Evaluation of the Teratogenic and Mutagenic Potential of the Oxidative Dyes, 4-Chlororesorcinol, M-Phenylenediamine, and Pyrogallol

Abstract

Three oxidative dyes were screened for mutagenic and teratogenic potential. A range of mutagenic response was observed using Salmonella typhimurium tester strains, TA 1538 and TA 98 in the presence or absence of metabolic activation. M-phenylenediamine exhibited activity with both strains while 4-chlororesorcinol showed no response in either strain. Pyrogallol exhibited a weak response that showed no linear correlation only in TA 98 in the absence of activation. In teratogenicity studies, the 3 oxidative dyes were administered by gavage to Sprague-Dawley rats on days 6 through 15 of gestation at the following dose levels: 4-chlororesorcinoI at 50,100, and 200 mg/kg; m-phenylenediamine at 45,90, and 180 mg/kg; and pyrogallol at 100,200, and 300 mg/kg. A significant reduction in mean maternal weight gain was noted at the high dose level of each dye. The high dose levels of 4-chlororesorcinol and pyrogallol were embryolethal as indicated by an increase in resorptions. The high dose level of pyrogallol was fetotoxic as evidenced by a decrease in fetal body weights. Evaluation of the number of gross, visceral, or skeletal anomalies/variations revealed no statistically significant differences between dye treated and control groups. Exposure to the positive control agents, Vitamin A and aspirin, resulted in a statistically significant increase in abnormal fetuses with a broad spectrum of gross visceral and skeletal anomalies ranging from a frequency of 18-60%. These studies indicated that the predictability of teratogenicity from bacterial mutagenicity screening is low with the chemical categories under investigation.