B Liebl

Human exposure to polybrominated diphenyl ethers (PBDE), as evidenced by data from a duplicate diet study, indoor air, house dust, and biomonitoring in Germany.

Polybrominated diphenyl ethers (PBDE) are used as flame retardants in a wide variety of products. As part of the Integrated Exposure Assessment Survey (INES), this study aimed to characterize the exposure of an adult German population using duplicate diet samples, which were collected daily over seven consecutive days, and indoor air and house dust measurements. Our study population consisted of 27 female and 23 male healthy subjects, aged 14-60 years, all of whom resided in 34 homes in southern Bavaria. In these 34 residences the air was sampled using glass fiber filters and polyurethane foams and the dust was collected from used vacuum cleaner bags. The median (95th percentile) daily dietary intake of six Tetra- to HeptaBDE congeners was 1.2 ng/kg b.w. (3.3 ng/kg b.w.) or 67.8 ng/day (208 ng/day) (calculated from the 7-day median values of each study subject). Concentrations in indoor air and dust (cumulative Tri- to DecaBDE congener readings) ranged from 8.2 to 477 pg/m(3) (median: 37.8 pg/m(3)) and 36.6 to 1580 ng/g (median: 386 ng/g), respectively. For some congeners, we identified a significant correlation between air and dust levels. The median (95th percentile) blood concentration of total Tetra- to HexaBDE congener readings was 5.6 (13.2)ng/g lipid. No significant sex differences were observed, but higher blood concentrations were found in younger participants. Using a simplified toxicokinetic model to predict the body burden from exposure doses led to results that were of the same order of magnitude as the measured blood concentrations. Based on these measurements and given our exposure assumptions, we estimated for the total tetra- to heptabrominated congener count an average (high) comprehensive total daily intake of 1.2 ng/kg b.w. (2.5 ng/kg b.w.). Overall, our results suggest that dietary exposure is the dominant intake pathway at least in our study population, responsible for 97% (average intake) and 95% (high intake) of the total intake of an adult population.

Evidence for increased internal exposure to lower chlorinated polychlorinated biphenyls (PCB) in pupils attending a contaminated school.

External and internal exposure to six WHO-indicator congeners of polychlorinated biphenyls (PCB 28, 52, 101, 138, 153, 180) as well as subjective health complaints of a group of 377 pupils attending a PCB-contaminated school were compared with a control group of 218 pupils attending a non-contaminated school. Indoor air of the contaminated school revealed total PCB concentrations (sum of six indicator congeners times 5) ranging between 690 and 20,800 ng/m3 (median 2044 ng/m3). The lower chlorinated congeners PCB 28, 52, 101 were the prevailing contaminants (median 33, 293, and 66 ng/m3). Using improved analytical procedures at least one of the lower chlorinated congeners could be detected in 95% of the blood samples of pupils attending the contaminated school. Median concentrations for PCB 28, 52, 101, and for the sum of lower chlorinated congeners were 6, 9, 5, and 22 ng/l blood plasma, respectively, whereas the corresponding values in the control group were all < 1 ng/l. In contrast, no significant differences were found for the higher chlorinated congeners (PCB 138, 153, 180) which were detected in 1-2 orders of magnitude higher concentrations in both groups. Due to the dietary intake of these congeners similar total PCB levels were found (95th percentile 1070 and 1010 ng/l plasma in participants of the contaminated and control school). Using the Giessen Subjective Complaint List for Children and Adolescents no statistically significant differences in health complaints were observed between both groups of children. It is concluded that exposure of pupils to PCB in indoor air of the contaminated school caused increased blood concentrations of lower chlorinated congeners. Compared to background levels the detected excess body burden was very low indicating no additional health risk. Exposure was not associated to any specific subjective complaints.

Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany

The lack of epidemiological data on the frequency and/or burden of organic acidurias (OA) and mitochondrial fatty acid transport and oxidation disorders (mtFATOD) is one reason for hesitation to expand newborn screening (NBS) by tandem mass spectrometry (MS-MS). From 1999 to 2000, the frequency of ten potentially treatable OA and mtFATOD was assessed by active nation-wide surveillance on cases presenting with clinical symptoms using the German Paediatric Surveillance Unit (ESPED) system. Case ascertainment was complemented by a second independent source: 3-monthly inquiries in the metabolic laboratories performing secondary selected screening for OA and mtFATOD. Frequency estimates for clinically symptomatic cases older than 7 days in a birth cohort of 844,575 conventionally screened children was compared to the frequency found in a cohort of 382,247 screened by MS-MS in Bavaria and Baden-Württemberg. The overall frequency of the ten conditions considered was 1:8,000 (95% CI 1:11,000–1:6,000) by MS-MS as compared to 1:23,000 (95% CI 1:36,000–1:17,000) in symptomatic cases presenting mainly with metabolic crisis. The contributions of medium-chain acyl-CoA dehydrogenase deficiency (MCADD), other mtFATOD and OA were 29, 4 and 13 among the 46 cases identified by MS-MS, and 19, 1 and 13 among the 33 clinically symptomatic cases, respectively. Acute metabolic crisis, with a lethal outcome in four patients, was reported for 22/33 clinically symptomatic cases. No clinically symptomatic cases were reported from cohorts with screened by MS-MS. Conclusion: ten potentially treatable organic acidurias and mitochondrial fatty acid transport and oxidations disorders were more common than phenylketonuria with organic acidurias accounting for 28% of the cases detected by newborn screening and 39% of the cases identified on high risk screening. These conditions were related to considerable morbidity and mortality. Considerations for their inclusion in expanded newborn screening programmes might be warranted.

Assessing the environmental health relevance of cooling towers--a systematic review of legionellosis outbreaks.

Bioaerosols from cooling towers are often suspected to cause community-acquired legionellosis outbreaks. Although Legionella infections can mostly be assigned to the emission sources, uncertainty exists about the release and distribution into the air, the occurrence of the respirable virulent form and the level of the infective concentration. Our study aimed to evaluate studies on legionellosis outbreaks attributed to cooling towers published within the last 11 years by means of a systematic review of the literature. 19 legionellosis outbreaks were identified affecting 12 countries. Recurring events were observed in Spain and Great Britain. In total, 1609 confirmed cases of legionellosis and a case-fatality rate of approximately 6% were reported. Duration of outbreaks was 65 days on average. For diagnosis the urinary antigen test was mainly used. Age, smoking, male sex and underlying diseases (diabetes, immunodeficiency) could be confirmed as risk factors. Smoking and underlying diseases were the most frequent risk factors associated with legionellosis in 11 and 10 of the 19 studies, respectively. The meteorological conditions varied strongly. Several studies reported a temporal association of outbreaks with inadequate maintenance of the cooling systems. A match of clinical and environmental isolates by serotyping and/or molecular subtyping could be confirmed in 84% of outbreaks. Legionella-contaminated cooling towers as environmental trigger, in particular in the neighbourhood of susceptible individuals, can cause severe health problems and even death. To prevent and control Legionella contamination of cooling towers, maintenance actions should focus on low-emission cleaning procedures of cooling towers combined with control measurements of water and air samples. Procedures allowing rapid detection and risk assessment in the case of outbreaks are essential for adequate public health measures. Systematic registration of cooling towers will facilitate the identification of the source of outbreaks and help to shorten their duration.

Advances in analytical mass spectrometry to improve screening for inherited metabolic diseases

Gas chromatography/mass spectrometry became available more than 30 years ago and has subsequently profoundly contributed not only in the identification of a wide range of inborn errors but also as a key tool for clinical diagnostic screening of genetic metabolic disease. Due to extraordinary advances in liquid chromatography and mass spectrometry (MS) developed in the last decade, the utilisation of MS and the potential number of applications for the purpose of metabolic screening is currently undergoing considerable expansion. Conclusion: This overview aims to describe only current new developments in clinically most relevant applications, in particular with focus on low molecular weight compounds.

Intake and body burden of dioxin-like compounds in Germany: the INES study.

