tert-Butyl methacrylate

メタクリル酸tert-ブチルエステル

[CAS No. 585-07-9]

Molecular formula: C8H14O2 Molecular weight: 142.20

ABSTRACT

tert-Butyl methacrylate was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 20, 100 and 500 mg/kg/day.

Transient salivation after administration was observed in the 500 mg/kg/day group. Blood chemical examination showed increases in total cholesterol, total protein, and albumin, and a decrease in alkaline phosphatase in the 100 and 500 mg/kg/day groups. Urinalysis showed increases in protein, occult blood, bilirubin, erythrocytes, and epithelial cells in the 100 and 500 mg/kg/day groups. Absolute and relative weights of the liver and kidneys increased in the 500 mg/kg/day group and relative liver weights were increased in the 100 mg/kg/day group. Histopathological examination showed centrilobular hypertrophy of hepatocytes, an increase in hyaline droplets in the proximal renal tubules and basophilic change of renal tubules in the 100 and 500 mg/kg/day groups. The NOEL for the repeat dose toxicity is considered to be 20 mg/kg/day for both sexes.

tert-Butyl methacrylate was not mutagenic to Salmonella typhimurium, TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA. In the absence of an exogenous metabolic activation system, this chemical induced structural chromosomal aberrations in CHL/IU cells. Polyploidy was not induced under the conditions of the present study.

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose Oral Toxicity 1)

Purity	:	99.8%
Test species/strain	:	Rat/Crj:CD (SD)
Test method	:	Guidelines for 28-Day Repeat Dose Toxicity Testing for Chemicals (Japan)
Route	:	Oral (gavage)
Doses	:	0 (vehicle), 20, 100, 500 mg/kg
Number of animals/group	:	Males, 6 ; females, 6
Vehicle	:	0.5% Sodium Carboxymethyl Cellulose solution containing 0.1% Tween 80
Administration period	:	Males and females, 28 days
Terminal kill	:	Days 29 or 43
GLP	:	Yes

　 Test results:

There were no deaths throughout the course of the study. Transient salivation after administration was observed in both sexes given 500 mg/kg/day. The body weights and food consumption revealed no differences between the control and treated groups. There were no observed effects of the test substance on hematological findings. Blood chemical examination showed increases in total cholesterol and total protein in both sexes given 100 and 500 mg/kg/day, an increase in albumin in females given 100 mg/kg/day and both sexes given 500 mg/kg/day, and a decrease in alkaline phosphatase in males given 100 mg/kg/day and both sexes given 500 mg/kg/day. Urinalysis showed an increase in protein in both sexes given 500 mg/kg/day, an increase in occult blood in males given 100 and 500 mg/kg/day and an increase in bilirubin in males given 500 mg/kg/day. In addition, microscopic examination of urinary sediment revealed an increase in erythrocytes in males given 500 mg/kg/day and an increase in epithelial cells in females given 500 mg/kg/day. Absolute and relative liver and kidneys weight were increased in both sexes given 500 mg/kg/day, and relative weight of the liver increased in males given 100 mg/kg/day. Necropsy revealed hypertrophy of the liver in three males and five females given 500 mg/kg/day. Histopathological examination showed centrilobular hypertrophy of hepatocytes in four males given 100 mg/kg/day and all animals of both sexes given 500 mg/kg/day. Increase in the amounts of hyaline droplets of proximal renal tubules was observed in two males given 100 mg/kg/day and four males given 500 mg/kg/day. Basophilic change of renal tubules was observed in one male given 100 mg/kg/day and three males given 500 mg/kg/day. These changes disappeared or tended to recover during the recovery period.

The NOEL for the repeat dose toxicity is considered to be 20 mg/kg/day for both sexes.

2. Genetic Toxicity

2-1. Bacterial test 2)

Purity	:	99.8%
Test species/strains	:	Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test methods	:	OECD guideline (No. 471, 472) and Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Procedures	:	Modified pre-incubation method for volatile substances
Solvent	:	Acetone
Positive controls	:	-S9 mix, AF-2 (TA100, TA98), sodium azide (TA1535), ENNG (WP2 uvrA) and 9-aminoacridine (TA1537) +S9 mix, 2-aminoanthracene (all strains)
Doses	:	-S9 mix: 9.77, 19.5, 39.1, 78.1, 156, 313 μg/plate (TA100) 19.5, 39.1, 78.1, 156, 313, 625 μg/plate (TA1535, TA98, TA1537, WP2 uvrA) +S9 mix: 9.77, 19.5, 39.1, 78.1, 156, 313 μg/plate (TA100) 19.5, 39.1, 78.1, 156, 313, 625 μg/plate (TA1535, TA98, TA1537, WP2 uvrA)
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	3
Number of replicates	:	2
GLP	:	Yes

　 Test results:

This chemical did not induce gene mutations in the S. typhimurium and E. coli strains. Toxicity was observed at a concentration of 313 μg/plate, with or without metabolic activation.

Genetic effects:

Salmonella typhimurium TA100, TA1535, TA98, TA1537

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

Escherichia coli WP2 uvrA

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

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

Purity	:	99.8%
Type of cell used	:	Chinese hamster CHL/IU cells
Test method	:	OECD guideline (No. 473) and Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Solvent	:	Acetone
Positive controls	:	-S9 mix, Mitomycin C +S9 mix, Benzo[a]pyrene
Doses	:	-S9 mix (24 h treatment): 0, 100, 200, 400 μg/ml -S9 mix (48 h treatment): 0, 50, 100, 200 μg/ml -S9 mix (6 h pulse treatment): 0, 175, 350, 700 μg/ml +S9 mix (6 h pulse treatment): 0, 188, 375, 750 μg/ml
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　 Test results:

This chemical induced structural chromosomal aberrations in the presence of an exogenous metabolic activation system.

Lowest concentration producing cytogenetic effects in vitro:

Without metabolic activation (24 h treatment): 400 μg/ml

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 +81-479-46-2871 Fax +81-479-46-2874