Perfluoroalkyl acids (PFAAs) and anthropometric measures in the first year of life: Results from the Duisburg Birth Cohort.

In the context of the Duisburg Birth Cohort, this retrospective cohort study provides results of internal exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) in 156 mother-child pairs, and investigates whether and to what extent in utero exposure of these chemicals at German background levels exerts an effect on newborn and infant weight and length, and weight in relation to length expressed by ponderal index, in order to examine whether any reduction in weight is disproportionate to length. The levels of PFOA, PFOS, and PFHxS were determined in 81 maternal and 83 umbilical cord stored frozen plasma samples and 105 umbilical cord blood samples. Calculated factors were used to convert umbilical cord values to maternal levels. Weights and lengths were retrieved at birth and at 1, 4, 6, and 12 mo from examination booklets and ponderal index (kg/m3) was calculated. Subsequently, correlations were assessed using multiple linear regressions and generalized estimation equations with each of the measures as a continuous outcome variable and with PFOA, PFOS, and PFHxS concentration quartiles as categorized predictor variables, while adjusting for relevant covariates. PFOA, PFOS, and PFHxS were generally within German background exposure levels. There was a significant association between PFOA, PFOS, and PFHxS concentration quartiles and decrease in ponderal index at birth but not weight or height. A nonsignificant negative association between exposure to all three compounds and birth weight was noted. Follow-up showed no sustained effect of the PFAA on anthropometric measures during the first year.

Mercury analysis in hair: Comparability and quality assessment within the transnational COPHES/DEMOCOPHES project.

Human biomonitoring (HBM) is an effective tool for assessing actual exposure to chemicals that takes into account all routes of intake. Although hair analysis is considered to be an optimal biomarker for assessing mercury exposure, the lack of harmonization as regards sampling and analytical procedures has often limited the comparison of data at national and international level. The European-funded projects COPHES and DEMOCOPHES developed and tested a harmonized European approach to Human Biomonitoring in response to the European Environment and Health Action Plan. Herein we describe the quality assurance program (QAP) for assessing mercury levels in hair samples from more than 1800 mother-child pairs recruited in 17 European countries. To ensure the comparability of the results, standard operating procedures (SOPs) for sampling and for mercury analysis were drafted and distributed to participating laboratories. Training sessions were organized for field workers and four external quality-assessment exercises (ICI/EQUAS), followed by the corresponding web conferences, were organized between March 2011 and February 2012. ICI/EQUAS used native hair samples at two mercury concentration ranges (0.20-0.71 and 0.80-1.63) per exercise. The results revealed relative standard deviations of 7.87-13.55% and 4.04-11.31% for the low and high mercury concentration ranges, respectively. A total of 16 out of 18 participating laboratories the QAP requirements and were allowed to analyze samples from the DEMOCOPHES pilot study. Web conferences after each ICI/EQUAS revealed this to be a new and effective tool for improving analytical performance and increasing capacity building. The procedure developed and tested in COPHES/DEMOCOPHES would be optimal for application on a global scale as regards implementation of the Minamata Convention on Mercury.

Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) in blood samples of occupationally exposed workers from a transformer recycling plant in Dortmund, Germany-initial findings.

Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) were determined in 23 blood samples of exposed workers from a transformer recycling plant in Dortmund, Germany. Compared to the most recent studies on German background levels of adults, elevated concentrations of up to 71.6 pg WHO(2005)-TEq/g(lipid base) were found for 8 participants, and for individual PCDF congeners for 15 participants.

Determination of bisphenol a in urine from mother-child pairs-results from the duisburg birth cohort study, Germany.

