[The occurrence of plasticisers (phthalates) in communal facilities under special consideration of results from LUPE 3]. / Vorkommen von Weichmachern (Phthalaten) in Gemeinschaftseinrichtungen unter besonderer Bedeutung der Ergebnisse von LUPE 3.

Children are a very susceptible subgroup of the general population and therefore health authorities have a special interest to prevent them from health hazards. In a study of 3 German Bundesländer the indoor air and dust samples of altogether 63 German daycare centres were analysed for the presence of phthalate diesters in 2011/12 (LUPE 3 study). Inhalable dust and gas phases were collected with a glass fibre filter and polyurethane foam over approximately 6 h while children were attending these facilities. Settled dust was collected by vacuuming the floor of the room using an ALK dust sampler. Indoor air and dust were analysed using a GC/MS system. Median values in the dust samples were 888 mg/kg for di-2-ethylhexyl phthalate (DEHP), 302 mg/kg for diisononyl phthalate (DiNP), 34 mg/kg for diisodecyl phthalate (DiDP), 21 mg/kg for di-n-butyl phthalate (DnBP), and 20 mg/kg for diisobutyl phthalate (DiBP). For DEHP and DiNP maximum values of 10,086 mg/kg and 7,091 mg/kg were observed, respectively. DEHP and DiNP were responsible for 70% and 24% of the total phthalate concentration in the dust. In indoor air phthalates are found mainly in the particulate phase of the filters. Only the more volatile phthalates dimethyl phthalate and diethyl phthalate were found also in the gas phase. The median values in the indoor air were 470 ng/m³ for DiBP, 230 ng/m³ for DnBP, 190 ng/m³ for DEHP, and 100 ng/m³ for DiNP. DnBP and DiBP were together responsible for 55% of the total phthalate concentration in the indoor air. Overall, our study showed that the concentrations of phthalates in indoor air of daycare centers are slightly higher and in dust samples lower compared with schools.

[Swallowing disorders after partial laryngectomy. Prevalence and predictors]. / Schluckstörungen nach Kehlkopfteilresektion. Auftrittshäufigkeit und Prädiktoren.

BACKGROUND: Improvements in surgical techniques have led to a higher percentage of larynx preservations. These do not always include preservation of the swallowing function. This study investigates the prevalence of swallowing disorders after partial laryngectomy and their predictors. PATIENTS AND METHODS: In a multicenter cross-sectional study with patients who received a partial laryngectomy (n=154) the prevalences of problems related to swallowing and eating were gathered. Additionally, medical and sociodemographic data were obtained as well as information about alcohol and tobacco consumption. RESULTS: Twenty percent of the patients had problems related to swallowing and eating; more specifically, eating solid foods and eating in public. Chances of having swallowing disorders were significantly lower for patients who received laser therapy (OR=0.12; 95% CI: 0.04-0.37; p<0.01), when time since the last laryngeal surgery was longer (OR=0.89; 95% CI: 0.75-0.99; p<0.03) and when patients were non-smokers (OR=3.39; 95% CI: 1.29-8.94; p<0.02). CONCLUSION: Swallowing disorders correlate with post-surgery smoking. Physicians and therapists should focus more on the negative side effects of smoking on swallowing during patient consultations.

The oral bioavailability of di-2-ethylhexyl phthalate (DEHP), di-isononyl phthalate (DiNP) and di-(isononyl)-cyclohexane-1,2-dicarboxylate (DINCH®) in house dust.

