German Human Biomonitoring Commission Research Articles

Mercury Exposure among Artisanal and Small-Scale Gold Miners in Four Gold Mining Districts in the East Region of Cameroon

Artisanal and small-scale gold mining (ASGM) is the single largest intentional-release of mercury (Hg) in the world. In Cameroon, there is paucity of data concerning the contribution of ASGM to human mercury contamination. This study aimed at providing new data for a region in Cameroon where ASGM is practiced, through an assessment of the concentration of total mercury (T-Hg) in hair as a function of occupational exposure, and investigating symptoms related to Hg toxicity. A quantitative cross-sectional survey design was employed involving 60 gold miners from four gold mining districts: Batouri, Kette, Ngoura and Bétaré-Oya. Questionnaire was used to collect sociodemographic data, nature of work processes and symptoms of Hg toxicity. Scalp hair samples were drawn from all 60 respondents and analysis for total mercury (T-Hg) in hair was done via a milestone DMA-80 Mercury Analyzer. The results show that males (86.7%) were generally represented than females (13.3%). The minimum, maximum and mean concentrations of Hg in hair of miners across the four districts was 0 μg/g, 8.97 μg/g and 2.09±1.84 μg/g respectively. Over three-quarters (71.7%) of the miners had T-Hg in hair above the occupational toxic threshold of 1 μg/g set by the United States Environmental Protection Agency (USEPA), also identified as 66.7% in the “alert level” and 5% as “high” according the German Human Biomonitoring (HBM) Commission. The factors affecting the concentration of mercury in hair according to a multiple linear regression model (R2 = 0.400 and p = 0.03) were living in Bétaré-Oya, younger age, male sex, burning of amalgam, and increased number of working days per week. According to the same model (R2 = 0.076 and p = 0.940), the symptoms associated with mercury exposure were unusual tiredness, excessive sleeping, dizziness and visual difficulties. ASGM in the east region of Cameroon, therefore, is significantly contributing to Hg contamination in humans as a result of occupational exposures to Hg, and there is urgent need for interventions to mitigate human exposure, especially as adverse health effects cannot be excluded following long-term exposures.

A revised concept for deriving reference values for internal exposures to chemical substances and its application to population-representative biomonitoring data in German children and adolescents 2014–2017 (GerES V)

HBM reference values, in contrast to toxicologically derived values, are statistically derived values that provide information on the exposure of the population. The exceedance frequency (if applicable for individual population groups) is often a first assessment standard for the local exposure situation for municipalities. More than 25 years have passed since the German Human Biomonitoring Commission (HBMC) formulated the first recommendations for the derivation of population-based reference values (HBM reference values, RV95) for substance concentrations based on HBM studies. A fundamental revision is timely, for several reasons. There have been considerable advances in relevant statistical methods, which meant that previously time-consuming and inaccessible procedures and calculations are now widely available. Furthermore, not all steps for the derivation of HBM reference values were clearly elaborated in the first recommendations. With this revision we intended to achieve a rigorous standardization of the entire process of deriving HBM reference values, also to realise a higher degree of transparency.In accordance with established international practice, it is recommended to use the 95th percentile of the reference distribution as the HBM reference value. To this end, the empirical 95th percentile of a suitable sample should be rounded, ensuring that the rounded value is within the two-sided 95% confidence interval of the percentile. All estimates should be based on distribution-free methods, and the confidence interval should be estimated using a bootstrap approach, if possible, according to the BCa (“bias-corrected and accelerated bootstrap”). A minimum sample size of 80 observations is considered necessary. The entire procedure ensures that the derived HBM reference value is robust against at least two extreme values and can also be used for underlying mixed distributions.If it is known in advance that certain subgroups (different age groups, smokers, etc.) show differing internal exposures, it is recommended that group-specific HBM reference values should be derived. Especially when the sample sizes for individual subgroups are too small, individual datasets with potential outliers can be excluded in advance to homogenize the reference value population.In the second part, new HBM reference values based on data of the German Environmental Survey for Children and Adolescents (GerES V, 2014–2017) were derived in accordance with the revised recommendations. The GerES V is the most recent population-representative monitoring of human exposure to pollutants in Germany on children and adolescents aged 3–17 years (N = 2294). RV95 for GerES V are reported for four subgroups (males/females and 3–11/12-17 years) for 108 different substances including phthalates and alternative plasticisers, metals, organochlorine pesticides, polychlorinated biphenyls (PCB), per- and polyfluoroalkyl substances (PFAS), parabens, aprotic solvents, chlorophenols, polycyclic aromatic hydrocarbons (PAH) and UV filter, in total 135 biomarkers. Algorithms implemented in R were used for the statistics and the determination of the HBM reference values. To facilitate a quality control of the study data, the corresponding R source code is given, together with graphical representations of results.The HBM reference values listed in this article replace earlier RV95 values derived by the HBMC for children and adolescents from data of precedent GerES studies (e.g. published in Apel et al., 2017).

