This technical protocol describes a laboratory test method to evaluate the transformation of chemicals in liquid bovine and pig manures under anaerobic conditions and is primarily designed for veterinary medicinal products (VMP) and biocides. The environmentally relevant entry routes into liquid manures occur via urine and feces of cattle and pigs in stable housings after excretion of VMP (as parent compounds or metabolites) and after the application of biocides in animal housings (e.g., as disinfectants or insecticides). In loose housing stables with slatted floors, the excrements are discharged into manure aboveground silos or underground pits. After the storage of liquid manures up to several months, they are applied to farmland and grassland soils as organic fertilizers. Via this route, VMP and biocides may enter soil environments. Thus, the persistence of the chemicals during manure storage under anaerobic conditions decides on the environmental relevance of this entry route.
The aim of this project was the determination of the biokinetics of TiO2 nanoparticles (NP) in the whole body of healthy adult rats after NP administration to the respiratory tract – either via inhalation or instillation. Here we offered applying our previously developed methodology of quantitative biokinetics using radio-labelled NP. Quantitative biokinetics means that not only the NP absolute contents and concentrations of NP in primary and secondary organs and tissues of interest are determined but also those of the remaining body (carcass) and those in faecal and urinary excretion. Veröffentlicht in Umwelt & Gesundheit | 04/2010.
Moos, Rebecca K.; Koch, Holger M.; Angerer, Jürgen; Apel, Petra; Schröter-Kermani, Christa; Brüning, Thomas; Kolossa-Gehring, Marike International Journal of Hygiene and Environmental Health 218 (2015), 7, 666-674 Parabens are widely used as antimicrobial preservatives in personal care and consumer products, food and pharmaceuticals. Due to their ubiquity, humans are constantly exposed to these chemicals. We assessed exposure to nine parabens (methyl-, ethyl-, n- and iso-propyl-, n- and iso-butyl-, benzyl-, pentyl- and heptyl paraben) in the German population from 1995 to 2012 based on 660 24 h urine samples from the German Environmental Specimen Bank (ESB) using on-line HPLC coupled to isotope dilution tandem mass spectrometry. The limit of quantification (LOQ) was 0.5 μg/L for all parabens. We detected methyl-, ethyl- and n-propyl paraben in 79–99% of samples, followed by n-butyl paraben in 40% of samples. We infrequently detected iso-butyl-, iso-propyl- and benzyl paraben in 24%, 4% and 1.4% of samples, respectively. Urinary concentrations were highest for methyl paraben (median 39.8 μg/L; 95th percentile 319 μg/L) followed by n-propyl paraben (4.8 μg/L; 95th percentile 74.0 μg/L) and ethyl paraben (2.1 μg/L; 95th percentile 39.1 μg/L). Women had significantly higher urinary levels for all parabens than men, except for benzyl paraben. Samples from the ESB revealed that over the investigation period of nearly 20 years urinary paraben levels remained surprisingly constant; only methyl paraben had a significant increase, for both men and women. We found strong correlations between methyl- and n-propyl paraben and between n- and iso-butyl paraben. These results indicate that parabens are used in combination and arise from common sources of exposure. Urinary excretion factors are needed to extrapolate from individual urinary concentrations to actual doses. doi:10.1016/j.ijheh.2015.07.005 Verwandte Publikation: Daily intake and hazard index of parabens based upon 24 h urine samples of the German Environmental Specimen Bank from 1995 to 2012