Phthalates and other plasticizers are detected in high amounts in the indoor environment and therefore house dust can be an exposure source. Especially children have a relatively high unintended uptake of house dust, thus a higher exposure to plasticizers compared to adults may be possible. As accurate as possible exposure assessment data of the oral bioavailability of these compounds are necessary, however only one in vivo study with piglets is available so far. The aim of this study was to examine the oral bioavailability of phthalates and DINCH® in humans, which occur in typical house dust samples. We focused on the high molecular weight phthalates DEHP and DINP and their substitute DINCH®. Eleven volunteers ingested 6 g of house dust sieved to 2 mm. The urine was collected over a period of 36 h. The excreted plasticizers metabolites were quantified by an LC-MS/MS method. The mean recovery of urine metabolites was 51 % ± 20 % for DEHP, 26 % ± 13 % for DINP and 19 % ± 6% for DINCH® based on the parent compounds administered as dust samples. The metabolites of DEHP, DINP and DINCH® reached their maximum concentration after 2-19 hours post dose in urine. The bioavailability of DEHP was in agreement among the different dust samples. For DEHP, we were able to confirm previous findings from the oral bioavailability study with piglets and we could not observe a significant difference between the dust particle size (65 µm vs 2 mm) and the bioavailability. Considering the observed bioavailability, an estimated dust intake of 50 mg/d for toddlers can substantially contribute to the total plasticizer exposure.

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A.

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two- and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies.

[Occurrence and relevance to health of persistent organic substances and phthalates in breast milk]. / Vorkommen und gesundheitliche Bedeutung von persistenten organischen Substanzen und Phthalaten in der Muttermilch.

The aim of this study is to give an overview of the concentrations of persistent organic pollutants like the polychlorinated dibenzo- P-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), polychlorinated biphenyls (PCB), polybrominated diphenyl ether (PBDE), perfluorinated compounds (PFC) and of phthalates in breast milk. On the basis of median and 95 (th) percentile values an "average" and a "high" intake were calculated for a 3-month-old infant exclusively breast-fed. Moreover, the actual daily intake was compared with tolerable daily intakes (TDI) recommended by scientific institutions. On this basis, we found an "average" ("high") daily intake of 70 (140) pg TEQ/kg body weight (b. w.) for PCDD/F and dioxin-like PCB (dl-PCB), 10 (20) ng/kg b. w. for PFOS (perfluorooctanesulfonate), 20 (50) ng/kg b. w. for PFOA (perfluorooctanoate), 1.7 (7.5) ng/kg b. w. for BDE 47, and 0.6 (2.1) ng/kg b. w. for BDE 99. For di-2-ethylhexyl phthalate (DEHP) and di- N-butyl phthalate (DnBP) an "average" and "high" intake of 400 ng/kg b. w. and 2,000 ng/kg b. w. and of 100 and 500 ng/kg b.w. were assumed, respectively. For all of these substances we found a daily intake via breast milk below the TDI, established on a livelong basis. On contrary, the daily intake for the sum of the PCDD/F and dl-PCB considerably exceeded the recommended TDI value. Even with regard to the "high" daily intake values the share of PBDE, PFC, and phthalates on the TDI was only in the lower percentage. Scientific organisations assume that an exceeding of the PCDD/F and dl-PCB intake in relation to the TDI value is acceptable only on the basis of the still declining levels in breast milk and the fact that this high exposure only occurs during some months of the entire life when breast milk is consumed. On the basis of the recent exposure situation mothers can exclusively breast-feed their infants for 6 months without any hesitation. The well established health benefits for mothers and infants when exclusively breast-feeding should be utilised. There is also no health concern if the mother decides to breast-feed the baby for longer than 6 months when the infant also receives additional food.

[The use of resorbable osteosynthesis materials]. / Erfahrungen bei der Verwendung resorbierbarer Osteosynthesematerialien.

INTRODUCTION: Different materials can be used for fixation of fractures or for osteoplastic operations in head and neck surgery. Especially metallic and resorbable implants are at the market now. Advantages and disadvantages of the different implants should be considered as decisive for different indications. PATIENTS AND METHODS: We retrospectively analyzed the patients since 1999 which we operated using such resorbable materials. From 1999 until 2006 we used LactoSorb(®). 2007 we introduced the Resorb X(®) plates and -meshs and the SonicWeld Rx-System(®). Here the plates or meshs will be fixed by an ultrasonically welded pin. RESULTS: In 52 cases we implanted LactoSorb(®) and Resorb X(®) with the SonicWeld Rx-System(®). In 2 cases we saw a foreign body reaction that resulted in a fistula. In one case a plate broke after fixing. CONCLUSION: The use of resorbable materials with ultrasonically welded pin osteosynthesis resulted in a stable mechanical connection, an easy intraoperative handling and a low rate of complications. Those materials can be used for traumatologic and osteoplastic reconstructions in head and neck surgery.

