Pattern of anomalies following single oral doses of ethylenethiourea to pregnant rats

Ruddick, Joseph A.; Khera, K. S.

doi:10.1002/tera.1420120309

Cited by 67 publications

(17 citation statements)

References 9 publications

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“…The utilization of rats enables study of larger fetuses, which is an advantage. Khera, in 1973 10 , and Ruddick & Khera, in 1975 11 , published results from experiments in which ETU administration (the degradation product from the fungicide ethylene-bis-thiocarbonate) to pregnant rats and rabbits was capable of inducing anomalies in various organs of the fetuses generated. The potential for inducing anorectal anomalies was studied by Hirai & Kuwabara, in 1990 12 .…”

Section: Resultsmentioning

confidence: 99%

Evaluation of an experimental model for anorectal anomalies induced by ethylenethiourea

2007

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PURPOSE: To evaluate an experimental model for anorectal anomalies and their principal associated malformations induced by ethylene thiourea (ETU). METHODS: Rat fetuses were utilized, divided into two groups: experimental group - fetuses from rats that received ETU on the 11th day of gestation at the dose of 125 mg/kg, diluted in distilled water to 1% concentration (12.5 ml/kg); and control group - fetuses from rats that received distilled water alone, at a volume of 12.5 ml/kg. On the 21st day of gestation, the animals were sacrificed by hypoxia in a carbon dioxide chamber, followed by laparotomy to remove the fetuses. These were initially examined externally to determine the sex and whether anorectal anomalies and malformations of the vertebral column and tail were present. Then, with the aid of microscopy, the fetuses underwent exploratory laparotomy to characterize the type of anorectal anomaly and investigate urological malformations. RESULTS: None of the fetuses in the control group presented anorectal anomaly, vertebral column malformation or urological structural alterations. In the experimental group, 71% presented anorectal anomaly, 80% presented vertebral column alterations and 35% presented urological alterations. CONCLUSION: The model described was shown to be easy to implement and presented results that allow its use in studying anorectal anomalies and associated malformations.

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Section: Resultsmentioning

confidence: 99%

Evaluation of an experimental model for anorectal anomalies induced by ethylenethiourea

2007

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“…The present study showed no significant incidences of external malformations in the 20-day-old pups treated prenatally with ETU on GD8.5, GD9.5 and GD10.5 when the dose was 30 mg/kg. However, some investigators have demonstrated that several types of anomalies including neural tube defects were produced by ETU administration at higher doses in the neurulation and early neural-tube stages (Ruddick and Khera, 1975;Nakagata et al, 1985;Sato et al, 1985). In the present study, significant incidences of congenital hydrocephalus were indicated in the pups treated with ETU on any day from GD12.5 to GD20.5.…”

Section: Discussionmentioning

confidence: 39%

“…Teratogenicity of ETU: ETU has been shown to produce a wide variety of malformations in rats and hamsters when administered singly at high doses (> 50 mg/kg) (Ruddick and Khera, 1975;Teramoto et al, 1978;Khera and Shah, 1979;Khera et al, 1983;Nakagata et al, 1985;Sato et al, 1985) or daily at low doses (Khera, 1973;Lu and Saples, 1978;Teramoto et al, 1978b). Only a few studies have been published on the effect of single and low doses of ETU on pregnant rats.…”

Section: Discussionmentioning

confidence: 99%

“…However, some investigators have demonstrated that several types of anomalies including neural tube defects were produced by ETU administration at higher doses in the neurulation and early neural-tube stages (Ruddick and Khera, 1975;Nakagata et al, 1985;Sato et al, 1985). However, some investigators have demonstrated that several types of anomalies including neural tube defects were produced by ETU administration at higher doses in the neurulation and early neural-tube stages (Ruddick and Khera, 1975;Nakagata et al, 1985;Sato et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

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Congenital Hydrocephalus Induced in Rats by Prenatal Administration of Ethylenethiourea

Takeuchi

1990

Congenital Anomalies

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Pregnant Wistar rats were given a single i.p. injection of 30 mg/kg ethylenethiourea (ETU) on one of gestational days 8.5 to 20.5. After rearing to postnatal day 20, the offspring were sacrificed and their brains were excised. Numerous brains removed from the pups prenatally treated with ETU on any day from gestational days 12.5 to 20.5 showed dilatation of lateral ventricle in various degrees. Histological examination revealed forking and stenosis of third ventricle in these brains. Since the degree of the third-ventricular stenosis roughly corresponded to the degree of dilatation of lateral ventricle, this anomaly is considered to be the main cause of congenital hydrocephalus induced in rats by prenatal ETU-treatment. The embryological study showed that the ependymal lining of the third ventricle was partially denuded in the fetuses 24-48 hours after ETU-treatment , and also that the denuded ependymal lining was never repaired during the following gestational days; instead, the ventricular walls fused laterally in the area where the ependymal lining had been denuded.

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“…ETU has been found to be teratogenic but the teratological mechanism remains unknown (Khera, 1973;Ruddick and Khera, 1975). …”

Section: Resultsmentioning

confidence: 99%

Micromass Culture of Midbrain Cells and its Relevance to in Vitro Mechanistic Studies*

Tsuchiya

Eto

Bürgin

et al. 1992

Congenital Anomalies

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The relationship between ethylenethiourea (ETU)-induced malformations of cultured rat whole embryos and the alterations of midbrain (MB) cells was investigated and species-specific ETU-induced alterations between rat and mouse MB cells were determined.Herefore, we developed new methods for monitoring teratogenic activities in serum fluids without heat treatment. The serum samples were prepared from rats and mice given ETU, and ETU-teratogenicity was evaluated in both species. We determined that the different sensitivity of the midbrain of the rat and mouse may be the main reason that ETU was teratogenic in rats but not in mice.Next, we showed that MB-cultures are unsuitable for estimating the teratogenic potential of arotinoids. MB differentiation was adversely affected only at concentrations which caused cell death. Finally, we demonstrated that the embryolethal action of new herbicides is not detectable in the micromass teratogenic test. However, the V79 colony assay may be useful for preliminary screening of embryolethal effects of herbicides.OX-#, ~~~~t~ TI13 %g$g?LZE/%%l 5-45 t 158 %%% k H %El ffl R 1-18-1

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Pattern of anomalies following single oral doses of ethylenethiourea to pregnant rats

Cited by 67 publications

References 9 publications

Evaluation of an experimental model for anorectal anomalies induced by ethylenethiourea

Evaluation of an experimental model for anorectal anomalies induced by ethylenethiourea

Congenital Hydrocephalus Induced in Rats by Prenatal Administration of Ethylenethiourea

Micromass Culture of Midbrain Cells and its Relevance to in Vitro Mechanistic Studies*

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