Bisphenol A (BPA) may alter endocrine functions, and human exposure is widespread. In the Duisburg birth cohort study the influence of several contaminants was examined on the neuropsychological and pubertal development of children. This study reports the biomonitoring results on BPA within the 6-yr follow-up study (children's age 6-8 yr). Total BPA and free (unconjugated) BPA concentrations in 208 urine samples of 104 mother-child pairs were measured. For quality control, total BPA was analyzed by two independent laboratories. BPA was detected in all urine samples, while free BPA was observed above the limit of quantification (LOQ) in only 33 samples. Total BPA concentrations were significantly associated between the two laboratories. BPA concentrations (median; range) tended to be higher in children than in mothers but the difference was not significant. Total BPA levels in children and mothers correlated at low levels but significantly to each other. Multivariate linear regression analysis revealed positive associations between creatinine and the BPA concentrations and a negative association with German nationality (mothers only). Evidence indicates that BPA exposure is omnipresent but levels in mother-child pairs are low. Only small amounts (less than 16%) were detectable as free (unconjugated) BPA. Analytical reliability is high even at such low levels, provided that external contamination is minimized.

Prenatal and early life exposure to polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls may influence dehydroepiandrosterone sulfate levels at prepubertal age: results from the Duisburg birth cohort study.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) and polychlorinated biphenyls (PCB) are postulated to act as endocrine disrupters. In the ongoing Duisburg birth cohort study, started in 2000-2002, influence of persistent organic pollutants (POP) on child development was monitored. For the first time, associations were reported between prenatal and postnatal PCDD/F and PCB exposures and early endocrinological changes concerning adrenarchal development. PCDD/F and PCB concentrations were measured in blood samples taken in wk 32 of pregnancy and in breast milk using gas chromatography and high-resolution mass spectrometry (GC/HRMS). At the age of 6-7 and 8-9 yr, serum samples were collected from 111 children. The samples were assayed for the sex hormones testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), and 17-OH-progesterone (17-OHP) by using an automated chemiluminescence assay system. Analyses of repeated measurements of DHEA-S serum levels were performed by linear regression analysis using generalized estimating equations (GEE). Linear regression analysis showed a positive association between DHEA-S and breast milk levels of PCDD/F and PCB expressed as toxicity equivalents according to toxicity equivalent factors published by the World Health Organization (WHO) in 2005 (WHO(2005)-TEq) (increase of 29%, geometric mean ratio, GMR: 1.29, 95% CI 1.06-1. 58 per doubling of PCDD/F + PCB WHO(2005)-TEq levels). Results for the association with the WHO(2005)-TEq levels in blood of mothers were in the same direction (increase of 15%, GMR 1.15, 95% CI 0.93-1.42 per doubling of PCDD/F + PCB WHO(2005)-TEq levels), but not significant. Data indicate that PCDD/F and PCB exposure in infancy may influence DHEA-S serum levels in prepubertal children. Increased DHEA-S serum levels are considered to indicate acceleration of the adrenal maturation.

Surveillance program for former PCB-exposed workers of a transformer and capacitor recycling company, family members, employees of surrounding companies, and area residents--executive summary.

In a German company polychlorinated biphenyls (PCB)-containing transformers and capacitors were recycled on a large scale. Human biomonitoring revealed a high PCB body burden in workers of the recycling company, in surrounding locations of this plant, in companies in the neighborhood of this plant, and in family members of these employees. In order to clarify whether possible adverse health effects occurred or may occur in the future, a prospective surveillance program was initiated. After an extensive literature search, an interdisciplinary group of experts developed a surveillance program based on current knowledge with respect to possible adverse health effects that might occur in the recycling process of transformers and capacitors. Exposure to various hazardous substances (PCB, polychlorinated dibenzo-p-dioxins and dibenzo-furans [PCDD/F], metals, solvents) was considered. Criteria derived from human biomonitoring results of PCB were used for admission to the program. Participants in the surveillance program are first informed about risks and aims of the program. Subsequently, physicians started a detailed documentation of participants' general and occupational history, with their complaints, diseases, and nutritional habits, as well as information regarding their living areas, by means of a standardized questionnaire. In addition, separate examinations were performed to detect possible neurological, immunological, (neuro)psychological, hormonal, and skin effects. Moreover, DNA exposure as assessed by the comet assay and antioxidative status were determined. The program will be offered at yearly intervals for 3 years, and then at 5 and 10 years after program onset. Until now the program has proved to be feasible, and acceptance among workers and their families has been high. Based on the results, criteria will be developed to define adverse health effects that might be attributable to a hazardous substance exposure.

