2-(Dimethylamino)ethyl acrylate

アクリル酸 2-(ジメチルアミノ)エチルエステル

[CAS No. 2439-35-2]

Dimethylaminoethyl acrylate

(ジメチルアミノ)エチルアクリレート

Molecular formula: C7H13NO2 Molecular weight: 143.21

ABSTRACT

With regard to repeat dose toxicity, two females died, and suppression of body weight gain and decrease in food consumption were observed in males in the 100 mg/kg group. Increased in reticulocyte, platelet and segmented neutrophil counts, and a decrease in albumin were also noted in this group. Histopathological examination revealed ulceration, inflammatory cell infiltration and hyperplasia of the mucosa in the forestomach, and hyperplasia of plasma cells in the pancreatico-duodenal lymph nodes in both sexes, and atrophy of the thymus in females of the same group. In the 20 mg/kg group, similar histopathological changes were observed in the forestomach in males. The NOELs for repeat dose toxicity are considered to be 4 mg/kg/day for males and 20 mg/kg/day for females. In terms of reproductive/developmental toxicity, the compound had no effects on any relevant parameters. The NOELs for reproductive/developmental toxicity are considered to be 100 mg/kg/day for parental animals and offspring.

2-(Dimethylamino)ethyl acrylate was mutagenic in Salmonella typhimurium TA98, with an exogeneous metabolic activation system.

Genotoxicity of 2-(dimethylamino) ethyl acrylate was studied by chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells. Structural chromosomal aberrations were induced with continuous treatment at 0.060 mg/ml (high concentration), and short-term treatment with and without an exogenous metabolic activation system at 0.050 and 0.010 mg/ml (both high concentrations), respectively. Polyploidy was induced with continuous treatment at 0.060 mg/ml, short-term treatment with the metabolic activation system at 0.025 and 0.050 mg/ml (low and high concentrations), and short-term treatment without metabolic activation system at 0.0050 and 0.010 mg/ml (low and high concentrations).

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose and Reproductive/Developmental Toxicity１）

Purity	:	99.9%
Test species/strain	:	Rats/Crj:CD (SD)
Test method	:	OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
Route	:	Oral (gavage)
Dosage	:	0 (Vehicle), 4, 20, 100 mg/kg/day
Number of animals	:	Males, 12; females, 12/group
Vehicle	:	Corn 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 100 mg/kg group, two females died, and males showed a transient suppression of body weight gain and a decrease in food consumption. At necropsy, thickening of the wall of the forestomach and enlargement of the pancreatico-duodenal lymph nodes were observed in both sexes. Histopathological examination revealed ulceration, inflammatory cell infiltration and hyperplasia of the mucosa in the forestomach, and hyperplasia of plasma cells in the pancreatico-duodenal lymph nodes in both sexes. Atrophy of the thymus was also observed in females. Hematological and blood chemical examinations in males showed increased reticulocyte, platelet and segmented neutrophil counts, and a decrease in albumin. In the 20 mg/kg group, similar histopathological changes were observed in the forestomach in males.

The NOELs for repeat dose toxicity are considered to be 4 mg/kg/day for males and 20 mg/kg/day for females.

<Reproductive and developmental toxicity>

The compound had no effects on reproductive parameters such as the mating index, the fertility index, number of corpora lutea or implantations, the implantation index, the gestation index, the delivery index, gestation length, parturition or maternal behavior. On examination of neonates, there were no significant differences in number of offspring or live offspring, the sex ratio, the live birth index, the viability index or body weight. No abnormal findings ascribable to the compound were found for external features, clinical signs or necropsy of the offspring.

The NOELs for reproductive and developmental toxicity are considered to be 100 mg/kg/day for parental animals and offspring.

2. Genetic Toxicity

2-1. Bacterial test２）

Purity	:	99.9 wt%
Test species/strains	:	Salmonella typhimurium, TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline No. 471 and 472
Procedures	:	Pre-incubation method
Solvent	:	Water
Positive controls	:	-S9 mix, 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide (TA100, TA98, WP2), Sodium azide (TA1535) and 9-Aminoacridine (TA1537) +S9 mix, 2-Aminoanthracene (five strains)
Doses	:	-S9 mix; 0, 78.1, 156, 313, 625, 1250, 2500 μg/plate (TA98, TA1537) 0, 156 - 5000 μg/plate (TA100, TA1535, WP2) +S9 mix; 0, 156 - 5000 μg/plate (TA100, TA1535, TA98, TA1537) 0, 313 - 5000 μg/plate (WP2)
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	3
Number of replicates	:	2
GLP	:	Yes

　Test results:

This chemical induced mutations in S. typhimurium TA98 with an S9 mix. Toxicity was observed at 1250 μg/plate (TA98, TA1537), 2500 μg/plate (TA1535), 5000 μg/plate (TA100, WP2) without S9 mix, and at 2500 μg/plate (TA1535), 5000 μg/plate (TA100, TA98, TA1537) with an S9 mix. Toxicity was not observed in WP2 with an S9 mix.

Genetic effects:
Salmonella typhimurium TA98

	+	?	-
Without metabolic activation:	[ ]	[ ]	[*]
With metabolic activation:	[*]	[ ]	[ ]

Salmonella typhimurium TA100, TA1535, 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	:	99.9 wt%
Type of cell used	:	Chinese hamster lung (CHL/IU) cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline No. 473
Solvent	:	Distilled water
Positive controls	:	-S9 mix, Mitomycin C +S9 mix, Cyclophosphamide
Doses	:	-S9 mix (continuous treatment):0, 0.015, 0.030, 0.060 mg/ml -S9 mix (short-term treatment):0, 0.0050, 0.010 mg/ml +S9 mix (short-term treatment):0, 0.025, 0.050 mg/ml
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

Cytogenetic effect were seen as follows.

Structural chromosomal aberrations (including gap) were induced under the following conditions: 24 h continuous treatment (0.060 mg/ml: high concentrations, 23.5%); 48 h continuous treatment (0.060 mg/ml, 8.5%); short-term treatment with an exogenous metabolic activation system (0.050 mg/ml: high concentration, 12.5%); short-term treatment without the metabolic activation system (0.010 mg/ml: high concentration, 16.0%). Polyploidy was induced under the following conditions: 24 h continuous treatment (0.060 mg/ml, 10.75%); 48 h continuous treatment (0.060 mg/ml, 6.21%); short-term treatment with an exogenous metabolic activation system (0.025 and 0.050 mg/ml: low and high concentrations, 1.25 and 5.25%); short-term treatment without the metabolic activation system (0.0050 and 0.010 mg/ml: low and high concentrations, 1.25 and 10.88%).

Lowest concentration producing cytogenetic effects in vitro:

Without metabolic activation (continuous treatment)	:0.060 mg/ml (clastogenicity) :0.060 mg/ml (polyploidy)
Without metabolic activation (short-term treatment)	:0.010 mg/ml (clastogenicity) :0.0050 mg/ml (polyploidy)
With metabolic activation (short-term treatment)	:0.050 mg/ml (clastogenicity) :0.025 mg/ml (polyploidy)

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
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