Reproductive toxicity of the psoralens.

The psoralens are naturally occurring secondary metabolites in plants, including many fruits and vegetables. Health risks have been associated with handling or ingesting psoralen-containing plants, and with the use of synthetic psoralens in photochemotherapy of skin disorders. Our research has demonstrated that administration of the psoralens bergapten (5-methoxypsoralen) and xanthotoxin (8-methoxypsoralen) in the diet of female rats reduced birthrates, number of implantation sites, pups, corpora lutea, full and empty uterine weight, and circulating estrogen levels in a dose-dependent manner. Psoralens induced mRNAs of the liver enzymes CYP1A1 and UGT1A6, suggesting that enhanced metabolism of estrogens by psoralen treatment may explain the reproductive toxicity and the observed reduction of ovarian follicular function and ovulation. Rats also avoided repeated consumption of a flavored solution associated with psoralen administration. The findings indicate that the psoralens constitute a novel group of ovarian toxicants. Further examination of the safety of their use in photochemotherapy and diet is warranted.