RM. 2001. Hormones
and testis development and the possible adverse effects of environmental
chemicals. Toxicology Letters 120:221-232.
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):
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
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).
the review, Sharpe focuses considerable attention on phthalates:
but not all phthalates "have surprising 'anti-androgenic
impacts of these phthalates is "remarkably similar to the testicular
dysgenesis syndrom in humans discussed above [in the review].
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
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."