Studies on the mechanism of enhancement of butylated hydroxytoluene-induced mouse lung toxicity by butylated hydroxyanisole.
Toxicol Appl Pharmacol 1988 Oct; 96(1):122-131
Mechanisms by which butylated-hydroxyanisole (25013165) (BHA) enhances the lung toxicity induced by butylated-hydroxytoluene (128370) (BHT) were examined in CD1-mice. In glutathione depleted lung slices BHA enhanced covalent binding of BHT to protein by 360 percent. Although BHT at 175mg/kg intraperitoneally (ip) had no effect on lung to body weight ratios (LBR), BHA at 250mg/kg or diethyl-maleate (141059) (DEM) at 1mg/kg given subcutaneously 30 minutes prior to BHT at that dose significantly increased the LBR. Neither 250mg/kg BHA nor 1500mg/kg BHA had an effect on lung glutathione levels 4 hours after treatment. The covalent binding of BHT to mouse lung microsomes in the presence of hydrogen-peroxide (H2O2) was increased by the addition of BHA to the reaction media. Other peroxides also increased the binding of BHT to lung microsomes. In lung and liver microsomes, NADPH oxidation and H2O2 formation significantly increased in the presence of BHA. A scheme of the possible mechanisms of BHA enhancement of BHT was included. The authors conclude that BHA may enhance the toxicity of BHT by facilitating the activation of BHT.
NIOSH-Publication; NIOSH-Grant; In-vitro-studies; In-vivo-studies; Antioxidants; Liver-microsomal-metabolism; Liver-microsomes; Laboratory-animals; Lung-cells; Synergism; Food-additives
25013-16-5; 128-37-0; 141-05-9
Toxicology and Applied Pharmacology
Johns Hopkins University