Urinary toxicokinetics of di-(isononyl)-cyclohexane-1,2-dicarboxylate (DINCH(®)) in humans following single oral administration.

Phthalates such as di-2-ethylhexyl phthalate (DEHP) were restricted due to their toxic mainly reprotoxic effects. Therefore compounds such as di-(isononyl)-cyclohexane-1,2-dicarboxylate (DINCH(®)) substitute these phthalates and the exposure of humanes to substitutes may occur. Here, kinetic data are presented to assess the exposure of humans. Male and female volunteers excreted nearly the complete orally administered dose (1mg/kg b.w. corresponding to the tolerable daily intake of EFSA) of di-(isononyl)-cyclohexane-1,2-dicarboxylate within 70 h. More than 75% were excreted within 24h. Besides the main metabolite cyclohexane-1,2-dicarboxylic acid (CHDA) quantitated after hydrolysis four further metabolites of DINCH(®) are determined. Cyclohexane-1,2-dicarboxylic acid-mono-(7-hydroxy-4-methyl)octyl ester (OH-MINCH) is the main secondary metabolite with about 14% of the administered dose. Differences in excretion of all metabolites between male and females are small. Based on the generated toxicokinetic data exposure of 20 humans is recalculated from their spot urine sample collected in 2014 and the exposure are clearly below the current tolerable daily intake of 1mg/kg b.w.

Phthalate intake by infants calculated from biomonitoring data.

Urine samples (n=207) of 47 infants between 1- and 5-month of age were quantitated for 12 metabolites of 7 phthalates and compared with samples collected from the mothers of the infants at different time points. Median and 95-percentile were lower for all metabolites in urine samples of infants compared to mothers. For di-2-ethylhexyl phthalate (DEHP) the 95-percentile daily intake was 23.3µg/kg b.w. for mothers and 5.4µg/kg b.w. for infants and for di-isobutyl phthalate (DiBP) 10.1µg/kg b.w. and 8.5µg/kg b.w. Some values exceeded the corresponding tolerable daily intake (TDI) for DiBP for infants and mothers and for DEHP and di-n-butyl phthalate (DnBP) only for mothers. Both, infants and mothers are able to efficiently form phase II metabolites but infants with a slightly lower degree. Therefore, a distinguished risk assessment with respect to the formed toxic metabolites of phthalates would be necessary in combination with a reduction of the most toxic phthalates.

Phthalate and di-(2-ethylhexyl) adipate (DEHA) intake by German infants based on the results of a duplicate diet study and biomonitoring data (INES 2).

Phthalates as well as di-(2-ethylhexyl) adipate (DEHA) are used as plasticizers in diverse applications and are of toxicological concern. The study was conducted with a study population of 25 German subjects aged between 15 and 21 months. Overall, 16 phthalates and DEHA were measured by gas chromatography-mass spectrometry in a total of 171 duplicate diet samples collected over 7 consecutive days, and 20 phthalate metabolites were analyzed in the urine samples collected over 7 consecutive days using a liquid chromatography-tandem mass spectrometry method. The median "high" daily dietary intake based on 95th percentiles was 4.66 µg/kg b.w. for di-2-ethylhexyl phthalate (DEHP), 1.03 µg/kg b.w. for di-isobutyl phthalate (DiBP), and 0.70 µg/kg b.w. for di-n-butyl phthalate (DnBP), and 1.0 µg/kg b.w. for DEHA. The "high" daily total intake from biomonitoring data was 4.9 µg/kg b.w. for DEHP, 2.2 µg/kg b.w. for DnBP, 3.9 µg/kg b.w. for DiBP, and 2.6 µg/kg b.w. for di-isononyl phthalate. The comparison of the two intake estimates indicates that the dominant intake source of DEHP was food ingestion, whereas other sources considerably contributed to the total intake of other phthalates. Using our "high" intake scenario, none of the analyzed phthalates reached the recommended tolerable daily intake levels.

High concentrations of cadmium, cerium and lanthanum in indoor air due to environmental tobacco smoke.

BACKGROUND: Environmental tobacco smoke (ETS) is one of the most important sources for indoor air pollution and a substantial threat to human health, but data on the concentrations of the trace metals cerium (Ce) and lanthanum (La) in context with ETS exposure are scarce. Therefore the aim of our study was to quantify Ce and La concentrations in indoor air with high ETS load. METHODS: In two subsequent investigations Ce, La and cadmium (Cd) in 3 smokers' (11 samples) and 7 non-smokers' (28 samples) households as well as in 28 hospitality venues in Southern Germany were analysed. Active sampling of indoor air was conducted continuously for seven days in every season in the smokers' and non-smokers' residences, and for 4h during the main visiting hours in the hospitality venues (restaurants, pubs, and discotheques). RESULTS: In terms of residences median levels of Cd were 0.1 ng/m(3) for non-smokers' and 0.8 ng/m(3) for smokers' households. Median concentrations of Ce were 0.4 ng/m(3) and 9.6 ng/m(3), and median concentrations of La were 0.2 ng/m(3) and 5.9 ng/m(3) for non-smokers' and for smokers' households, respectively. In the different types of hospitality venues median levels ranged from 2.6 to 9.7 ng/m(3) for Cd, from 18.5 to 50.0 ng/m(3) for Ce and from 10.6 to 23.0 ng/m(3) for La with highest median levels in discotheques. CONCLUSIONS: The high concentrations of Ce and La found in ETS enriched indoor air of smokers' households and hospitality venues are an important finding as Ce and La are associated with adverse health effects and data on this issue are scarce. Further research on their toxicological, human and public health consequences is urgently required.