Prevalence of nickel sensitization and urinary nickel content of children are increased by nickel in ambient air.

In a cross-sectional study performed in 2000, an unexpected positive association between nickel (Ni) in ambient air, urinary Ni content and the prevalence of Ni sensitization in a subgroup of 6-yr-old children living near a steel mill was observed. Between 2005 and 2006, in a different and larger study population, we examined if Ni from ambient air or urinary Ni concentration was related to Ni sensitization in children living next to Ni-emitting steel mills. We studied 749 school beginners living in four Ni-polluted industrial areas of North Rhine-Westphalia, Germany. We assessed Ni in ambient air, Ni in urine from children and mothers, and Ni in tap water, conducted patch tests in children (including the NiSO(4)-dilution test) and collected questionnaire data. Statistics were done by linear and logistic regression analyses, adjusted for covariates. At increased Ni concentration in ambient air (unit of increase: 10 ng/m(3)), urinary Ni concentrations rose in both mothers (9.1%; 95% CI: 6.8-11.4%) and children (2.4%; 95% CI: 0.4-4.4%). The prevalence of Ni sensitization in children was associated with increased Ni from ambient air (unit of increase: 18 ng/m(3); odds ratio 1.28; 95% CI: 1.25-1.32) and urinary Ni concentration (unit of increase: 7.1 µg/L; odds ratio 2.4; 95% CI: 1.20-4.48). Ni in ambient air of areas with Ni-emitting factories contributes to internal Ni exposure in residents via inhalation and, furthermore, is a risk factor for the development of Ni sensitization in children.

Investigations on the estrogenic activity of the metallohormone cadmium in the rat intestine.

Cadmium (Cd), a toxic heavy metal and an important environmental pollutant, is now also regarded as potential endocrine disruptor. Its estrogenic effects have been examined so far just in classical target tissues, e.g. uterus, and mostly upon intraperitoneal (i.p.) injection of CdCl(2). Yet, estrogen receptors are also expressed in the gut, and food is the main source of cadmium intake in the general population. Therefore, possible estrogenic effects were now investigated in the intestine of ovariectomized Wistar rats after oral short- and long-term administration of CdCl(2) (0.05-4 mg/kg bw on 3 days by gavage and 0.4-9 mg/kg bw for 4 weeks in drinking water) or upon i.p. injection (0.00005-2 mg CdCl(2)/kg bw), and compared to steroid estrogen (estradiol or ethinylestradiol) treated groups. Analysis of Cd in kidneys and small intestine by atomic absorption spectrometry showed dose-dependent increases in tissue levels with rather high Cd concentrations in the gut, both after oral and i.p. administration. Expression of metallothionein (MT1a), a typical metal response parameter, was clearly induced in kidney and small intestine of several CdCl(2) treated groups, but also notably increased by steroid estrogens. Levels of estrogen-regulated genes, i.e. pS2/TFF1, vitamin D receptor (VDR), and estrogen receptor alpha and beta (ER alpha/beta) were studied as parameters of hormonal activity: The intestinal mRNA expression of pS2/TFF1 was significantly decreased in the estrogen reference groups, but also after single i.p. injection and oral long-term administration of CdCl(2). In contrast, the mRNA and protein expression of the VDR were unaffected by long-term administration of Cd via drinking water. We detected expression of ERbeta, but not ERalpha in the small intestine of OVX rats. ERbeta mRNA and protein expression were significantly down-regulated by Cd, similar to the ethinylestradiol reference group. The mRNA expression and immunostaining of proliferating cell nuclear antigen (PCNA), as an index for cell proliferation, revealed decreases after long-term administration of Cd and ethinylestradiol. In summary, cadmium exposure was shown to modulate molecular and functional parameters of estrogenicity in the intestinal tract of OVX rats. As the intestine is known to express predominantly ERbeta, and is an important site of interaction with dietary contaminants, it is indicated to further investigate specific molecular mechanisms of cadmium and estrogen receptor interactions in more detail.

