Wojciech Hanke

Exposure to phthalates: Reproductive outcome and children health. A review of epidemiological studies

Phthalates are a family of industrial chemicals that have been used for a variety of purposes. As the potential consequences of human exposure to phthalates have raised concerns in the general population, they have been studied in susceptible subjects such as pregnant women, infants and children. This article aims at evaluating the impact of exposure to phthalates on reproductive outcomes and children health by reviewing most recent published literature. Epidemiological studies focusing on exposure to phthalates and pregnancy outcome, genital development, semen quality, precocious puberty, thyroid function, respiratory symptoms and neurodevelopment in children for the last ten years were identified by a search of the PubMed, Medline, Ebsco, Agricola and Toxnet literature bases. The results from the presented studies suggest that there are strong and rather consistent indications that phthalates increase the risk of allergy and asthma and have an adverse impact on children’s neurodevelopment reflected by quality of alertness among girls, decreased (less masculine) composite score in boys and attention deficit hyperactivity disorder. Results of few studies demonstrate negative associations between phthalate levels commonly experienced by the public and impaired sperm quality (concentration, morphology, motility). Phthalates negatively impact also on gestational age and head circumference; however, the results of the studies were not consistent. In all the reviewed studies, exposure to phthalates adversely affected the level of reproductive hormones (luteinizing hormone, free testosterone, sex hormone-binding globulin), anogenital distance and thyroid function. The urinary le vels of phthalates were significantly higher in the pubertal gynecomastia group, in serum in girls with premature thelarche and in girls with precocious puberty. Epidemiological studies, in spite of their limitations, suggest that phthalates may affect reproductive outcome and children health. Considering the suggested health effects, more epidemiologic data is urgently needed and, in the meantime, precautionary policies must be implemented.

Prenatal and Childhood Exposure to Pesticides and Neurobehavioral Development: Review of Epidemiological Studies

OBJECTIVES Conventional pesticides comprise a diverse group of substances intended to destroy, repel or control organisms identified as pests. Compared to the studies on lead, mercury, and PCBs, few epidemiological studies have assessed the developmental neurotoxicity of pesticides. MATERIALS AND METHODS Epidemiological studies focused on the neurobehavioural development of children exposed to pesticides were identified by searching the PubMed, Medline, EBSCO, Agricola and TOXNET databases. RESULTS The findings of the studies reviewed imply that childrens exposure to pesticides may bring about impairments in their neurobehavioral development. Children exposed to organophosphate pesticides (OP), both prenatally and during childhood, may have difficulties performing tasks that involve short-term memory, and may show increased reaction time, impaired mental development or pervasive developmental problems. In newborns, the effects of OP exposure are manifested mainly by an increased number of abnormal reflexes, while in adolescents, by mental and emotional problems. The studies investigating association between exposure to organochlorine pesticides and neurodevelopmental effects show inconsistent results. While some studies report impairments in mental and psychomotor functions, other studies do not confirm the above. CONCLUSION The information deriving from epidemiological studies indicate a need to increase awareness among people and children exposed to pesticides about the association between the use of pesticides and neurodevelopmental impairments. Therefore, the principle of prudence should become a rule.

Environmental factors and semen quality.

OBJECTIVES An increasing number of reports suggest that chemical and physical agents in the environment, introduced and spread by human activity, may affect male fertility in humans. This article aims at evaluating the impact of environmental exposures (pesticides, phthalates, PCBs, air pollution, trihalomethanes (THMs), mobile phones) on semen quality, by reviewing most recent published literature. MATERIALS AND METHODS Epidemiological studies focusing on exposure to environmental factors and semen quality for the last ten years were identified by a search of the Pubmed, Medline, Ebsco, Agricola and Toxnet literature bases. RESULTS The results from the presented studies suggest that there are strong and rather consistent indications that some pesticides besides DBCP (e.g. DDT/Dichlorodiphenyldichloroethylene [DDE], ethylenedibromide, organophosphates) affects sperm count. PCBs are detrimental to sperm motility. In case of air pollution, studies suggest a link between ambient air pollutants and various semen characteristics. Additional research is needed to corroborate this association and to establish the causal agents. Results of few studies on subfertile men demonstrate associations between phthalate levels commonly experienced by the public and impaired sperm quality (impact on sperm concentration, morphology, motility), but the findings have not been corroborated in studies of men from the general population. Mobile phones might adversely affect the quality of semen by decreasing mostly motility but also the sperm counts, viability and morphology. In spite of their consistent results, most of the studies are rather small. Association between exposure to THMs and poor semen quality was not observed. CONCLUSIONS Epidemiological studies suggest awareness of environmental factors which may affect semen quality. In case both of well proven and disputable reproductive and developmental hazards, it is necessary to prevent parental exposure to the agents associated with those hazards.

