Biliary plutonium excretion in the rat.
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J O Hess
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Effect of dose level and pregnancy on the distribution and toxicity of intravenous lead in rats.
Female Wistar rats were injected intravenously with tracer levels of 210Pb, alone or combined with carrier Pb(NO3)2 at 5 or 25 mg/kg body weight at 9 or 15 days of gestation (dg). Tissue 210Pb distribution and retention, and lead excretion, were measured several times during the first 30 h and at 20 dg. Toxic effects following the administration of 25 mg/kg (a teratogenic dose) included an early decrease in hematocrit, hematuria, gastrointestinal hemorrhage, and diarrhea, as well as an eventual loss of body weight and an increase in spleen and kidney weights. The stage of pregnancy at injection did not affect the retention and distribution of lead in major organs other than the reproductive system. Following injection of the 25-mg/kg dose, deposition of lead in the liver, kidney, spleen, and lung was elevated. Disproportionately high plasma lead levels were also observed at early times after the injection of the 25-mg/kg dose, and may act as a significant factor in placental lead transfer and subsequent malformations or fetal mortality.
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Distribution and effects of intravenous lead in the fetoplacental unit of the rat.
Lead metabolism was studied in the fetoplacental unit (FPU) of Wistar rats during the genesis of developmental abnormalities and embryonic death. Female rats were injected iv with tracer 210Pb(NO3)2, alone or in combination with 5 or 25 mg Pb(NO3)2/kg, at 9 or 15 days of gestation (dg). The distribution of lead and its effects were determined in the FPUs during the ensuing 30-h period and at 20 dg. Hemorrhage of the egg cylinder was noted as early as 6 h postinjection of 25 mg/kg at 9 dg. By 20 dg, fetuses exhibited characteristic stunting and external malformations (gastroschisis and severe skeletal defects). Administration of this dose at 15 dg produced petechial hemorrhage in fetal brain within 90 min; more massive hemorrhage was a consistent observation by 24 h. At 20 dg, embryo mortality was 44% in rats injected with 25 mg/kg at 9 dg and 100% in those injected at 15 dg. At 90 min after injection, lead content of 15-dg FPUs was 10 times that of the 9-dg FPUs, but the weights of the 15-dg FPUs were 16 times greater. Values remained relatively constant in 15-dg FPUs for 30 h, but early clearance was observed after injection at 9 dg, with a return to 90-min values by 20 dg. In the 15-dg FPUs, placental clearance was followed by fetal lead incorporation, which reached a maximum at 6 h. Fetal lead values were constant from 6 to 30 h after injection at tracer and 5-mg/kg dose levels, but values increased progressively at 25 mg/kg. Both temporal and quantitative relationships of fetal lead metabolism were disrupted by the 25-mg/kg dose, but the nature of the effect was determined by the stage of fetal development at exposure.
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