The effect of nitrofen [4-(2,4-dichlorophenoxy)nitrobenzene] on the reproductive performance of male rats

Technical grade nitrofen was fed to 4 groups (25/group) of male Sprague-Dawley rats for 13 weeks at dietary concentrations of 0, 100, 500, or 2500 ppm. Untreated female rats of the same age and strain were mated with treated males and fertility, gestation, and lactation indices were monitored. After mating, males were bled for clinical chemistry and hematology analyses, killed, and necropsied; organ weights were recorded, and liver, testes, and kidneys evaluated histopathologically. Offspring were observed for 35 days to determine general health and viability. At 2500 ppm, body weights of paternal animals were reduced throughout the dosing period. No hematologic abnormalities were seen. Statistically significant changes noted in clinical chemistry parameters included increased total protein, albumin, globulin, and cholesterol and decreased glucose. Testes, kidneys, and liver weights were increased at 500 and 2500 ppm, but histologic changes were limited to the liver with hypertrophy and cytoplasmic basophilia of centrilobular hepatocytes occurring at 500 and 2500 ppm. There were no effects on fertility, gestation, litter size, weight, or sex ratio in any group. Offspring health and survival to day 35 was unaffected. Based on the parameters examined, the no-observed effect level (NOEL) for male rats fed nitrofen for 13 weeks was 100 ppm. Male reproductive performance was not affected at dietary concentrations up to and including 2500 ppm.