(Methacryloyloxyethyl)trimethylammonium chloride

(メタクリロイルオキシエチル)トリメチルアンモニウムクロリド


[CAS No. 5039-78-1]

(2-Methylpropenoyloxyethyl)trimethylammonium chloride

(2-メチルプロペノイルオキシエチル)トリメチルアンモニウムクロリド

Molecular formula: C9H18ClNO2　Molecular weight: 207.70

ABSTRACT

A single dose oral toxicity test of (methacryloyloxyethyl)trimethylammonium chloride revealed an LD50 value of more than 2000 mg/kg for both sexes.

(Methacryloyloxyethyl)trimethylammonium chloride was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 50, 150 and 500 mg/kg. However, the toxicity profile of the test substance could not thereby be clarified. Thus, a supplementary test was carried out using the limiting dose, 1000 mg/kg, stated in the test guidelines. No deaths were observed in either sex. Repeated administration at 1000 mg/kg caused transient decrease in fecal excretion in some animals of both sexes during administration period, and slightly inhibited the body weight gain. However, the examinations revealed no evident functional and morphological alteration or signs of toxicity thought to have relevance to the test substance administered. Thus, the NOEL for the 28-day repeat dose oral toxicity test of (methacryloyloxyethyl)trimethylammonium chloride is considered to be 1000 mg/kg/day for males and females.

Genotoxicity of (methacryloyloxyethyl)trimethylammonium chloride was studied by reverse mutation test in bacteria and chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

(Methacryloyloxyethyl)trimethylammonium chloride was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

(Methacryloyloxyethyl)trimethylammonium chloride induced structural chromosomal aberrations in CHL/IU cells after continuous treatment without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:78.1 %(water solution)
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral(gavage)
　Doses:Males, 1000, 2000 mg/kg
Females, 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. One female of the 2000 mg/kg group demonstrated salivation immediately after administration. No effects were found on body weight or autopsy findings.

The LD50 value was concluded to be more than 2000 mg/kg for both sexes.

2. Repeat Dose Toxicity 1)

Purity:78.1 %(water solution)
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:Guideline for 28-Day Repeated Dose Toxicity Test in Mammalian Species (Chemical Substances Control Law of Japan)
　Route:Oral(gavage)
　Doses:First test: 0(vehicle), 50, 150, 500 mg/kg/day
Additional test: 0(vehicle), 1000 mg/kg/day
　Number of animals/group:First test:
Males, 10; females, 10(0, 500 mg/kg)
Males, 5; females, 5(50, 150 mg/kg)
Additional test:
Males, 10; females, 10(0, 1000 mg/kg)
　Vehicle:Water for injection
　Administration period:Males and females, 28 days
　Terminal kill:Males and females, on days 29 and 43
GLP:Yes

　Test results:

In the repeated dose study, no deaths were observed in either sex. One male and two females given 1000 mg/kg showed a transient decrease in fecal excretion and, nearly in parallel, body weights were decreased slightly and body weight gain tended to be inhibited. Although no significant differences was found between the mean body weights of the control and the 1000 mg/kg groups, significant lowering was apparent in males when compared just before autopsy. Additionally, in the female animals, food consumption of the 1000 mg/kg group was decreased significantly compared to that in the control group in the 1st and the 2nd weeks of administration. It was also decreased in the 2nd and the 3rd weeks in the male animals. There were, on the other hand, no signs of toxicity suspected to be due to the test substance in terms of urinalysis, hematology, blood chemistry, organ weight and pathology.

Thus, the NOEL for the 28-day repeat dose toxicity is considered to be 1000 mg/kg/day for males and females.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:78.1 %
Test species/strain:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals(Chemical Substances Control Law of Japan) and OECD Test Guideline 471
　Procedures:Pre-incubation method
　Solvent:DMSO
　Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98, WP2 uvrA), Sodium azide (TA1535) and 9-Aminoacridine (TA1537)
+S9 mix; 2-Aminoanthracene (all strains)
　Doses:-S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate
+S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate
　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 not observed in any strain, with and without S9 mix.

Genotoxic 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:78.1 % Type of cell used : Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals(Chemical Substances Control Law of Japan) and OECD Test Guideline 473
　Solvent:DMSO
　Positive controls:-S9 mix; 1-Methyl-3-nitro-1-nitrosoguanidine
+S9 mix; 3,4-Benzo[a]pyrene
　Doses:-S9 mix(6 hr short-term treatment); 0, 525, 1050, 2100 μg/mL
+S9 mix(6 hr short-term treatment); 0, 525, 1050, 2100 μg/mL
-S9 mix(24 hr continuous treatment); 0, 525, 1050, 2100 μg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

With 24 hr continuous treatment, structural chromosomal aberrations were induced at 1050 and 2100 μg/mL (6.0 and 10.5 %), respectively, without S9 mix. Polyploidy was not induced in any treatment group.

Cytotoxicity was not observed in any treatment group.

Lowest concentration producing cytogenetic effects in vitro:
　Without metabolic activation (24 hr continuous treatment):1050 μg/mL(clastogenicity)

Genotoxic effects:
clastogenicitypolyploidy
+?-+?-
　Without metabolic activation:[*][ ][ ][ ][ ][*]
　With metabolic activation:[ ][ ][*][ ][ ][*]

1)The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257-8523, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627
2)The tests were performed by the Research Institute for Animal Science in Biochemistry and Toxicology, 3-7-11 Hashimotodai, Sagamihara-shi, Kanagawa 229-1132, Japan. Tel +81-42-762-2775 Fax +81-42-762-7979