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.

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.

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.

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.

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.

[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.

[Management of antibiotic-resistant pathogens in Bavarian hospitals: results of a systematic survey and prospects to establish a statewide network "multidrug-resistant pathogens"]. / Management von Antibiotika-resistenten Erregern in bayerischen Kliniken: Ergebnisse einer systematischen Erhebung und Perspektiven zur Bildung eines landesweiten Netzwerks "multiresistente Erreger"

BACKGROUND: Infections caused by multidrug-resistant pathogens are a serious infection control problem with considerable public-health relevance. Regional networks coordinated by local public health departments are to be originated to establish a broader implementation of currently available official guidelines on infection prevention and control which consider the nosocomial transmission of MRSA. This is also due to the raise of awareness for the need of infection control implications to fight other multidrug-resistant pathogens. METHOD: A standardised guidance and survey in Bavarian hospitals on the basis of a checklist concerning structure, process and outcome quality parameters was done by the local public health departments. The data analysis was carried out by the Bavarian Health and Food Safety Authority. OUTCOMES: Checklists from 130 hospitals spread on 92% of the local districts of Bavaria were analysed. The results point out the need for improvements considering working time and duties of infection control professionals, especially infection control nurses, screening concepts and the compliance with legal regulations on the surveillance of nosocomial infections. On the other hand, the available guidelines for the management of patients carrying MRSA seem to be held serious.