Sodium 1-methoxycarbonylpentadecane-2-sulfonate

1-メトキシカルボニルペンタデカンスルホン酸ナトリウム

[CAS No. 4016-24-4]

Molecular formula: C₁₇H₃₃NaO₅S　Molecular weight: 372.50

ABSTRACT

The single dose oral toxicity test revealed LD₅₀ values of 2142 mg/kg for males and 1819 mg/kg for females.

With regard to repeated dose toxicity, transitional softening of the stools in a few males and females was noted in the 80 and 300 mg/kg groups. Blood biochemical examination revealed an increase in GPT activity and a decrease in triglyceride levels in males of the 300 mg/kg group. Macroscopic thichening of the forestomach mucosa was observed in both sexes of the 80 and 300 mg/kg groups. Histopathologically, squamous hyperplasia, erosion, and edema of lamina propria and/or submucosa and inflammatory cell infiltration were observed in the forestomach. The NOELs for repeated dose toxicity are considered to be 20 mg/kg/day for males and females. With regard to reproductive and developmental toxicity, the test substance showed no effects on any reproductive parameters of the parental animals or developmental parameters of the offspring. The NOELs for reproductive/developmetal toxicity are considered to be 300 mg/kg/day for both reproductive performance of parental animals and offspring development.

Genotoxicity of sodium 1-methoxycarbonylpentadecane-2-sulfonate was studied by a reverse mutation test in bacteria and by a chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

Sodium 1-methoxycarbonylpentadecane-2-sulfonate was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

Sodium 1-methoxycarbonylpentadecane-2-sulfonate did not induce chromosomal aberrations in CHL/IU cells, with and without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity ¹⁾

Purity	:	97.0 %
Test species/strain	:	Rat/Crj:CD(SD)IGS
Test method	:	OECD Test Guideline 401
Route	:	Oral (gavage)
Dosage	:	0 (vehicle), 786, 983, 1229, 1536, 1920, 2400 mg/kg
Number of animals/group	:	Males, 5; females, 5
Vehicle	:	Olive oil
GLP	:	Yes

　Test results:

Deaths of males occurred at doses of 983 mg/kg or more and of females at 1536 mg/kg or more. Most mortality was observed 6 to 24 hours after administration. Clinical signs such as decreased locomotor activity, ptosis, diarrhea, soiling of the perineal region and piloerection were observed in treated groups. Most clinical signs in the survivors showed a tendency for recovery on the day following administration and all had disappeared after 6 days. Body weights in the treated groups were dose-dependently suppressed. However, a tendency for recovery was noted 3 days after the administration. On necropsy, distention of the stomach with a watery content was observed in most of the animals which died.

The LD₅₀ values were estimated to be 2142 mg/kg for males and 1819 mg/kg for females.

2. Repeated Dose and Reproductive/Developmental Toxicity ¹⁾

Purity	:	97.0 %
Test species/strain	:	Rat/Crj:CD(SD)IGS
Test method	:	OECD Test Guideline 422
Route	:	Oral (gavage)
Dosage	:	0 (vehicle), 5, 20, 80, 300 mg/kg/day
Number of animals/group		Males, 10; females, 10
Vehicle	:	Olive oil
Administration period	:	Males, 47 days Females, from 14 days before mating to day 4 of lactation
Terminal killing	:	Males, day 48 Females, day 5 of lactation
GLP	:	Yes

　Test results:

<Repeated dose toxicity>

Transitional softening of stools in a few males and females was observed in the 80 and 300 mg/kg groups. Blood biochemical examination revealed an increase in GPT activity and a decrease in triglyceride level in males of the 300 mg/kg group. Thickening of the forestomach mucosa was observed macroscopically in both sexes of the 80 and 300 mg/kg groups. Histopathologically, squamous hyperplasia, erosion, and lamina proprial and/or submucosal edema and inflammatory cell infiltration were observed in the forestomach.

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

<Reproductive and developmental toxicity>

The parental animals exhibited no alteration in reproductive parameters. There were also no significant differences in offspring parameters.

The NOELs for reproductive/developmetal toxicity are considered to be 300 mg/kg/day for reproductive performance of parental animals and for offspring development.

3. Genetic Toxicity

3-1. Bacterial test ¹⁾

Purity	:	97.0 %
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	:	Dimethyl sulfoxide
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)
Dosage	:	-S9 mix; 0, 0.625, 1.25, 2.5, 5, 10, 20 μg/plate (TA100, TA1535, TA1537) -S9 mix; 0, 156, 313, 625, 1250, 2500, 5000 μg/plate (WP2 uvrA) -S9 mix; 0, 3.13, 6.25, 12.5, 25, 50, 100 μg/plate (TA98) +S9 mix; 0, 62.5, 125, 250, 500, 1000, 2000 μg/plate (TA100) +S9 mix; 0, 31.3, 62.5, 125, 250, 500, 1000 μg/plate (TA1537) +S9 mix; 0, 6.25, 12.5, 25, 50, 100, 200 μg/plate (TA1535, TA98) +S9 mix; 0, 156, 313, 625, 1250, 2500, 5000 μg/plate (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 20 μg/plate (TA100, TA1535 and TA1537) and at 100 μg/plate (TA98) without S9 mix, and observed at 2000 μg/plate (TA100), at 1000 μg/plate (TA1537), and at 200 μg/plate (TA1535 and TA98) with 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) ¹⁾

Purity	:	97.0 %
Type of cell used	:	Chinese hamster lung (CHL) cells
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals(Chemical Substances Control Law of Japan) and OECD Test Guideline 473
Solvent	:	Physiological saline
Positive controls	:	-S9 mix; 1-Methyl-3-nitro-1-nitrosoguanidine +S9 mix; 3,4-Benzo[a]pyrene
Dosage	:	-S9 mix (6 hr short-term treatment); 0, 31.3, 62.5, 125, 187.5, 250 μg/mL +S9 mix (6 hr short-term treatment); 0, 31.3, 62.5, 125, 187.5, 250 μg/mL -S9 mix (24 hr continuous treatment); 0, 15.6, 31.3, 62.5, 125, 187.5, 250 μg/mL
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

With the 6 hr short-term treatment, chromosomal aberrations were not induced with or without S9 mix. Moreover, chromosomal aberrations and/or polyploidy were not induced after 24 hr continuous treatment without S9 mix.

Cytotoxicity was observed at 187.5 and 250 μg/mL without S9 mix and at 250 μg/mL with S9 mix after the 6 hr short-term treatment, and observed at 187.5 and 250 μg/mL after the 24 hr continuous treatment without S9 mix.

Genotoxic effects:

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

1)	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