completed in July 1995 were not available at the time this CICAD was prepared. oncogene (Keith et al., 1996); as well as a test for tumour formation in FVB/N transgenic mice (Keith et al., 1996). Although the results of in vitro tests for mutagenicity of 2-butoxyethanol are inconsistent, the absence of structural alerts as well as the negative results from in vivo studies are sufficiently reassuring to allow the conclusion that 2-butoxyethanol is not mutagenic.     Mutagenicity studies have also been performed on two metabolites of 2-butoxyethanol -- 2-butoxyacetic acid and 2-butoxyacetaldehyde. 2-Butoxyacetic acid was not mutagenic in a series of in vitro assays, in addition to an in vivo micronucleus assay in mice administered the chemical by intraperitoneal injection (Hoflack et al., 1995; Elias et al., 1996; Elliott & Ashby, 1997). 2-Butoxyacetaldehyde exhibited mutagenic potential in several in vitro studies (including tests for HPRT gene mutation, chromosomal aberrations, micronuclei, aneuploidy, and sister chromatid exchange); however, in the absence of data from in vivo studies, it is not possible to reach a final conclusion concerning the possible mutagenic hazard of this metabolite (Chiewchanwit & Au, 1995; Hoflack et al., 1995; Elias et al., 1996; Elliott & Ashby, 1997). References ・Elliott BM, Ashby J (1997) Review of the genotoxicity of 2-butoxyethanol. Mutation research, 387: 89-96. ・Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K (1992) Salmonella mutagenicity tests: V. Results from the testing of 311 chemicals. Environmental and molecular mutagenesis, 19 (Suppl. 21): 2-141. ・Hoflack JC, Lambolez L, Elias Z, Vasseur P (1995) Mutagenicity of ethylene glycol ethers and of their metabolites in Salmonella typhimurium his-. Mutation research, 341(4): 281-287. ・Gollapudi BB, Barber ED, Lawlor TE, Lewis SA (1996) Re-examination of the mutagenicity of ethylene glycol monobutyl ether to Salmonella tester strain TA97a. Mutation research, 370: 61-64. ・McGregor DB (1984) The genotoxicity of glycol ethers. Environmental health perspectives, 57: 97-103. ・Chiewchanwit T, Au WW (1995) Mutagenicity and cytotoxicity of 2-butoxyethanol and its metabolite, 2-butoxyacetaldehyde, in Chinese hamster (CHO-AS52) cells. Mutation research, 334(13): 341-346. ・Elias Z, Daniere MC, Marande AM, Poirot O, Terzelti F, Schneider O (1996) Genotoxic and/or epigenetic effects of some glycol ethers: results of different short-term tests. Occupational hygiene, 2:187-212. ・Keith G, Coulais C, Edo?h A, Botlin MC, Rihn B (1996) Ethylene glycol monobutyl ether has neither epigenetic nor genotoxic effects in acute treated rats and in subchronic treated v-Ha- ras transgenic mice. Occupational hygiene, 2: 237-249.

 
●Butter flavor 70
　　      Food

AM	Sal.	Max (?)	□	１)
CA	CHL/IU	Max ( 0.5 mg/ml, -S9), 24-48h	□	2)

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

● n-Butyl acetate 　（n-ブチルアセテート）
　　　123-86-4　　Natural/Industry　 116.16

AM	Sal.	Max ( 2/ml, ±S9)	□	１)
AM	Sal.	Max ( 5 mg/Plate, ±S9)	□	2)
AM	Sal./E.coli	Max ( 1.250 mg/plate, ±S9)	□	3)
YM	D.61M	Max (?)	□	4)
CA	CHL/IU	Max ( 2.0 mg/ml, -S9), 24-48h	□	5, 6)

1) Anonymous: Final Rep.,: J. Am. Coll.Toxicol., 8, 681-705 (1989)
2) Ishidate, MJr (Ed); Data Book of Mutagnicity Tests on  Chemicals, LIC/Tokyo (1991)  (Tables in English)
3) Ministry of Labour, Japan; Mutagen. Test Data of Exist. Chem. Substa., JEYOC (Ed.) Suppl. (1997)  (Tables in English)
4)  Zimmermann FK., et al.: Mutation Res., 40, 19-30 (1976)
5) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test i In Vitro, LIC, Tokyo (1998)  (Tables in English)
6) Ishidate MJr., et al., Fd. Chem. Toxicol., 22(8), 623-636 (1984)
　　　　
US-NTP Genotoxicity Screening:
○　Ames Test :　□

● N-Butyl-N-(1-acetoxybutyl) nitrosamine
　　　56986-35-7　　Laboratory　 216.28

AM	Sal.	Min (?), +S9)	◎	１)
CA	CHL/IU	Min ( 0.03 mg/ml, -S9), 24-48h; D20= 0.016; TR= 1100	◎	2)

1) Camus AM., et al.: Mutation Res., 49, 187-194 (1978)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro, LIC, Tokyo (1998)  (Tables in English)

●Top Page　（トップページ）

●Abbreviation 　（省略記号）

●Mutagenicity （変異原性）

●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）