A six-month chronic dietary toxicity study of pyriproxyfen in rats

Abstract

Groups of 21 male and 21 female Sprague-Dawley (SD) rats were fed diets containing pyriproxyfen at concentrations of 0, 80, 400, 2,000 and 10,000 ppm for 6 months. No death was found in any group. Alopecia in the neck and/or back, and soft feces were noticed in both sexes fed 10,000 ppm. A marked decrease in body weight gain was observed in both sexes fed 10,000 ppm throughout the treatment period, accompanying a decrease in food-consumption and an increase in water-intake during the initial stage of treatment. In terms of urinalysis, proteinuria, increases in K excretion, and, in number, yellowness or browish-yellowness in appearance, were observed in both sexes fed 10,000 ppm. In females fed 10,000 ppm, increased in bilirubin, Na excretion and specific gravity, and a decrease in keton bodies, were observed. In hematology, decreases in erythrocyte count, hemoglobin concentration and hematocrit value, were observed in both sexes fed 10,000 ppm and in males fed 2,000 ppm. Also, an increase in MCH (in males), decreases in MCHC and platelet count (in females) were observed in 10,000 ppm group. Blood biochemistry revealed increases in total protein, albumin, α2-globulin fraction, blood urea nitrogen, calcium (in both sexes fed 10,000 ppm), A/G ratio (in males fed 2,000 and 10,000 ppm), total cholesterol, phospholipid (in males fed 2,000 and 10,000 ppm, and in females fed 10,000 ppm), sodium (in females fed 2,000 and 10,000 ppm), γ-glutamyl transpeptidase activity (in males fed 10,000 ppm) and α1-globulin fraction (in females fed 10,000 ppm), and decreases in glucose, GOT (in both sexes fed 10,000 ppm, and on females fed 10,000 ppm), GPT (in females fed 2,000 and 10,000 ppm) β-globulin fraction (in males fed 2,000 and 10,000 ppm), triglyceride, potassium (in males fed 10,000 ppm), and cholinesterase activity (in female fed 10,000 ppm). In organ weight, increases in liver (in males fed 2,000 ppm and 10,000 ppm, and in females fed 10,000 ppm), kidney (in both sexes fed 10,000 ppm) and thyroid (in females fed 10,000 ppm) and a decrease in pituitary (in females fed 2,000 and 10,000 ppm) were observed. Gross pathology revealed a higher incidence of blackish-brown coloration of the liver, and a lower incidence of accentuated lobular pattern of the liver (in males fed 10,000 ppm). An enlargement of the liver was seen in a few of both sexes led 10,000 ppm. Histopathological examination showed that the sole effect attributable to treatment of this compound was on slight hypertrophy in the liver of both sexes fed 10,000 ppm, with a higher incidence. Based on the above results, pyriproxyfen administered to SD rats for 6 months revealed slight toxic effects such as an increased liver weight associated with hypertrophy of hepatocyte and an increased kidney weight at the highest dose level at which body weight gain was clearly suppressed. It is concluded that the non-effective level is 400 ppm for both sexes (24.0 mg/kg for males, 27.5 mg/kg for females).