Docosanoic acid

ドコサン酸


[CAS No. 112-85-6]

Behenic acid

ベヘン酸

Molecular formula: C22H44O2     Molecular weight: 340.59

ABSTRACT

Docosanoic acid was studied for oral toxicity in rats in a single dose toxicity test at doses of 0 and 2000 mg/kg. An LD50 value of more than 2000 mg/kg was found for both sexes.

Docosanoic acid was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 100, 300 and 1000 mg/kg/day.

With regard to repeat dose toxicity, no deaths or abnormalities in general condition were observed in any male and female animals. Also, there were no adverse changes related to the dosing of the compound in body weights and food consumption. The findings for internal organs and histopathological and biochemical examinations revealed no adverse changes in any animals.

With regard to the reproductive/developmental toxicity, there were no adverse effects on copulation, ovulation and fertility in any docosanoic acid-treated animals. In addition, no adverse changes related to the dosing were observed in gestation length, delivery and lactation. There were no changes in sex ratio, body weights and viability of the docosanoic acid-treated pups compared to those of the control pups. Also, no morphological abnormalities were noted in any pups of the docosanoic acid-treated group.

In conclusion, the NOEL for toxicity of docosanoic acid is considered to be 1000 mg/kg/day in male and female animals, and that for reproductive and developmental toxicity was also 1000 mg/kg/day in males and females.

Docosanoic acid was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

Docosanoic acid did not induce structural chromosomal aberrations and polyploidy in CHL cells, with or without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity1)

Purity:85.9 wt%
Test species/strain:Rat/Crj:CD(SD)
Test method:OECD Test Guideline 401
 Doses:2000 mg/kg
 Number of animals/group:Males, 5; females, 5
GLP:Yes

 Test results:

No deaths occurred of either males or females in the treated groups. No effects were found on general condition, body weight changes or autopsy findings.

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

2. Repeat Dose and Reproductive/Developmental Toxicity1)

Purity:85.9 %
Test species/strain:Rat/Crj:CD(Sprague-Dawley)
Test method:OECD Combined Repeat Dose and Reproductive/ Developmental Toxicity Screening Test
 Route:Oral(Gavage)
 Doses:0(vehicle), 100, 300, 1000 mg/kg/day
 Number of animals/group:Males, 13; females, 13
 Vehicle:Corn oil
 Administration:Males, 42 days
Females, from 14 days prior to mating to day 3 of lactation
 Terminal killing:Males, day 43
Females, day 4 of lactation
GLP:Yes

 Test results:

<Repeated dose toxicity>

a)Males: No deaths or abnormalities in general condition were observed in any of the treated groups. Also, there were no changes related to the dosing of compound in body weight gain and food consumption. At autopsy following treatment for 42 days, no adverse effects were found for internal organs and findings of histopathological, hematological and biochemical examinations.

b)Females: No deaths were observed in any treated groups. Also, there were no changes related to the dosing of compound in general condition, body weight gain and food consumption. No abnormal findings were evident at autopsy on postpartum day 4 and on histopathological examination.

<Reproductive and developmental toxicity>

The compound showed no adverse effects on copulation or fertility. No changes related to the dosing of compound were observed in gestation length, gestation index, delivery and lactation. The compound did not demonstrate any adverse effects on the sex ratio, body weights or viability of pups. Also, no morphological abnormalities in pups were observed in any of the treated groups.

The no observed effect dose level(NOEL) for toxicity is considered to be 1000 mg/kg/day in males and females, and that for reproductive and developmental toxicity also 1000 mg/kg/day in males and females.

3. Genetic Toxicity

3-1. Bacterial test2)

Purity:85.9 %
Test species/strains:S. typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)and OECD Guidelines No. 471 and 472
 Procedures:Pre-incubation method
 Solvent:DMSO
 Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide(TA100, TA98 and WP2 uvrA), Sodium azide(TA1535), 9-Aminoacridine hydrochloride(TA1537)
+S9 mix; 2-Aminoanthracene(all strains)
 Doses:-S9 mix; 156, 313, 625, 1250, 2500 and 5000 μg/plate
+S9 mix; 156, 313, 625, 1250, 2500 and 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. No toxicity was observed up to a concentration of 5000 μg/plate, with or without metabolic activation.

Genetic effects:
S. typhimurium TA100, TA1535, TA98 and TA1537
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

E. coli WP2 uvrA
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

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

Purity:85.9 %
Type of cell used:Chinese hamster lung(CHL)cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)and OECD Guideline No. 473
 Vehicle:1% Carboxymethylcellulose sodium
 Positive controls:-S9 mix, Mitomycin C
+S9 mix, Cyclophosphamide
 Doses:-S9 mix(24hr continuous exposure): 0, 350, 700, 1400, 2800 μg/mL
-S9 mix(48hr continuous exposure): 0, 288, 575, 1150, 2300 μg/mL
-S9 mix(short-term exposure): 0, 875, 1750, 3500 μg/mL
+S9 mix(short-term exposure): 0, 875, 1750, 3500 μg/mL
 S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
 Plates/test:2
GLP:Yes

 Test results:

This chemical did not induce structural chromosomal aberrations in the absence or presence of an exogenous metabolic activation system.

Genetic 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, 257-0025, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627
2)The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides(An-pyo Center), Japan, 582-2 Shioshinden Arahama, Fukude-cho, Iwata-gun, Shizuoka, 437-1213, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393