Bartel-Steinbach, Martina; Lermen, Dominik; Gwinner, Frederik; Schäfer, Moritz; Göen, Thomas; Conrad, André; Weber, Till; von Briesen, Hagen; Kolossa-Gehring, Marike Environmental Research 207 (2022), 112592; online 31. Dezember 2021 As highlighted in the Minamata Convention, Mercury (Hg) in its various forms poses a substantial risk to human health and the environment. The health relevance of Hg is also recognized by the European Human Biomonitoring Initiative (HBM4EU), which classifies Hg as a priority substance, since considerable knowledge and data gaps on Hg exposure levels and their changes over time still exist in Europe. The German Environmental Specimen Bank (German ESB) provides valuable policy relevant data and long-term trends of substance exposure on a national level for international comparison and evaluation. In this study we analysed data of the German ESB on Hg exposure of young adults aged 20 to 29 including data on urinary Hg levels from 1995 to 2018 and whole blood Hg levels from 2001 to 2010. Results show a clear decrease in both, about 86% in urine total daily Hg excretion from 1995 (0.76 μg/L) to 2018 (0.11 μg/L) (n = 10,069) and about 57% in blood concentrations of Hg from 2001 (1.76 μg/L) to 2010 (0.77 μg/L) (n = 4085). Over the investigated timeframe only a few values exceeded the toxicologically derived health based guidance value HBM I for blood and urine, with these exceedances decreasing over time in line with the general trend. The factors mostly influencing Hg excretion identified in this study are dental amalgam as well as fish and seafood consumption. Besides other factors (e.g. age and sex), also airborne Hg exposure appears to be a low but evident influencing factor in Germany. Although a considerable decrease in internal Hg exposure is recognized in the last decades, the current low-level exposure may cause adverse health effects especially to vulnerable groups such as pregnant women and children. To further elucidate and evaluate current exposure sources and to reduce human exposure to Hg, continuous environmental and human biomonitoring is needed. doi: 10.1016/j.envres.2021.112592
Göen, Thomas; Dobler, Lorenz; Koschorreck, Jan; Müller, Johannes; Wiesmüller, Gerhard A.; Drexler, Hans; Kolossa-Gehring, Marike International Journal of Hygiene and Environmental Health 215 (2011), 1, 36-45 The exposure of the general population to phthalates is of increasing public health concern. Variations in the internal exposure of the population are likely, because the amounts, distribution and application characters of the phthalate use change over time. Estimating the chronological sequences of the phthalate exposure, we performed a retrospective human biomonitoring study by investigating the metabolites of the five most prominent phthalates in urine. Therefore, 24 h-urine samples from the German Environmental Specimen Bank (ESB) collected from 240 subjects (predominantly students, age range 19-29 years, 120 females, 120 males) in the years 2002, 2004, 2006 and 2008 (60 individuals each), were analysed for the concentrations of mono-n-butyl phthalate (MnBP) as metabolite of di-n-butyl phthalate (DnBP), mono-iso-butyl phthalate (MiBP) as metabolite of di-iso-butyl phthalate (DiBP), mono-benzyl phthalate (MBzP) as metabolite of butylbenzyl phthalate (BBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) and mono-(2-carboxymethyl hexyl) phthalate (2cx-MMHxP) as metabolites of di(2-ethylhexyl) phthalate (DEHP), monohydroxylated (OH-MiNP), monooxidated (oxo-MiNP) and monocarboxylated (cx-MiNP) mono-iso-nonylphthalates as metabolites of di-iso-nonyl phthalates (DiNP). Based on the urinary metabolite excretion, together with results of a previous study, which covered the years 1988-2003, we investigated the chronological sequences of the phthalate exposure over two decades. In more than 98% of the urine samples metabolites of all five phthalates were detectable indicating a ubiquitous exposure of people living in Germany to all five phthalates throughout the period investigated. The medians in samples from the different years investigated are 65.4 (2002), 38.5 (2004), 29.3 (2006) and 19.6 μg/l (2008) for MnBP, 31.4 (2002), 25.4 (2004), 31.8 (2006) and 25.5 μg/l (2008) for MiBP, 7.8 (2002), 6.3 (2004), 3.6 (2006) and 3.8 μg/l (2008) for MBzP, 7.0 (2002), 5.6 (2004), 4.1 (2006) and 3.3 μg/l (2008) for MEHP, 19.6 (2002), 16.2 (2004), 13.2 (2006) and 9.6 μg/l (2008) for 5OH-MEHP, 13.9 (2002), 11.8 (2004), 8.3 (2006) and 6.4 μg/l (2008) for 5oxo-MEHP, 18.7 (2002), 16.5 (2004), 13.8 (2006) and 10.2 μg/l (2008) for 5cx-MEPP, 7.2 (2002), 6.5 (2004), 5.1 (2006) and 4.6 μg/l (2008) for 2cx-MMHxP, 3.3 (2002), 2.8 (2004), 3.5 (2006) and 3.6 μg/l (2008) for OH-MiNP, 2.1 (2002), 2.1 (2004), 2.2 (2006) and 2.3 μg/l (2008) for oxo-MiNP and 4.1 (2002), 3.2 (2004), 4.1 (2006) and 3.6 μg/l (2008) for cx-MiNP. The investigation of the