Respiratory allergy in apprentice bakers: do occupational allergies follow the allergic march?

Background:  This prospective study describes the incidence, risk factors and natural history of occupational respiratory allergy in apprentice bakers.

Human urinary phthalate metabolites level and main semen parameters, sperm chromatin structure, sperm aneuploidy and reproductive hormones

The aim of the study was to assess the association of phthalate metabolites levels in urine with semen parameters (sperm concentration, motility, morphology, CASA parameters), sperm chromatin structure, sperm aneuploidy and reproductive hormones. The study population consisted of 269 men who were attending an infertility clinic and had normal semen concentration (20-300mln/ml) or slight oligozoospermia (15-20mln/ml). Participants were interviewed and provided a semen sample. The phthalate metabolites were analysed in the urine using a procedure based on the LC-MS/MS method. Urinary phthalate metabolites levels were significantly associated with a decrease in sperm motility (5OH MEHP, MEHP, MINP), CASA parameters (MBP), testosterone level (MEHP) and an increase sperm DNA damage (MBP) and sperm aneuploidy (MBzP, MBP, MEHP, MEP). In view of the importance of human reproductive health and the widespread usage of phthalates, it is important to further investigate these correlations.

Fish intake during pregnancy, fetal growth, and gestational length in 19 European birth cohort studies.

BACKGROUND Fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants. OBJECTIVE We assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel of European birth cohort studies. DESIGN The study sample of 151,880 mother-child pairs was derived from 19 population-based European birth cohort studies. Individual data from cohorts were pooled and harmonized. Adjusted cohort-specific effect estimates were combined by using a random- and fixed-effects meta-analysis. RESULTS Women who ate fish >1 time/wk during pregnancy had lower risk of preterm birth than did women who rarely ate fish (≤ 1 time/wk); the adjusted RR of fish intake >1 but <3 times/wk was 0.87 (95% CI: 0.82, 0.92), and for intake ≥ 3 times/wk, the adjusted RR was 0.89 (95% CI: 0.84, 0.96). Women with a higher intake of fish during pregnancy gave birth to neonates with a higher birth weight by 8.9 g (95% CI: 3.3, 14.6 g) for >1 but <3 times/wk and 15.2 g (95% CI: 8.9, 21.5 g) for ≥ 3 times/wk independent of gestational age. The association was greater in smokers and in overweight or obese women. Findings were consistent across cohorts. CONCLUSION This large, international study indicates that moderate fish intake during pregnancy is associated with lower risk of preterm birth and a small but significant increase in birth weight.

Review of current evidence on the impact of pesticides, polychlorinated biphenyls and selected metals on attention deficit / hyperactivity disorder in children

The aim of this review was to investigate the association between attention deficit / hyperactivity disorder (ADHD) or ADHD-related symptoms and industrial chemicals, such as organophosphates and organochlorine pesticides, polychlorinated biphenyls (PCBs), lead, mercury and manganese. Medline, PubMed and EBSCO searches were performed to identify the studies that analyzed the association of prenatal and postnatal child exposure to such toxicants and ADHD or ADHD-related symptoms. The review is restricted to human studies published in English in peer-reviewed journals since 2000. Most of the presented studies focused on pesticides, PCB and lead. The impact of mercury and manganese was investigated less frequently. The findings indicate that children’s exposure to organophosphate pesticides may cause symptoms consistent with pervasive developmental disorder, ADHD or attention problems. Exposures to organochlorine pesticides and PCBs were associated with ADHD-like behaviors such as alertness, quality of alert response, and cost of attention. The studies provided evidence that blood lead level below 10 μg/dl was associated with ADHD or ADHD-related symptoms. Information on the association between exposure to mercury and neurotoxicity is limited, and requires further confirmation in future research. Two studies indicated that exposure to manganese is related to ADHD; such exposure and its impact on children neurodevelopment need to be further investigated. Future studies should use a prospective design with multiple biological samples collected over time for better assessment of exposure and its critical windows. Additionally, inclusion of potential confounding factors and co-exposures is crucial.

Exposure to secondhand smoke in terraces and other outdoor areas of hospitality venues in eight European countries.

