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Subchronic toxicology of diethystilbestrol in the mouse
Abstract:
This study evaluated the subchronic (14-day) toxicity of selected (0.2, 1.0, and 4.0 mg/kg) daily subcutaneous injections of diethylstilbestrol (DES) in female (C57B1/6 X C3H)F1 mice. Parameters observed included body and organ weights, gross organ morphology, histopathology, clinical chemistry, and hepatic microsomal enzyme activities. The liver, bone marrow, and thymus are major target organs for DES. Liver enlargement, with associated histopathological changes consistent with mild hepatitis, centrolobular necrosis, and sinusoidal changes were observed. Supporting the histological changes were alterations in serum enzyme levels and microsomal enzyme activity. Bone marrow changes included decreases in the number of cells as well as the number of colony forming units per gram stem cells. Toxicity to the thymus was evidenced by decreased thymic weights and lymphocyte depletion. The hepatic and thymic effects were observed at the lowest (0.2 mg/kg) dose. Although all parameters were not assessed for recovery, those that were evaluated returned to control levels by thirty days after treatment.
Insights
Diethylstilbestrol (DES) caused significant liver, bone marrow, and thymus toxicity in mice. Effects were seen at the lowest dose and were reversible after treatment cessation.
Area of Science:
- Toxicology
- Endocrinology
- Pharmacology
Background:
- Diethylstilbestrol (DES) is a synthetic estrogen with known endocrine-disrupting properties.
- Understanding the subchronic toxicity of DES is crucial for assessing potential health risks.
Purpose of the Study:
- To evaluate the 14-day toxicity profile of diethylstilbestrol (DES) in female mice.
- To identify target organs and dose-dependent effects of DES exposure.
Main Methods:
- Subcutaneous injections of DES (0.2, 1.0, 4.0 mg/kg) were administered daily for 14 days to female mice.
- Evaluated parameters included body/organ weights, gross morphology, histopathology, clinical chemistry, and hepatic microsomal enzyme activity.
Main Results:
- Liver, bone marrow, and thymus were identified as major target organs for DES toxicity.
- Observed effects included liver enlargement with hepatitis, necrosis, altered enzyme levels, decreased bone marrow cellularity, and thymic atrophy with lymphocyte depletion.
- Hepatic and thymic effects were evident even at the lowest dose of 0.2 mg/kg.
Conclusions:
- Subchronic exposure to DES induces significant toxicity in the liver, bone marrow, and thymus of mice.
- These toxic effects, particularly on the liver and thymus, occur at low doses and are reversible.
- DES poses a risk of subchronic toxicity affecting multiple organ systems.