Induction of coagulation effects by Wyeth-14,643 in Crl:CD BR rats

Drug and Chemical Toxicology
M E HurttL B Biegel

Abstract

A two-year mechanistic bioassay in male Crl:CD BR rats was initiated with 50 ppm Wyeth-14,643 (WY) to investigate the relationship between peroxisome proliferating compounds and Leydig cell adenoma formation. After 154 days, the survival rate in the WY group decreased below control levels. After 300 days, the dose was lowered to 25 ppm for the remainder of the study. Gross examination of WY-treated rats either found dead or euthanized in extremis revealed hemorrhages at several sites. To investigate this observation, blood was then collected on test day 281 from 10 randomly selected control and WY-treated rats and a clinical pathological examination was performed. The WY-treated rats had significantly decreased red blood cell count, hemoglobin, and hematocrit, and elevated platelet counts. In the WY-treated rats, prothrombin times in undiluted plasma were similar to the controls, but were markedly prolonged in 2 of 10 rats when the plasma samples were diluted to 25%. Subsequently, blood was collected prior to sacrificing WY-treated rats which were exhibiting clinical signs of anemia. These rats had prolonged prothrombin times, activated partial thromboplastin time, and thrombin clot time when compared to laboratory historical c...Continue Reading

References

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Nov 1, 1992·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·L B BiegelJ C Cook
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Citations

Aug 14, 2002·Drug and Chemical Toxicology·G D CapponM E Hurtt
Aug 1, 1997·Toxicology and Applied Pharmacology·J D ObournJ C Cook
Feb 27, 2001·Toxicological Sciences : an Official Journal of the Society of Toxicology·L B BiegelJ C Cook
Jan 14, 2010·Archives of Toxicology·Gayathri D WarnasuriyaClifford R Elcombe

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