[show abstract][hide abstract] ABSTRACT: Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that have been characterized as endocrine disrupting chemicals (EDCs).
Within the Duisburg birth cohort study we studied associations of prenatal exposure to PCDD/Fs and PCBs with parent-reported sexually dimorphic behavior in children.
We measured lipid-based and WHO2005-TEq-standardized PCDD/Fs and PCBs in maternal blood samples and in early breast milk using gas chromatography/high-resolution mass-spectrometry (GC/HRMS). At the age of 6 - 8 years parents (mostly mothers) reported sex-typical characteristics, preferred toys and play activities using the Preschool Activities Inventory (PSAI) which was used to derive feminine, masculine and difference (feminine - masculine) scores. We estimated exposure-outcome associations using multivariate linear regression. Between 91 and 109 children were included in this follow-up.
Mean blood levels of WHO2005-TEq-standardized dioxins (Σ PCDD/Fs) were 14.5 ± 6.4 pg/g blood lipids, and of Σ PCBs 6.9 ± 3.8 pg/g blood lipids, with similar values for milk lipids. Regression analyses revealed some highly significant interactions between sex and exposure, e.g. for Σ PCBs in milk, pronounced positive (boys: β = 3.24; CI = 1.35, 5.14) or negative (girls: β = -3.59; CI = -1.10, -6.08) associations with reported femininity. Less pronounced and mostly insignificant but consistent associations were found for the masculinity score, positive for boys and negative for girls.
Based on our results and the findings of previous studies, we conclude that there is sufficient evidence that EDCs modify behavioral sexual dimorphism in children, presumably by interacting with the hypothalamic-pituitary-gonadal (HPG) axis.
Environmental Health Perspectives 11/2013; · 7.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Neurobehavioral measures of attention, and clinical features of the attention-deficit hyperactivity disorder (ADHD) have been studied in pediatric environmental lead research. However rarely, if ever, have performance measures of attention or executive functions and questionnaire-based quantitative ADHD-observations been studied in the same subjects. We examined associations between pediatric blood lead concentrations (PbB), as well as those of mercury (Hg), and aluminum (Al), and performance in four different attention tasks, as well as behavioral ratings from an ICD-10 (hyperactivity) and DSM-IV-coded (attention deficit) German questionnaire (FBB-ADHS). Asymptomatic, 8-12 year old children from two Romanian cities were studied, namely Bucharest and Pantelimon, a city near a metal-processing plant. Blood was analyzed for Pb, Al, and Hg. Data from 83 children were available for final analysis. We assessed attention performance by means of four tasks of the computer-based ADHD-taylored German KITAP-battery. We also received questionnaire ratings from parents and teachers covering three ADHD-dimensions. Multiple linear regression analysis was used to estimate associations between the three neurotoxic trace metals in blood and the different ADHD features. After adjusting for eleven potentially confounding variables we found consistent borderline to significant associations between Pb, but not other metals, in blood and various performance- and questionnaire data. False alarm responses (FAR) in the KITAP subtests rather than response latencies exhibited positive associations with PbB. Questionnaire ratings for ADHD dimensions also revealed PbB-related adversity. With any two-fold increase of PbB outcome changed markedly, namely up to 35%. Restriction to children with PbBs<10mug/dl had only a marginal influence on outcome.The converging evidence from performance- and questionnaire data confirms that core elements of ADHD are adversely affected by low environmental PbB even below 10mug/dl, but not by other neurotoxic trace metals. Observed effect-sizes are considerably larger than those typically found for lead-related IQ-deficit, thus suggesting that attention deficit could be the more basic adverse effect of lead in children. This is the first study from Central and Eastern Europe dealing with links between environmental exposure of children to neurotoxic metals and ADHD.
