National Toxicology Program

TR-403
Toxicology and Carcinogenesis Studies of Resorcinol (CAS No. 108-46-3) in F344 Rats and B6C3F₁ Mice (Gavage Studies)

Chemical Formula:  C6H6O2	-	3D Structure*
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Resorcinol is used in the manufacture of adhesives and dyes and as an ingredient in pharmaceutical preparations for the topical treatment of skin conditions. Toxicity and carcinogenicity studies were conducted by administering resorcinol (>99% pure) in water by gavage to groups of F344/N rats and B6C3F₁ mice of each sex for 17 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Chinese hamster ovary cells, mouse lymphoma cells, and Drosophila melanogaster.

17-Day Studies:

Groups of five rats of each sex were administered 0, 27.5, 55, 110, 225, or 450 mg/kg resorcinol and groups of five mice of each sex were administered 0, 37.5, 75, 100, 300, or 600 mg/kg resorcinol in deionized water by oral gavage. No rats died during the studies. All female and four male mice receiving 600 mg/kg and one male receiving 300 mg/kg died as a result of resorcinol administration. Final mean body weights of dosed rats and mice were similar to those of the control groups. No gross or microscopic lesions attributable to resorcinol administration were observed.

13-Week Studies:

Groups of 10 rats of each sex were administered 0, 32, 65, 130, 260, or 520 mg/kg resorcinol and groups of 10 mice of each sex were administered 0, 28, 56, 112, 225, or 420 mg/kg resorcinol in deionized water by oral gavage. All female and eight male rats receiving 520 mg/kg and eight mice of each sex receiving 420 mg/kg resorcinol died of chemical-related toxicity during the studies. The final mean body weights of dosed rats and mice were similar to those of the control groups. No chemical-related gross or microscopic lesions were observed.

2-Year Studies:

Doses were selected for the 2-year studies based on the decreased survival observed in the 13-week studies. Groups of 60 male rats and male and female mice were administered 0, 112, or 225 mg/kg resorcinol in deionized water by gavage, five days per week for up to 104 weeks. Groups of 60 female rats were initially administered the same doses as male rats, but by week 22 of the study 16 of the high-dose females had died. Consequently, the female rat study was restarted using doses of 0, 50, 100, or 150 mg/kg. After 15 months of exposure interim evaluations were performed on 10 animals from each group. No chemical-related changes in clinical pathology parameters or incidence of neoplasms or nonneoplastic lesions were found during the 15-month interim evaluations.

Body Weights and Survival in the 2-Year Studies:

Mean body weights of high-dose male rats were 10% to 15% lower than those of the controls from week 87 to study termination. Mean body weights of high-dose female rats were 11% to 14% lower than those of controls from week 95 to study termination. Mean body weights of other dosed rat groups were similar to those of controls. Survival of high-dose male and female rats was significantly lower than controls. Decreased survival in high-dose groups was attributed to chemical-related toxicity.

Mean body weights of high-dose female mice were 10% to 15% lower than those of controls from week 85 to study termination, whereas those of the remaining dosed mouse groups were similar to those of the controls. Survival of dosed mice was similar to that of controls. Clinical signs suggestive of a chemical-related effect on the central nervous system, including ataxia, recumbency, and tremors, were observed in rats and mice in the 2-year studies.

Neoplasms and Nonneoplastic Lesions in the 2-Year Studies:

There were no treatment-related increased incidences of neoplasms or nonneoplastic lesions in rats or mice administered resorcinol for 2 years.

Mammary gland fibroadenomas occurred at significantly reduced incidences in all exposed groups of female rats (25/50, 14/50, 12/50, 9/50). The incidence of subcutaneous fibroma or sarcoma in high-dose male mice was significantly lower than for the controls (8/50, 6/50, 1/50).

Genetic Toxicity:

Resorcinol was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation (S9). Induction of trifluorothymidine resistance was observed in mouse L5178Y lymphoma cells treated with resorcinol in the absence of S9 activation; this test was not performed with S9. Resorcinol induced sister chromatid exchanges in Chinese hamster ovary cells with and without S9. Resorcinol was positive for induction of chromosomal aberrations in Chinese hamster ovary cells in the presence of S9; an equivocal response was obtained in this test in the absence of S9. No induction of sex-linked recessive lethal mutations was observed in the germ cells of male Drosophila melanogaster when resorcinol was administered in the feed, but an equivocal response was observed when the chemical was administered by injection.

Conclusions:

Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of resorcinol in male F344/N rats given 112 or 225 mg/kg or female F344/N rats given 50, 100, or 150 mg/kg. There was no evidence of carcinogenic activity of resorcinol in male or female B6C3F₁ mice given 112 or 225 mg/kg.

Clinical signs suggestive of a chemical-related effect on the central nervous system, including ataxia, recumbency, and tremors, were observed in rats and mice in the 2-year studies.

Synonyms: 1,3-benzenediol; m-dihydroxybenzene; resorcin

Report Date: July 1992

Pathology Tables, Survival and Growth Curves from NTP 2-year Studies

Target Organs & Incidences from 2-year Studies

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