3-Methyl-1,5-pentanediol

3-メチル-1,5-ペンタンジオ−ル


[CAS No. 4457-71-0]

Molecular formula:C6H14O2 Molecular weight: 118.20

ABSTRACT

A single oral dose toxicity test of 3-methyl-1,5-pentanediol revealed an LD50 value of more than 2000mg/kg for both sexes.

The compound was also studied for oral toxicity in rats in a combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 100, 300 and 1000mg/kg/day.

With regard to repeat dose toxicity, salivation was observed as a treatment related sign in both sexes in the 1000mg/kg group. Further, disappearance of fat deposits and an increase in glycogen accumulation in hepatocytes in the histopathological examination and an increase in the liver weight were recorded in females of the 1000mg/kg group. The NOEL for repeat dose toxicity is considered to be 300mg/kg/day for both sexes.

With regard to reproductive/developmental toxicity, no effects of the test article on estrous cycle, copulation, fertility, delivery or lactation were noted. The NOELs for reproductive performance of males and females and development of pups are considered to be 1000mg/kg/day.

3-Methyl-1,5-pentanediol was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

Genotoxicity of 3-methyl-1,5-pentanediol was studied by chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells. Structural chromosomal aberrations and polyploidy were not induced in CHL/IU cells up to a maximum concentration of 1.2 mg/ml (10 mM) with continuous treatment, or with short-term treatment with and without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Toxicity１）

Purity:99.18 %
Test species/strain:Rat/Crj:CD (SD)
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Doses:0 (water), 1000, 2000 mg/kg
　Number of animals:Males, 5; females, 5/group
　Vehicle:None (without any dilution)
GLP:Yes

　Test results:

No deaths occurred of either males or females in either of the treatment groups. An ataxic gait was observed from 15 minutes to 2 hours after administration in males given 2000 mg/kg and from 15 to 30 minutes in females given 2000 mg/kg and decreased locomotive activity was observed for 30 minutes after administration in males given 2000 mg/kg. No effects were detected in terms of body weight changes or autopsy findings.

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

2. Repeat Dose and Reproductive/Developmental Toxicity１）

Purity:99.18%
Test Species/Strain:Rat/Crj:CD (SD)
Test method:OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
　Rout:Oral (gavage)
　Dose:0 (Vehicle), 100, 300 and 1000mg/kg/day
　Number of animals/Group:Males, 12; females,12
　Vehicle:Water for injection
　Administration period:Males, 49 days
Females, from 14 days before mating to the day before autopsy (day 3 of lactation)
　Terminal Kill:Males, day 50 of administration
Females, day 4 of lactation
GLP:Yes

　Test results:

<Repeat dose toxicity>
In the 1000mg/kg group, salivation, which appeared immediately after dosing and lasted for about 1 hour, was observed in approximately half of the animals, in males from day 29 of dosing and in females from day 10 of gestation. Further, disappearance of fat deposits and increased in glycogen accumulation in hepatocytes were recorded in females of the 1000mg/kg group on histopathological examination. In the 300 and 100mg/kg groups, there were no effects of administration of the test article on general condition, body weights, food consumption, hematological and blood chemical parameters or histopathological findings.

The NOEL for repeat dose toxicity is considered to be 300mg/kg/day for both sexes.

<Reproductive/developmental toxicity>
With regard to reproductive performance, there were no effects of administration of the test article on the estrous cycle, copulation index, fertility index, length of gestation, delivery, the gestation index, numbers of corpora lutea and implantation sites or implantation index.

With regard to the pups, there were no effects of administration of the test article on the number of pups born, number of dead pups, live birth index, sex ratio, external anomalies, viability index, body weight or necropsy findings.

The NOELs for the reproductive/developmental toxicity are considered to be 1000mg/kg/day for reproduction in both sexes as well as for development of pups.

3. Genetic Toxicity

3-1. Bacterial test２）

Purity:99.18 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, 313, 625, 1250, 2500, 5000 μg/plate (five strains)
+S9 mix; 0, 313 - 5000 μg/plate (five strains)
　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 mutations in the S. typhimurium and E. coli strains. Toxicity was not observed at 5000 μg/plate in the five strains with or without an 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:99.18%
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, 0.30, 0.60, 1.2 mg/ml
-S9 mix (short-term treatment):0, 0.30, 0.60, 1.2 mg/ml
+S9 mix (short-term treatment):0, 0.30, 0.60, 1.2 mg/ml
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

Cytogenetic effects were not seen under the conditions of this experiment.

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

1)The tests were performed by Bozo Research Center Inc, 1284, Kamado, Gotemba-shi, Shizuoka, 412, Japan. Tel +81-550-82-2000 Fax +81-550-82-2379
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