Ethylenethiourea-induced hydrocephalus: pre- and postnatal pathogenesis in offspring from rats given a single oral dose during pregnancy.
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Biomedical subjects
Publications and source records attributed to K S Khera.
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Following administration of single oral doses of [14C]ethylenethiourea (ETU) to pregnant rats maternal blood maintained peak radioactivity for 2 h, and the radioactivity was dispersed uniformly between the red blood cells and plasma. The level of radioactivity was distributed equally among several maternal tissues but was present in lower amounts in embryos. Twenty-four hours after treatment all tissues examined, except blood, were relatively clear of radioactivity and 72.8% of the total radioactivity given had been excreted in the urine. Elution patterns of metabolites from Sephadex separation suggested that ethylenethiourea was degraded very little. The teratological mechanism is discussed.
Pregnancy was timed in cats following induced ovulation. Methotrexate, (0.5 mg/kg), aminopterin, (0.1 mg/kg), and acetylsalicylic acid, (25 or 50 mg/kg) were administered orally in gelatin capsules in single daily doses on different days of gestation, methotrexate (MTX) on days 11-14, 14-17, or 17-20, aminopterin on day 12, 14, or 16, and acetylsalicylic acid (ASA) on days 10-15 or 15-20. Maternal toxicity was produced only by MTX. MTX given on days 11-14 and 14-17 produced high frequencies of malformations including umbilical hernia. Aminopterin caused no conclusive teratogenic response. An overall increased frequency of anomalies occurred after 50 mg/kg ASA but no single anomaly predominated.
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Timed pregnancies were induced in cats by synchronizing gonadotropin-stimulated estrus and ovulation with natural mating. The cats were given daily oral doses of thalidomide as follows: 10 mg/kg on days 10-20 of pregnancy, 240 mg/kg on days 10-14, and 120, 240, and 480 mg/kg on days 15-17 or 18-20 of pregnancy. Fetuses were delivered by cesarean section on day 44 or 45 or earlier if threatened abortion was considered imminent. A wide variety of cardiovascular anomalies was observed on gross and microscopic examination including the following ventricular septal defect, right atrial distension primarily involving the coronary sinus, malpositioned great vessels, and narrowed left ventricular chamber with hypertrophied walls. The overall incidence of these anomalies appeared related to dose and treatment period.
Single oral administration to rats of 240 mg/kg ethylenethiourea on days 10-21 of gestation produced visceral anomalies involving the nervous, urogenital, and ocular systems, and osseous anomalies affecting the axial and appendicular skeletons. The types of anomalies and organs affected were dependent on the stage of prenatal development at the time of treatment.
The fungicide, pentachloronitrobenzene (PCNB), and fire retardants, pentachloro- (QCB) and hexabromobenzene (HBB) were administered orally to rats at 0, 50, 100 or 200 mg/kg on day 6-15 of gestation. The highest doses were associated with loss of maternal body weight gain but the loss was not statistically significant. At term, all dams were killed and foetuses removed to determine effects on prenatal survival and morphological development. All doses of QCB increased the foetal incidence of extra ribs in a dose-related manner while the 200 mg/kg dose also reduced the mean foetal weight and increased the incidence of sternal defects. PCNB and HBB had no effect at all doses.
The present study was carried out to provide information on the placental transfer of three organohalogens of environmental concern. Pentachloro-, pentachloronitro-, and hexabromobenzene were administered per os to rats daily on days 6 through 15 of gestation at level of 40, 100, and 200 mg/kg body weight. On day 22, the dams were killed and fetuses removed by caesarean section. Maternal brain, heart, kidney, liver, spleen and adipose tissue as well as whole fetus, fetal liver and fetal brain were analyzed for organohalogen residue by GLC. Pentachlorobenzene accumulated in the fetus to a greater extent than hexabromobenzene. In maternal tissues pentachlorobenzene accumulated to the greatest extent in adipose tissue, followed by liver, spleen, brain, heart and kidney. With hexabromobenzene, the greatest accumulation was observed in adipose tissue, followed by spleen, liver, heart, kidney and brain. Pentachloronitrobenzene was not detected (0.05 p.p.m.) in any maternal or fetal tissue.
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