30-day oral toxicity study of L-selenomethionine in female long-tailed macaques (Macaca fascicularis).
Twenty female long-tailed macaques received nasogastric intubation of 0-600 micrograms/kg-day L-selenomethionine 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 micrograms/kg-day died. One animal from the 300 micrograms/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 micrograms/kg-day levels such that the final time-weighted average doses were 0, 25, 62-117, 150, 188-203, and 300 micrograms/kg-day. Six animals at the 188 micrograms/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 micrograms/kg-day L-selenomethionine 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 micrograms/kg-day or greater.
California Primate Research Center, University of California, Davis 95616.
M J
MJ
Cukierski
C C
CC
Willhite
B L
BL
Lasley
T A
TA
Hendrie
S A
SA
Book
D N
DN
Cox
A G
AG
Hendrickx
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004970:Estrone / Q000652:urine; D005260:Female; D008252:Macaca fascicularis; D008598:Menstruation / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D012643:Selenium / Q000633:toxicity*; D012645:Selenomethionine / Q000633:toxicity*
D004970:Estrone; D011374:Progesterone; D012645:Selenomethionine; D012643:Selenium