Background Outdoor secondhand smoke (SHS) concentrations are usually lower than indoor concentrations, yet some studies have shown that outdoor SHS levels could be comparable to indoor levels under specific conditions. The main objectives of this study were to assess levels of SHS exposure in terraces and other outdoor areas of hospitality venues and to evaluate their potential displacement to adjacent indoor areas. Methods Nicotine and respirable particles (PM2.5) were measured in outdoor and indoor areas of hospitality venues of 8 European countries. Hospitality venues of the study included night bars, restaurants and bars. The fieldwork was carried out between March 2009 and March 2011. Results We gathered 170 nicotine and 142 PM2.5 measurements during the study. The median indoor SHS concentration was significantly higher in venues where smoking was allowed (nicotine 3.69 µg/m3, PM2.5: 120.51 µg/m3) than in those where smoking was banned (nicotine: 0.48 µg/m3, PM2.5: 36.90 µg/m3). The median outdoor nicotine concentration was higher in places where indoor smoking was banned (1.56 µg/m3) than in venues where smoking was allowed (0.31 µg/m3). Among the different types of outdoor areas, the highest median outdoor SHS levels (nicotine: 4.23 µg/m3, PM2.5: 43.64 µg/m3) were found in the semi-closed outdoor areas of venues where indoor smoking was banned. Conclusions Banning indoor smoking seems to displace SHS exposure to adjacent outdoor areas. Furthermore, indoor settings where smoking is banned but which have a semi-closed outdoor area have higher levels of SHS than those with open outdoor areas, possibly indicating that SHS also drifts from outdoors to indoors. Current legislation restricting indoor SHS levels seems to be insufficient to protect hospitality workers – and patrons – from SHS exposure. Tobacco-free legislation should take these results into account and consider restrictions in the terraces of some hospitality venues to ensure effective protection.

Lifestyle and semen quality: role of modifiable risk factors

Abstract The relationship between exposure to lifestyle factors and adverse effects on human reproductive health is debated in the scientific literature and these controversies have increased public and regulatory attention. The aim of the study was to examine the association between modifiable lifestyle factors and main semen parameters, sperm morphology, and sperm chromatin structure. The study population consisted of 344 men who were attending an infertility clinic for diagnostic purposes with normal semen concentration of 20–300 M/ml or with slight oligozoospermia (semen total concentration of 15–20 M/ml) [WHO 1999]. Participants were interviewed and provided semen samples. The interview included questions about demographics, socio-economic status, medical history, lifestyle factors (consumption of alcohol, tobacco, coffee intake, cell phone and sauna usage), and physical activity. The results of the study suggest that lifestyle factors may affect semen quality. A negative association was found between increased body mass index (BMI) and semen volume (p = 0.03). Leisure time activity was positively associated with sperm concentration (p = 0.04) and coffee drinking with the percentage of motile sperm cells, and the percentage of sperm head and neck abnormalities (p = 0.01, p = 0.05, and p = 0.03, respectively). Drinking red wine 1–3 times per week was negatively related to sperm neck abnormalities (p = 0.01). Additionally, using a cell phone more than 10 years decreased the percentage of motile sperm cells (p = 0.02). Men who wore boxer shorts had a lower percentage of sperm neck abnormalities (p = 0.002) and percentage of sperm with DNA damage (p = 0.02). These findings may have important implications for semen quality and lifestyle.

Phthalate exposure and child development: the Polish Mother and Child Cohort Study.

BACKGROUND Widespread phthalate exposure has prompted investigations concerning their potential adverse health effects. AIM The objective of this study was to evaluate the impact of pre and early postnatal phthalate exposure on child psychomotor development based on the data from the prospective Polish Mother and Child Cohort Study (REPRO PL). STUDY DESIGN, SUBJECTS AND OUTCOME MEASURES Phthalate exposure was determined by measuring 11 phthalate metabolites (MEP, MiBP, MnBP, 3OH-MnBP, MBzP, MEHP, 5OH-MEHP, 5oxo-MEHP, OH-MiNP, oxo-MiNP, and MnOP) in the urine collected from mothers during the third trimester of pregnancy (prenatal exposure) and from their children at the 24th month of age (postnatal exposure). The analysis was performed by the HPLC-MS/MS method. Psychomotor development was assessed in children at the age of 2years by the Bayley Scales of Infant and Toddler Development. RESULTS Child motor development was inversely associated with natural log concentrations (μg/g creatinine) of 3OH-MnBP (β= -2.3; 95% CI -4.0 to -0.6), 5OH-MEHP (β= -1.2; 95% CI -2.2 to -0.3), 5oxo-MEHP (β= -1.8; 95% CI -3.3 to -0.2) and sum of DEHP metabolites (β= -2.2; 95% CI -3.6 to -0.8), DnBP metabolites (β= -1.9; 95% CI -3.4 to -0.4), and high molecular weight phthalates (β= -2.5; 95% CI -4.1 to -0.9) in the urine collected from mothers during pregnancy after adjustment for a variety of potential confounders. Additional adjustment for postnatal phthalate exposure did not change the results. Postnatal child exposure to phthalates was not associated with any of the measured scores of child psychomotor development. CONCLUSIONS The study findings add further support to the possibility that prenatal phthalate exposure may be detrimental to child neurodevelopment and underscore the importance of policies and public health interventions aiming at reduction of such exposure.