© 1989 Oxford University Press
research-article |
30-Day Oral Toxicity Study of L-Selenomethionine in Female Long-Tailed Macaques (Macaca fascicularis)
*California Primate Research Center, University of California Davis, California 95616
Department of Health Services, State of California 2151 Berkeley Way, Berkeley, California 94704
Health and Welfare Agency, Slate of California Sacramento, California 95814
§California Public Health Foundation 2001 Addtson Street, Berkeley, California 94704
Received September 8, 1988; accepted December 19, 1988
Twenty female long-tailed macaques received nasogastric intubation of 0–600 µg/kg-day L-sele-nomethionine for up to 30 consecutive days. Selenium ingestion was well tolerated at all dose levels until the second to third week of the study at which time two animals given 600 µg/kg-day died. One animal from the 300 µg/kg-day group was removed from study on Treatment Day 19 due to selenium-induced hypothermia. In some cases, administered doses were reduced at the 300 and 600 µg/kg-day levels such that the final time-weighted average doses were 0, 25, 62–117, 150, 188–203, and 300 µg/kg-day. Six animals at the 188 µg/kg-day level or greater required nonscheduled fruit and dietary supplementation to prevent their impending demise. As the dose and duration of exposure increased, the incidence of anorexia, gastrointestinal distress, mucocutaneous toxicity, and frequency of reduced body temperature also increased. A dose-dependent reduction in body weight was also observed. At the greater doses, disturbances in menstrual function were evident, and were accompanied by the absence of serum progesterone concentrations above 1.0 ng/ml, reduced luteal phase lengths, increased intermenstrual intervals, and lowered estrogen excretion. A maximum tolerated dose of 150 µg/kg-day L-seleno-methionine for 30 days was identified based on mean body weight reduction, hypothermia, dermatitis, xerosis, cheilitis, disturbances in menstruation, and the necessity of dietary intervention to prevent death at doses of 188 µg/kg-day or greater.