The structure-activity relationship (SAR) for phthalate-mediated developmental and reproductive toxicity in males.

Testicular dysgenesis syndrome includes the hypospadias, cryptorchidism and abnormal fetal testis in male neonate. This is possibly caused by the environmental phthalates, which down-regulate the expression of androgen synthetic genes and Insl3 or directly inhibits steroidogenic enzymes. There are distinct structure-activity relationships (SARs) for phthalate-mediated developmental and reproductive toxicity. Here, we review the SAR for phthalate-mediated testicular dysgenesis syndrome. Of phthalates of straight side chains, C5-C6 ones are the most potent, C4 or C7 are moderate, C3 is weakest, and C1-2 or C8-13 are ineffective. The branching and unsaturation of side chains increases the toxicity. The cycling of side chains does not increase the toxicity.