Toxicity and carcinogenicity of hydroquinone in F344/N rats and B6C3F1 mice.
Toxicology and carcinogenesis studies were conducted by administering hydroquinone (more than 99% pure) by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 wk or 2 yr. 14-day studies were conducted by administering hydroquinone in corn oil to rats at doses ranging from 63 to 1000 mg/kg body weight and to mice at doses ranging from 31 to 500 mg/kg, 5 days/wk. In the 13-wk studies, doses for rats and mice ranged from 25 to 400 mg/kg. At those doses showing some indication of toxicity in the 14-day and 13-wk studies, the central nervous system, forestomach and liver were identified as target organs in both species and renal toxicity was observed in rats. Based on these results, 2-yr studies were conducted by administering 0, 25 or 50 mg hydroquinone/kg in deionized water by gavage to groups of 65 rats of each sex, 5 days/wk. Groups of 65 mice of each sex were given 0, 50 or 100 mg/kg on the same schedule. 10 rats and 10 mice from each group were killed and evaluated after 15 months. Mean body weights of high-dose male rats and high-dose mice were approx. 5-14% lower than those of controls during the second half of the study. No differences in survival were observed between dosed and control groups of rats or mice. Nearly all male rats and most female rats in all vehicle control and exposed groups had nephropathy, which was judged to be more severe in high-dose male rats. Hyperplasia of the renal pelvic transitional epithelium and renal cortical cysts were increased in male rats. Tubular cell hyperplasia of the kidney was seen in two high-dose male rats, and renal tubular adenomas were seen in 4/55 low-dose and 8/55 high-dose male rats; none was seen in vehicle controls or in female rats. Mononuclear cell leukaemia in female rats occurred with increased incidences in the dosed groups (vehicle control, 9/55; low dose, 15/55; high dose, 22/55). Compound-related lesions observed in the liver of high-dose male mice included anisokaryosis, syncytial alteration and basophilic foci. The incidences of hepatocellular neoplasms, primarily adenomas, were increased in dosed female mice (3/55; 16/55; 13/55). Follicular cell hyperplasia of the thyroid gland was increased in dosed mice.(ABSTRACT TRUNCATED AT 400 WORDS)
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
F W
FW
Kari
J
J
Bucher
S L
SL
Eustis
J K
JK
Haseman
J E
JE
Huff
D000284:Administration, Oral; D000818:Animals; D003314:Corn Oil; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006873:Hydroquinones / Q000008:administration & dosage / Q000633:toxicity*; D006965:Hyperplasia; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced*; D007951:Leukemia, Myeloid / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D012640:Seizures / Q000139:chemically induced; D012737:Sex Factors; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013964:Thyroid Neoplasms / Q000139:chemically induced; D014202:Tremor / Q000139:chemically induced
D006873:Hydroquinones; D003314:Corn Oil; C031927:hydroquinone