Academic journal article Environmental Health Perspectives

Estimated Daily Phthalate Exposures in a Population of Mothers of Male Infants Exhibiting Reduced Anogenital Distance

Academic journal article Environmental Health Perspectives

Estimated Daily Phthalate Exposures in a Population of Mothers of Male Infants Exhibiting Reduced Anogenital Distance

Article excerpt

Phthalate diesters have been shown to be developmental and reproductive toxicants in animal studies. A recent epidemiologic study showed certain phthalates to be significantly associated with reduced anogenital distance in human male infants, the first evidence of subtle developmental effects in human male infants exposed prenatally to phthalates. We used two previously published methods to estimate the daily phthalate exposures for the four phthalates whose urinary metabolites were statistically significantly associated with developmental effects in the 214 mother-infant pairs [di-n-butyl phthalate (DnBP), diethyl phthalate (DEP), butylbenzyl phthalate (BBzP), diisobutyl phthalate (DiBP)] and for another important phthalate [di-2-ethylhexyl phthalate (DEHP)]. We estimated the median and 95th percentile of daily exposures to DBP to be 0.99 and 2.68 [micro]g/kg/day, respectively; for DEP, 6.64 and 112.3 [micro]g/kg/day; for BBzP, 0.50 and 2.47 [micro]g/kg/day; and for DEHP, 1.32 and 9.32 [micro]g/kg/day. The U.S. Environmental Protection Agency (EPA) reference doses for these chemicals are 100 (DBP), 800 (DEP), 200 (BBzP), and 20 (DEHP) [micro]g/kg/day. The median and 95th percentile exposure estimates for the phthalates associated with reduced anogenital distance in the study population are substantially lower than current U.S. EPA reference doses for these chemicals and could be informative to any updates of the hazard assessments and risk assessments for these chemicals. Key words: anogenital distance, butylbenzyl phthalate, di(2-ethylhexyl) phthalate, dibutyl phthalate, diethyl phthalate, diisobutyl phthalate, exposure estimates, reference dose. Environ Health Perspect 114:805-809 (2006). doi:10.1289/ehp.8663 available via http://dx.doi.org/ [Online 2 February 2006]

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Phthalates are used in a variety of industries and are present in many consumer products, such as soaps, perfumes, cosmetics, shampoos, building products, shower curtains, aerosols, plastic toys, and plastic packaging [Agency for Toxic Substances and Disease Registry (ATSDR) 1995, 2001, 2003]. Di(2-ethylhexyl) phthalate (DEHP) is the primary plasticizer in polyvinyl chloride, and diethyl phthalate (DEP) and dibutyl phthalates (DBPs) are commonly used in consumer and personal care products such as lotions, fragrances, cosmetics, deodorants, and pharmaceutical coatings (ATSDR 1995, 2001, 2003). The reproductive and developmental toxicities of some phthalates have been demonstrated extensively in animal studies. Prenatal exposure to DEHP, DBP, butylbenzyl phthalate (BBzP), or, more weakly, diisononyl phthalate reduces testosterone production in fetal testes (Lehmann et al. 2004; Mylchreest and Foster 2000; Mylchreest et al. 2002; Parks et al. 2000), which can result in incomplete development of the male reproductive tract and malformations of the external genitalia (Ema and Miyawaki 2001; Ema et al. 2003; Foster et al. 2000; Gray et al. 2000; Mylchreest et al. 1998).

In a study published in a previous issue of this journal by some authors participating in the current study, Swan et al. (2005) provided the first demonstration of subtle developmental effects, similar to those seen in animal studies, in human male infants exposed prenatally to phthalates. The study population for Swan et al. (2005), described below, included 134 women whose male offspring had a physical examination by 17 December 2004, of whom 85 had also given a urine sample during pregnancy. These prenatal maternal urine samples were analyzed for nine phthalate metabolites commonly used as biomarkers of exposure to phthalates, using an analytical method described before (Silva et al. 2004b). One hundred thirty-four male infants, including 49 for whom no maternal prenatal urine sample had been collected, were physically examined to determine anogenital distance (AGD)--a marker for prenatal antiandrogen exposure--and other reproductive organ measurements. Of nine urinary phthalate metabolites, Swan et al. …

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