Reproductive toxicity of phthalate esters

Phthalate esters are ubiquitous environmental contaminants that in general display low-toxicity. Overall, the reproductive effects of these compounds are well characterized in adult's animals, with gonadal injury observed after high dose exposure. However, results of recent transgeneration studies indicate that the reproductive system of developing animals is particularly vulnerable to certain phthalates. The phenotypic alterations observed in male offspring rats exposed during the perinatal period have remarkable similarities with common human reproductive disorders, including cryptorchidism, hypospadias and low-sperm counts. Recent results also indicate that high phthalate doses can adversely affect adult and developing female rats. However, the main question involving phthalates is whether the current level of human exposure is sufficient to adversely affect male and/or female reproductive health. Here, we review the reproductive toxicity data of phthalates in adult and developing animals as well as possible modes of action. In addition, we briefly discuss the relevance of animal studies to humans in light of recent epidemiological data and experimental research with low (human relevant) doses. Finally, we point out some critical issues that should be addressed in order to clarify the implications of phthalates for human reproduction.