1,2-Butanediol

1,2-ブタンジオール


CAS No. 584-03-2

1,2-Butylene glycol

1,2−ブチレングリコール

1,2-Butanediol was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 40, 200 and 1000 mg/kg/day, and for mutagenicity with assays for reverse mutation in bacteria and chromosomal aberrations in cultured Chinese hamster (CHL) cells.

For repeat dose toxicity, 1,2-butanediol was found to cause only slight clinical signs including transient hypolocomotion and hypopnea among the females given 1000 mg/kg. There were no significant differences between the treated and control animals of both sexes in body weight, food consumption, hematological and blood chemical parameters, organ weight, or histopathological findings. NOELs for repeat dose toxicity were 1000 mg/kg/day in males and 200 mg/kg/day in females. With regard to reproductive/developmental toxicity, 1,2-butanediol showed no effects on reproductive parameters (copulation, implantation, pregnancy, parturition, or lactation) or on offspring. NOELs for reproductive performance and offspring development were both 1000 mg/kg/day.

1,2-Butanediol was not mutagenic to S. typhimurium TA100, TA98, TA97 and TA102 with or without exogenous metabolic activation up to 5000 μg/plate. This chemical induced neither chromosomal aberrations nor polyploidy in CHL cells with or without exogenous metabolic activation up to 0.9 mg/ml.

1,2-Butanediol[584-03-2]

1. Repeat Dose and Reproductive/Developmental Toxicity 1)

Purity:> 99 %
Test species/strain:Rat/Crj:CD (SD)
Test method:OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
　Route:Oral (gavage)
　Doses:0 (vehicle), 40, 200, 1000 mg/kg/day
　Number of animals:Male;10, Female10
　Vehicle:Distilled water
　Administration period:Male, 42 days
Female, from 14 days before mating to day 3 of lactation
　Terminal kill:Male, day 43
Female, day 4 of lactation
GLP:Yes

　Test results:

<Repeat dose toxicity>
There were no deaths throughout the observation period. Transient hypolocomotion and hypopnea were found among the females of the 1000 mg/kg group. There were no significant differences in body weight, food consumption, hematological and blood chemical parameters, organ weight, and pathological findings between the treated and control animals of either sex.

NOEL: Male 1000 mg/kg/day, female 200 mg/kg/day

<Reproductive and developmental toxicity>
There were no effects on the reproductive/developmental parameters of copulation, implantation, pregnancy, parturition, and lactation. No abnormal pups were observed, or any loss of offspring.

NOEL for P generation: 1000 mg/kg
NOEL for F1 generation: 1000 mg/kg

3. Genetic Toxicity

3-1 Bacterial test 2)

Purity:> 99%
Test species/strains:S. typhimurium TA100, TA1535, TA98, TA1537
E. coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
　Procedure:Plate method
　Solvent:DMSO
　Positive controls:-S9, AF-2 (TA100,WP2,TA98), sodium azide (TA1535) and 9-aminoacridine (TA1537)
+S9, 2-Aminoanthracene (all strains)
　Doses:0, 312.5, 625, 1250, 2500, 5000 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 to bacteria was observed:
No toxicity was observed up to a concentration of 5000 μg/plate with or without metabolic activation.

Genotoxic effects:
S. typhimurium TA100, TA1535, TA98, TA1537
+?-
with metabolic activation:[ ][ ][*]
without metabolic activation:[ ][ ][*]

E. coli WP2 uvrA
+?-
with metabolic activation:[ ][ ][*]
without metabolic activation:[ ][ ][*]

3-2 Non-bacterial in vitro test (Chromosomal aberration) 2)

Purity:>99 %
Type of cell used:Chinese hamster CHL cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
　Solvent:DMSO
　Positive controls:-S9, Mitomycin C
+S9, Cyclophosphamide
　Doses:-S9: 0, 0.23, 0.45, 0.90 mg/ml
+S9: 0, 0.23, 0.45,0.90 mg/ml
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:
1,2-Butanediol did not induce chromosomal aberrations or polyploidy in CHL cells up to the limit concentration (10 mM) with or without exogenous metabolic activation.

Lowest concentration producing cell toxicity:
with metabolic activation: > 0.9 mg/ml
without metabolic activation: > 0.9 mg/ml

Genotoxic effects:
+?-
with metabolic activation:[ ][ ][*]
without metabolic activation:[ ][ ][*]

1)The test was performed by the Mitsubishi-Kasei Institute of Toxicological and Environmental Sciences, 14 Sunayama, Hazaki-machi, Kashima-gun, Ibaraki, 314-02, Japan. Tel 81-479-46-2871 Fax 81-479-46-2874
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