Does airborne nickel exposure induce nickel sensitization?

BACKGROUND AND OBJECTIVE: Nickel is one of the most prevalent causes of contact allergy in the general population. This study focuses on human exposure to airborne nickel and its potential to induce allergic sensitization. MATERIALS AND METHODS: The study group consisted of 309 children at school-starter age living in the West of Germany in the vicinity of two industrial sources and in a rural town without nearby point sources of nickel. An exposure assessment of nickel in ambient air was available for children in the Ruhr district using routinely monitored ambient air quality data and dispersion modelling. Internal nickel exposure was assessed by nickel concentrations in morning urine samples of the children. RESULTS: The observed nickel sensitization prevalence rates varied between 12.6% and 30.7%. Statistically significant associations were showed between exposure to nickel in ambient air and urinary nickel concentration as well as between urinary nickel concentration and nickel sensitization. Furthermore, an elevated prevalence of nickel sensitization was associated with exposure to increased nickel concentrations in ambient air. CONCLUSION: The observed associations support the assumption that inhaled nickel in ambient air might be a risk factor for nickel sensitization; further studies in larger collectives are necessary.

Early Life Exposure to Perfluoroalkyl Substances (PFAS) and ADHD: A Meta-Analysis of Nine European Population-Based Studies.

INTRODUCTION: To date, the evidence for an association between perfluoroalkyl substances (PFAS) exposure and attention deficit and hyperactivity disorder (ADHD) is inconclusive. OBJECTIVE: We investigated the association between early life exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and ADHD in a collaborative study including nine European population-based studies, encompassing 4,826 mother-child pairs. METHODS: Concentrations of PFOS and PFOA were measured in maternal serum/plasma during pregnancy, or in breast milk, with different timing of sample collection in each cohort. We used a validated pharmacokinetic model of pregnancy and lactation to estimate concentrations of PFOS and PFOA in children at birth and at 3, 6, 12, and 24 months of age. We classified ADHD using recommended cutoff points for each instrument used to derive symptoms scores. We used multiple imputation for missing covariates, logistic regression to model the association between PFAS exposure and ADHD in each study, and combined all adjusted study-specific effect estimates using random-effects meta-analysis. RESULTS: A total of 399 children were classified as having ADHD, with a prevalence ranging from 2.3% to 7.3% in the studies. Early life exposure to PFOS or PFOA was not associated with ADHD during childhood [odds ratios (ORs) ranging from 0.96 (95% CI: 0.87, 1.06) to 1.02 (95% CI: 0.93, 1.11)]. Results from stratified models suggest potential differential effects of PFAS related to child sex and maternal education. CONCLUSION: We did not identify an increased prevalence of ADHD in association with early life exposure to PFOS and PFOA. However, stratified analyses suggest that there may be an increased prevalence of ADHD in association with PFAS exposure in girls, in children from nulliparous women, and in children from low-educated mothers, all of which warrant further exploration. https://doi.org/10.1289/EHP5444.

Persistent organic pollutants and the incidence of type 2 diabetes in the CARLA and KORA cohort studies.

BACKGROUND: Associations between several persistent organic pollutants (POPs) and type 2 diabetes have been found in humans, but the relationship has rarely been investigated in the general population. The current nested case-control study examined internal exposure to polychlorinated biphenyls (PCB) and pesticides and the incidence of type 2 diabetes among participants of two population-based German cohort studies. METHODS: We retrospectively selected 132 incident cases of type 2 diabetes and 264 age- and sex-matched controls from the CARdiovascular Living and Aging in Halle (CARLA) study (2002-2006, East Germany) and the Cooperative Health Research in the Region of Augsburg (KORA) study (1999-2001, South Germany) based on diabetes status at follow-up examinations in 2007-2010 and 2006-08, respectively (60% male, mean age 63 and 54 years). We assessed the association between baseline POP concentrations and incident diabetes by conditional logistic regression adjusted for cohort, BMI, cholesterol, alcohol, smoking, physical activity, and parental diabetes. Additionally, we examined effect modification by sex, obesity, parental diabetes and cohort. RESULTS: In both cohorts, diabetes cases showed a higher BMI, a higher frequency of parental diabetes, and higher levels of POPs. We observed an increased chance for incident diabetes for PCB-138 and PCB-153 with an odds ratio (OR) of 1.50 (95%CI: 1.07-2.11) and 1.53 (1.15-2.04) per interquartile range increase in the respective POP. In addition, explorative results suggested higher OR for women and non-obese participants. CONCLUSIONS: Our results add to the evidence on diabetogenic effects of POPs in the general population, and warrant both policies to prevent human exposure to POPs and additional research on the adverse effects of more complex chemical mixtures.

The Duisburg birth cohort study: influence of the prenatal exposure to PCDD/Fs and dioxin-like PCBs on thyroid hormone status in newborns and neurodevelopment of infants until the age of 24 months.

Prenatal exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) can affect neurobehavioral development of infants and children. This effect may be mediated through disruption of thyroid hormone homeostasis. However, epidemiological studies reveal no consistent influence of PCDD/Fs and PCBs on thyroid status and neurodevelopment at environmental background levels. The effects may resolve with time of further decreasing exposure to these compounds. The aim of this study was to find out if there are still effects related to prenatal PCDD/F and PCB observable at the meanwhile decreased levels of exposure by using the same methods which have been applied in similar studies during the last 10 years in Europe. The birth cohort study was initiated in the year 2000 in the industrialized city of Duisburg, Germany. 232 healthy mother-infant pairs were recruited between 2000 and 2002. Dioxins, dioxin-like PCBs and six indicator PCBs were analyzed in maternal blood during pregnancy and in maternal milk following extraction and sample clean-up by HRGC/HRMS. Thyroid stimulating hormone (TSH), total thyroxine (T4), total triiodothyronine (T3), free thyroxine (FT4) and free triiodothyronine (FT3) were measured in serum samples of the pregnant women and in cord serum samples by chemiluminescent immunometric assay. Neurological examinations were performed at ages 2 weeks and 18 months using the neurological optimality score (NOS), mental and motor development were assessed using the Bayley Scales of Infant Development (BSID) at ages 12 and 24 months. Multiple linear regression analysis was used to describe the association of PCDD/F and PCB in maternal blood or milk with the outcome measurements after adjustment for confounding. Blood levels (n=182) of WHO 2005 toxic equivalents (TEQ) (PCDD/F+PCB) were in the range of 3.8-58.4 pg/glipid base (median: 19.3 pg/glipid base). The corresponding data for human milk (n=149) were 2.6-52.4 pg/glipid base (median: 19.7 pg/glipid base). Multiple regression analysis showed no decrease of thyroid hormones related to WHO 2005 TEQ in blood and milk of mothers and their newborns. Furthermore, no associations between exposure and neurological and developmental measures were observed. This study supports the view that the current decreased exposure to PCDD/Fs and PCBs does not impair thyroid function of newborns and neurodevelopment of infants until the age of 24 months.

Polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and organochlorine pesticides in human blood of pregnant women from Germany.

Blood samples from 226 pregnant women aged between 19 and 41 yr, living in an industrialized area of Germany (Duisburg birth cohort study), were collected between September 2000 and November 2002 and analyzed for their content of persistent organic pollutants (POPs). Levels of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) were in the range of 4.34-97.3 pg WHO 1998 TEq/g(lipid base) (median: 25.96) or 3.77-63.56 pg WHO 2005 TEq/g(lipid base) (median: 19.38), respectively. Whole blood volume-based concentrations of organochlorine pesticides and their metabolites were 0.036-0.53 microg/L (median: 0.15) hexachlorobenzene (HCB), 4.5-1300 ng/L (median: 67) beta-hexachlorocyclohexane (HCH), 0.6-520 ng/L (median: 18) 4,4'-dichlorodiphenyltrichloroethane (DDT), and 0.1-9.1 microg/L (median: 0.54) 4,4'-dichlorodiphenyldichloroethene (DDE). Parameters influencing the POP levels in human blood were examined using multiple regression models. Levels and the levels scatter widths of most PCDD/F and PCB congeners and HCB increased significantly with age. Within the multiple regression model a weak age dependence was also found for beta-HCH and DDT, whereas blood levels of alpha- and gamma- HCH and DDE were not age dependent. The total lactation period for earlier born children decreased most POP blood levels, except for alpha- and gamma-HCH. Over the study period of 27 mo only a low decreasing effect on human POP blood levels was observed. The body mass index had in general no or a low positive influence on contaminant levels. Because exposure to PCDD/F and PCB is higher in most industrialized countries in comparison to less industrialized ones, lower levels of these substances were detected in blood samples of women who had lived outside Western Europe for a longer period. In contrast, these women showed higher blood levels of organochlorine pesticides, indicating that these chemicals are still in use outside Western Europe.