time series 1988-2008 indicates a decrease of the internal exposure to DnBP by the factor of 7-8 and to DEHP and BzBP by the factor of 2-3. In contrast, an increase of the internal exposure by the factor of 4 was observed for DiNP over the study period. The exposure to DiBP was found to be stable. In summary, we found decreases of the internal human exposure for legally restricted phthalates whereas the exposure to their substitutes increased. Future investigations should verify these trends. This is of increasing importance since the European Commission decided to require ban or authorization from 1.1.2015 for DEHP, DnBP, DiBP and BzBP according to REACh Annex XIV. doi: 10.1016/j.ijheh.2011.07.011
Pluym, Nikola; Petreanu, Wolf; Weber, Till; Scherer, Max; Kolossa-Gehring, Marike International Journal of Hygiene and Environmental Health 227 (2020), Juni 2020, 113508; online 12. März 2020 7-Hydroxy-3,7-dimethyl-1-octanal, also known as 7-hydroxycitronellal (7-HC, CAS No. 107-75-5) is a synthetic fragrance widely used in cosmetic and hygiene products. Because of its wide spread use and its known sensitizing properties, 7-HC was selected as one of 50 chemicals within the frame of the cooperation project between the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) and the German Chemical Industry Association (VCI) to develop a suitable human biomonitoring (HBM) method in order to assess the exposure of the general population in Germany. Within this scope, the recently published analytical method for urinary 7-hydroxycitronellylic acid (7-HCA), the major metabolite of 7-HC, was applied to 329 24h-urine samples of young adults (20 to 29 years) collected between 2000 and 2018 and stored in the Environmental Specimen Bank (ESB). The widespread exposure to 7-HC as already observed in a pilot study with 40 volunteers could be confirmed with quantifiable concentrations of 7-HCA in all 329 study samples (mean: 14.9 ng/mL; median: 8.1 ng/mL). A significant, chronological decrease in 7-HCA levels was found for the monitored years (2000, 2004, 2008, 2012, 2015, 2018). The most pronounced decline occurred between 2000 and 2004 (means: 34.37 versus 23.31, medians: 20.97 versus 12.49 μg/24h; p < 0.01). On average, females exhibited higher levels of urinary 7-HCA compared to males (29.34 versus 17.21 μg/24h, p < 0.05). Based on the urinary 7-HCA excretion, the daily intake (DI) of 7-HC normalized for body weight (bw) was estimated. Over all sampling years, average DI in females was significantly higher compared to males (0.99 versus 0.46 μg/kg bw/d). Assuming dermal exposure as the main route of 7-HC intake, the mean DIs correspond to <0.1% of the derived no effect level (DNEL) of 1,100 μg/kg bw/d defined by the European Chemical Agency (ECHA). The presented results for the exposure to the widely used fragrance 7-HC in Germany can be substantiated by applying the described methodology to the representative cohort of the launched German Environmental Survey in adults (GerES VI). doi: 10.1016/j.ijheh.2020.113508
Pluym, Nikola; Stöckelhuber, Markus; Weber, Till; Scherer, Gerhard; Scherer, Max; Kolossa-Gehring, Marike International Journal of Hygiene and Environmental Health 239 (2022), 113880; online 10. November 2021 Geraniol (trans-3,7-dimethyl-2,6-octadiene-1-ol) is an acyclic isoprenoid monoterpene with a widespread use as fragrance in consumer products, agrochemicals and pharmaceuticals. The class of terpene chemicals has been associated with varying sensitizing potencies. A recently developed sensitive LC- MS/MS method for the analysis of geraniol metabolites was further improved and validated for the two metabolites, 8-carboxygeraniol and Hildebrandt acid. The successfully validated method was applied to 250 urine samples derived from the Environmental Specimen Bank (ESB) collected between 2004 and 2018. Both metabolites of this allergen of special concern were quantified in all urine samples of this study. Correlation analysis revealed that 8-carboxygeraniol appears to be the sole specific biomarker in urine for geraniol exposure. Overall, the excreted amounts of 8-carboxygeraniol remained unchanged in urine samples collected from 2004 to 2018. However, a significantly higher 8-carboxygeraniol excretion per 24 h was observed in females compared to males across the sampling years from 2004 to 2012. This trend equalized in the years 2015 and 2018. We could demonstrate that 8-carboxygeraniol may be a suited biomarker for assessing the geraniol exposure in the general population. Regardless of the fact that additional, preferably population representative studies combining HBM and health examination were helpful to further elucidate the risks of a geraniol exposure, the current study adds important data for identifying time trends and body burden of geraniol in the environment and shows the ubiquitous exposure towards mixtures of sensitizing chemicals. doi: 10.1016/j.ijheh.2021.113880
