Showing papers by "Mariana F. Fernández published in 2007"

Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study

Abstract: Ten years ago, it was hypothesized that exposure of the developing male fetus to environmental estrogens may be responsible for anomalies of sexual maturation and reproductive function in adult life (Anonymous 1995). Male sexual differentiation and reproductive functioning are critically dependent on a balanced androgen:estrogen ratio. In this regard, two common male reproductive-tract malformations—cryptorchidism (failure of one or both testicles to descend into scrotum) and hypospadias (urethral opening on ventral side of penis)—are birth defects of prenatal origin that may be related to in utero exposure to estrogens/androgens. Animal (Edwards et al. 2006) and human data (Nurminen 2001) point toward a causal relationship between exposure to pesticides during pregnancy and the development of congenital malformations. In fact, parental involvement in agricultural work and/or parental exposure to pesticides has been associated with higher risk of a wide range of congenital malformations (Kristensen et al. 1997). For example, in Spain, maternal involvement in agricultural activity during the month before conception and the first trimester of pregnancy was followed by a 3-fold increase in the risk of bearing a child with a malformation (Garcia et al. 1999). Moreover, an ecologic investigation into variations in orchidopexy rates in the Spanish province of Granada found an association between exposure to pesticides and the risk of cryptorchidism (Garcia-Rodriguez et al. 1996). A later retrospective case–control study in the same geographic area suggested that cryptorchidism was related to the father’s employment in agriculture (Rueda-Domingo et al. 2001). Because of their persistence in the environment, pesticides are common contaminants in soil, water, and wildlife and are present in tissues of mothers and children, especially in regions devoted to intensive agriculture (Botella et al. 2004; Cerrillo et al. 2006; Olea et al. 1999). Their ubiquity supports the plausibility of embryo-fetal exposure during pregnancy, although mutagenic or epigenetic parental germ cell damage cannot be ruled out. Some organochlorine pesticides are endocrine disrupting chemicals (EDCs) (Soto et al. 1995), defined as exogenous substances or mixtures with the ability to disrupt hormonal homeostasis, alter endocrine system functions, and consequently cause adverse health effects in an intact organism or its progeny or sub-populations. EDC pesticides are now considered to include not only chemicals with estrogenic and androgenic properties but also those with antihormonal and enzymatic/metabolic properties (Almstrup et al. 2002). Maternal exposure to pesticides has been associated with urogenital malformations, semen quality impairment, and testicular, prostate, ovarian, and breast cancer (Koifman et al. 2002). Thus, an excess of cryptorchidism but not of hypospadias was reported in sons of women working in farming, especially horticulture (Weidner et al. 1998), whereas the occupation of the father had no influence on the risk of either cryptorchidism or hypospa-dias. Kristensen and coworkers (1997), who studied the association of different birth defects with farm purchases of pesticides and tractor pesticide spraying equipment, found a positive relationship with cryptorchidism and a moderate association with hypospadias. However, when exposure assessment was based on parental occupation (farmers vs. other jobs), no significant differences were observed. Occupational exposure of the father was associated with cryptorchidism in a nested case–control study conducted by Pierik et al. (2004), and with hypospadias in an investigation by Irgens et al. (2000). In contrast with the above studies, other authors found no association between cryptorchidism and maternal exposure to pesticides during pregnancy (Restrepo et al. 1990), between hypospadias and occupational exposure to EDCs by the mother (Aho et al. 2000; Vrijheid et al. 2003), or between serum levels of dichlorodiphenyl-dichloroethene (DDE) in the third trimester of pregnancy and risk of malformations (Longnecker et al. 2002). These inconsistent results led to the conclusion that epidemio-logic studies do not provide sufficient grounds to support a role for environmental estrogens in urogenital malformations, and that a more focused exposure assessment methodology is required, with more specific markers of embryo-fetal exposure (Dolk and Vrijheid 2003; Silva et al. 2002; Vidaeff and Sever 2005). The need for data to support the endocrine disruptor hypothesis prompted the European Community to support a prospective multi-center cohort study in five European countries (Denmark, England, Finland, France, and Spain) to explore the possible association between exposure of the male fetus to endocrine disruptors and sex differentiation disorders. A prospective mother–child cohort was established in Granada (southern Spain), in which a case–control study was nested for investigation of the main risk factors for male urogenital malformations. In the present study, we examined the relationship between cryp-torchidism or hypospadias and environmental factors, with special emphasis on exposure to xenoestrogens, estimated by assessment of the combined estrogenic effects of chemicals extracted from placentas.

