1-Chlorobutane

1-クロロブタン

CAS No. 109-69-3

Butyl chloride

ブチルクロリド／塩化ブチル

Molecular formula: C4H9Cl Molecular weight: 92.58

ABSTRACT

In the preliminary reproduction toxicity screening test, 1-chlorobutane caused increased salivation in all treated groups. Lower values for body weight gain and food consumption were observed for both sexes receiving 300 mg/kg. One out of 12 dams given the 300 mg/kg dose died on day 22 of pregnancy and two dams died on day 4 of lactation. This test substance is considered to affect dams in the perinatal period and neonatal development in spite of a lack of changes in copulation or fertility indexes. NOELs for reproductive performance are considered to be 300 mg/kg/day for males and 2.4 mg/kg/day for females. The NOEL for development of pups is considered to be 60 mg/kg/day.

1-Chlorobutane was not mutagenic in Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA. Neither structural nor numerical chromosomal aberrations were induced in CHL/IU cells up to the limit concentration of 10 mM, in the absence or presence of an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Preliminary Reproductive/Developmental Toxicity 1)

Purity	:	> 99.5%
Test species/strains	:	Rat/Crj:CD (SD)
Test method	:	OECD Preliminary Reproduction Toxicity Screening Test
Route	:	Oral (gavage)
Dosage	:	2.4, 12, 60, 300 mg/kg/day
Number of animals	:	Male, 12 ; Female, 12/group
Vehicle	:	Corn oil
Administration period	:	Male, 49 days Female, from 14 days before mating to Day 3 of lactation
Terminal kill	:	Male, Day 50 Female, Day 4 of lactation
GLP	:	Yes

　Test results:

<Reproductive/Developmental Toxicity>

One dam died on Day 22 of pregnancy, and two dams died on Day 4 of lactation in the 300 mg/kg group. In the 12, 60 and 300 mg/kg groups, lack of pup care behavior was observed in one female each. Therefore, 1-chlorobutane exerts effects on the dams in the perinatal period and during neonatal development, although neither the copulation index nor fertility index were affected.

NOELs for reproductive performance are considered to be 300 mg/kg/day for males and 2.4 mg/kg/day for females. NOEL for development of pups is considered to be 60 mg/kg/day.

<Repeat Dose Toxicity>

1-Chlorobutane exhibited an influence on general signs (salivation) in the treated groups of both sexes, and body weight gain as well as food consumption in both sexes receiving 300 mg/kg. An increase in mucous secretion and erosion or epithelial desquamation in the glandular stomach were observed in females of the 300 mg/kg group.

The NOEL is considered to be less than 2.4 mg/kg/day for both sexes in terms of general toxicological effects.

2. Genetic Toxicity

2-1 Bacterial test 2)

Purity	:	> 99.5%
Test species/strains	:	S.typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Procedures	:	Plate incorporation method
Solvent	:	Acetone
Positive controls	:	-S9, AF-2 (TA100, WP2, TA98), sodium azide (TA1535) and 9-aminoacridine (TA1537) +S9, 2-aminoanthracene (all strains)
Dosage	:	0, 2.441, 4.882, 9.765, 19.53, 39.06, 78.12 μg/plate
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	3
Number of replicates	:	2
GLP	:	Yes

　Test results:

Minimum concentration of test substance at which toxicity was observed.

Toxicity was observed at the concentration of 78.12 μg/plate with or without metabolic activation.

Genetic effects:

S. typhimurium TA100, TA1535, TA 98, TA1537

	+	?	-
with metabolic activation	[ ]	[ ]	[*]
without metabolic activation	[ ]	[ ]	[*]

E. coli WP2 uvrA

with metabolic activation	[ ]	[ ]	[*]
without metabolic activation	[ ]	[ ]	[*]

2-2 Non-bacterial in vitro test (chromosomal aberration test) 2)

Purity	:	99.5%
Type of cell used	:	Chinese hamster CHL/IU cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Solvent	:	Acetone
Positive controls	:	-S9, Mitomycin C +S9, Cyclophosphamide
Doses	:	-S9 (continuous treatment): 0, 0.23, 0.47, 0.93 mg/ml -S9 (short-term treatment): 0, 0.23, 0.47, 0.93 mg/ml +S9 (short-term treatment): 0, 0.23, 0.47, 0.93 mg/ml
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

Lowest concentration producing cytogenetic effects in vitro:

without metabolic activation (continuous treatment ): > 0.93 mg/ml

without metabolic activation (short-term treatment): > 0.93 mg/ml

with metabolic activation (short-term treatment): > 0.93 mg/ml

Genotoxic effects:

	clastogenicity			polyploidy
	+	?	-	+	?	-
with metabolic activation:	[ ]	[ ]	[*]	[ ]	[ ]	[*]
without metabolic activation:	[ ]	[ ]	[*]	[ ]	[ ]	[*]

1)	The test was performed by Nihon Bioresearch Inc. Hashima Laboratory, 6-104 Majima, Fukuju-cho, Hashima, Gifu, 501-62 Japan. Tel +81-58-392-6222 Fax +81-58-392-1284
2)	The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa 257, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627