Schmidtkunz, Christoph; Küpper, Katja; Weber, Till; Leng, Gabriele; Kolossa-Gehring, Marike International Journal of Hygiene and Environmental Health 228 (2020), Juli 2020, 113541; online 5. Mai 2020 The antioxidant 2,6-di-tert-butyl-4-methylphenol (butylated hydroxytoluene, BHT) is used ubiquitously in food, cosmetics, pharmaceuticals, fuels, plastics, rubbers and many other products. Therefore, exposure of the general population to this substance is likely. We analyzed the BHT metabolite 3,5-di-tert-butyl-4-hydroxybenzoic acid (“BHT acid”) in 24-h urine samples from the German Environmental Specimen Bank with the aim of gaining a better understanding of the internal burden of BHT in young nonspecifically exposed adults. The study population consisted of students between 20 and 29 years of age at the time of sampling, all from Halle/Saale in Central Germany. In total, 329 samples collected in the years 2000, 2004, 2008, 2012, 2015, and 2018 were measured by ultra high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). BHT acid was detected above the limit of quantification (0.2 μg/L) in 98% of the samples. The median of the measured concentrations was 1.06 μg/L and 1.24 μg/g creatinine respectively, the median of the daily excretion was 1.76 μg/24 h and – additionally normalized for body weight – 26.8 ng/24 h × kg bw respectively. The corresponding 90th percentiles were 3.28 μg/L, 3.91 μg/g creatinine, 5.05 μg/24 h, and 81.9 ng/24 h × kg bw. Medians of creatinine-corrected values were slightly higher in women than in men, while the opposite situation was observed for the volume concentrations and the 24-h excretion values (not corrected for body weight). Values simultaneously normalized both for 24-h excretion and body weight did not exhibit any significant differences between males and females, probably indicating a virtually identical magnitude of exposure for both genders. The background exposure of the investigated population was found to be largely constant since the year 2000, with only weak temporal trends at most. Daily intakes were estimated from excretion values and found to be largely below the acceptable daily intake (ADI) of BHT at 0.25 mg/kg bw: our worst-case estimate is a daily BHT intake of approximately 0.1 mg/kg bw at the 95th percentile level. However, these intake assessments rely on very limited quantitative data regarding human metabolism of BHT. doi: 10.1016/j.ijheh.2020.113541
Lermen, Dominik; Bartel-Steinbach, Martina; Gwinner, Frederik; Conrad, André; Weber, Till; von Briesen, Hagen; Kolossa-Gehring, Marike International Journal of Hygiene and Environmental Health (2019), online 26. April 2019 To document trends in human exposure to environmental pollutants, the German Environmental Specimen Bank (ESB) has been routinely collecting and archiving 24-h urine samples from young adults at four sampling sites in Germany on an annual basis. For the purpose of normalizing measured analyte concentrations, urinary creatinine (UC), specific gravity (SG), conductivity (CON), and total urine volume (UV tot ) of 24-h urine samples have also been recorded. These parameters are however susceptible to variation over time, as well as within/among participants and normalization against them can thus affect the interpretation of data regarding exposure to environmental pollutants. To evaluate the influence of normalization against these parameters, we first sought to determine variations of these parameters with regard to differences between sexes and trends over time. We analysed data from 8619 urine samples collected from 1997 to 2016. We observed an inverse relation between UVtot and