Lack of neurodevelopmental adversity by prenatal exposure of infants to current lowered PCB levels: comparison of two German birth cohort studies.

Polychlorinated biphenyls (PCBs), persistent environmental contaminants, may affect neurodevelopment of infants following prenatal exposure. A negative impact of prenatal PCB exposure on neurodevelopment was found in the Dusseldorf (Germany) cohort study (1993-2000). PCB levels of the sum of the three indicator congeners in breast milk were negatively associated with mental/motor development as assessed by the Bayley Scales of Infant Development (BSID) in infants. Since general exposure to PCB has decreased, a new birth cohort study was initiated in 2000 in the industrial city of Duisburg, which is located 30 km downstream from Dusseldorf on the River Rhine. A subgroup of the Duisburg birth cohort study was used to compare PCB exposure and developmental effects with results from the Dusseldorf cohort. The recruitment phase of the Duisburg cohort study occurred from 2000 to 2002. Mental and motor development was assessed by means of the BSID at the ages of 12 and 24 mo. Prenatal PCB exposure of newborns from Duisburg cohort was about two- to threefold lower than the Dusseldorf cohort. Although in the Dusseldorf birth cohort mental and motor development at ages 18 and 30 mo were negatively associated with PCB exposure, there was no association observed in the Duisburg study. Evidence indicates that exposure to PCB at current exposure levels no longer apparently impair neurodevelopment of infants.

Environmental exposure to dioxins and polychlorinated biphenyls reduce levels of gonadal hormones in newborns: results from the Duisburg cohort study.

BACKGROUND: Endocrine dysfunction related to the hypothalamic-pituitary-thyroid (HPT) and/or the hypothalamic-pituitary-gonadal axis (HPG) is being discussed as underlying developmental adversity of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs). This study was done to evaluate effects related to the HPG axis. METHODS: A birth-cohort study was initiated in the year 2000. Healthy mother-infant pairs were recruited in the industrialized city of Duisburg, Germany. Dioxins, dioxin-like PCBs and six indicator PCBs were measured in maternal blood during pregnancy and in maternal milk. Testosterone and estradiol levels were measured in maternal and cord serum of 104 mother-infant pairs representing a subsample with a complete data set of the total basic sample of 232 participants. Linear regression analysis was used to describe the association of PCDD/Fs or PCB in maternal blood or milk with sex steroid concentrations after adjustment for confounding. RESULTS: Median concentrations for PCDD/Fs in maternal blood fat and milk fat in terms of WHO-TEq were 15.3 and 13.1pg WHO-TEq/g, respectively, and for the sum of the indicator PCBs (#28, #52, #101, #138, #153, #180) 149 and 177ng/g. The adjusted ratio of geometric means when doubling the concentration of PCDD/Fs in maternal blood fat was 0.86, 95% confidence interval (95% CI): 0.72-1.03 for testosterone and 0.73 (0.61-0.87) for estradiol in cord serum. Typically, testosterone reduction was more pronounced in cord serum of female and estradiol reduction in that of male babies. Reduction of hormone levels was generally more pronounced for dioxins than for indicator PCBs. CONCLUSIONS: The hypothalamic-pituitary-gonadal axis of newborn babies is influenced by prenatal exposure to PCDD/Fs and PCBs in a manner suggestive of AhR-mediation. The clinical relevance of this finding remains to be established, however.

