1-Methylethenylbenzene

1-メチルエテニルベンゼン

CAS No. 98-83-9

a-Methylstyrene / Isopropenylbenzene

a-メチルスチレン／イソプロペニルベンゼン

Molecular formula: C9H10 Molecular weight: 118.19

ABSTRACT

With regard to repeat dose toxicity, one male rat died due to ischuria with urinary calculi in the 1000 mg/kg/day group. Increases in GPT, BUN and K, a decrease in triglyceride were observed in this group. Histopathological examination revealed acidophilic changes in the liver cells, hyaline degeneration of tubular epithelium of kidneys and fatty droplets in adrenal cortex of both sexes, and epithelial hyperplasia of urinary bladder in male rats, and atrophy of thymus in female rats in the 1000 mg/kg/day group. In the 200 mg/kg/day group, similar histopathological changes were observed in the liver, kidneys and thymus. The NOELs for repeat dose toxicity are considered to be 40 mg/kg/day for both sexes. In terms of reproductive/developmental toxicity, the compound exerted effects on the body weight of neonates and the viability index, due to total litter loss in two of eight dams receiving 1000 mg/kg/day. The NOELs for reproductive/developmental toxicity are considered to be 1000 mg/kg/day for parental males, and 200 mg/kg/day for parental females and offspring.

1-Methylethenylbenzene was not mutagenic in Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA in the absence or presence of an exogenous metabolic activation system.

Neither structural chromosomal aberrations nor polyploidy were induced in CHL/IU cells up to the concentration giving 50% cell growth inhibition, in the absence or presence of an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose and Reproductive/Developmental Toxicity1)

Purity	:	99.6%
Test species/strain	:	Rat/Crj:CD (SD)
Test method	:	OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
Route	:	Oral (gavage)
Dosage	:	0 (Vehicle), 40, 200, 1000 mg/kg/day
Number of animals	:	Males, 10; females, 10/group
Vehicle	:	Olive oil
Administration period	:	Males, 43 days Females, from 14 days before mating to day 3 of lactation
Terminal kill	:	Males, day 44 Females, day 4 of lactation
GLP	:	Yes

　Test results:

<Repeat dose toxicity>

In the 1000 mg/kg group, male rats showed suppression of body weight gain, and a decrease in food consumption, and one animal died due to ischuria with urinary calculi. Female rats of 1000 mg/kg group showed a slight suppression of body weight gain in the late gestation period. Histopathological examination demonstrated acidophilic change of hepatocytes and increase of fatty droplets in the fascicular zone of the adrenals in both sexes, increase of hyaline droplets and basophilic change in the renal tubular epithelium and hyperplasia of the mucosal epithelium in the urinary bladder in male rats, and vacuolation and infiltration of lymphocytes in the renal tubular epithelium and atrophy of the thymus in female rats. Blood chemical examination in male rats showed increases in GPT, urea nitrogen and potassium, and a decrease in triglyceride.

In the 200 mg/kg group, similar histopathological changes were found in the liver and kidneys of both sexes, and the thymus of female rats, and an increase in GPT was observed in male rats.

The NOELs for repeat dose toxicity are considered to be 40 mg/kg/day for both sexes.

<Reproductive and developmental toxicity>

The compound had no effects on reproductive parameters such as the mating index, the fertility index, gestation length, number of corpora lutea or implantations, the implantation index, the gestation index, the delivery index or parturition. Two dams of the 1000 mg/kg/day group, however, lost all their pups dung the lactation period. On examination of neonates, the 1000 mg/kg/day group showed a decrease of body weight and low viability index due to the total litter losses of the two dams. There were no significant differences in numbers of offspring or live offspring at birth, the sex ratio, the live birth index, or body weight gain after birth. No abnormal findings ascribable to the compound were found for external examination, clinical signs, or necropsy of the offspring. The NOELs for reproductive and developmental toxicity are considered over 1000 mg/kg/day for parental males, 200 mg/kg/day for parental females and offspring.

2. Genetic Toxicity

2-1. Bacterial test2)

Purity	:	99.6%
Test species/strain	:	S.typhimurium TA100, TA1535, TA98, TA1537 E. coli WP2 uvrA
Test method	:	Guideline for Screening Mutagenicity Testing of Chemicals (Japan)
Procedures	:	Plate incorporation method
Solvent	:	DMSO
Positive controls	:	-S9 Mix, AF-2 (TA100, WP2, TA98), sodium azide (TA1535) and 9-aminoacridine (TA1537) +S9 Mix, 2-aminoanthracene (all strains)
Doses	:	0, 12.5, 25, 50, 100, 200 and 400 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:

200 μg/plate -S9 Mix and 400 μg/plate (200 μg/plate for TA1537) +S9 Mix

　Genetic effects:

S. typhimurium TA100, TA1535, TA 98, TA1537

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

E. coli WP2 uvrA

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

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

Purity	:	99.6%
Type of cell used	:	Chinese hamster lung (CHL/IU) cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Solvent	:	Dimethyl sulfoxide
Positive controls	:	-S9, Mitomycin C +S9, Cyclophosphamide
Doses	:	-S9 (continuous treatment): 0, 0.04, 0.09, 0.17 mg/ml -S9 (short-term treatment): 0, 0.04, 0.09, 0.17 mg/ml +S9 (short-term treatment): 0, 0.06, 0.12, 0.23 mg/ml
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

Cytogenetic effect was not seen under the conditions in this experiment.

Lowest concentration producing cytogenetic effects in vitro:

without metabolic activation (continuous treatment ): 0.17 mg/kg

without metabolic activation (short-term treatment): 0.17 mg/kg

with metabolic activation (short-term treatment): 0.17 mg/kg

　Genotoxic effects:

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

1)	The tests were performed by the Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki-machi, Kashima-gun, Ibaraki, 314-02, Japan. Tel +81-46-2871 Fax +81-46-2874
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