Bioavailability of phthalate and DINCH® plasticizers, after oral administration of dust to piglets.

For decades, phthalates have been widely used as plasticizers in a large number of consumer products, leading to a complex exposure to humans via ingestion, inhalation or dermal uptake. Children may have a higher unintended dust intake per day compared to adults. Therefore, dust intake of children could pose a relevant exposure and subsequently a potential health risk. The aim of this study was to determine the relative bioavailability of certain phthalates, such as di(2-ethylhexyl) phthalate (DEHP), di-isononyl phthalate (DINP) and the non-phthalate plasticizer diisononyl 1,2-cyclohexanedicarboxylic acid (DINCH®, Hexamoll®), after ingestion of dust. Seven 5-week-old male piglets were fed five different dust samples collected from daycare centers. Overall, 0.43 g to 0.83 g of dust sieved to 63 µm were administered orally. The piglets' urine was collected over a period of 38 h. The excreted metabolites were quantified using an LC-MS/MS method. The mean uptake rates of the applied doses for DEHP, DINP, and DINCH® were 43% ± 11%, 47% ± 26%, and 9% ± 3.5%, respectively. The metabolites of DEHP and DINP showed maximum concentrations in urine after three to five hours, whereas the metabolites of DINCH®, reached maximum concentrations 24 h post-dose. The oral bioavailability of the investigated plasticizers was higher compared to the bioaccessibility reported from in vitro digestion tests. Furthermore, the bioavailability of DEHP did not vary substantially between the dust samples, whereas a dose-dependent saturation process for DINP was observed. In addition to other intake pathways, dust could be a source of plasticizers in children using the recent intake rates for dust ingestion.

Perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) in human breast milk: results of a pilot study.

Perfluorinated compounds (PFC) are a large group of chemicals produced for several decades and widely used for many industrial and consumer applications. Because of their global occurrence in different environmental media, their persistence and their potential to bioaccumulate in organisms they are of toxicological and public concern. In the present study, perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) were quantified in 70 breast milk samples. Samples were obtained from Leipzig, Germany (38 archived samples), Munich, Germany (19 fresh samples) and Gyor, Hungary (13 frozen samples). PFOS could be quantified in all 70 samples. The concentration in samples from Germany ranged between 28 and 309 ng/l (median: 119 ng/l). Samples from Hungary showed significantly higher PFOS concentrations (median 330 ng/l, range 96-639 ng/l). In only 11 of 70 samples (16%) PFOA reached the LOQ (200 ng/l); values ranged from 201 to 460 ng/l. If only those samples with PFOA values above the LOQ were considered, we found a significant correlation between the PFOS and PFOA concentrations (r=0.75, p=0.008). Based on the results of the German sample, we estimated an intake of 0.10 microg PFOS/day (using median) or 0.27 PFOS microg/day (using maximum value) via breast milk for an infant of 5 kg bodyweight. Our data suggest that fully breastfed infants are unlikely to exceed the recommended tolerable daily intake of PFC. However, more target-oriented studies are needed to identify the amount and time-trend of PFOS and PFOA in maternal blood during pregnancy, after delivery, as well as in the growing infant and in its diet (e.g., breast milk and formula).

Overall internal exposure to mycotoxins and their occurrence in occupational and residential settings--An overview.

Mycotoxins are toxic secondary metabolites of various fungal species that can contaminate food and feed, as well as indoor environments. Numerous studies have summarized the adverse health effects of mycotoxins and described severe intoxications of humans and animals. The major health concerns are caused via the alimentary route which unambiguously is the main source for human internal exposure; however, the relevance of other pathways under environmental and occupational conditions should also be considered. Thus firstly, this review aims in summarizing literature data on potentially inhalable mycotoxins occurring in dusts or air in residences and in working environments. Secondly, it gives an overview of the overall internal body burden of mycotoxins in humans in an attempt to characterize total human exposure. These data are also discussed in relation to the current toxicologically based values used for risk assessment.

