Methyl dodecanoate

ドデカン酸メチルエステル

[CAS No. 111-82-0]

Methyl laurate

ラウリン酸メチル

Molecular formula: C13H26O2　Molecular weight: 214.35

ABSTRACT

The single dose oral toxicity test revealed an LD50 value of more than 2000 mg/kg for both sexes.

Methyl dodecanoate was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 250, 500 and 1000 mg/kg/day.

In the repeat dose study, the test substance showed no general toxicological effects in either sex. The NOEL for repeat dose toxicity is considered to be 1000 mg/kg/day in both sexes. No effects were observed on reproductive performance in either sex or on development of the next generation. The NOEL for reproductive performance of males and females, as well as pup development are considered to be 1000 mg/kg/day in each case.

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

Methyl dodecanoate induced neither structural chromosomal aberrations nor polyploidy in CHL/IU cells, in the absence or presence of an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity １）

Purity	:	99.2%
Test species/strains	:	Rats/Crj:CD (SD)
Test method	:	OECD Test Guideline 401
Route	:	Oral (gavage)
Doses	:	0 (vehicle), 2000 mg/kg
Number of animals/group	:	Male 5; female, 5
Vehicle	:	Corn oil
GLP	:	Yes

　 Test results:

Loosening of stools attributable to the treatment with corn oil was observed for 3 hours from the administration for both sexes in the groups given 0 and 2000 mg/kg. However, no deaths occurred in either male or female groups. The test substance did not cause any changes in body weight. No macroscopic abnormalities that could be attributed to treatment with the test substance were seen on pathological examination.

LD50: Male, > 2000 mg/kg; female, > 2000 mg/kg

2. Repeat Dose and Reproductive/Developmental Toxicity １）

Purity	:	99.2%
Test species/strains	:	Rat/Crj:CD (SD)
Test method	:	OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
Route	:	Oral (gavage)
Doses	:	0 (Vehicle), 250, 500, 1000 mg/kg/day
Number of animals/group	:	Males, 12; females, 12
Vehicle	:	Corn oil
Administration period	:	Males, 45 days Females, from 14 days before mating to day 3 of lactation
Terminal kill	:	Males, day 45 Females, day 4 of lactation
GLP	:	Yes

　 Test results:

There were no clinical observations attributable to the administration of test substance and there was no mortality in any of the groups. No effects were observed in terms of body weights, food consumption, hematology, blood chemistry, organ weight, necropsy or histopathological findings.

The NOEL for repeat dose toxicity is considered to be 1000 mg/kg/day in both sexes.

There were no effects of the test substance on the estrous cycle, copulation index, fertility index, gestation length, number of corpora lutea or implantations, implantation index, delivery index or parturition.

No effects attributable to the test substance were revealed in terms of the number of pups born, numbers of live pups on Days 0 or 4 of lactation, number of dead pups, live birth index, sex ratio, viability index and body weights of live pups of both sexes in any treated group.

The NOELs for reproductive performance of males and females, as well as pup development are considered to be 1000 mg/kg/day in each case.

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)
Doses	:	-S9 mix, 0, 1.56, 3.13, 6.25, 12.5, 25 and 50 μg/plate (TA100 and TA1537), 0, 6.25 - 200 μg/plate (TA1535 and TA98), 0, 313 - 5000 μg/plate (WP2) +S9 mix, 0, 12.5, 25, 50, 100, 200 and 400 μg/plate(TA1537), 0, 25 - 800 (TA100 and TA1535), 0, 50-1600 (TA98), 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 did not induce gene mutations in the S. typhimurium and E. coli strains. Toxicity was observed at 25 μg/plate (TA100 and TA1537), 50 μg/plate (TA1535 and TA98) with the -S9 mix and at 150 μg/plate (TA1537), 400 μg/plate (TA100), 500 μg/plate (TA1535) and 800 μg/plate (TA98) with the +S9 mix. No toxicity was observed in WP2 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, 0.015, 0.030,0.060 mg/ml -S9 mix (short-term treatment): 0, 0.53, 1.1, 2.1 mg/ml +S9 mix (short-term treatment): 0, 0.025, 0.050,0.10 mg/ml
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes