A critical assessment of the endocrine susceptibility of the human testis to phthalates from fetal life to adulthood.
BACKGROUND
A very large proportion of the literature on the endocrine disruptors categorized as anti-androgens deals with phthalates, which are produced in large amounts for use as plastic emollients and additives. In this review, we bring together and analyse work on the effects of phthalates in animals and humans at different stages of their development to assess whether or not their possible anti-androgenic properties represent a significant threat to human health.


METHODS
The database PubMed was systematically searched for all English language articles until July 2013 in each subject area discussed.


RESULTS
We provide an up-to-date exhaustive, comparative and critical assessment of both in vivo and in vitro studies undertaken to explore the effects of phthalates on the human testis from fetal life to adulthood. These results are compared and discussed in the light of the key data reported in the literature for mice and rats.


CONCLUSIONS
The current literature highlights the fact that (i) there is a huge difference between the number of studies performed in animals and in humans, with many fewer for humans; (ii) there are differences in the way rats, mice, primates and humans respond to phthalates, for reasons that need to be further explored; (iii) more work is required to clarify the contradictions, in the few existing human epidemiological studies at all stages of development, which may be partly explained by varying methods of exposure assessment; (iv) in accordance with recent findings in rodents, it cannot be excluded that transgenerational effects of phthalates and/or epigenetic changes exist in humans; (v) a number of methodological limitations need to be solved for the in vitro and xenografting models using human fetal testis to fulfil their 'missing link' role between epidemiological studies in humans and rodent models; and (vi) epidemiological and in vitro studies generally converge sufficiently to conclude that phthalate anti-androgenicity is plausible in adult men.
INSERM (Institut National de la Santé et de la Recherche Médicale), IRSET, U1085, SFR Biosit, Campus de Beaulieu, F-35042 Rennes CEDEX, France.
Océane
O
Albert
Bernard
B
Jégou
D000293:Adolescent; D000328:Adult; D000726:Androgen Antagonists / Q000633:toxicity; D000818:Animals; D002648:Child; D004195:Disease Models, Animal; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects; D047109:Fetal Development / Q000187:drug effects; D005832:Genital Diseases, Male / Q000139:chemically induced*; D006803:Human Development / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D010795:Phthalic Acids / Q000633:toxicity*; D051381:Rats; D012377:Rodentia; D013737:Testis / Q000187:drug effects* / Q000196:embryology
D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D010795:Phthalic Acids; C032279:phthalic acid
animal experiments; epidemiology; human risk assessment; human testis; phthalates