Levels of per- and polyfluoroalkyl substances (PFAS) in Norwegian children stratified by age and sex - Data from the Bergen Growth Study 2.

Due to the persistence, bioaccumulation and potential adverse health effects, there have been restrictions and phase out in the production of certain per- and polyfluoroalkyl substances (PFAS) since the early 2000s. Published serum levels of PFAS during childhood are variable and may reflect the impact of age, sex, sampling year and exposure history. Surveying the concentrations of PFAS in children is vital to provide information regarding exposure during this critical time of development. The aim of the current study was therefore to evaluate serum concentrations of PFAS in Norwegian schoolchildren according to age and sex. Serum samples from 1094 children (645 girls and 449 boys) aged 6-16 years, attending schools in Bergen, Norway, were analyzed for 19 PFAS. The samples were collected in 2016 as part of the Bergen Growth Study 2. Statistical analyses included Student t-test, one-way ANOVA and Spearman's correlation analysis of log-transformed data. Of the 19 PFAS examined, 11 were detected in the serum samples. Perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS) and perfluorononaoic acid (PFNA) were present in all samples with geometric means of 2.67, 1.35, 0.47 and 0.68ng/mL, respectively. In total, 203 children (19%) had PFAS levels above the safety limits set by the German Human Biomonitoring Commission. Significantly higher serum concentrations were found in boys compared to girls for PFOS, PFNA, PFHxS and perfluoroheptanesulfonic acid (PFHpS). Furthermore, serum concentrations of PFOS, PFOA, PFHxS and PFHpS were significantly higher in children under the age of 12 years than in older children. PFAS exposure was widespread in the sample population of Norwegian children analyzed in this study. Approximately one out of five children had PFAS levels above safety limits, indicating a potential risk of negative health effects. The majority of the analyzed PFAS showed higher levels in boys than in girls and decreased serum concentrations with age, which may be explained by changes related to growth and maturation.

Methylmercury Risk Assessment Based on European Human Biomonitoring Data.

A risk assessment (RA) was conducted to estimate the risk associated with methylmercury (MeHg) exposure of vulnerable European populations, using Human Biomonitoring (HBM) data. This RA was performed integrating published data from European HBM surveys and earlier EFSA approaches (EFSA 2012). Children/adolescents (3 to 17 years old) and women of childbearing age (18 to 50 years old) were selected as relevant study population groups for this RA. Two types of HBM datasets were selected: HBM studies (n = 18) with mercury (Hg) levels (blood and hair, total Hg and/or MeHg) in the general population in different EU countries and the DEMOCOPHES harmonized study in child–mother pairs (hair, total Hg) in 17 EU countries as a reference. Two approaches were included in the RA strategy: the first one was based on estimations of the fraction of children/adolescents and women of childbearing age, respectively, from the EU general population exceeding the HBM-I value established by the German Human Biomonitoring Commission, measured as Hazard Quotients (HQ); and the second approach was based on estimations of the fraction of the two population groups exceeding the Tolerable Weekly Intake (TWI) (or their equivalent to Tolerable Daily Intake (TDI)) defined by EFSA in 2012. The HQ approach showed that for both groups, the risk varies across EU countries and that some EU areas are close to or exceeding the exposure guidance values. This is the case of Spain and Portugal, which showed the highest HQ (GM and/or P95), probably due to their higher fish consumption. Results from the EFSA approach show that hair values of children/adolescents and women of childbearing age (both in selected HBM studies and in DEMOCOPHES study) are below the TDI of 1.9 µg/g; therefore, in general, the European population does not exceed the daily average/intake dose for MeHg and/or Hg. A possible risk underestimation was identified in our assessment since for many studies no data on P95 were available, causing loss of relevant information for risk characterization on the upper bound. In addition, data from other European countries also with high seafood consumption, such as France, Greece or Iceland, were not available. For this reason, further RA refinement is needed with harmonized and more widespread HBM data to account for differences in European exposure and associated risks, so that interventions to protect vulnerable citizens, can be applied.