Brominated flame retardants - Exposure and risk assessment for the general population.

Brominated flame retardants (BFRs) are a large group of different substances used in numerous products to prevent fire hazards. Some of them are persistent in the environment, accumulate in the food chain and are of toxicological concern, while for others current data are limited. Meanwhile, BFRs have been found in many environmental media, foods, and biota including humans. This review presents recent findings obtained from monitoring data in environmental media relevant for human exposure, as well as dietary exposure. In this context, concentrations in indoor and ambient air and in house dust are outlined. Furthermore, we summarize human biomonitoring data on BFR levels in blood and breast milk. Current estimates of the overall exposure of the general population using different relevant subsets are also addressed. All of these data are discussed in relation to currently available toxicological reference values used for risk assessment purposes. Obviously, the exposure of the general population varies considerably in different parts of the world and even within countries. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) show the highest intake during infancy. While the highest intake for BDE 47 for all groups was observed in the US, the total BDE 209 and HBCD intake was highest in the UK. For HBCD and all PBDEs except BDE 209, diet accounts for a large proportion of the total intake during infancy in all countries. With regard to toddlers and adults, the contribution of diet to total intake is high in Germany and the UK, while in the US, the high concentrations of PBDE in dust resulted in a notably smaller proportion of the intake being attributed to diet.

Non-phthalate plasticizers in German daycare centers and human biomonitoring of DINCH metabolites in children attending the centers (LUPE 3).

Plasticizers have been widely used for decades as additives in diverse applications, including consumer and building products, toys, cables, and floorings. Due to toxicological concerns and restrictions of different dialkyl ortho-phthalates, other plasticizers have been increasingly used in recent years. Therefore, di-isononyl cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHT), di(2-ethylhexyl) adipate (DEHA), acetyl tri-n-butyl citrate (ATBC), and trioctyl trimellitate (TOTM) plasticizer levels in indoor air and dust samples from 63 daycare centers in Germany were measured. Moreover, the urine samples of 208 children who attend 27 of these facilities were analyzed for the presence of four DINCH metabolites. DINCH, DEHT, and DEHA were present in indoor air with median values of 108 ng/m(3), 20 ng/m(3), and 34 ng/m(3), respectively. Median values of 302 mg/kg for DINCH, 49 mg/kg for DEHA, 40 mg/kg for DEHT, and 24 mg/kg ATBC were found in dust. In the urine samples, the three secondary metabolites of DINCH were observed with median values (95th percentiles) of 1.7 µg/l (10.0 µg/l) for OH-MINCH, 1.5 µg/l (8.0 µg/l) for oxo-MINCH, and 1.1 µg/l (6.1 µg/l) for cx-MINCH. Overall, these metabolite levels are orders of magnitude lower than the current HBM I values set by the German Human Biomonitoring Commission. Using general exposure assumptions, the intake resulting from dust ingestion and inhalation is low for children. The total daily DINCH intake calculated from biomonitoring data was 0.5 µg/kg b.w. using median values and 9.8 µg/kg b.w. as the maximum value. At present, non-phthalate plasticizers, especially DINCH, can be found in considerable amounts in dust samples from daycare centers and as DINCH metabolites in the urine of children. In relation to previous studies, the concentrations of DINCH in dust and urine have an increasing time trend. Compared with tolerable daily intake values, the total daily intake of DINCH reached only 1% of its maximum value to date; however, due to its increased use, higher exposure of DINCH is expected in the future.

Slow oxidation of acetoxime and methylethyl ketoxime to the corresponding nitronates and hydroxy nitronates by liver microsomes from rats, mice, and humans.

