Nitrofen: a review and perspective.

With the exception of occasional reports of skin irritation, 20 years of commercial nitrofen use has not produced indications of toxicity in man. In mature non-pregnant laboratory animals nitrofen is only slightly toxic after acute oral, dermal, or respiratory exposures, and it is not a sensitizer. However, absorption through skin occurs rapidly from solvent-based formulations. Chronic administration in the diet at doses of 20 mg/kg body wt/day and higher produced liver toxicity in mice, rats, and dogs with liver tumors developing in mice at dose levels at 470 mg/kg/day. In addition to liver tumors in mice, the National Cancer Institute's Carcinogen Bioassay Program also found a dose-related incidence of pancreatic tumors in females of 1 of 2 strains of rat after lifetime feeding at levels at and above 65 mg/kg/day. Single and repeated doses given during pregnancy to rats and mice produce neonatal lethality accompanied by signs of impaired breathing, diaphragmatic hernias, heart anomalies, hydronephrosis, and apparent eye anomalies which are due to effects on the Harderian gland. These anomalies were produced by both oral and dermal doses, but did not occur in the rabbit or when dosing was restricted to the male parent only. Neonatal deaths appear after repeated maternal doses of 3 mg/kg/day and higher; the overall no observed effect level for effects in the offspring was 0.17 mg/kg/day. Based on a 10(-6) level of tumorigenic risk the acceptable average daily intake for man is 1 microgram/kg/day; pregnant women should not be exposed to more than 1.7 micrograms/kg in any single 24-h period.