Acenaphthene

アセナフテン


CAS No. 83-32-9

1,2-Dihydroacenaphthylene

1,2-ジヒドロアセナフチレン

Molecular formula: C12H10　Molecular weight: 154.22

ABSTRACT

A single dose oral toxicity test revealed an LD50 value of above 2000mg/kg for both sexes.

Acenaphthene was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 12, 60 and 300 mg/kg. Laboratory examinations revealed an increase in total cholesterol in both sexes receiving 300 mg/kg, and an increase in phospholipids in 60 mg/kg females and both sexes given 300 mg/kg and an increase in total bilirubin in males given 300 mg/kg. The liver weight increased in both sexes given 300 mg/kg and hypertrophy of the centrilobular hepatocytes was histopathologically, noted in both sexes treated with 300 mg/kg. In the kidneys, a high incidence of eosinophilic bodies in tubular epithelium was observed in males given 60 or 300 mg/kg. All changes disappeared after a 14-day recovery period. The NOEL is considered to be 12 mg/kg/day for both sexes.

Acenaphthene was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with and without an exogeneous metabolic activation system. It was not mutagenic in TA97 without metabolic activation.

Genotoxicity of acenaphthene was studied by the chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

Structural chromosomal aberrations were induced at 0.10 and 0.20 mg/ml (mid and high concentrations) after short-term treatment with an exogenous metabolic activation system. Polyploidy was not induced in any treatment group.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Toxicity １）

Purity:99.9%
Test species/strain:Rat/Crj:CD (SD)
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Doses:0 (vehicle), 1000, 2000 mg/kg
　Number of animals:Male, 5; Female, 5/group
　Vehicle:0.5% methylcellulose solution
GLP:Yes
　Test results:
No deaths occurred in any of the treated groups. No effects were detected in terms of general condition, body weight changes or autopsy findings.
LD50: Male, >2000mg/kg; female, >2000mg/kg

2. Repeat Dose Toxicity １）

Purity:99.9 %
Test species/strain:Rat/Crj:CD (SD)
Test method:Guidelines for 28-Day Repeat Dose Toxicity Testing of Chemicals (Japan)
　Route:Oral (gavage)
　Doses:0 (vehicle), 12, 60, 300 mg/kg/day
　Number of animals:Males, 6; females, 6/group
　Vehicle:0.5% methylcellulose solution
　Administration period:Males and females, 28 days
　Terminal kill:Days 29 or 43
GLP:Yes

　Test results:

A temporary decrease in food consumption was noted in males given 300 mg/kg during the early period of administration.

Laboratory examinations revealed an increase in total cholesterol in both sexes given 300 mg/kg, an increase in phospholipids in 60 mg/kg females and both sexes given 300 mg/kg, and an increase in total bilirubin in 300 mg/kg males. An increase in liver weight was noted in both sexes receiving 300 mg/kg. Histopathologically, hypertrophy of the centrilobular hepatocytes was noted in both sexes given 300 mg/kg and the kidney, a high incidence of eosinophilic bodies in tubular epithelium was observed in males given 60 or 300 mg/kg. All changes disappeared after a 14-day recovery period. The NOEL is considered to be 12 mg/kg/day for both males and females under the conditions of the present study.

3. Genetic Toxicity

3-1. Bacterial test２）

Purity:above 99.9 %
Test species/strains:Salmonella typhimurium, TA100, TA1535, TA98, TA1537, TA97 (without S9 mix), Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline No. 471 and 472
　Procedure:Pre-incubation method
　Solvent:DMSO
　Positive controls:-S9 mix, 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide (TA100, TA98, WP2), Sodium azide (TA1535) and 9-Aminoacridine (TA1537, TA97)
+S9 mix, 2-Aminoanthracene (five strains)
　Doses:-S9 mix;
0, 1.56, 3.13, 6.25, 12.5, 25.0, 50.0 μg/plate (TA1537, TA97)
0, 6.25 - 200 μg/plate (TA100, TA1535, TA98)
0, 313 - 5000 μg/plate (WP2)

+S9 mix;
0, 15.6 - 500 μg/plate (TA1537)
0, 313 - 5000 μg/plate (TA100, TA1535, TA98, WP2)

　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:3
　Number of replicates:2 and 4 (TA1537)
GLP:Yes
　Test results:

This chemical did not induce mutations in the S. typhimurium and E. coli strains. Toxicity was observed at 50.0 μg/plate (TA1537, TA97), 100 μg/plate (TA100, TA1535, TA98) without an S9 mix, and at 250 μg/plate (TA1537) with an S9 mix. Toxicity was not observed at 5000 μg/plate in TA100, T1535, or T98 with an S9 mix and in WP2 with or without an S9 mix.

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

Salmonella typhimurium TA97
+?-
without metabolic activation:[ ][ ][*]
with metabolic activation:Not done

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

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

Purity:More than 99.9 %
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
　Vehicle:0.5 % carboxymethylcellulose sodium
　Positive controls:-S9 mix, Mitomycin C
+S9 mix, Cyclophosphamide
　Doses:-S9 mix (continuous treatment):0, 0.38, 0.75, 1.5 mg/ml
-S9 mix (short-term treatment):0, 0.19, 0.38, 0.75 mg/ml
+S9 mix (short-term treatment):0, 0.050, 0.10, 0.20 mg/ml
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

Cytogenetic effects were seen as follows.

In the short-term treatment with an exogenous metabolic activation system, structural chromosomal aberrations (4.5 and 16.9%, including gap) were induced at 0.10 and 0.20 mg/ml (mid and high concentrations), respectively. Polyploidy was not induced in any treatment group.

Lowest concentration producing cytogenetic effects in vitro:
With metabolic activation (short-term treatment): 0.10 mg/ml (clastogenicity)

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