Comparison of lung injury induced in 4 strains of mice by butylated hydroxytoluene.
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 LD50s 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 LD50s 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 LD50 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.
Kehrer
J P
JP
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin 78712-1074.
DiGiovanni
J
J
D000818:Animals; D002084:Butylated Hydroxytoluene / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007928:Lethal Dose 50; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains / Q000378:metabolism / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced; D013997:Time Factors
D002084:Butylated Hydroxytoluene; D004247:DNA; D006909:Hydroxyproline