Reproductive and developmental effects of phthalate diesters in males

Abstract

Phthalate diesters are a diverse group of chemicals used to make plastics flexible and are found in personal care products, medical equipment, and medication capsules. Ubiquitous in the environment, human exposure to phthalates is unavoidable; however, the clinical relevance of low concentrations in human tissues remains uncertain. The epidemiological literature was inadequate for prior reviews to conclusively evaluate the effects of phthalates on male reproductive tract development and function, but recent studies have expanded the literature. Therefore, we conducted a systematic review of the literature focused on the effects of phthalate exposure on the developing male reproductive tract, puberty, semen quality, fertility, and reproductive hormones. We conclude that although the epidemiological evidence for an association between phthalate exposure and most adverse outcomes in the reproductive system, at concentrations to which general human populations are exposed, is minimal to weak, the evidence for effects on semen quality is moderate. Results of animal studies reveal that, although DEHP was the most potent, different phthalates have similar effects and can adversely affect development of the male reproductive tract with semen quality being the most sensitive outcome. We also note that developmental exposure in humans was within an order of magnitude of the adverse effects documented in several animal studies. While the mechanisms underlying phthalate toxicity remain unclear, the animal literature suggests that mice are less sensitive than rats and potentially more relevant to estimating effects in humans. Potential for chemical interactions and effects across generations highlights the need for continued study.

Keywords:

• cryptorchidism
• developmental
• hypospadias
• phthalates
• puberty
• reproductive
• semen
• testosterone

Acknowledgments

The authors gratefully acknowledge the administrative support of Ms. Margaret Talbot during the preparation of this manuscript.

Declaration of interest

The employment affiliation of the authors is shown on the cover page. Funding has been provided by Ferring Pharmaceutical to WGF for the qualification of phthalate exposure in patients prescribed medications containing phthalates in slow-release capsules. No external funding support was provided for the preparation of this manuscript. The manuscript was prepared during the normal course of the authors’ employment. The authors have not participated in any legal or regulatory proceedings related to the subject matter of the manuscript. The authors have sole responsibility for the preparation of the manuscript and the views and opinions expressed in the manuscript.

Notice of correction

The version of this article published online ahead of print on 06 June 2014 contained two minor typographical errors. These have been corrected for this version.