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Abstract for TOX-85

Toxicity Studies of Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) Administered by Gavage to F344/NTac Rats and B6C3F1/N Mice

CASRN: 21850-44-2
Chemical Formula: C21H20Br8O2
Molecular Weight: 943.619
Synonyms/Common Names: 2,2-Bis[3,5-dibromo-4-(2,3-dibromopropoxy)phenyl]propane; 2,2-bis[3,5-dibromo-4-(2,3-dibromopropyloxy)phenyl]propane; 2,2-bis[4-(2,3-dibromopropoxy)-3,5-dibromophenyl]propane; 2,2-bis[4-(2,3-dibromopropyloxy)-3,5-dibromophenyl]propane; bis(2,3-dibromopropoxy)tetrabromobisphenol A; bis(2,3-dibromopropyl)tetrabromobisphenol A; 1,1′-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)benzene]; 1,1′-(1-methylethylidene)bis[3,5-dibromo-4-(2,3-dibromopropoxy)]benzene; TBBPA-DBPE; 3,3′,5,5′-tetrabromobisphenol A bis(2,3-dibromopropyl) ether; tetrabromobisphenol A dibromopropyl ether
Report Date: August 2017

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Abstract

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) is used as a flame retardant in electronics, building and construction materials, and automotive materials. Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) was nominated for toxicology and in vivo genotoxicity study by the National Institute of Environmental Health Sciences because, although human exposure potential may be low, there was concern that this chemical has carcinogenic potential and has not been adequately studied. The compound was also selected for study because dibromo-1-propanol (the core structure of the 2,3-dibromopropyl ether side chain) has been studied by the NTP and found to be carcinogenic. Male and female F344/NTac rats and B6C3F1/N mice were administered tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (approximately 94% pure) in corn oil by gavage for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes.

Groups of 10 male and 10 female F344/NTac rats were administered 0, 62.5, 125, 250, 500, or 1,000 mg tetrabromobisphenol A-bis(2,3-dibromopropyl ether)/kg body weight in corn oil by gavage, 5 days per week for 14 weeks, and additional groups of 10 male and 10 female rats were administered the same doses for 23 days. Groups of 10 male and 10 female mice were administered 0, 125, 250, 500, 1,000, or 2,000 mg/kg for 14 weeks. Two 62.5 mg/kg male rats died during week 6 (one dosing accident), and one vehicle control female rat died during week 8. All mice survived to the end of the study. Final mean body weights and body weight gains of male and female rats and mice were similar to those of the vehicle controls except the final mean body weight of 250 mg/kg female mice was 11% more than that of the vehicle controls. There were no treatment-related clinical findings. Microsomal protein levels were increased in treated rats and mice. There were no chemical-related changes in absolute or relative organ weights in male or female rats or mice. There were no gross or histologic lesions in rats or mice that were considered treatment related. There were no chemical-related hematology or clinical chemistry findings in rats or mice.

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) was not mutagenic in Salmonella typhimurium strains TA98, TA100, or TA102, with or without rat liver S9 metabolic activation enzymes. In vivo, no significant increases in the frequencies of micronucleated erythrocytes were observed in peripheral blood samples from male or female B6C3F1/N mice in the 3-month study. In addition, no significant changes in the percentage of polychromatic erythrocytes were seen in these mice, suggesting that tetrabromobisphenol A-bis(2,3-dibromopropyl ether) did not cause bone marrow toxicity.

Under the conditions of these 3-month gavage studies, there were no clinical findings or treatment-related lesions in male or female F344/NTac rats or B6C3F1/N mice administered tetrabromobisphenol A-bis(2,3-dibromopropyl ether) at 0, 62.5, 125, 250, 500, or 1,000 mg/kg in rats or 0, 125, 250, 500, 1,000, or 2,000 mg/kg in mice. Final mean body weights of treated rats and mice were generally within 10% of vehicle controls, and there were no treatment-related effects on organ weights.

Studies

Summary of Findings Considered to be Toxicologically Relevant in Rats and Mice Administered Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) by Gavage for 3 Months
  Male
F344/NTac Rats
Female
F344/NTac Rats
Male
B6C3F1/N Mice
Female
B6C3F1/N Mice
Doses in corn oil 0, 62.5, 125, 250, 500, or 1,000 mg/kg 0, 62.5, 125, 250, 500, or 1,000 mg/kg 0, 125, 250, 500, 1,000, or 2,000 mg/kg 0, 125, 250, 500, 1,000, or 2,000 mg/kg
Survival rates 10/10, 8/10, 10/10, 10/10, 10/10, 10/10 9/10, 10/10, 10/10, 10/10, 10/10, 10/10 10/10, 10/10, 10/10, 10/10, 10/10, 10/10 10/10, 10/10, 10/10, 10/10, 10/10, 10/10
Body weights Dosed groups similar to the vehicle control group Dosed groups similar to the vehicle control group Dosed groups similar to the vehicle control group 250 mg/kg group 11% more than the vehicle control group
Clinical findings None [a] None None None
Organ weights None None None None

Hematology/clinical chemistry [hematology includes: rats (day 23), rats and mice (week 14); clinical chemistry includes: rats (days 4, 23, week 14)]

None None None None
Sperm parameters and vaginal cytology None None None None
Nonneoplastic effects None None None None
Genetic Toxicology
Assay Results
Bacterial gene mutations:
 
Negative in S. typhimurium strains TA98, TA100, and TA102 with or without S9
Micronucleated erythrocytes
Mouse peripheral blood in vivo:
Negative in males and females

[a] None = no treatment-related effects for this endpoint