To see if results in rats, rabbits, and dogs at high dose levels justified extrapolation, the fate of butylated hydroxyanisole in man was studied. Further possible pathways were sought in dogs. Dogs excreted 60% of a 350 mg. per kg. dose unchanged in the feces within 3 days, and the remainder in the urine largely as sulfate conjugates of BHA, ferf-butylhydroquinone, and an unidentified phenol. Little glucuronide was formed. Procedures used for low dose levels in rats were applied to man, where 0.5 to 0.7 mg. per kg. yields in the urine less than 1% of the dose as unchanged BHA, and 27 to 77% as the glucuro-
Seven phthalate esters, representing a variety of chain lengths and degrees of branching in the alcohol moiety, were tested for their ability to produce peroxisome proliferation in the Fischer 344 rat. Di(2-ethylhexyl)adipate (DEHA) was tested using the same protocol and di(2-ethylhexyl)phthalate (DEHP) was run with each study as an internal control. Each ester was administered in the feed for a period of 21 days at levels of 2.5%, 1.2% and either 0.6% or 0.3%. DEHP and DEHA were also fed at levels of 0.1% and 0.01%. The animals were sacrificed and samples of liver were prepared for both light and electron microscopy. Serum samples were assayed for both triglyceride and cholesterol. The remaining portion of the liver was homogenized and assayed for cyanide-insensitive palmitoyl-CoA oxidation, lauric acid 11-hydroxylase and lauric acid 12-hydroxylase. The results show that there is approximately a ten-fold difference between the weakest and strongest esters in terms of their potency to induce changes in relative liver weight and in several of the biochemical parameters. In general, the longer chain esters were more potent than the shorter chain ones, and branched chain esters seemed more potent than straight. Several statistical analyses of the dataset have been performed and all render similar conclusions. The results of one of these evaluations are presented elsewhere in this volume (Lin, 1987).
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