Tetrabromoethane

四臭化エタン


[CAS No. 79-27-6]

1,1,2,2-Tetrabromoethane

1,1,2,2-テトラブロモエタン

Molecular formula: C2H2Br4　Molecular weight: 345.65

ABSTRACT

Tetrabromoethane was studied for oral toxicity in rats in a single dose toxicity test at doses of 0, 612, 722, 852, 1005, 1186 and 1400 mg/kg, and in a 28-day repeated dose toxicity test at doses 0, 6, 20, 60 and 200 mg/kg.

The single dose oral toxicity test revealed LD50 values of 924 mg/kg for males and 925 mg/kg for females.

With regard to repeated dose toxicity, there was a transient softening of the stools in males and females of the 200 mg/kg group. Urinalysis revealed a decrease in pH in males of the 200 mg/kg group. Hematological and blood biochemical examinations revealed increases in γ-GTP, total protein, albumin, A/G ratio, total cholesterol and calcium, and decreases in platelet count, potassium and total bilirubin in males, females or both sexes of the 20 mg/kg or more groups. Necropsy revealed enlargement of livers in both sexes of the 20 mg/kg or more groups. There were increases in relative liver weight in 20 mg/kg males and absolute and relative liver weight in both sexes of the 60 and 200 mg/kg groups. The 200 mg/kg group also showed increases in relative kidney weights in males and absolute and relative kidney weights in females. Histopathological examination revealed centrilobular hypertrophy of hepatocytes in males and females of the 20, 60 and 200 mg/kg groups. Hypertrophy of the follicular cells in the thyroid was also observed in both sexes of the 60 and 200 mg/kg groups. No chemical-related changes were observed in the kidney. The alterations showed a tendency for recovery or complete recovery at the end of 14-day recovery period. The NOEL is considered to be 6 mg/kg/day for both sexes.

Genotoxicity of tetrabromoethane was studied in a reverse mutation test in bacteria and by a chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

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

Tetrabromoethane did not induce chromosomal aberrations in CHL/IU cells, with or without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:99.2 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Dosage:0 (vehicle), 612, 722, 852, 1005, 1186, 1400 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:Olive oil
GLP:Yes

　Test results:

Clinical signs such as decreased locomotor activity, adoption of a prone position and tremors were observed in the treated groups. Deaths of males occurred at doses of 722 mg/kg or more and of females at 852 mg/kg or more, 1 to 24 hr after administration. Body weight gain showed suppression with dose-dependence. Necropsy revealed retention of urine in the urinary bladder in the animals that died.

The LD50 value was estimated to be 924 mg/kg for males and 925 mg/kg for females.

2. Repeated Dose Oral Toxicity 1)

Purity:99.2 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:Guideline for 28-Day Repeated Dose Toxicity Test in Mammalian Species (Chemical Substances Control Law of Japan)
　Route:Oral (gavage)
　Dosage:0 (vehicle), 6, 20, 60, 200 mg/kg
　Number of animals/groupMales, 5; females, 5
　Vehicle:Olive oil
　Administration period:Males and females, 28 days
　Terminal killing:Males and females, days 29 or 43
GLP:Yes

　Test results:

There was a transient softening of the stool in males and females of the 200 mg/kg group. Urinalysis revealed a decrease in pH in males of the 200 mg/kg group. The 200 mg/kg females showed a decrease in platelet count. Blood biochemical examination revealed increases in total protein and albumin in females, a decrease in chloride in 200 mg/kg males and females, a decrease in potassium in 60 mg/kg males and 200 mg/kg males and females, increases in the A/G ratio in 200 mg/kg males and 60 and 200 mg/kg females and calcium in 60 and 200 mg/kg females. Additionally, 200 mg/kg males and females showed an increase in total cholesterol and 200 mg/kg males showed an increase in γ-GTP and a decrease in total bilirubin. Necropsy revealed liver enlargement in both sexes of the 20 mg/kg or more groups. There were increases in relative liver weights in 20 mg/kg males and absolute and relative liver weights in both sexes of the 60 and 200 mg/kg groups. The 200 mg/kg group also showed increases in relative kidney weights in males and absolute and relative kidney weights in females. Histopathological examination revealed centrilobular hypertrophy of hepatocytes in males and females of the 20, 60 and 200 mg/kg groups and hypertrophy of the follicular cells in the thyroid in both sexes of the 60 and 200 mg/kg groups. These changes showed a tendency for recovery or complete recovery at the end of 14-day recovery period. The NOEL for repeated dose toxicity is considered to be 6 mg/kg/day for both sexes.

3. Genetic Toxicity

3-1. Bacterial test 1)

Purity:99.2 %
Test species/strain:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 471
　Procedures:Pre-incubation method
　Solvent:Dimethyl sulfoxide
　Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98, WP2 uvrA), Sodium azide (TA1535) and 9-Aminoacridine (TA1537)
+S9 mix; 2-Aminoanthracene (all strains)
　Dosage:-S9 mix; 0, 15.6, 31.3, 62.5, 125, 250, 500 μg/plate (all strains)
+S9 mix; 0, 15.6, 31.3, 62.5, 125, 250, 500 μg/plate (TA98, TA100, TA1535, TA1537)
+S9 mix; 0, 31.3, 62.5, 125, 250, 500, 1000 μg/plate (WP2 uvrA)
　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 or E. coli strains. Toxicity was observed at 500 μg/plate (all strains) without S9 mix, and observed at 500 μg/plate (TA98, TA100, TA1535, TA1537), and at 1000 μg/plate (WP2 uvrA) with S9 mix.

Genetic effects:
S. typhimurium TA100, TA1535, TA98, 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) 1)

Purity:99.2 %
Type of cell used:Chinese hamster lung (CHL) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 473
　Solvent:Dimethyl sulfoxide
　Positive controls:-S9 mix; 1-Methyl-3-nitro-1-nitrosoguanidine
+S9 mix; 3,4-Benzo[a]pyrene
　Dosage:-S9 mix (6 hr short-term treatment); 0, 55, 110, 220, 330, 440, 880 μg/mL
+S9 mix (6 hr short-term treatment); 0, 55, 110, 220, 330, 440 μg/mL
-S9 mix (24 hr continuous treatment); 0, 55, 110, 220, 330, 440 μg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

With the 6 hr short-term treatment, chromosomal aberrations were not induced with or without S9 mix. Moreover, chromosomal aberrations were not induced after 24 hr continuous treatment without S9 mix.

Cytotoxicity was observed at 880 μg/mL after 6 hr short-term treatment without S9 mix..

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

1)The tests were performed by the Research Institute for Animal Science in Biochemistry and Toxicology, 3-7-11 Hashimotodai, Sagamihara-shi, Kanagawa 229-1132, Japan. Tel +81-42-762-2775 Fax +81-42-762-7979