A study of the enhancement of butylated-hydroxytoluene (128370) (BHT) induced mouse lung damage by butylated-hydroxyanisole (25013165) (BHA) was presented. Male CD-1-mice treated with intraperitoneal injections of BHT at 250 to 500mg/kg had significantly elevated lung to body weight ratio (LBR) 4 days after treatment. BHA given subcutaneously (SC) at 100 to 500mg/kg did not alter the LBR. BHT did not significantly alter LBR at a concentration of 175mg/kg but mice pretreated with BHA at 50 or 250mg/kg 30 minutes prior to the BHT had an enhanced LBR. Toxicity was enhanced by doses of BHA ranging from 50 to 250mg/kg when given 30 minutes prior to BHT 250mg/kg. BHA was effective when given simultaneous with or up to 4 hours prior to BHT. When given after BHT, or when given intraperitoneally, BHA had no effect. Deuteration of BHT prevented the BHA enhanced BHT induced increases in LBR. The authors conclude that BHA can reduce the threshold for BHT induced lung toxicity and that interactions of other antioxidants should be examined.
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