The human body burden of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) and the dietary intake of dl-PCB were investigated in Germany. In total, 50 adults (between 14 and 60 years old) were recruited, and duplicate diet samples were collected over seven consecutive days from each participant. Blood samples were acquired from 48 participants. Seventeen PCDD/Fs and 12 dl-PCBs (non- and mono-ortho congeners) were measured in the blood, and all dl-PCBs were measured in duplicate diet portions. Daily intake via food was calculated by multiplying the measured concentrations by the consumption data. Median (95th percentile) concentrations in the blood (expressed as WHO-TEQ) for PCDD/Fs, non-ortho PCBs and mono-ortho PCBs were 10.1 (25.0) pg g(-1) lipid, 4.2 (14.9) pg g(-1) lipid and 4.5 (14.2) pg g(-1) lipid, respectively. The contribution of mono-ortho PCBs and non-ortho PCBs to total TEQ was 25% and 24%, respectively. For each study subject, median intake levels for seven consecutive days were calculated. From these data, the median (95th percentile) daily intake via food was 0.12 (0.32) pg TEQ kg(-1)b.w. for non-ortho congeners and 0.06 (0.12) pg TEQ kg(-1)b.w. for the mono-ortho congeners. PCB 126, PCB 118 and PCB 156 accounted for about 93% of the total PCB intake. Our study indicates that dl-PCB exposure in adults consuming a normal mixed diet is quite low at present in Germany. The median and maximum daily intake contributed to 10% and 25% to the tolerable daily intake recommended for total PCDD/Fs and dl-PCBs.

Erweiterung des Neugeborenenscreenings durch Tandemmassenspektrometrie

ZusammenfassungDie Tandemmassenspektrometrie ist eine neue, vielversprechende Screeningtechnologie. Neben der Phenylketonurie können im gleichen Analysengang ohne Mehraufwand eine Vielzahl weiterer behandelbarer Aminoazidopathien, Erkrankungen der Fettsäureoxidation und Organoazidurien erfasst werden. Dem potenziellen Nutzen stehen Risiken einer unkontrollierten, nicht qualitätsgesicherten Anwendung wie spätes Screening, mangelhafte Intervention/Nachsorge oder Beunruhigung von Familien durch falsch-positive Befunde gegenüber. Die Technik wird in Bayern seit 1.1.1999 im Rahmen eines wissenschaftlich begleiteten Modellprojektes erprobt. Der vorliegende Beitrag beschreibt die technischen und medizinischen Voraussetzungen einer sachgerechten Einführung sowie bisherige Ergebnisse an über 300.000 Neugeborenen. Bei insgesamt niedrigen Belastungen durch Kontrollen wurde durch die neue Technologie eine Früherkennungsrate von Defekten von insgesamt 1:2.700 dargestellt. Insbesondere die hohe Frequenz von Defekten in der Oxidation von Fettsäuren (1:8.500) lässt einen hohen präventiven Effekt erwarten.

Gesundheits-Monitoring-Einheiten (GME) in Bayern

ZusammenfassungIn Bayern wurde 2004 mit der Etablierung von Gesundheits-Monitoring-Einheiten (GME) in 3 Landkreisen und 3 kreisfreien Städten begonnen. Die GME haben zum Ziel, aktuelle und relevante Daten zur gesundheitlichen Situation vor allem von Kindern in Bayern zu gewinnen und Gesundheitsförderungs- und Präventionsmaßnahmen zu evaluieren. Im ersten Survey 2004/2005 wurde eine Querschnittsstudie zur umweltbezogenen Gesundheit von Kindern im Alter von 5–7 Jahren durchgeführt. Es sind Daten für 3030 Mädchen und 3319 Jungen verfügbar (Teilnahmerate 78%). Der Beitrag gibt einen Überblick über die Untersuchungsregionen und die soziodemographischen Charakteristika der Studienpopulation des 1. Surveys, die sich deutlich zwischen den städtischen und ländlichen Regionen unterschieden. Wesentliche Themenschwerpunkte des Surveys waren: (1) soziale Ungleichheit bei Wohnbedingungen, damit verbundenen Umweltexpositionen und der Gesundheit von Kindern, (2) Unfälle und unfallbedingte Verletzungen, (3) Passivrauchbelastung der Kinder und Vorsichtsmaßnahmen der Eltern, (4) Ernährung, Bewegung und Adipositas und (5) zeitlicher Trend bei der Prävalenz von Asthma und Allergien. Die in den GME gewonnenen Erkenntnisse sollen zur Identifikation und Quantifizierung von Gesundheitsrisiken einerseits und zur Etablierung von Interventionsstrategien unter besonderer Berücksichtigung der Belange des öffentlichen Gesundheitsdienstes andererseits beitragen.AbstractStarting in 2004, health monitoring units (GME) were established in three rural and three urban regions of the federal state Bavaria, Germany. The GME´s aim is to gain current and relevant health data especially of children in Bavaria and to evaluate health promotion and prevention strategies. The first survey 2004/2005 was a cross-sectional study of the environmental health of children aged 5 to 7 years. There are data available from 3030 girls and 3319 boys (response rate 78%). This paper describes the study regions and the sociodemographic characteristics of the study population which differed substantially between urban and rural regions. The thematic focus of the survey was: (1) Social disparities in housing conditions, related environmental exposures, and children’s health, (2) accidents and injuries, (3) environmental tobacco smoke exposure of children and precautionary measures of their parents, (4) nutrition, physical activity and obesity, and (5) temporal trends of the prevalence of asthma and allergies. The insights gained within the health monitoring units will contribute to the identification and quantification of health risks as well as to the establishment of intervention strategies with special focus on the needs of the public health service.

