Abstract

Butylated hydroxytoluene (BHT) is a phenolic antioxidant which induces lung injury in all strains of mice which have been tested, but not in any other species. The mortality of mice treated with BHT is also highly strain-dependent, with LD 50s ranging from 138 to 1739 mg kg . Despite this wide range of toxic doses, the relationship between lung damage and dose has not been well studied. The data presented here demonstrate that BALB/c, ICR and C57BL/6NHsd mice, with LD 50s of 1739, 1243 and 917 respectively, exhibit similar time courses of repair (as assessed by the incorporation of radiolabelled thymidine into DNA) and pulmonary fibrosis (as assessed by lung hydroxyproline content) when given a single 400 mg kg dose of BHT. SSIn mice, with an LD 50 of approximately 350 mg kg , also exhibited a similar time course of repair when given a single dose of 300 mg kg BHT, although fibrosis did not develop in these animals. These data indicate that all strains of mice develop similar levels of lung injury at equivalent doses and that the extent of lung damage produced in mice does not correlate with the lethal dose.

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