Developmental toxicity of L-selenomethionine in Macaca fascicularis

Alice F Tarantal, Calvin C. Willhite, Bill L. Lasley, Christopher J Murphy, Chris J Miller, Matthew J. Cukierski, Steven A. Book, Andrew G Hendrickx

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Forty pregnant long-tailed macaques were dosed via nasogastric intubation 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, 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 (̃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, behavorial, 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 /ig/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 μg/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 Mg/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.

Original languageEnglish (US)
Pages (from-to)147-160
Number of pages14
JournalToxicological Sciences
Volume16
Issue number1
DOIs
StatePublished - Jan 1991

Fingerprint

Selenomethionine
Macaca fascicularis
Dams
Toxicity
Mothers
Animals
Myocardium
Gastrointestinal Intubation
Hysterotomy
Body Weight
Teratogenesis
Muscle
Pregnancy
Maternal Death
Clinical Chemistry
Fetal Death
Organogenesis
Estrone
Macaca
Anorexia

ASJC Scopus subject areas

  • Molecular Biology
  • Embryology
  • Cell Biology
  • Genetics
  • Developmental Biology
  • Toxicology

Cite this

Developmental toxicity of L-selenomethionine in Macaca fascicularis. / Tarantal, Alice F; Willhite, Calvin C.; Lasley, Bill L.; Murphy, Christopher J; Miller, Chris J; Cukierski, Matthew J.; Book, Steven A.; Hendrickx, Andrew G.

In: Toxicological Sciences, Vol. 16, No. 1, 01.1991, p. 147-160.

Research output: Contribution to journalArticle

Tarantal, Alice F ; Willhite, Calvin C. ; Lasley, Bill L. ; Murphy, Christopher J ; Miller, Chris J ; Cukierski, Matthew J. ; Book, Steven A. ; Hendrickx, Andrew G. / Developmental toxicity of L-selenomethionine in Macaca fascicularis. In: Toxicological Sciences. 1991 ; Vol. 16, No. 1. pp. 147-160.
@article{711d922f2ef64ed4936919938cdb68d3,
title = "Developmental toxicity of L-selenomethionine in Macaca fascicularis",
abstract = "Forty pregnant long-tailed macaques were dosed via nasogastric intubation 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, 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 (̃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, behavorial, 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 /ig/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 μg/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 Mg/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.",
author = "Tarantal, {Alice F} and Willhite, {Calvin C.} and Lasley, {Bill L.} and Murphy, {Christopher J} and Miller, {Chris J} and Cukierski, {Matthew J.} and Book, {Steven A.} and Hendrickx, {Andrew G}",
year = "1991",
month = "1",
doi = "10.1093/toxsci/16.1.147",
language = "English (US)",
volume = "16",
pages = "147--160",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Developmental toxicity of L-selenomethionine in Macaca fascicularis

AU - Tarantal, Alice F

AU - Willhite, Calvin C.

AU - Lasley, Bill L.

AU - Murphy, Christopher J

AU - Miller, Chris J

AU - Cukierski, Matthew J.

AU - Book, Steven A.

AU - Hendrickx, Andrew G

PY - 1991/1

Y1 - 1991/1

N2 - Forty pregnant long-tailed macaques were dosed via nasogastric intubation 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, 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 (̃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, behavorial, 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 /ig/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 μg/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 Mg/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.

AB - Forty pregnant long-tailed macaques were dosed via nasogastric intubation 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, 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 (̃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, behavorial, 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 /ig/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 μg/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 Mg/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.

UR - http://www.scopus.com/inward/record.url?scp=77957187154&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957187154&partnerID=8YFLogxK

U2 - 10.1093/toxsci/16.1.147

DO - 10.1093/toxsci/16.1.147

M3 - Article

C2 - 2019339

AN - SCOPUS:77957187154

VL - 16

SP - 147

EP - 160

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 1

ER -