Developmental toxicity of L-selenomethionine in Macaca fascicularis.
Forty pregnant long-tailed macaques were dosed via nasogastric intubation with 0, 25, 150, or 300 micrograms/kg of L-selenomethionine (Se) daily during organogenesis [Gestational Day (GD) 20-50]. Clinical examination of the dams, maternal body weights, sonographic evaluations, clinical chemistry screens, and measures of serum progesterone and urinary estrone conjugates were used as indicators of maternal and fetal status in all animals. The pregnancies of two to three dams from each dose group were followed until term (approximately GD 165); the remainder (N = 7/dose group) were scheduled for hysterotomy on GD 100 +/- 2. A standard teratologic evaluation was performed including visceral and skeletal 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 removed periodically for morphometric, neurologic, behavioral, and ophthalmologic assessments on Days 1, 8, 15, 22, and 30 of age. Dose-dependent maternal toxicity as evidenced by anorexia, vomiting, and a significant reduction in body weight increased with increasing duration of Se exposure. One growth-retarded fetus was recovered on GD 131 from a compromised dam exposed to 25 micrograms/kg-day; one early embryonic death (GD 35) and two fetal deaths [GD 68 (followed by maternal death) and GD 123] occurred among animals dosed with 300 micrograms/kg-day. Pregnancy loss among treated animals was not significantly different from concurrent or historical controls. No statistically significant treatment-related effects were observed at necropsy on GD 100 +/- 2. One infant exposed to 150 micrograms/kg-day prenatally exhibited a unilateral cortical cataract, which may have been a spontaneous occurrence. The limited developmental effects observed and reported teratogenesis in nonmammalian species suggest that comparative pharmacokinetic studies are required before the full public health significance of elevated Se is understood.
Tarantal
A F
AF
California Primate Research Center, University of California, Davis 95616.
Willhite
C C
CC
Lasley
B L
BL
Murphy
C J
CJ
Miller
C J
CJ
Cukierski
M J
MJ
Book
S A
SA
Hendrickx
A G
AG
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004970:Estrone / Q000652:urine; D005260:Female; D005333:Fetus / Q000187:drug effects; D006029:Glycosuria / Q000139:chemically induced; D006128:Growth / Q000187:drug effects*; D008252:Macaca fascicularis; D011247:Pregnancy; D011507:Proteinuria / Q000139:chemically induced; D012645:Selenomethionine / Q000493:pharmacokinetics / Q000633:toxicity*; D013723:Teratogens; D016216:Ultrasonography, Prenatal
D013723:Teratogens; D004970:Estrone; D012645:Selenomethionine