Possible impact of phthalates on infant reproductive health

Abstract

Phthalates adversely affect the male reproductive system in animals, inducing hypospadias, cryptorchidism, reduced testosterone production and decreased sperm counts. Phthalate effects are much more severe after in utero than adult exposure. Little is known about human health effects. This study discusses two recent studies on perinatal phthalate exposure, which indicated that human testicular development might be susceptible to phthalates. One study analysed phthalate monoesters in breast milk and reproductive hormone levels in infants. Five of six phthalates [monoethyl-(MEP), monobutyl- (MBP), monomethyl- (MMP), mono-2-ethylhexyl- (MEHP) and mono-isononyl phthalate (MiNP)] showed correlation with hormone levels in healthy boys, which were indicative of lower androgen activity and reduced Leydig cell function. MEP and MBP were positively correlated with serum sex hormone-binding globulin (SHBG) levels. MMP, MEP, MBP, MEHP and MiNP were positively correlated with the LH/testosterone ratio. Another study found a reduction of the anogenital index (AGI) in infant boys with increasing levels of MBP, MEP, monobenzyl- and mono-isobutyl phthalate in maternal urine samples during late-pregnancy. Boys with small AGI showed a high prevalence of cryptorchidism and small genital size. Taken together these studies suggest an antivirilizing effect of phthalates in infants. Most of these findings are in line with animal observations. However, the possible effects of MEP appear to be limited to humans. This may be due to differences in exposure routes (inhalation and dermal absorption which circumvents liver detoxification in addition to oral) and metabolism, or this association could be spurious. As phthalates are produced as bulk chemicals worldwide, these new findings raise concern about the safety of phthalate exposure for pregnant women and infants.

Di-n-Butyl Phthalate (DBP) Exposure Induces Oxidative Damage in Testes of Adult Rats

“…It is a phthalic acid ester used extensively as a plasticizer in many products including flexible plastics, medical devices, and some cosmetic formulations [Nair et al 2008;Lottrup et al 2006]. DBP has attracted special attention from the scientific community and the general public due to its high production volume, in million of tons annually [Guerra et al 2010].…”

Decreased Levels of Plasma Testosterone/LH Ratio in Male Mice Exposed to Sodium Arsenite

“…LH stimulates Leydig cells to produce T. Phthalates appear to exert an adverse effect on the function of Leydig cells in the testis, decreasing androgen production and thus, increasing LH secretion from the pituitary, as it is released from the negative feedback mechanism of T (Lottrup et al, 2006). Also, there is a correlation of many phthalates with elevated LH/T ratio, suggesting possible contribution to testicular dysgenesis .…”

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

“…diethylhexyl phthalate, dibutyl phthalate, and butyl benzyl phthalate) results in many changes in the male reproductive tract, such as decreased anogenital distance, hypospadias, cryptorchidism, disturbed development of prostate, epididymis, vas deferens, and seminal vesicles, retained nipples, and decreased sperm production (Mylchreest et al, 1998(Mylchreest et al, , 1999(Mylchreest et al, , 2000(Mylchreest et al, , 2002Gray et al, 2000;Kavlock et al, 2002a,b,c,d,e;Lottrup et al, 2006;Skakkebaek et al, 2006;Weisbach et al, 2006). The critical window for all of these effects is the latter half of gestation (days 12-21), which is the time during which male sexual differentiation occurs (Mylchreest et al, 1999).…”