The Teratogenic Profile of Sodium Arsenate in the Golden Hamster

Ferm, Vergil H.; Saxon, Andrew; Smith, Blaine E.

doi:10.1080/00039896.1971.10665901

Cited by 71 publications

(28 citation statements)

References 8 publications

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“…The use of FA and/or multivitamin supplementation as a means of reducing human NTDs is currently receiving considerable attention and study (6). The use ofOMPs as a method of delivery of FA assures the constancy of blood levels of this compound and precludes any problems associated with gastrointestinal absorption or variation in feeding habits.…”

Section: Resultsmentioning

confidence: 99%

“…Day 8 of gestation in this species has been shown to be the most sensitive period for the induction of NTDs by arsenate (6). Arsenate, in the hamster model, is a very potent and consistent inducer of NTDs (6). It is important to note that the 8th day of gestation in the hamster corresponds to the 17-to 28-day period in human embryonic development (7).…”

Section: Resultsmentioning

confidence: 99%

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Arsenate-Induced Neural Tube Defects Not Influenced by Constant Rate Administration of Folic Acid

Ferm

Hanlon

1986

Pediatr Res

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ABSTRACf. Serious suggestions have been made that dietary supplementation with folic acid (FA) and perhaps other vitamins during pregnancy may reduce the incidence of neural tube defect (NTD) in human newborns. The purpose of these experiments was to evaluate the effect of continuous infusion of FA on the incidence of NTDs induced by arsenate. This teratogen induces NTDs in up to 90% of golden hamster fetuses when administered acutely during critical stages of embryogenesis. FA was administered by subcutaneously implanted osmotic minipumps beginning on the 6th day of gestation, 48 h before an acutely administered dose of sodium arsenate. The protective effect of FA was examined at three teratogenic dose levels of arsenate: optimal, with 90% NTDs, intermediate, with 38% NTDs, and low, with 20% NTDs. Fetuses were recovered at day 13 of gestation and examined for NTDs and other malformations. Maternal red cell folate levels were determined on day 8, 48 h after implantation of the pumps. The results show that the maternal red blood cell level of FA can be significantly increased within 48 h by chronic infusion to levels which are almost two times (550 ng/ml) control levels. There was no significant protection against arsenate-induced NTDs following FA supplementation at any of three levels of this teratogen. (Pediatr Res 20:761-762,1986) Abbreviations FA, folic acid NTD, neural tube defect OMP, osmotic minipump further evidence that FA supplementation during pregnancy does not reduce the incidence of NTDs produced by a potent central nervous system teratogen. Specifically, we show in the hamster model that the incidence of NTDs produced by acute exposure to arsenate is not reduced by continuous dosing with FA prior or during the critical stages of embryogenesis. MATERIALS AND METHODSTimed pregnant hamsters (outbred strain of Lakeview Syrian hamsters) were obtained from the Charles River Co. One group was injected intraperitoneally on day 8 of gestation with a single dose of either 64.2, 48.2, or 40.1~M/kg of sodium arsenate (Table 1). A second group of animals was implanted with two OMP on the 6th day of gestation, charged with FA (Folvite) at a concentration of 5 mg/ml, in a manner described previously (2). Forty-eight hours later, on day 8 of gestation, they received the same dosage regimens of sodium arsenate as the animals in the first group. The presence in the mothers of one or two saline pumps or pumps containing FA alone has no teratogenic effect in the golden hamster (4). The animals were killed by CO 2 inhalation on day 13 and examined for NTDs in a manner described previously (4) Embryonic resorption sites were also recorded.A third group of animals was implanted with two pumps each filled with FA on day 6 ofgestation. These animals were sacrificed on day 8 of gestation and cardiac blood obtained for folate assays. Blood samples were collected in glass tubes with EDTA as anticoagulant and frozen immediately after the hematocrit was determined. The red cell folate levels in these blood samples were the...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Arsenate-Induced Neural Tube Defects Not Influenced by Constant Rate Administration of Folic Acid

Ferm

Hanlon

1986

Pediatr Res

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“…Teratogenic effects of arsenic compounds administered intravenously or intraperitoneally at high doses have been demonstrated in laboratory animals only (Ferm, 1971;Hood, 1972;EPA, 1984). Teratogenic effects, also referred t o as birth defects, are defined as effects resulting in structural or functional anomalies in live offspring.…”

Section: -1 3 Baseline Risk Assessment Of Ground Water Contaminationmentioning

confidence: 99%

Baseline risk assessment of ground water contamination at the uranium mill tailings sites near Rifle, Colorado. Revision 1

1995

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“…Teratogenic effects of arsenic compounds administered intravenously or intraperitoneally at high doses have been demonstrated in laboratory animals only (Ferm, 1971 ;Hood, 1972;EPA, 1984). Teratogenic effects, also referred t o as birth defects, are defined as effects resulting in structural or functional anomalies in live offspring.…”

Section: Arsenic Toxicitymentioning

confidence: 99%

Baseline risk assessment of ground water contamination at the Uranium Mill Tailings Sites near Rifle, Colorado

1995

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The Teratogenic Profile of Sodium Arsenate in the Golden Hamster

Cited by 71 publications

References 8 publications

Arsenate-Induced Neural Tube Defects Not Influenced by Constant Rate Administration of Folic Acid

Arsenate-Induced Neural Tube Defects Not Influenced by Constant Rate Administration of Folic Acid

Baseline risk assessment of ground water contamination at the uranium mill tailings sites near Rifle, Colorado. Revision 1

Baseline risk assessment of ground water contamination at the Uranium Mill Tailings Sites near Rifle, Colorado

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