Contract for Testing the Acute and Chronic Toxicity of Denatonium Benzoate, an Acerbic Ingredient Proposed for Use in Bad-Tasting Paint to Prevent Paint Pica. One Year Oral Toxicity Study in Monkeys. Report Number 3E

摘要

The objective of this cynomolgus monkey study was to determine the acute and chronic toxicity of denatonium benzoate, an acerbic ingredient proposed for use in bad - tasting paint to prevent paint pica. In a 1 - year toxicity study in cynomolgus monkeys, denatonium benzoate was administered by gavage at dosage levels of 1.6, 8, and 16 mg / kg / day. Eight male and eight female monkeys were initiated at each dosage levels and also as a control group. The monkeys were observed daily for changes in general behavior and appearance and for pharmacotoxic signs. Individual body weights were recorded twice weekly for the first 5 weeks of study and weekly thereafter. Ophthalmoscopy (indirect and slit lamp), electrocardiograms, hematological and biochemical studies, and urinalyses were conducted once in the control period and at 3, 6, and 12 months of study. No changes considered to be related to compound were seen in general behavior and appearance, ophthalmoscopy, electrocardiograms, body weights, hematological and biochemical studies, or urinalyses. One control monkey and a total of eight monkeys at the 1.6, 8 and 16 mg / kg / day dosage levels, at total of eight died during the study. No compound - related gross pathologic or organ-weight variations were observed at necropsy in any of the treated monkeys sacrificed at 3, 6 or 12 months or that died during the course of this study. Deaths of two of the three monkeys from the 8 mg / kg / day level and three of the four monkeys from the 16 mg / kg / day level may have been due to compound effect. Microscopically, no lesion considered compound related was seen in any of the tissues examined from monkeys sacrificed at 3 months at 8 or 16 mg / kg / day level and at 6 or 12 months at 16 mg / kg / day level or in any that died during the course of the study. Data tables and 11 references are given and appendices give results of ophthalmoscopic examinations and electrocardiograms. (Author abstract modified).