Environmental Research 07/2010; 110(5):476-83. · 3.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Exposure to environmental odours from industrial and agricultural premises, in addition to inducing annoyance responses in a dose-dependent manner, have been shown to be either directly associated with gastric symptoms as well as general health-related complaints under extreme exposure conditions, or indirectly mediated through odour annoyance under moderate odour exposure conditions. Objective: In order to examine the influence of hedonic tone (pleasantness-unpleasantness) and perceived odour strength (intensity) on symptom reporting the results of two pertinent field studies were analysed. Methods: In the vicinity of six industrial plants (sweets, rusk, textile, seed-oil, fat, cast iron) and eleven livestock operations (poultry, pig, cattle) assessment of odour exposure was done by means of systematic field inspections. Effect assessment was done by means of direct interviews (industrial: N=1456, agricultural: N=1053) using questionnaires covering odour annoyance, symptom reporting and relevant covariates. Data analysis: Multiple logistic regression analysis was used to establish dose-response associations between odour frequency, intensity and hedonic tone as independent variables and symptom reporting as dependent variable. Results: Exposure-symptom associations are strongly influenced by hedonic tone, whereas intensity has no additional predictive value. Adding odour annoyance to the regression model shows that symptom reporting is exclusively mediated by annoyance.
Water Science & Technology 02/2009; 59(7):1281-9. · 1.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: Risk-assessment for environmental odors and the development of an appropriate guideline for protection against undue odor annoyance have long been hampered by the difficulties of assessing odor exposure and community annoyance responses. In recent years, however, dose-response associations between frequency of odor events and odor annoyance level in the affected population were established. However, the influence of hedonic tone (pleasantness-unpleasantness) and perceived odor strength (intensity) on the degree of odor annoyance have long been neglected in such studies and accompanying guidelines. In order to close this gap a pertinent field study was conducted in the vicinity of six odor emitting plants, two with pleasant (sweets production, rusk bakery), with neutral (textile production, seed oil production), and with presumably unpleasant odor emissions (fat refinery, cast iron production).
A standardized sensory method was developed (described in Part I in the accompanying paper) to quantify intensity and hedonic tone within the assessment of odor exposure by systematic field inspection with trained observers. Additionally, exposure-information, the degree of annoyance, and the frequency of general health complaints and irritation symptoms were collected from the exposed residents through direct interviews. Multiple logistic regression analysis was used to establish dose-response associations between odor frequency, intensity and hedonic tone as independent variables and annoyance or symptom reporting as the dependent variable.
It is shown that exposure-annoyance as well as exposure-symptom associations are strongly influenced by odor hedonic. Whereas pleasant odors induced little to no annoyance, both neutral and unpleasant ones did. Additional inclusion of odor intensity did not improve the prediction of odor annoyance. Frequency of reported symptoms was found to be exclusively mediated by annoyance. The results are discussed in terms of environmental stress emphasizing the WHO-definition of health.
Based on these findings the existing German guideline against undue odor annoyance was modified.
International Archives of Occupational and Environmental Health 06/2008; 81(6):683-94. · 2.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: Odors can be evaluated as being pleasant or unpleasant (hedonic tone), but this differentiation was not incorporated into environmental odor regulation. In order to study the hedonic-induced modification of dose-response associations for community odor annoyance a pertinent field study was conducted. This paper covers the first step, namely the development and validation of a standardized human observation strategy for the direct quantification of the frequency, intensity, and hedonic tone of environmental odors in the field.
Grids with equidistant observation points were located around six industrial odor sources, two with pleasant (sweets, rusk bakery), two with neutral (textile production, seed oil production), and two with unpleasant odor emissions (fat refinery, cast iron production). These points were visited by trained observers, screened for normal olfaction and reliable performance, in a systematic fashion for an observation time of 10 min duration. Exposure-related information from the observers in terms of frequency, intensity (six-point scale) and hedonic tone (nine-point scale) were compared to that of 1,456 residents using the same rating scales.
Residents evaluated the industrial odors more intense and more unpleasant than the panelists. Furthermore, for the residents only negative relations between odor intensity and hedonic tone were found while for the observer pleasant odor became more pleasant with increasing intensity. Instead of three classes of industrial odors, namely pleasant, neutral and unpleasant, the responses allowed only for two odor classes, namely pleasant and not pleasant, the latter also covering the neutral category.
