Sharpe, RM. 2001. Hormones and testis development and the possible adverse effects of environmental chemicals. Toxicology Letters 120:221-232.
In this cautious and substantial review article, Sharpe describes normal patterns of development of the testes and then examines how development is vulnerable to interference by endocrine disrupting chemicals. He concludes (p230):
| "There are many examples of how disorders in hormone production and/or action can disturb this [testicular] development and result in various degrees of intersex or incomplete masculinization. At the more subtle level, it is gradually being appreciated that disorders of male reproductive health in phenotypically normal males, such as testicular cancer, low sperm counts and failure of testicular descent can be inter-connected, and may therefore have a common origin and cause in fetal life in some cases. Though it is unknown what the cause(s) of such changes may be in most cases, it is abundantly clear that disruption of hormone production or action is of central importance in the pathway of such disorders. With this in mind, exposures of humans and wildlife to numerous environmental chemicals with intrinsic hormonal activity, either oestrogenic or anti-androgenic (especially the latter), provides justifiable cause for concern. Based on the limited evidence available, this author is unconvinced that human exposure to any of these chemicals individually is sufficient to induce adverse changes to male reproductive health. However, as the example of the phthalates demonstrates, there is a remarkable similarity between the types of changes induced in the fetal testis by such compounds in laboratory animals and those known to occur in the dysgenetic human testis. Additionally, the limited new data for human exposure to such phthalates does not leave as comforting a safety margin as most of us would like to see. Of greatest concern , is what are the consequences when there is exposure to combinations of the various chemicals, as occurs in the real world we live in? (emphases added). |
In the review, Sharpe focuses considerable attention on phthalates:
- Several but not all phthalates "have surprising 'anti-androgenic activity'
- The impacts of these phthalates is "remarkably similar to the testicular dysgenesis syndrom in humans discussed above [in the review].
- Recent exposure data demonstrate that public exposure to phthalates is widespread and that the exposure of some is several hundred fold above the "no observed adverse effect level" established for pregnant rats.
He concludes that conclusive proof does not exist that human exposure to phthalates is sufficient to cause adverse effects, but that existing data and these lines of reasoning (above) "suggest that a thorough 're-look' a the human reproductive toxicity of phthalates is essential."