NTP Toxicology and Carcinogenesis Studies of Diglycidyl Resorcinol Ether (Technical Grade) (CAS No. 101-90-6) In F344/N Rats and B6C3F1 Mice (Gavage Studies).
Diglycidyl resorcinol ether (DGRE), a pale, yellow, translucent, amorphous solid at room temperature, is used as a liquid spray epoxy resin, as a diluent in the production of other epoxy resins used in electrical, tooling, adhesive, and laminating applications, and as a curing agent for polysulfide rubber. Approximately 3,000 workers are exposed to DGRE. The quantity of DGRE produced in the United States is not known. Toxicology and carcinogenesis studies of technical grade diglycidyl resorcinol ether (81% pure) were conducted by administering the chemical in corn oil by gavage to groups of 50 male and 50 female F344/N rats at doses of 25 or 50 mg/kg and to groups of 50 male and female B6C3F1 mice at doses of 50 or 100 mg/kg. A supplemental study of similar design in male and female rats (0 or 12 mg/kg) was started approximately 12 months later because of high mortality in the 50 mg/kg dose groups. Doses were administered five times per week for 103 weeks. Groups of 50 rats and 50 mice of each sex received corn oil by gavage on the same dosing schedule and served as vehicle controls. Throughout most of the primary study, mean body weights of high dose male and female rats and female mice were lower than those of the corresponding vehicle controls. In the supplemental study, body weights of both sexes of the dosed rats were unaffected by administration of DGRE. Survival of dosed rats of each sex in the primary study was dose related and was shorter (P<0.001) than that of the vehicle controls. No high dose male rats and only 1/50 high dose female rats lived to the end of the study. Bronchopneumonia was the most frequent cause of early death among the rats and may have resulted from the animals' aspiration of corn oil containing diglycidyl resorcinol ether. Survival of the dosed male rats in the supplemental study was reduced (P<0.005) when compared to controls. There was no significant difference in survival between dosed and control female rats in the supplemental study. Survival of dosed and control mice was comparable but poorer in females, with 20/50 (40%) of the controls, 13/50 (26%) of the low dose, and 10/50 (20%) of the high dose groups alive at the end of 2 years. These early deaths were due to suppurative and necrotizing inflammation of the reproductive tract, possibly caused by a Klebsiella sp. infection. The incidences of rats and mice with hyperkeratosis and hyperplasia of the forestomach were compound related. For rats and mice of each sex, incidences of animals with squamous cell papillomas, squamous cell carcinomas, or both occurred with statistically significant positive trends and the incidences observed in other organs in dosed groups relative to the controls. An audit of the experimental data was conducted for the 2-year studies of diglycidyl resorcinol ether. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year gavage studies, technical grade diglycidyl resorcinol ether caused hyperkeratosis and hyperplasia of the forestomach in rats and mice. DGRE was carcinogenic for male and female F344/N rats and for male and female B6C3F1 mice, causing both benign and malignant neoplasms of the forestomach. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive Synonym: DGRE