Acetoxime and methylethyl ketoxime (MEKO) are tumorigenic in rodents, inducing liver tumors in male animals. The mechanisms of tumorigenicity for these compounds are not well defined. Oxidation of the oximes to nitronates of secondary-nitroalkanes, which are mutagenic and tumorigenic in rodents, has been postulated to play a role in the bioactivation of ketoximes. In these experiments, we have compared the oxidation of acetoxime and methylethyl ketoxime to corresponding nitronates in liver microsomes from different species. The oximes were incubated with liver microsomes from mice, rats, and several human liver samples. After tautomeric equilibration and extraction with n-hexane, 2-nitropropane and 2-nitrobutane were quantitated by GC/MS-NCI (limit of detection of 250 fmol/injection volume). In liver microsomes, nitronate formation from MEKO and acetoxime was dependent on time, enzymatically active proteins, and the presence of NADPH. Nitronate formation was increased in liver microsomes of rats pretreated with inducers of cytochrome P450 and reduced in the presence of inhibitors (n-octylamine and diethyldithiocarbamate). Rates of oxidation of MEKO (Vmax) were 1.1 nmol/min/mg (mice), 0.5 nmol/min/mg (humans), and 0.1 nmol/min/mg (rats). In addition to nitronates, several minor metabolites were also enzymatically formed (two diastereoisomers of 3-nitro-2-butanol, 2-hydroxy-3-butanone oxime and 2-nitro-1-butanol). Acetoxime was also metabolized to the corresponding nitronate at rates approximately 50% of those observed with MEKO oxidation in the three species examined. 2-Nitro-1-propanol was identified as a minor product formed from acetoxime. No sex differences in the capacity to oxidize acetoxime and MEKO were observed in the species examined. The observed results show that formation of sec-nitronates from ketoximes occurs slowly, but is not the only pathway involved in the oxidative biotransformation of these compounds. Due to the lack of sex-specific oxidative metabolism, other metabolic pathways or mechanisms of tumorigenicity not involving bioactivation may be involved in the sex-specific tumorigenicity of ketoximes in rodents.

Quantitation of N epsilon-(dichloroacetyl)-L-lysine in proteins after perchloroethene exposure by gas chromatography-mass spectrometry using chemical ionization and negative ion detection followingimmunoaffinity chromatography.

An antibody specific to N epsilon-(dichloroacetyl)-L-lysine (DCA-Lys) was immobilized to immunoaffinity columns for the use in selective enrichment of dichloroacetylated proteins. These result from the reaction with dichlorothioketene the beta-lyase cleavage product of the perchloroethene metabolite S-(trichlorovinyl)-L-cysteine. Dichloroacetylated proteins from rat kidney mitochondria, rat plasma and human blood plasma were isolated after exposure to 40 ppm tetrachloroethene (PER) for 6 h. After acid hydrolysis of the protein fraction, DCA-Lys was derivatized with 1,3-dichloro-1,1,3,3-tetrafluoroacetone using N epsilon-(trifluoroacetyl)-L-lysine as internal standard. Recovery of dichloroacetylated reference proteins from immunoaffinity columns was about 73%. Samples were analyzed by GC-MS with chemical ionization and negative ion (NCI) detection showing DCA-Lys in proteins with 2.26 (+/- 0.02) pmol/mg protein in male rat kidney mitochondria and 1.92 (+/- 0.05) pmol/mg total mitochondrial protein in female rats. In rat plasma 0.47 (+/- 0.006) pmol DCA-Lys/mg protein in male and 0.34 (+/- 0.02) in female animals were found. DCA-Lys could not be detected in blood plasma of human volunteers exposed to PER with a detection limit of 20 fmol for the DCA-Lys derivative 2,2-bis(chlorodifluoromethyl)-4-(1-dichloroacetamido)-butyl- 1,3-oxazolidine-5-one. Immunoaffinity chromatography with specific antibodies provides a powerful tool for the enrichment of minor quantities of dichloroacetyled proteins in biological samples for GC-NCI-MS analysis of the modified amino acid lysine having broad utility in the biomonitoring of PER exposure.

