Reddish skin covering the entire body (erythroderma) was observed in a preliminary one-week oral toxicity study of a type of proton pump inhibitor in Beagle dogs. Histologically, full-thickness epidermal necrosis accompanied by apoptosis, evidenced by an immunohistochemical positive reaction to cleaved caspase-3, and detachment of the epidermis were observed in the skin. In the epidermis and upper dermis, a slight infiltration of mononuclear cells was seen, which was predominantly positive for MAC387 (macrophages) and partly positive for CD3 (T lymphocytes). These findings have some similarities to drug-induced severe skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and may represent incipient changes of such lesions. The skin lesions observed in these dogs are being considered as a potential animal model of cutaneous drug reactions. (J Toxicol Pathol 2007; 20: 257-261)

E7010 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonamide), a sulfonamide antitumor agent that inhibits tubulin polymerization, was orally administered to male Slc:SD rats at doses of 50 and 75 mg/kg once a day for 2 weeks. E7010 at a dose of 75 mg/kg induced severe testicular lesions characterized by marked decrease and/or loss of seminiferous epithelial cells, which sometimes resulted in tubules with only Sertoli cells. In the 50 mg/kg group, alteration of germ cells was evident at various stages of spermatogenesis, and apoptotic figures of meiotic spermatocytes at stage XIV were frequently observed. Single dose treatment of 50 mg/kg was also performed and was revealed a decrease of round spermatids in stage VII at necropsy after 1 week. Thus the target cells were considered to be meiotic spermatocytes at stage XIV. The present study indicates that 2-weeks repeated dosing is sufficient to detect the testicular toxicity of E7010.

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