The developed methodology has been shown to yield valid information about odor exposure in the field. With regard to different application settings the discrepancies between external observers and affected residents are discussed in terms of different information processing strategies, namely stimulus-based (bottom-up) for the panel and memory-based and, thus, subject to cognitive bias for the residents (top-down).
International Archives of Occupational and Environmental Health 06/2008; 81(6):671-82. · 2.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
International Journal of Hygiene and Environmental Health 04/2008; 211(1-2):30-9. · 3.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Journal of Toxicology and Environmental Health Part A 02/2008; 71(11-12):700-2. · 1.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Deux groupes d'hommes volontaires ont été soumis respectivement à 50 et à 10ppm (groupe contrôle) de perchloroéthylène (Per) quatre heures par jour pendant quatre jours consécutifs. La plus forte de ces deux concentrations correspond à la valeur MAK courante du Per en RFA. Une version allemande de la batterie NES a été administrée quotidiennement au début et à la fin de chaque session expérimentale; on a prévu un essai minimal de préexposition avant le premier test expérimentale. En outre, on a enregistré des potentiels évoqués visuels (VEP) et auditifs. Les VEP ont été obtenus grâce à différents stimuli en damier. L'analyse de covariance, avec l'exploitation des données minimales de préexposition, a mis en évidence des déficits significatifs pour la vigilance et la coordination oculo-motrice, ainsi qu'une prolongation limite du temps de réaction simple lors de l'exposition à la concentration élevée de Per (par rapport aux conditions contrôle). La comparaison des deux groupes a révélé une augmentation significative des latencies N75, P100 et N150 de la pointe VEP pendant l'exposition au taux de 50ppm de Per par opposition aux valeurs minimales, tandis qu'elles tendaient à baisser dans le groupe contrôle. On conclut que le “niveau d'effet non nocif” des signcs aigus de dépression CNS est endessous de la valeur MAK courante du Per.Two groups of male volunteers were exposed to 50ppm and 10ppm (controls) perchloroethylene (Per), respectively, for four h/day on four consecutive days. The higher of the two concentrations corresponds to the current MAK value for Per in Germany. A German version of the NES battery was given daily at the beginning and end of each experimental session; a pre-exposure baseline session was run before the first experimental test. Additionally, visual evoked potentials (VEPs) and brainstem auditory evoked potentials were recorded. Analysis of co-variance, with pre-exposure baseline values as co-variates, revealed significant performance deficits for vigilance and eye-hand coordination, as well as borderline prolongation of simple reaction times at elevated Per exposure, as compared to control conditions. A comparison of the two groups revealed a significant increase of the VEP peak latencies N75, P100 and N150 during the exposure to 50ppm Per as compared to the baseline values, whereas they tended to decrease in the control group. It is concluded that the “no adverse-effect level” for acute signs of CNS depression is below the current MAK value for Per.
[show abstract][hide abstract] ABSTRACT: 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.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 12/2007; 659(1-2):83-92. · 3.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: Psychological tests as developed and validated in the field of differential psychology have a longstanding tradition as tools to study individual differences. In clinical neuropsychology, global or more specific tests are used as neuropsychological tools in the differential diagnosis of various forms of brain damage or neurobehavioral dysfunction following chemical insults, such as mental sequelae of prenatal alcohol consumption by pregnant mothers (fetal alcohol syndrome) or of maternal thyroid deficiency during pregnancy. Psychometric tests are constructed to fulfill basic quality criteria, namely objectivity, reliability and validity. For strictly diagnostic purposes in individual cases they must also possess normative values based on representative reference groups. Intelligence tests or their developmental variants are often used as endpoints in environmental health research for studying neurodevelopmental adversity due to early exposure to neurotoxic chemicals in the environment. Intelligence as treated in psychology is a complex construct made up of specific cognitive functions which usually cover verbal, numerical and spatial skills, as well as perceptual speed, memory and reasoning. In this paper, case studies covering neurodevelopmental adversity of inorganic lead, of methylmercury and of polychlorinated biphenyls (PCBs) are reviewed, and the issue of postnatal behavioral sequelae of prenatal exposure is covered. In such observational studies precautions must be taken in order to avoid pitfalls of causative interpretation of associations between exposure and neurobehavioral outcome. This requires consideration of co-exposure and confounding. Important confounders considered in most modern developmental cohort studies are maternal intelligence and quality of the home environment.
