Chloropentabromocyclohexane

クロロペンタブロモシクロヘキサン


[CAS No. 87-84-3]

1,2,3,4,5-Pentabromo-6-chlorocyclohexane

1,2,3,4,5-ペンタブロモ-6-クロロシクロヘキサン

Molecular formula: C6H6Br5Cl Molecular weight: 513.09

ABSTRACT

Chloropentabromocyclohexane was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 20, 140, and 1000 mg/kg/day. An increase in relative liver weights was observed in males of the 1000 mg/kg/day group. Histological examination revealed an increase in hyaline droplets in the renal tubular epithelium in males of the 1000 mg/kg/day group. These changes were not observed at the end of the recovery period. No test substance-related changes were noted for clinical observations, body weights, food consumption, hematology, blood chemistry or urinalysis data. The NOELs for the repeat dose toxicity are considered to be 140 mg/kg/day for males and 1000 mg/kg/day for females.

Chloropentabromocyclohexane was not mutagenic to Salmonella typhimurium, TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA with or without an exogeneous metabolic activation system. Regardless of the presence or absence of an exogenous metabolic activation system, this chemical induced structural chromosomal aberrations in CHL/IU cells. Polyploidy was not induced under the conditions of the present study.

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose Toxicity １）

Purity:> 95%
Test species/strain:Rat/Crj:CD (SD)
Test method:Guidelines for 28-Day Repeat Dose Toxicity Testing for Chemicals (Japan)
　Route:Oral (gavage)
　Doses:0 (vehicle), 20, 140, 1000 mg/kg/day
　Number of animals/group:Males, 6; females, 6
　Vehicle:0.5% sodium carboxymethyl cellulose solution containing 0.1% Tween 80
　Administration period:Males and females, 28 days
　Terminal kill:Days 29 or 43
GLP:Yes

　Test results:

An increase in relative liver weight was observed in males of the 1000 mg/kg/day group. Histological examination revealed an increase in hyaline droplets in the renal tubular epithelium in males of the 1000 mg/kg/day group. These changes were not observed at the end of the recovery period.
No test substance-related changes were noted for clinical observations, body weights, food consumption, hematology, blood chemistry or urinalysis data.
The NOELs for the repeat dose toxicity are considered to be 140 mg/kg/day for males and 1000 mg/kg/day for females.

2. Genetic Toxicity

2-1. Bacterial test １）

Purity:≧ 95 %
Test species/strain:Salmonella typhimurium, TA100, TA1535, TA98, TA1537 Escherichia coli WP2 uvrA
Test method:OECD guidelines (No. 471, 472) and Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
　Procedures:Pre-incubation method
　Solvent:DMSO
　Positive controls:-S9 mix, AF-2 (TA100, TA98), sodium azide (TA1535), ENNG (WP2 uvrA) and 9-aminoacridine (TA1537)
+S9 mix, 2-aminoanthracene (all strains)
　Doses:313, 625, 1250, 2500, 5000 μg/plate
　S-9: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.

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

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

2-2. Non-bacterial in vitro test (chromosomal aberration test) １）

Purity:≧ 95 %
Type of cell used:Chinese hamster CHL/IU cells
Test method:OECD guidelino (No. 473) and Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
　Solvent:DMSO
　Positive controls:-S9 mix, Mitomycin C
+S9 mix, Benzo[a]pyrene
　Doses:-S9 mix (24 h treatment): 0, 15, 30, 60 μg/ml
-S9 mix (48 h treatment): 0, 7.5, 15, 30 μg/ml
-S9 mix (6 h pulse treatment): 0, 15, 30, 60 μg/ml
+S9 mix (6 h pulse treatment): 0, 37.5, 75, 150 μg/ml
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:
This chemical induced structural chromosomal aberrations in the absence or presence of an exogenous metabolic activation system.

Lowest concentration producing cytogenetic effects in vitro:
Without metabolic activation (24 h treatment): 15 μg/ml
Without metabolic activation (48 h treatment): 30 μg/ml
Without metabolic activation (6 h pulse treatment): 30 μg/ml
With metabolic activation (6 h pulse treatment): 75 μg/ml

Genotoxic effects:

clastogenicitypolyploidy

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

1)The tests were performed by the Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki-machi, Kashima-gun, Ibaraki, 314-02, Japan. Tel +81-479-46-2871 Fax +81-479-46-2874