2-Hydroxypropanenitrile

2-ヒドロキシプロパンニトリル


CAS No. 78-97-7

Lactonitrile

ラクトニトリル

2-Hydroxypropanenitrile was studied for oral toxicity in rats in a single dose toxicity test at doses of 15, 21, 30, 42 and 60 mg/kg in males, and 21, 30, 42, 60 and 84 mg/kg in females and in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 1.2, 6 and 30 mg/kg/day. 2-Hydroxypropanenitrile was also tested for mutagenicity with assays for reverse mutation in bacteria and chromosomal aberrations in cultured Chinese hamster (CHL) cells.

The single dose oral toxicity test revealed LD50s of 31.0 mg/kg in males and 41.1 mg/kg in females.

For repeat dose toxicity, a transient reduction of locomotor activity, as well as hypopnea and salivation were noted in the 30 mg/kg/day males and females, and macroscopically hypertrophy of the liver was evident in the 30 mg/kg males. Histopathologically, centrilobular hypertrophy and fatty change of hepatocytes were observed in the 30 mg/kg males. Blood chemical analyses showed a significant decrease in GOT, and significant increases in total protein, albumin and Ca in the 30 mg/kg males. The NOEL for repeat dose toxicity was 6 mg/kg/day.

2-Hydroxypropanenitrile was found to have no effects on any reproductive /developmental parameters. NOELs for reproductive performance and offspring development were both 30 mg/kg/day.

2-Hydroxypropanenitrile was not mutagenic for S. typhimurium TA100, TA1535, TA98, TA1537 and E. coli WP2 uvrA with or without exogenous metabolic activation up to 5000 μg/plate. However this chemical induced chromosomal aberrations with and without exogenous metabolic activation at concentrations of 0.71 and 0.38 mg/ml, respectively. Polyploidy was also weakly induced after 48 h treatment.

2-Hydroxypropanenitrile[78-97-7]

1. Single Dose Oral Toxicity 1)

Purity:92.3%
Test species/strains:Rat/Crj:CD (SD)
Test method:OECD Test Guideline 401
 Doses:Male: 15, 21, 30, 42, 60 mg/kg
Female: 21, 30, 42, 60, 84 mg/kg
Number of animals:Male, 5; Female, 5
GLP:Yes
Test results:LD50: Male, 31.0 mg/kg; Female, 41.1 mg/kg

2. Repeat dose and Reproductive/Developmental Toxicity1)

Purity:92.3%
Test species/strain:Rat/Crj:CD (SD)
Test method:OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
 Route:Oral (gavage)
 Doses:0 (vehicle), 1.2, 6, 30 mg/kg/day
 Number of animals:Male, 10; Female, 10
 Vehicle:Distilled water
 Administration period:Male, 43days
Female, from 14 days before mating to day 3 of lactation
 Terminal kill:Male, day 43
Female, day 4 of lactation
GLP:Yes

 Test results:

<Repeat dose toxicity>
Male and female rats given 30 mg/kg showed a transient hypolocomotion, hypopnea and salivation. On gross observation, swelling of the liver was noted in 9/10 males given 30 mg/kg.

Histopathologically, centrilobular hypertrophy (swelling) and fatty changes of hepatocytes were observed in males given 30 mg/kg. Blood chemical analyses for 30 mg/kg males revealed a significant decrease in GOT, and significant increase in total protein, albumin and Ca. All values obtained by hematological analysis were normal.

No changes were detected in body weight or food consumption in either sex.

NOEL: 6 mg/kg/day

<Reproductive and developmental toxicity>
The parental animals exhibited no effects on reproductive parameters including copulation index, fertility index, gestation period, behavior at delivery and lactation. There were no significant differences in offspring parameters including number of offspring, live offspring, sex ratio, survival index and body weight. The macroscopic and microscopic findings did not show any changes due to the test substance.

NOEL for P generation: 30 mg/kg/day
NOEL for F1 generation: 30 mg/kg/day

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:92%
Test species/strains:S. typhimurium TA100, TA1535, TA98, TA1537
E. coli WP2 uvrA
Test method:Guideline for Screening Mutagenicity Testing of Chemicals (Japan)
 Procedure:Plate method
 Solvent:DMSO
 Positive controls:-S9, AF-2 (TA100, WP2 uvrA, TA98), azide (TA1535) and 9-aminoacridine (TA1537)
+S9, 2-Aminoanthracene (all strains)
 Doses:TA100, TA1535, TA98, TA1537: 0, 4.69, 9.39, 18.75, 37.5, 75, 150 μg/plate WP2: 0, 75, 150, 300, 600, 1200, 2400 ug/plate
 S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
 Plates/test:3
 Number of replicate:2
GLP:Yes
 Test results:
Minimum concentration of test substance at which toxicity to bacteria was observed:
with metabolic activation: 150 μg/plate (TA), 1500 μg/plate (WP2)
without metabolic activation: 150 μg/plate (TA), 2400 μg/plate (WP2)

Genotoxic effects:
S.typhimurium TA100, TA1535, TA98, TA1537
+?-
with metabolic activation:[ ][ ][*]
without metabolic activation:[ ][ ][*]

E. coli WP2 uvrA
+?-
with metabolic activation:[ ][ ][*]
without metabolic activation:[ ][ ][*]

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

Purity:92%
Type of cell used:Chinese hamster CHL cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
 Solvent:water
 Positive controls:-S9, Mitomycin C
+S9, Cyclophosphamide
 Doses:-S9: 0, 0.10, 0.19, 0.38 mg/ml
+S9: 0, 0.18, 0.36, 0.71 mg/ml
 S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
 Plates/test:2
GLP:Yes

 Test results:
2-Hydroxypropanenitrile induced chromosomal aberrations with and without exogenous metabolic activation and weakly induced polyploidy

Lowest concentration producing cytogenetic effects in vitro:
with metabolic activation: 0.71 mg/ml
without metabolic activation: 0.38 mg/ml

Genotoxic effects:
+?-
with metabolic activation:[*][ ][ ]
without metabolic activation:[*][ ][ ]

1)The tests were performed by the Mitsubishi-Kasei Institute of Toxicological and Environmental Sciences, 14 Sunayama, Hazaki-machi, Kashima-gun, Ibaraki, 314-02, Japan. Tel 81-479-46-2871 Fax 81-479-46-2874
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