PCBs, PCDD/Fs, and PBDEs in blood samples of a rural population in South Germany

The body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like (dl-PCBs) and non-dioxin-like (ndl-PCBs) polychlorinated biphenyls, and polybrominated diphenyl ethers (PBDEs) was determined in blood samples from 70 subjects between 4 and 76 years old. The participants of the study were recruited in the neighborhood of a reclamation plant located in a rural area in Southern Germany. The median concentrations (95th percentiles in parentheses), expressed as WHO2005-TEQ (toxic equivalents), for PCDD/Fs and dl-PCBs were 4.5 (17.9)pgg(-1) l.w. and 2.6 (13.2)pgg(-1) l.w., respectively. The dl-PCBs contributed 40% of the total TEQ (median values), and the most abundant congener was PCB 156. Combined, the sum of the 6 non-dioxin-like PCBs had a median of 0.773μgL(-1) and a 95th percentile of 4.895μgL(-1). For the six tetra to hepta PBDE congeners, the median was 1.8ngg(-1) l.w. (95th percentile: 16.2ngg(-1) l.w.). None of our study subjects had a body burden that exceeded the biomonitoring equivalents for dioxins or PBDE congener 99 or the human biomonitoring values for ndl-PCBs. Likewise the study group did not exceed German reference values or values obtained in similar investigations. Overall, our study did not exhibit elevated internal exposures. The results also hint further decreasing tendencies for PCDD/Fs, PCBs, and PBDEs in Germany and demonstrates that people in the vicinity of a reclamation plant with no indication of an environmental contamination did not exhibit elevated internal exposures.

Data required for the evaluation of newborn screening programmes

Tandem mass spectrometry offers the chance to improve newborn screening (NBS) for phenylketonuria and to expand screening programmes at minimal additional costs. So far, however, there are only limited data available on the incidence of a broader range of disorders presently being considered, their natural course, the benefits achievable and potential harm associated with screening. Based on a literature search and experience from the Bavarian extended screening trial, these questions are addressed using medium-chain acyl-CoA dehydrogenase deficiency (MCADD) as an example. The data retrieved are sufficient for estimation of the incidence of MCADD cases identifiable by NBS and for diagnosis following clinical symptoms. Clinically detected cases ascertained by active surveillance in populations with highly developed and freely accessible health care systems consistently amount to only 33% of those identified by NBS. This difference cannot be explained by the difference in the proportion of the homozygous 985A→G mutation, which accounts for about 50% of cases identified in NBS. Further research is needed to assess the contribution of MCADD to unexplained deaths in infancy. Retrospective cohort studies enrolling at least 500,000 children would allow for a more precise estimate of the natural course of disease in particular with regard to less severe adverse outcomes. The most relevant gap in knowledge concerns the long-term outcome of children identified following symptoms and by newborn screening. Since randomised controlled trials are unlikely to be feasible on this issue, a standardised documentation protocol should be implemented in follow-up studies for cases identified either by high risk screening or newborn screening. A proposal for the content of such observational studies is made.