Abstract
Liver lesions were noted in control and dosed rats from a percutaneous toxicity study that involved wrapping of the torso to prevent oral ingestion following dermal application of test articles. Further investigation in a follow-up study revealed that the liver lesions were related to wrapping of the torso rather than to test-article administration because the liver lesions only appeared in wrapped animals, including sham-treated controls, but not in naive control animals. The liver lesions, which included centrilobular coagulative necrosis, inflammatory cell infiltration around biliary tracts, histiocytosis, fibrosis, and granulomatous inflammation, were compatible with infarction and associated inflammatory and reparative changes. There was no discernible pattern of involvement of specific hepatic lobes or regions of lobes. Many of the lesions were sufficiently severe to be considered life-threatening. This potentially significant complication should be considered when developing study protocols that involve wrapping of the torso of rats, and consideration should be given to inclusion of a naive control group that is not wrapped.