NTP technical report on the toxicity studies of Glyphosate (CAS No. 1071-83-6) Administered In Dosed Feed To F344/N Rats And B6C3F1 Mice.

Glyphosate is a systemic, broad-spectrum, post-emergence herbicide used for non-selective weed control. It was selected for study because of its widespread use, potential for human exposure, and the lack of published reports concerning comprehensive toxicity or carcinogenicity evaluations. Chemical disposition, 13-week toxicity, and mutagenicity studies of glyphosate were conducted. In disposition studies, male F344/N rats were administered an oral dose (5.6 or 56 mg/kg) of 14C-glyphosate. Blood, urine, fecal, and tissue samples were collected and analyzed for radioactivity. Within 72 hours after glyphosate dosing, 20-30% of the administered radioactivity was eliminated via urine, 70-80% via feces, and about 1% of the radioactivity remained in the tissues. Studies following oral, intravenous, and intraperitoneal administration of glyphosate indicated that the urinary radioactivity represented the amount of glyphosate absorbed and that the fecal radioactivity represented the amount unabsorbed from the gastrointestinal tract. In the 13-week toxicity studies, groups of 10 male and female F344/N rats and B6C3F1 mice were administered glyphosate in feed at 0, 3125, 6250, 12500, 25000, or 50000 ppm. Glyphosate administration induced increases in serum bile acids, alkaline phosphatase, and alanine aminotransferase activities in rats, suggesting mild toxicity to the hepatobiliary system. Clinical pathology measurements were not performed with mice. No histopathologic lesions were observed in the livers of rats or mice. There was no evidence of adverse effects on the reproductive system of rats or mice. Cytoplasmic alteration was observed in the parotid and submandibular salivary glands of rats and parotid salivary glands in mice. The salivary gland effects of glyphosate were demonstrated to be mediated through an adrenergic mechanism which could be blocked by the adrenergic antagonist, propanolol. Glyphosate was not mutagenic in Salmonella, and did not induce micronuclei in mice. The no-observed-adverse-effect level (NOAEL) for the salivary gland lesions was 3125 ppm in the diet for mice. A NOAEL could not be determined from the rat study. Synonyms: Glyphosate, technical grade; Glycine, N-(phosphonomethyl); N-phosphono-methyl glycine; N-(phosphonomethyl)glycine; MON 0573; MON 2139.