Developmental Toxicity of L-Selenomethionine in Macaca fascicularis

Forty pregnant long-tailed macaques were dosed via nasogastricintubation with 0, 25, 150, or 300 µg/kg of L-selenomethionine(Se) daily during organogenesis [Gestational Day (GD) 20–50].Clinical examination of the dams, maternal body weights, sonographicevaluations, clinical chemistry screens, and measures of serumprogesterone and urinary estrone conjugates were used as indicatorsof maternal and fetal status in all animals. The pregnanciesof two to three dams from each dose group were followed untilterm ({small tilde}GD 165); the remainder (N = 7/dose group)were scheduled for hysterotomy on GD 100 ± 2. A standardteratologic evaluation was performed including visceral andskeletal examinations. Fetal liver, kidney, skin, and smooth,cardiac, and skeletal muscles were examined by light microscopy;heart muscle was also evaluated by transmission electron microscopy.Neonates delivered at term remained with the dams and were removedperiodically for morphometric, neurologic, behavorial, and ophthalmologicassessments on Days 1, 8, 15, 22, and 30 of age. Dose-dependentmaternal toxicity as evidenced by anorexia, vomiting, and asignificant reduction in body weight increased with increasingduration of Se exposure. One growth-retarded fetus was recoveredon GD 131 from a compromised dam exposed to 25 /ig/kg-day; oneearly embryonic death (GD 35) and two fetal deaths [GD 68 (followedby maternal death) and GD 123] occurred among animals dosedwith 300 µg/kg-day. Pregnancy loss among treated animalswas not significantly different from concurrent or historicalcontrols. No statistically significant treatment-related effectswere observed at necropsy on GD 100 ± 2. One infant exposedto 150 Mg/kg-day prenatally exhibited a unilateral corticalcataract, which may have been a spontaneous occurrence. Thelimited developmental effects observed and reported teratogenesisin nonmammalian species suggest that comparative pharmacokineticstudies are required before the full public health significanceof elevated Se is understood.