Health Risk Assessment of Trace Metals Through Breast Milk Consumption in Saudi Arabia.

We previously measured the levels of inorganic mercury, methylmercury, lead, cadmium, and manganese in the breast milk of 203 healthy Saudi mothers who participated in a cross-sectional study between 2011 and 2013. The current study aimed to (1) calculate reference values (RVs) for these metals in breast milk based on the 95th percentile of the metal and the corresponding 95% confidence interval following the approach of the German Human Biomonitoring Commission, and (2) assess the health risk associated with these metals (except lead) by determining the hazard quotient (HQ) and hazard index (HI) for breastfed infants. The risk characterization for the lead was applied using the margin of exposure (MOE) approach. Moreover, the cancer risk (CR) associated with lead was calculated. The RV95s (percentage of samples for which the value was higher than the set value) for inorganic mercury, methylmercury, total mercury, cadmium, lead, and manganese in breast milk (μg/L) were 1.5 (7.9%), 1.5 (5.4%), 2.8 (8.9%), 2.5 (8.4%), 53 (11.3%), and 22.3 (11.8%) μg/L, respectively. The methylmercury, lead, and manganese levels in the present study were higher than those reported previously. The HQ for methylmercury greater than 1 was found in 68.5% of the samples, indicating there may be a potential non-carcinogenic health risk of infant exposure to the toxic metal via breast milk consumption. Despite the high cadmium and manganese levels in breast milk, our results suggested no health risk (HQ < 1). The HI representing the combined non-carcinogenic health risk of four metals was > 1, with methylmercury (74%) being the major contributor. The estimated MOE mean value of 0.134, less than 1, indicates that our breastfed infants may be at increased risk of neurodevelopmental impairments. The CR for lead in two infants was higher than the acceptable level of 1 × 10-4. Although our results may suggest potential carcinogenic and non-carcinogenic risks of infant exposure to toxic metals through breast milk consumption, the benefits of breastfeeding are well recognized and outweigh the potential risks.

Urinary Mercury Levels and Predictors of Exposure among a Group of Italian Children.

Urinary mercury (Hg) levels are suitable to assess long-term exposure to both elemental and inorganic Hg. In this study, the urinary Hg levels of 250 children (aged 6–11 years) from three areas with different anthropogenic impacts in the Rieti province, central Italy, were assessed. The Hg concentrations were in the range of 0.04–2.18 µg L−1 with a geometric mean equal to 0.18 µg L−1 [95% confidence interval (CI), 0.17–0.20 µg L−1] or 0.21 µg g−1 creatinine (95% CI, 0.19–0.23 µg g−1 creatinine), and a reference value calculated as 95th percentile of 0.53 µg L−1 (95% CI, 0.44–0.73 µg L−1) or 0.55 µg g−1 creatinine (95% CI, 0.50–0.83 µg g−1 creatinine). In all cases, urinary Hg data were below the HBM-I values (7 µg L−1 or 5 µg g−1 creatinine) established for urine, while the 95th percentile was above the German Human Biomonitoring Commission’s RV95 (0.4 µg L−1) set for children without amalgam fillings. A significant correlation (p < 0.05) was found between creatinine-corrected results and residence area, with higher urinary Hg levels in children living in the industrial area. Multiple linear regression analysis showed that creatinine was the main predictor of urinary Hg.

Human biomonitoring initiative (HBM4EU) - Strategy to derive human biomonitoring guidance values (HBM-GVs) for health risk assessment.

