TOXIC INJURY TO RAT GUT MUSCULATURE FOLLOWING INTRAPERITONEAL ADMINISTRATION OF 2-T-BUTYL-4-METHOXYPHENOL

The 100-fold increase in toxicity of intraperitoneal (i.p.) rather tha n orally administered 2-t-butyl-4-methoxyphenol (BHA) is adduced to th e depressive effect which this compound exerts on the contractility of the gut musculature. A structure/activity relation study shows the t- butyl group on the benzene ring as being the major determinant of i.p. BHA toxicity. Contractile activity, elicited by field electrical stim ulation, acetylcholine or Ba2+, of the ileum longitudinal muscle prepa ration from BHA-treated rats was greatly reduced 30 min after i.p. inj ection, and almost absent during the subsequent 48 h. Electron-microsc ope examination of ileum longitudinal muscle also showed partial destr uction of cell membranes 4 h after BHA administration with subsequent mitochondrial swelling and destruction of cristae, myofibrillar fragme ntation and cell necrosis. Comparable suppression of contractile activ ity and morphological damage were observed in BHA or t-butylbenzene in cubated ileum segments where longitudinal smooth muscle contractility was irreversibly depressed in a time- and dose-dependent manner. These convergent findings point to the toxic effect of i.p. BHA on gut musc ulature with consequent impairment of intestinal transit.