Determination of free and total bisphenol A in urine of infants.

Infants may be particularly sensitive regarding hormonally active compounds such as Bisphenol A (BPA), which is widely distributed and exhibits weak oestrogenic activity. Since only free (unconjugated) BPA exhibits endocrine activity, both free and total (after hydrolysis of conjugates) BPA were determined in urine samples of infants to support valid risk assessments. Free BPA was observed above the LOQ in only 3 of 91 (3%) samples from 47 infants. As total BPA was observed in only 38 (42%) urine samples, with concentrations between

Pre- and postnatal exposure to perfluorinated compounds (PFCs).

Perfluorinated compounds (PFCs) are a group of chemicals widely used for many applications. In this study PFCs were investigated in maternal blood during pregnancy (at two time points) (n = 40 and 38) and 6 months after delivery (n = 47), in cord blood (n = 33) and in blood of infants six (n = 40) and nineteen months (n = 24) after birth, and monthly in breast milk samples in Germany. Concentrations in maternal serum ranged from 0.5 to 9.4 µg/L for perfluorooctane sulfonate (PFOS) and 0.7 to 8.7 µg/L for perfluorooctanoic acid (PFOA). In cord serum, the values ranged from 0.3 to 2.8 µg/L and from 0.5 to 4.2 µg/L for PFOS and PFOA, respectively. The median results from serum at six and nineteen months of age were 3.0 and 1.9 µg/L for PFOS and 6.9 and 4.6 µg/L for PFOA, respectively. In breast milk samples, PFOS ranged from <0.03 to 0.11 µg/L (median: 0.04 µg/L), while PFOA was detected only in some samples as were all other PFCs. Overall, we found low levels of PFCs in cord sera and an increase in concentrations through the first months of infant life. Although the concentrations in breast milk were low, this intake led to a body burden at the age of six months similar to (PFOS) or higher than (PFOA) that found in adults.

Determination of free and total bisphenol A in human urine to assess daily uptake as a basis for a valid risk assessment.

Bisphenol A (BPA) is widely distributed and exhibits weak estrogenic activity. In contrast to BPA, the corresponding glucuronide metabolite is not estrogenic. Therefore, free and total BPA were determined in human urine samples to assess the significance of free BPA for risk assessment. In only 10% of 474 samples from 287 subjects was free BPA detected in a range from

Exposure to environmental tobacco smoke in German restaurants, pubs and discotheques.

In contrast to other countries, there is an on-going debate but still no smoke-free legislation in Germany. Exposure to environmental tobacco smoke (ETS) in hospitality venues is assumed to be high, but air quality data are lacking. Therefore, the aim of our study was to perform a comprehensive exposure assessment by analysing the indoor air concentration of toxic or carcinogenic ETS compounds in restaurants, pubs, and discotheques. Active sampling of indoor air was conducted for 4 h during the main visiting hours in 28 hospitality venues. Polycyclic aromatic hydrocarbons (PAH), volatile organic compounds (VOC), aldehydes/ketones, and cadmium were analysed. In addition, particle mass concentration was assessed with two different methods and particle number concentration (PNC) was determined. Median nicotine levels were 15 microg/m(3) in restaurants, 31 microg/m(3) in pubs, and 193 microg/m(3) in discotheques. Across these three sampling site categories median levels of 3-ethenylpyridine ranged from 3 to 24 microg/m(3), median levels of benzene from 8 to 20 microg/m(3), median levels of cadmium from 3 to 10 ng/m(3), and median levels of the sum of 16 PAH according to US-EPA from 215 to 375 ng/m(3), respectively. Median PM(2.5) mass concentration assessed gravimetrically varied between 178 and 808 microg/m(3) and PNC between 120,000 and 210,000 particles per cm(3) in restaurants, pubs, and discotheques. The majority of the particles had a size of 0.01-0.5 microm. Concentrations of ETS compounds were always highest in discotheques. The strong correlation between ETS-specific markers (nicotine, 3-ethenylpyridine) and PM(2.5), PAH, VOC, aldehydes/ketones, and cadmium indicated ETS as main source of these toxic or carcinogenic substances. In conclusion, indoor air concentrations of ETS constituents were high in German hospitality venues and represented a substantial health threat. Effective measures to protect patrons and staff from ETS exposure are necessary from a public health point of view.