Gas chromatography-negative ion chemical ionization mass spectrometry as a powerful tool for the detection of mercapturic acids and DNA and protein adducts as biomarkers of exposure to halogenated olefins.

The studies on metabolism of halogenated olefins presented here outline the advantages of modern mass spectrometry. The perchloroethene (PER) metabolite N-acetyl-S-(trichlorovinyl)-L-cysteine (N-ac-TCVC) is an important biomarker for the glutathione dependent biotransformation of PER. In urine of rats and humans exposed to PER, N-ac-TCVC was quantified as methyl ester after BF3-MeOH derivatization by gas chromatography with chemical ionization and negative ion detection mass spectrometry (GC-NCI-MS). The detection limit was 10 fmol/microliter injected solution using [2H3]N-ac-TCVC methyl ester as the stable isotope internal standard. Cleavage of S-(trichlorovinyl)-L-cysteine by beta-lyase enzymes results in an electrophilic and highly reactive thioketene which reacts with nucleophilic groups in DNA and proteins. Protein adduct formation was shown in kidney mitochondria by identification of dichloroacetylated lysine after derivatization with 1,1,3,3-tetrafluoro-1,3-dichloroacetone by GC-NCI-MS. In addition, chlorothioketene was generated in organic solvents and reacted with cytosine to give N4-chlorothioacetyl cytosine. After derivatization with pentafluorobenzyl bromide this compound exhibited good gas chromatographic properties and was detectable with a limit of detection of 50 fmol/injected volume. The detection of chemically induced protein modifications in the target organ of toxic metabolite formation and the study of DNA modifications with chemically generated metabolites provide important information on organ toxicity and possible tumorigenicity of halogenated olefins.

Polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD) and "novel" brominated flame retardants in house dust in Germany.

Brominated flame retardants (BFRs) are used in a wide variety of products such as electronic devices, upholstery and carpets and in insulation boards. The study presented here aimed to quantify the amounts of BFRs in house dust in Germany. For this purpose 20 residences' dust samples were collected from vacuum cleaner bags and analysed with LC-MS/MS and simultaneously with GC/MS. Using GC/MS, the median (95th percentile) concentrations of PBDEs (sum of tetra- to hepta-congeners), BDE 209, Σ-HBCD (sum of three congeners), and decabromodiphenylethane (DBDPE) were 42ng/g (230ng/g), 950ng/g (3426ng/g), 335ng/g (1545ng/g), and 146ng/g (1059ng/g), respectively. Using LC-MS/MS some "novel" flame retardants were found in median concentrations of 343ng/g (bis(2-ethyl-1-hexyl)tetrabromophthalate, TBPH), and 28ng/g (tetrabromobisphenol A, TBBPA). Whilst 1,2-bis-(2,4,6-tribromophenoxy)ethane (BTBPE) and 2-ethyl-1-hexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) could not be detected. Based on these measurements an exposure assessment for the sum of tetra- to heptabrominated congeners, BDE 209, and Σ-HBCD resulted in a "high" daily intake for toddlers (based on 95th percentiles) of 1.2ng/kg b.w., 0.69ng/kg b.w., and 8.9ng/kg b.w., respectively. For TBPH the "high" intake was calculated at 4.1ng/kg b.w. and for DBDPE at 5.3ng/kg b.w. A clear tendency was observed to apply "novel" BFRs in Germany. Moreover, the results suggest that the recent exposure to PBDEs and HBCD via house dust in Germany is well below the levels that are associated with health effects. For the "novel" brominated flame retardants such an assessment is not possible due to limited toxicological information.

Organophosphate flame retardants and plasticizers in the air and dust in German daycare centers and human biomonitoring in visiting children (LUPE 3).