UC, SG, and CON. We also found differences between sexes for UC, SG and CON, but not UVtot. UC, SG, and CON showed significant decreasing trends over time in both sexes. In contrast, a significant increase of over 30% in UV tot , independent of participant age and BMI, was revealed. This increase in UVtot and the concomitant sample dilution is likely to have an impact on measured analyte concentrations in 24-h urine samples. Hence, normalization of urinary concentrations is warranted when interpreting time trends of human exposure. Next, urinary calcium (Ca 2+ ) concentrations of ESB participants were used to demonstrate the effects of normalization against each of the four urine parameters. From 1997 to 2016, measured Ca 2+ concentrations showed a statistically significant but scientifically implausible decrease. Normalization of Ca 2+ concentrations against UVtot (by calculating the total daily excretion), UC, or CON, but not SG, eliminated this decrease. Consistent with previous work, Ca 2+ concentrations in urine and total daily Ca 2+ excretion were higher for males than females. Normalization against UC, SG, or CON, however, attenuated this difference. Thus, to avoid misinterpretation in trend analysis and sex-specific excretion in 24-h urine samples, the calculation of the total daily excretion is recommended. doi: 10.1016/j.ijheh.2019.04.009
Wittassek, Matthias; Wiesmüller, Gerhard A.; Koch, Holger M.; Eckard, Rolf; Dobler, Lorenz; Helm, Dieter; Müller, Johannes; Angerer, Jürgen; Schlüter, Christoph International Journal of Hygiene and Environmental Health 210 (2007), 3-4, 319-333 In a retrospective human biomonitoring study we analysed 24h urine samples taken from the German Environmental Specimen Bank for Human Tissues (ESBHum), which were collected from 634 subjects, (predominantly students, age range 20-29 years, 326 females, 308 males) in 9 years between 1988 and 2003 (each n≥60), for the concentrations of primary and/or secondary metabolites of di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP). Based on the urinary metabolite excretion we estimated daily intakes of the parent phthalates and investigated the chronological course of the phthalate exposure. In over 98% of the urine samples metabolites of all five phthalates were detectable indicating a ubiquitous exposure of the German population to all five phthalates throughout the last 20 years. The median daily intakes in the subsets between 1988 and 1993 were quite constant for DnBP (approx. 7 μg/kg bw/d) and DEHP (approx. 4 μg/kg bw/d). However, from 1996 the median levels of both phthalates decreased continuously until 2003 (DnBP 1.9 μg/kg bw/d; DEHP 2.4 μg/kg bw/d). By contrast, the daily intake values for DiBP were slightly increasing over the whole time frame investigated (median 1989: 1.0 μg/kg bw/d; median 2003: 1.4 μg/kg bw/d), approximating the levels for DnBP and DEHP. For BBzP we observed slightly decreasing values, even though the medians as of 1998 levelled off at around 0.2 μg/kg bw/d. Regarding daily DiNP exposure we found continuously increasing values, with the lowest median being 0.20 μg/kg bw/d for the subset of 1988 and the highest median for 2003 being twice as high. The trends observed in phthalate exposure may be associated with a change in production and usage pattern. Female subjects exhibited significantly higher daily intakes for the dibutyl phthalates (DnBP p=0.013; DiBP p=0.004). Compared to data from US National Health and Nutrition Examination Surveys (NHANES) exposure levels of the dibutyl phthalates were generally higher in our German study population, while levels of BBzP were somewhat lower. Overall, for a considerable 14% of the subjects we observed daily DnBP intakes above the tolerable daily intake (TDI) value deduced by the European Food Safety Authority (EFSA) (10 μg/kg bw/d). However, the frequency of exceedance decreased during the years and was beneath 2% in the 2003 subset. Even though transgressions of the exposure limit values of the EFSA and the US Environmental Protection Agency (US EPA) occurred only in a relatively small share of the subjects, one has to take into account the cumulative exposure to all phthalates investigated and possible dose-additive endocrine effects of these phthalates. doi: 10.1016/j.ijheh.2007.01.037