Prenatal and postnatal exposure to persistent organic pollutants and attention-deficit and hyperactivity disorder: a pooled analysis of seven European birth cohort studies.

Background: Attention-deficit/hyperactivity disorder (ADHD) is increasing worldwide for reasons largely unknown and environmental chemicals with neurotoxic properties, such as persistent organic pollutants (POPs), have been proposed to play a role. We investigated the association between prenatal and postnatal exposure to polychlorinated biphenyl-153 (PCB-153), p-p´-dichlorodiphenyldichloroethylene (p-p'-DDE) and hexachlorobenzene (HCB) and ADHD in childhood. Methods: We pooled seven European birth cohort studies encompassing 4437 mother-child pairs from the general population with concentrations of PCB-153, p-p´-DDE and HCB measured in cord blood, maternal blood or milk. We then calculated prenatal (birth) and postnatal (3, 6, 12 and 24 months) POP concentrations using a pharmacokinetic model. The operational definition of ADHD varied across cohorts and ranged from doctor diagnosis obtained from patient registries to maternal or teachers reports. We used multilevel (mixed) logistic regression models to estimate the associations between exposure to POPs at birth, 3, 6, 12 and 24 months and ADHD. Results: The global prevalence of ADHD in our study was 6%. The mean age at assessment of ADHD was 5.8 years (range: 3.8-9.5 years). We found no association between exposure to PCB-153, p-p´-DDE and HCB at any age point between birth and 24 months and ADHD, in the pooled analyses (pooled odds ratios ranging from 1.00 to 1.01). A number of sensitivity analyses gave basically the same results. Conclusions: In the largest study to date of 4437 children in seven European birth cohorts, we did not observe any association between either pre- or postnatal exposure (up to 24 months) to PCB-153, p-p´-DDE and HCB and the risk of ADHD before the age of 10 years.

The 2005 World Health Organization re-evaluation of TEFs for dioxins and dioxin-like compounds--what are the consequences for German human background levels?

In 2005 the World Health Organization (WHO) re-evaluated toxicity equivalency factors (TEFs) for dioxins and dioxin-like compounds. WHO 2005 toxicity equivalent (TEq) levels were calculated based on our data on German background levels of polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF) and polychlorinated biphenyls (PCB) in human blood and milk of the Duisburg birth cohort study. Levels of WHO 2005 TEq (PCDD/F+PCB) were in the range of 3.77-63.6 pg/g(lipid base) (n=226, median: 19.38, arithmetic mean: 20.86) for blood, or 2.62-59.2 pg/g(lipid base) (n=176, median: 19.78, arithmetic mean: 20.57) for milk, respectively. Compared to WHO 1998 TEq values WHO 2005 TEq levels were about 25% lower in both matrices. The shares of PCB (31% blood, 43% milk), especially of mono-ortho-substituted PCB (4% blood and milk), on total WHO 2005 TEq has become lower. If similar congener patterns can be assumed for certain matrices, appropriate multiplication factors can be used to convert TEq values of other TEF models sufficiently to WHO 2005 TEq values.

Human biomonitoring studies in North Rhine-Westphalia, Germany.

The areas along the rivers Rhine, Ruhr and Wupper in North Rhine-Westphalia (NRW), Germany, represent the largest urban and industrial agglomeration in Europe with about 10 million inhabitants. Human biomonitoring (HBM) studies have been conducted in these areas since more than 30 years, mainly designed to evaluate internal exposure to air pollutants. Recent studies were focussed on residents living near industrial sources. The contaminants studied comprise heavy metals, metabolites of polycyclic aromatic hydrocarbons (PAH), persistent organic pollutants (POPs), volatile organic compounds (VOC), and markers of DNA exposure. Study groups were mainly children and elderly subjects. Human milk, blood, urine, teeth, hair and nails were investigated. Time trend analyses demonstrate a significant decline of exposure to many contaminants such as POPs and heavy metals. More recent studies suggest that there still is an increased internal exposure to metals, PAH and DNA damaging agents in children and women living very close to industrial sources.

