title: Pyrogallol-associated dermal toxicity and carcinogenicity in F344/N rats and B6C3F1/N mice.
abstract: Pyrogallol (CAS No. 87-66-1), a benzenetriol used historically as a hair dye and currently in a number of industrial applications, was nominated to the National Toxicology Program (NTP) for testing based on the lack of toxicity and carcinogenicity data. Three-month and two-year toxicity studies to determine the toxicity and carcinogenicity of pyrogallol when applied to naïve skin (i.e. dermal administration) were conducted in both sexes of F344/N rats and B6C3F1/N mice. In the three-month studies, adult rodents were administered pyrogallol in 95% ethanol five days per week for 3 months at doses of up to 150 mg/kg body weight (rats) or 600 mg/kg (mice). Based on the subchronic studies, the doses for the two-year studies in rats and mice were 5, 20 and 75 mg/kg of pyrogallol. All mice and most rats survived until the end of the three-month study and body weights were comparable to controls. During the two-year study, survival of dosed rats and male mice was comparable to controls; however survival of 75 mg/kg female mice significantly decreased compared to controls. The incidences of microscopic non-neoplastic lesions at the site of application were significantly higher in all dosed groups of rats and mice and in both the 3-months and two-year studies. In the two-year study, hyperplasia, hyperkeratosis and inflammation tended to be more severe in mice than in rats, and in the mice they tended to be more severe in females than in males. The incidence of squamous cell carcinoma at the site of application (SOA) in 75 mg/kg female mice and SOA squamous cell papillomas in 75 mg/kg male mice were greater than controls. Pyrogallol was carcinogenic in female mice and may have caused tumors in male mice.
authors.affiliation: National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Minerva
authors.initials: M
authors.lastname: Mercado-Feliciano
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Herbert
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wyde
authors.forename: Diane K
authors.initials: DK
authors.lastname: Gerken
authors.forename: Milton R
authors.initials: MR
authors.lastname: Hejtmancik
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Hooth
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D006202:Hair Dyes; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D007642:Keratosis / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D010212:Papilloma / Q000139:chemically induced* / Q000473:pathology; D011748:Pyrogallol / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology; D036401:Toxicity Tests, Chronic; D059550:Toxicity Tests, Subchronic
chemical_list: D002273:Carcinogens; D006202:Hair Dyes; D011748:Pyrogallol