The European Joint Program "HBM4EU" is a joint effort of 30 countries and the European Environment Agency, co-funded under the European Commission's Horizon 2020 program, for advancing and implementing human biomonitoring (HBM) on a European scale and for providing scientific evidence for chemical policy making. One important outcome will be a Europe-wide improvement and harmonization of health risk assessment following the coordinated derivation or update of health-related guidance values referring to the internal body burden. These guidance values - named HBM guidance values or HBM-GVs - can directly be compared with HBM data. They are derived within HBM4EU for priority substances identified by the HBM4EU chemicals prioritization strategy based on existing needs to answer policy relevant questions as raised by national and EU policy makers. HBM-GVs refer to both the general population and occupationally exposed adults. Reports including the detailed reasoning for the values' proposals are subjected to a consultation process within all partner countries of the consortium to reach a broad scientific consensus on the derivation approach and on the derived values. The final HBM-GVs should be applied first within the HBM4EU project, but may also be useful for regulators and risk assessors outside this project. The subsequent adoption of derived HBM-GVs at EU-level needs to be discussed and decided within the responsible EU bodies. Nevertheless, the establishment of HBM-GVs as part of HBM4EU is already a step forward in strengthening HBM-based policy efforts for public and occupational health. The strategy for deriving HBM-GVs which is based on already existing approaches from the German HBM Commission, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) as well as from the US-based scientific consultant Summit Toxicology, the allocation of a level of confidence to the derived values, and the consultation process within the project are comprehensively described to enlighten the work accomplished under the HBM4EU initiative.

Reference values for heavy metals in the urine and blood of Saudi women derived from two human biomonitoring studies.

We previously assessed the exposure of Saudi women to mercury, cadmium and lead based on reference values (RVs) established for other populations experiencing differences in environmental exposure, diet and lifestyle as an indicator of background exposure to pollutants. The present study aimed to (1) calculate RV95 for mercury, cadmium and lead in blood and urine from Saudi women based on the 95th percentile of the metal and its corresponding 95% confidence interval (95%CI) as defined by the German Human Biomonitoring Commission, and (2) compare with RV95s established in other countries. RV95s were derived using data from two different human biomonitoring studies measured three metals in the blood (2005-2006), and both urine and blood (2011-2013) from healthy non-smokers and non-occupationally exposed women living in Al-Kharj and Riyadh. RV95s for mercury, cadmium and lead in Al-Kharj (Riyadh) blood were 5.9 (1.6) μg/l, 1.4 (1.9) μg/l and 4.3 (4.8) μg/dl, respectively. RV95s for urinary mercury, cadmium and lead in Riyadh samples expressed in μg/l (μg/g creatinine) were 2.5 (1.9), 1.2 (0.96) and 14 (10.8), respectively. Values in both matrices remained high even when potential factors such as secondhand smoking, dental amalgam, and/or fish consumption excluded. RV95s for metals in blood were generally higher than in other countries, except for mercury in Riyadh samples, which was also 4-fold lower than in Al-Kharj. However, due to the time lag between the two studies, and since the Al-Kharj study was conducted 13 years ago, the most recent RV95s derived from the Riyadh study are recommended for Saudi women living in the Central region. The RV95s for urinary mercury and cadmium were comparable to other countries, but lead requires closer attention. To our knowledge, this study is the first to propose RV95s for mercury, cadmium, and lead in blood and urine of Saudi women of childbearing age, a population that is highly susceptible to the adverse health effects of these metals.

Pediatric reference values for chromium and mercury in urine in the City of Buenos Aires and Greater Buenos Aires.

Due to the heavy industrialization of the Autonomous City of Buenos Aires and Greater Buenos Aires, the population may have become exposed to metals. To assess the level of exposure to chromium and mercury in children, it is critical to have local reference values (RVs). Our objective was to determine pediatric RV s for chromium and mercury in a single urine sample. Children who were not exposed to the studied contaminants and who attended the Department of Low Risk Conditions and the Daycare Center Office of Hospital de Pediatría S.A.M.I.C. "Prof. Dr. Juan P. Garrahan" were included. Urinary chromium (UCr), urinary mercury (UHg), and urinary creatinine were measured. The p95 and its corresponding 95 % confidence interval (CI) were estimated based on the RV concept proposed by the German Human Biomonitoring Commission. The study included 160 patients. A total of 144 samples from children aged 1-17 years (median: 7 years) were collected. UCr was measured in 137 samples and UHg, in 129 samples. The median value of chromium was 0.54 µg/g of creatinine (range, undetectable to 3.06), while that of mercury was 0.49 µg/g of creatinine (range, undetectable to 7.57). The RVs for UCr were up to 1.5 µg/L [1.2-2.8] and up to 2.2 µg/g of creatinine [1.8-3.0], and for UHg, up to 2.5 µg/L [1.8-4.8] and 3.2 µg/g of creatinine [2.5-4.7].

