Chloroform Toxicity

Adult male mice of certain genotypes such as DBA and C3H are exquisitely sensitive to development of renal tubular necrosis and mineralization when exposed to chloroform fumes, with high mortality. One factor asso­ciated with the sex-related susceptibility appears to be the increased renal binding of chloroform in males, compared with females. Castration of males will elimi­nate their susceptibility to chloroform nephrotoxicity. Severely affected mice develop swollen, pale kidneys. Microscopic changes are characterized by coagulation necrosis of renal tubules, particularly the proximal con­voluted tubules. Surviving mice have residual nephro- calcinosis. “Outbreaks” of mortality, with selective deaths among male mice of sensitive genotypes, have been described.