International Journal of Hygiene and Environmental Health 11/2007; 210(5):601-9. · 3.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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).
[show abstract][hide abstract] ABSTRACT: We addressed the question if patients with multiple chemical sensitivity (MCS) differ from participants with self-reported odor sensitivity without MCS and asymptomatic controls in terms of chemosensory, cognitive, and clinical psychological endpoints.
In a clinical study 23 MCS patients, 21 participants with self-reported odor sensitivity, and 23 controls were investigated using electrophysiological and psychophysical olfactometric tests [chemosensory-event-related potentials (CSERP), olfactory thresholds, odor identification, trigeminal sensitivity]. The participants filled in a mood list, a list of complaints (BL), a Symptom Check List, a State-Trait Anxiety Inventory (STAI), and an MCS questionnaire.
The olfactometric investigations revealed no significant differences between the groups. The MCS group reached significantly higher scores on negative mood states following odorant exposure, on health complaints, global indices, and the somatization subscale of the Symptom Check List, trait and state anxiety and symptoms, and triggering matters of the MCS questionnaire.
Our findings reveal that neither olfactory functions, nor chemosensory or cognitive olfactory information processing are impaired in MCS patients. They rather support findings of altered psychological profile and moderate psychopathology.
Journal of Psychosomatic Research 03/2006; 60(2):199-209. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Based on our own findings from a previous study we aimed to establish if cognitive deficit, shown to be induced by perinatal exposure to polychlorinated biphenyls (PCBs) at earlier ages, persists into school-age. Seventy-seven percent of a cohort last examined at 42 months of age using the Kaufman Assessment Battery for Children were reexamined with the same test at 72 months. At this point, and contrary to the results at 30 and 42 months no adverse PCB-effects were found. However, the positive effect of the home environment became even more pronounced. Conclusion: early PCB-exposure at current environmental background levels possibly induces transient delay in cognitive development rather than irreversible deficit.
Environmental Toxicology and Pharmacology 05/2005; 19(3):701-6. · 2.01 Impact Factor
[show abstract][hide abstract] ABSTRACT: During development, gonadal steroids exert effects on the nervous system which are long-lasting or organizational, in contrast to the transient activational actions in adulthood. Therefore, disturbance of neuroendocrine functions by developmental exposure to polyhalogenated aromatic hydrocarbons (PHAHs) is likely to affect sex-dependent behavior in adults. Our previous data revealed effects of maternal PCB exposure on sexual differentiation of the brain and subsequent sweet preference as sexually dimorphic behavior in adult offspring. Present research is focused on brominated flame retardants because of their wide-spread use and accumulation in human breast milk. Pregnant Long Evans rats were SC injected with PBDE 99 (2,2',4,4',5-PBDE) daily from gestational day 10 to 18. For comparison, an additional group was exposed to Aroclor 1254. Preliminary results indicate a dose-related increase in sweet preference in adult male offspring exposed to PBDE. Exposure also led to decreases in testosterone and estradiol serum levels. Additional decreases were detected in male anogenital distance. There were no changes of locomotor activity in the open field. On haloperidol-induced catalepsy, latencies were prolonged in all exposed males. In summary, PBDE induced endocrine effects and concomitant changes of sex-dependent behavior similar to PCBs. Outcome of general behavior suggests an involvement of dopaminergic processes in developmental PBDE exposure.
Environmental Toxicology and Pharmacology 05/2005; 19(3):757-9. · 2.01 Impact Factor