The effects of phthalate esters on the tryptophan-niacin metabolism.

Several phthalate esters (PhE), used as a plasticizer for numerous plastic devices, induce liver tumors and testicular atrophy, although the precise nature and mechanism for the action of PhE on these organs have remained unclear. We have previously reported that the administration of a large amount of di(n-butyl)phthalate (DBP) increased the conversion ratio of tryptophan to niacin in rats. To clarify the mechanism for the toxicity of PhE, we investigated the effects of di(2-ethylhexyl) phthalate (DEHP), one of the most frequently used additives, on the conversion ratio and how altering the conversion ratio of tryptophan to niacin depended on the concentration of DEHP. Rats were fed with a diet containing 0%, 0.01%, 0.05%, 0.1%, 0.5%, 1.0%, or 3.0% DEHP for 21 days. To assess the conversion ratio of tryptophan to niacin, urine samples were collected at the last day of the experiment and measured for metabolites on the tryptophan-niacin pathway. The conversion ratio increased with increasing dietary concentration of DEHP above 0.05%; the conversion ratio was about 2% in the control group, whereas it was 28% in the 3.0% DEHP group. It is suggested that the inhibition of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) by DEHP or its metabolites caused this increase in the conversion ratio. We conclude that PhE such as DEHP and DBP disturbed the Tryptophan-niacin metabolism.