Multigeneration reproduction and carcinogenicity studies in Sprague-Dawley rats exposed topically to oxidative hair-colouring formulations containing p-phenylenediamine and other aromatic amines.

Two-generation reproduction and chronic toxicity-carcinogenicity studies were conducted in Sprague-Dawley rats receiving topical applications of six oxidative hair-colouring formulations. These formulations were prepared as prototypes of permanent hair colourings using the base ingredients and primary intermediates and couplers most often used in this kind of product. Among the dyes included in the various formulations were p-phenylenediamine, p-toluenediamine, p-aminophenol, resorcinol, m-aminophenol, 1-naphthol, 2-amino-4-nitrophenol, 4-chlororesorcinol, p-aminodiphenylamine hydrochloride and N-methyl-p-aminophenol sulphate. The dye solutions were mixed with an equal volume of 6% hydrogen peroxide prior to application. In the reproduction study the samples were applied topically twice weekly throughout the growth, mating, gestation and lactation phases of the F0 parents to the weaning of the F1a and F2b litters. Fertility, gestation and foetal viability indices and body weights were evaluated for the six treatment groups and these were compared with the values for the three concurrent control groups. Weanlings selected from the F1a litters were the subjects for the lifetime carcinogenesis study. For 24 months they received twice-weekly topical applications of the same dyes as were administered to their parents. Clinical chemistry, haematological and urinalysis studies were performed at months 3, 12, 18 and 24, and five animals/sex/group were killed at month 12 and autopsied for histological examination of the rat tissues. All animals in the chronic study were evaluated for incidence of neoplastic and non-neoplastic lesions. In the reproduction phase the application of hair dyes had no adverse effect on the fertility of the males or females, or on gestation, lactation and weaning indices. The average number weaned per litter and the mean body weights of the weanlings were comparable among the treated and control groups. No treatment-related gross lesions were observed in any animals necropsied at month 12 or at study termination, or in any rats that died during the course of the carcinogenicity study. Comparison of the tumour incidences among the six treated and three control groups showed some significant variations among those tumours occurring most frequently in this strain of rats, and pituitary adenomas were also increased significantly (P less than 0.05) in the females of one of the treated groups. The incidence of this tumour is known to be high and variable in untreated female Sprague-Dawley rats.(ABSTRACT TRUNCATED AT 400 WORDS)