Oestrogenicity of paper and cardboard extracts used as food containers.

Abstract: Bisphenol-A (BPA), dibutyl phthalate (DBP), and di-2-ethylhexyl phthalate (DEHP), which are common chemical residues in food-packaging materials, were investigated in paper and cardboard containers used for take-away food. The oestrogenicity of aqueous extracts was tested in E-Screen bioassay and analysis carried out by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC/MS). Oestrogenicity was demonstrated in 90% of extracts (geometric mean [GM] = 11.97 pM oestradiol equivalents g(-1)). DEHP, DBP, and BPA (GM = 341.74, 37.59, and 2.38 ng g(-1) of material) were present in 77.50, 67.50, and 47.50% of samples, respectively. In bivariate analyses, no significant association was found between the levels of these chemicals and oestrogenicity in cardboard/paper extracts. A close-to-significant association was found between oestrogenicity and DBP (beta = 1.25; p = 0.06) in paper extracts, which reached statistical significance in multivariate analysis (beta = 1.61; p = 0.03). Paper and cardboard used in food packaging may contribute to the inadvertent exposure of consumers to endocrine-disrupting chemicals.

Oestrogenicity of paper and cardboard extracts used as food containers Part A Chemistry, analysis, control, exposure & risk assessment

Abstract: Bisphenol-A (BPA), dibutyl phthalate (DBP), and di-2-ethylhexyl phthalate (DEHP), which are common chemical residues in food-packaging materials, were investigated in paper and cardboard containers used for take-away food. The oestrogenicity of aqueous extracts was tested in E-Screen bioassay and analysis carried out by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC/MS). Oestrogenicity was demonstrated in 90% of extracts (geometric mean [GM] = 11.97 pM oestradiol equivalents g(-1)). DEHP, DBP, and BPA (GM = 341.74, 37.59, and 2.38 ng g(-1) of material) were present in 77.50, 67.50, and 47.50% of samples, respectively. In bivariate analyses, no significant association was found between the levels of these chemicals and oestrogenicity in cardboard/paper extracts. A close-to-significant association was found between oestrogenicity and DBP (beta = 1.25; p = 0.06) in paper extracts, which reached statistical significance in multivariate analysis (beta = 1.61; p = 0.03). Paper and cardboard used in food packaging may contribute to the inadvertent exposure of consumers to endocrine-disrupting chemicals.

Chemicals in the environment and human male fertility

Abstract: Study shows that progressive replacement of some chemical components may have a beneficial effect on semen quality In an article published in this issue (see page 467) , Luc Multigner and colleagues1 show that male exposure to short-chain glycol ethers has long-lasting negative effects on semen quality. Occupational exposure to chemicals in the workplace and their effects on testicular functions and male fertility is not a novel observation. Over the past few decades, investigations into the professional exposure of men have provided convincing evidence on the association between exposure to particular types of chemicals and male reproductive disorders.2 This study reveals that precautionary measures focused on the progressive replacement of some chemical compounds by others may have a beneficial effect on semen quality. In contrast to the relative consensus achieved around occupational chemical exposure, strong disagreements have arisen between supporters and opponents of the role of environmental chemicals in the decline in sperm production and quality …

Endocrine disrupter exposure and male congenital malformations

Abstract: Exposure of the developing animal male fetus to environmental pollutants, in particular to endocrine disrupting chemicals (EDC), is responsible for sexual maturation anomalies and reproductive malfunction in adult life. Human maternalinfant exposure during pregnancy is of special importance because it represents a very likely window of high susceptibility that can lead to severe and irreversible effects during critical developmental periods. This chapter reviews the epidemiological evidence linking EDC exposure to human male tract malformations, e.g. cryptorchidism and hypospadias, focusing on exposure to pesticides as potential EDCs. Epidemiological studies have yielded contradictory results and do not provide sufficient grounds to confirm the hypothesis that environmental estrogens are associated with these urogenital anomalies. The main reason for the conflicting data may be the difficulty of comparing studies that consider different exposure times and study populations, and do not use the same clinical definitions or diagnostic criteria for these diseases. In addition, the EDC hypothesis poses several challenges to the exposure assessment process that need to be addressed: i) classification of exposure by using direct determinations instead of crude proxies, ii) interpretation of complex dose-effect relationships based on U- or inverted U-shaped dose-response curves, iii) estimation of exposure that takes account of the highly heterogeneous chemical classes implicated, and iv) development of biomarkers that allow investigators to quantify exposure to mixtures of EDCs and to differentiate their effects from those of endogenous hormones.