2-Hydroxypropyl methacrylate

メタクリル酸(2-ヒドロキシプロピル)エステル

[CAS No. 923-26-2]

Molecular formula: C7H12O3 Molecular weight: 144.17

ABSTRACT

2-Hydroxypropyl methacrylate was studied for its oral toxicity in rats in a single dose toxicity test at doses of 0, 500, 1000 and 2000 mg/kg. The single dose oral toxicity test revealed an LD50 value of more than 2000 mg/kg for both sexes.

2-Hydroxypropyl methacrylate was studied for its oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 30, 100, 300 and 1000 mg/kg/day. With regard to repeat dose toxicity, for the males, salivation, decreases in locomotor activity, ptosis, hematocrit, RBC and hemoglobin and an increase in the relative liver weight were seen at 1000 mg/kg, and 2 of the 12 animals died. For the females, salivation, decreases in locomotor activity and ptosis were seen at 1000 mg/kg, and 1 of the 12 animals died. The NOEL for repeat dose toxicity is considered to be 300 mg/kg for both sexes. With regard to reproductive/developmental toxicity, no effects of the test substance on copulation, fertility, delivery as lactation were noted. The NOELs for reproductive performance of males and females, and for pup development are considered to be 1000 mg/kg/day for both sexes.

2-Hydroxypropyl methacrylate was not mutagenic to Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA, with or without an exogeneous metabolic activation system.

2-Hydroxypropyl methacrylate induced structural chromosomal aberrations in CHL/IU cells with and without an exogeneous metabolic activation system. Polyploidy was induced without an exogeneous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity	:	98%
Test species/strain	:	Rat/Crj:CD (SD)
Test method	:	OECD Guidelines 401
Route	:	Oral (gavage)
Doses	:	0 (vehicle), 500, 1000, 2000 mg/kg
Number of animals/group	:	Males, 5 ; females, 5
Vehicle	:	Water for injection
GLP	:	Yes

　 Test results:

No deaths occurred in any group. Males of the 2000 mg/kg group demonstrated salivation immediately after administration.

Based on the above results, the LD50 value of 2-hydroxypropyl methacrylate was concluded to be 2000 mg/kg or more for both sexes.

2. Repeat Dose and Reproductive/Developmental Toxicity 1)

Purity	:	98%
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), 30, 100, 300, 1000 mg/kg/day
Number of animals/group	:	Males, 12 ; females, 12
Vehicle	:	Water for injection
Administration period	:	Males, 49 days Females, from 14 days before mating to day 3 of lactation
Terminal kill	:	Males, day 50 Females, day 4 of lactation
GLP	:	Yes

　 Test results:

For the males, salivation, decrease in locomotor activity and ptosis were found in the 1000 mg/kg group, and 2 animals of the group died. Decrease in hematocrit, tendencies for decrease in RBC and hemoglobin, and increase in the relative liver weights were also found in the 1000 mg/kg group.

For the females, salivation, decrease in locomotor activity and ptosis were found in the 1000 mg/kg group, and 1 animal died.

The NOEL for the repeated dose toxicity is considered to be 300 mg/kg/day for both sexes.

There were no effects of the test substance on the estrus frequency, copulation index, number of days to conception, fertility index, length of gestation, number of corpora lutea or gestation index.

There were no effects of the test substance on the number of live pups born, birth index, number of dead pups, number of pups born, delivery index, live birth index, sex ratio, viability index, external anomalies, body weight or necropsy findings.

The NOELs for the reproductive/developmental toxicity are considered to be 1000 mg/kg/day for reproduction in both sexes as well as for development of pups.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity	:	98%
Test species/strains	:	S.typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test methods	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD (471 and 472)
Procedures	:	Plate incorporation method
Solvent	:	Acetone
Positive controls	:	-S9 mix, 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, WP2, TA98), Sodium azide (TA1535) and 9-Aminoacridine (TA1537), +S9 mix, 2-Aminoanthracene (five strains)
Dosage	:	0, 313, 625, 1250, 2500 and 5000 μg/plate in five strains, -S9 mix and +S9 mix
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. No toxicity was observed in the five strains with either the -S9 mix or the +S9 mix.

Genetic effects:

Salmonella typhimurium TA100, TA1535, TA98, TA1537

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

Escherichia coli WP2 uvrA

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

3-2. Non-bacterial in vitro test (chromosomal aberration test) 2)

Purity	:	98%
Type of cell used	:	Chinese hamster lung (CHL/IU) cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
Solvent	:	Acetone
Positive controls	:	-S9 mix, Mitomycin C +S9 mix, Cyclophosphamide
Doses	:	-S9 mix (continuous treatment): 0, 0.18, 0.35, 0.70 mg/ml -S9 mix (short-term treatment): 0, 0.35, 0.70, 1.4 mg/ml +S9 mix (short-term treatment): 0, 0.35, 0.70, 1.4 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)	:	0.35 mg/ml (clastogenicity) 0.18 mg/ml (polyploidy)
Without metabolic activation (short-term treatment)	:	1.4 mg/ml (clastogenicity)
With metabolic activation (short-term treatment)	:	0.35 mg/ml (clastogenicity and polyploidy)

Genotoxic effects:

	clastogenicity			polyploidy
	+	?	-	+	?	-
without metabolic activation:	[*]	[ ]	[ ]	[*]	[ ]	[ ]
with 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 +81-58-391-3171

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

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 +81-58-391-3171
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