Organophosphate (OP) flame retardants and plasticizers are chemicals that have been used in large quantities in diverse consumer and building-related products for decades. In the present study, OPs were measured in paired indoor air and dust samples from 63 daycare centers in Germany. Moreover, the urine of 312 children between 22 and 80 months old who attend these facilities was analyzed for the presence of eight OP metabolites. Tri-(2-butoxyethyl)-phosphate (TBEP), tris-(2-chloroisopropyl) phosphate (TCPP), and tri-n-butyl-phosphate (TnBP) were present in low concentrations in indoor air, with median values of 49 ng/m(3), 2.7 ng/m(3), and 2.2 ng/m(3), respectively. In dust, median values of 225 mg/kg for TBEP, 2.7 mg/kg for TCPP, 1.1mg/kg for diphenyl(2-ethylhexyl) phosphate, and 0.5mg/kg for tri-phenyl-phosphate (TPhP) were found. In the urine samples, the metabolites di-phenyl-phosphate, di-n-butyl-phosphate, and di-(2-butoxyethyl)-phosphate had median values (95th percentiles) of 0.8 µg/l (4.0 µg/l), 0.2 µg/l (0.9 µg/l), and 2.0 µg/l (10.7 µg/l), respectively. A significant correlation was found between the dust and air samples in the levels of TnBP, tris(2-chloroethyl) phosphate (TCEP), and TBEP. For TCEP and TBEP, significant correlations were also observed between the levels in dust and the respective metabolite levels in urine. For TCEP, there was also a significant correlation between the concentration in indoor air and metabolite levels in urine. Based on the 95th percentile in dust and air in our study and data from residences in a previously published study, the daily intake of the most abundant OP (TBEP) is high (i.e., 3.2 µg/kg b.w.). This level is approximately 6.4% of the reference dose (RfD) established by the NSF, U.S.A. Overall, our study shows that daycare centers are indoor environments that contribute to OP exposure.

Occurrence of chlorinated paraffins in house dust samples from Bavaria, Germany.

Levels and distribution of chlorinated paraffins were studied in randomly taken house dust samples (<63 µm) from the greater area of Munich, Germany. Quantification of short- (SCCPs, C(10)-C(13)) and medium-chain chlorinated paraffins (MCCPs, C(14)-C(16)) were performed using gas chromatography electron capture negative ion mass spectrometry (GC-ECNI-MS). Concentrations of MCCPs in private household samples varied between 9 µg/g and 892 µg/g, and exceeded levels of SCCPs, which were in the range of 4-27 µg/g. Two dust samples from a public building contained up to 2050 µg/g SCCPs but no MCCPs. Among MCCPs, chlorinated tetradecanes were major components with a proportion of almost 50%. Among SCCPs, chlorinated dodecanes were usually present at higher concentrations than the congeners of any C10, C11, and C13 chains. The results indicate that particularly MCCPs may be present in relatively high concentrations in house dusts.

Phthalates in German daycare centers: occurrence in air and dust and the excretion of their metabolites by children (LUPE 3).

Phthalates have been used for decades in large quantities, leading to the ubiquitous exposure of the population. In an investigation of 63 German daycare centers, indoor air and dust samples were analyzed for the presence of 10 phthalate diesters. Moreover, 10 primary and secondary phthalate metabolites were quantified in urine samples from 663 children attending these facilities. In addition, the urine specimens of 150 children were collected after the weekend and before they went to daycare centers. Di-isobutyl phthalate (DiBP), dibutyl phthalate (DnBP), and di-2-ethylhexyl phthalate (DEHP) were found in the indoor air, with median values of 468, 227, and 194ng/m(3), respectively. In the dust, median values of 888mg/kg for DEHP and 302mg/kg for di-isononyl phthalate (DiNP) were observed. DnBP and DiBP were together responsible for 55% of the total phthalate concentration in the indoor air, whereas DEHP and DiNP were responsible for 70% and 24% of the total phthalate concentration in the dust. Median concentrations in the urine specimens were 44.7µg/l for the DiBP monoester, 32.4µg/l for the DnBP monoester, and 16.5µg/l and 17.9µg/l for the two secondary DEHP metabolites. For some phthalates, we observed significant correlations between their concentrations in the indoor air and dust and their corresponding metabolites in the urine specimens using bivariate analyses. In multivariate analyses, the concentrations in dust were not associated with urinary metabolite excretion after controlling for the concentrations in the indoor air. The total daily "high" intake levels based on the 95th percentiles calculated from the biomonitoring data were 14.1µg/kg b.w. for DiNP and 11.9µg/kg b.w. for DEHP. Compared with tolerable daily intake (TDI) values, our "high" intake was 62% of the TDI value for DiBP, 49% for DnBP, 24% for DEHP, and 9% for DiNP. For DiBP, the total daily intake exceeded the TDI value for 2.4% of the individuals. Using a cumulative risk-assessment approach for the sum of DEHP, DnBP, and DiBP, 20% of the children had concentrations exceeding the hazard index of one. Therefore, a further reduction of the phthalate exposure of children is needed.