Bioavailability of PCDD/F from contaminated soil in young Goettingen minipigs.

For the general population the intake of food of animal origin is the main route of human exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F). Besides this the ingestion of contaminated soil might be an important exposure path for small children. For risk assessment the knowledge of the bioavailable fraction of soil bound contaminants is important. In a balance study with young Goettingen minipigs the oral bioavailability of PCDD/F from contaminated soil was estimated by determination of the retention of PCDD/F from soil in different organs and tissues. Relative bioavailability was estimated by comparing the retention from soil to the retention of PCDD/F in organs and tissues after oral administration of a PCDD/F mixture extracted from the same soil by solvent. The soil had a PCDD/F-contamination of 5.3 microg I-TEq/kg and originated from a former arable land that had been treated with sludge from the port of Hamburg some years ago. Two groups of each four animals were exposed daily for 28 days via their diet either to 0.5 g soil per kg body weight and day (2.63 ng I-TEq/(kg(bw).d)) or to a daily dose of 1.58 ng I-TEq/(kg(bw).d) given to the diet by solvent. Five unexposed animals were used as a control group. Liver, adipose tissue, muscle, brain and blood were analyzed for their PCDD/F content. Accumulation of PCDD/F from soil or solvent in comparison to control animals was only observed for congeners with 2378-chlorosubstitution and predominantly took place in the liver. Bioavailability of 2378-chlorosubstituted congeners was in the range of 0.64%-21.9% (mean: 10.1%) from soil and 2.8%-59.8% (mean: 31.5%) when administered by solvent. The soil matrix reduced the bioavailability by about 70%. Expressed as I-TEq only 13.8% of the PCDD/F contamination were bioavailable from soil. The relative bioavailability of 2378-chlorosubstituted congeners from soil in relation to administration by solvent was in the range of 2%-42.2% (mean: 28.4%). When not considering the bioavailability, the risk by oral uptake of PCDD/F contaminated soil might be overestimated.

PCDD/F and dioxin-like PCB in human blood and milk from German mothers.

Blood samples of pregnant women aged between 19 and 42 years at the time they gave birth and milk samples from the same women following delivery were collected between September 2000 and January 2003 from 169 participants living in an industrialized area of Germany (Duisburg birth cohort study). All samples were analyzed for their content of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) as well as dioxin-like and indicator polychlorinated biphenyls (PCB). Levels of WHO-TEq were in the range of 4.34-97.3 pg/g(lipid base) (median: 26.37, arithmetic mean: 28.36) for blood, or 3.01-78.7 pg/g(lipid base) (median: 26.40, arithmetic mean: 27.27) for milk, respectively. The four congeners 12378-PeCDD, 23478-PeCDF, 33'44'5-PeCB (# 126) and 233'44'5-HxCB (# 156) contribute the main share to total WHO-TEq. The contribution of PCDD/F in relation to PCB to total WHO-TEq was 60:40% in blood and 52:48% in milk. Good correlations of the contaminant levels in lipid base between both matrices were found. The distribution between blood and milk depends on the molecular weight of the substances. Higher chlorinated PCDD/F- and PCB-congeners were found in 2-4-fold higher concentrations in blood in relation to milk and the concentrations of lower chlorinated PCB-congeners were up to 2-fold higher in milk in relation to blood. The body burden of PCDD/F and PCB increases with age and decreases over the total nursing period. Women who had lived outside highly industrialized countries showed lower concentrations of PCDD/F and PCB. In some cases, elevated levels of PCB were observed when the women had previously lived in Eastern Europe for a long time. In comparison with recent data, the decline in human PCDD/F and PCB levels observed during the nineties seems to have stopped. The individual exposures of the infants due to breastfeeding within the first 18 months were calculated to be from 4.4 to 318 ng WHO-TEq (median: 106, arithmetic mean: 118). The actual mean daily exposure of a breastfed infant can be estimated to 131 pg WHO-TEq/kg(body weight).