Analysis of common and emerging brominated flame retardants in house dust using ultrasonic assisted solvent extraction and on-line sample preparation via column switching with liquid chromatography-mass spectrometry.

Brominated flame retardants (BFRs) are persistent and widespread chemicals. Therefore human beings are exposed to BFRs. House dust may be one source of exposure and contains a lot of xenobiotics in relatively high concentrations. In contrast to common GC-MS based methods here an online LC-MS/MS method is presented to quantify 16 BFRs in dust using ultrasonic solvent extraction as a single sample work up step. LOQ from 0.6 (tetrabromobisphenol A) to 80 (polybrominated diphenylethers (BDE 28) ng/g dust were achieved. Data for accuracy, precision and recovery are presented and are comparable to common LC-MS/MS methods in different matrices. In addition 5 real house dust samples were analyzed with high concentration (535 ng/g) for bis(2-ethyl-1-hexyl)tetrabromophthalate which is a novel alternative BFRs to replace common BDE's.

Phthalates and their metabolites in breast milk--results from the Bavarian Monitoring of Breast Milk (BAMBI).

Phthalates have long been used as plasticizers to soften plastic products and, thus, are ubiquitous in modern life. As part of the Bavarian Monitoring of Breast Milk (BAMBI), we aimed to characterize the exposure of infants to phthalates in Germany. Overall, 15 phthalates, including di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DnBP), di-isobutyl phthalate (DiBP), di-isononyl phthalate (DiNP), three primary metabolites of DEHP [mono-(2-ethylhexyl) phthalate (MEHP), mono-isobutyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP)], and two secondary metabolites of DEHP were analyzed in 78 breast milk samples. We found median concentrations of 3.9 ng/g for DEHP, 0.8 ng/g for DnBP, and 1.2 ng/g for DiBP, while other parent phthalates were found in only some or none of the samples at levels above the limit of quantitation. In infant formula (n=4) we observed mean values of 19.7 ng/g (DEHP), 3.8 ng/g (DnBP), and 3.6 ng/g (DiBP). For MEHP, MiBP, and MnBP, the median values in breast milk were 2.3 µg/l, 11.8 µg/l, and 2.1 µg/l, respectively. The secondary metabolites were not detected in any samples. Using median and 95th percentile values, we estimated an "average" and "high" daily intake for an exclusively breast-fed infant of 0.6 µg/kg body weight (b.w.) and 2.1 µg/kg b.w., respectively, for DEHP, 0.1 µg/kg b.w. and 0.5 µg/kg b.w. for DnBP, and 0.2 µg/kg b.w. and 0.7 µg/kg b.w. for DiBP. For DiNP, intake values were 3.2 µg/kg b.w. and 6.4 µg/kg b.w., respectively, if all values in milk were set half of the detection limit or the detection limit. The above-mentioned "average" and "high" intake values corresponded to only about 2% to 7%, respectively, of the recommended tolerable daily intake. Thus, it is not likely that an infant's exposure to phthalates from breast milk poses any significant health risk. Nevertheless, other sources of phthalates in this vulnerable phase have to be considered. Moreover, it should be noted that for infants nourished with formula, phthalate intake is of the same magnitude or slightly higher (DEHP) than for exclusively breast-fed infants.