Austrian reference values for phthalate metabolite exposure in children/adolescents and adults

Reference values (RV95) are statistically derived values comprising the rounded 95th percentiles within the 95% confidence interval and indicate the upper margin of background exposure to chemical substances in a population at a given time period. Based on representative national human biomonitoring data on several urinary phthalate metabolites in children, adolescents and adults from 2010 to 2011, RV95 were derived for the Austrian population based on a IUPAC guideline and the recommendation of the German Human Biomonitoring Commission. The RV95 (rounded values) for phthalate metabolites in children and adolescents aged 6-15 years are 110 μg/l (confidence interval of 95th population percentile: 83.7-163) for mono-ethyl phthalate (MEP), 45 μg/l (40.9-60.6) for mono-n-butyl phthalate (MnBP), 130 μg/l (126-161) for mono-isobutyl phthalate (MiBP), 25 μg/l (17.8-33.6) for mono-benzyl phthalate (MBzP), 100 μg/l (94.0-126) for the sum of the di(2-ethylhexyl) phthalate (DEHP) metabolites including mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP), and 1.5 μg/l (0.64-1.6) for mono-cyclohexyl phthalate (MCHP). In adults aged 18-81 years, RV95 are 440 μg/l (353-636) for MEP, 40 μg/l (33.1-52.1) for MnBP, 110 μg/l (87.3-118) for MiBP, 10 μg/l (7.2-11.8) for MBzP, 50 μg/l (44.6-68.3) for the sum of MEHP, 5OH-MEHP, 5oxo-MEHP and 5cx-MEPP, and 1.5 μg/l (0.95-1.8) for MCHP. For almost all investigated metabolites, children and adolescents exhibit higher RV95 than adults, with the exceptions being MEP and MCHP. Compared to available RV95 for Germany and Canada, Austrian values are lower for all investigated population groups.

Ableitung von HBM-I-Werten für Perfluoroktansäure (PFOA) und Perfluoroktansulfonsäure (PFOS) – Stellungnahme der Kommission „Humanbiomonitoring“ des Umweltbundesamts

Ableitung von HBM-I-Werten für Perfluoroktansäure (PFOA) und Perfluoroktansulfonsäure (PFOS) – Stellungnahme der Kommission „Humanbiomonitoring“ des Umweltbundesamts

New HBM values for emerging substances, inventory of reference and HBM values in force, and working principles of the German Human Biomonitoring Commission.

The German Human Biomonitoring Commission (HBM Commission) derives health-related guidance values (Human Biomonitoring assessment values, HBM values) according to the procedures described in the HBM Commission's position papers. Since the last adaption of the methodology in 2014, the HBM Commission has established a series of new HBM values, mainly on the basis of internationally agreed TDI/RfD values, or of toxicologically well- founded points of departure observed in animal studies. The derivation of these new HBM values for HBCDD, triclosan, 2-MBT, PFOA and PFOS as well as for the metabolites of glycol ethers, of Hexamoll® DINCH®, DPHP, DEHTP, NMP, NEP, and 4-MBC is specified, and the HBM values are presented together with already established HBM values for other substances. Furthermore, the HBM Commission has defined provisional reference values for 2-methoxyacetic acid and for several parabens in the urine of the German population. It has also updated provisional reference values for PCB in the blood of the German population. An overview of all available reference values is given.

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.

Current data on the background burden to the persistent organochlorine pollutants HCB, p,p'-DDE as well as PCB 138, PCB 153 and PCB 180 in plasma of the general population in Germany.

Despite their long-term ban, persistent organochlorine compounds like hexachlorobenzene (HCB), p,p'-dichlorodiphenylethylene (DDE) as well as polychlorinated biphenyls (PCBs) are still of environmental concern. For the evaluation of potential occupational or environmental exposures to these substances, it is essential to know the current background burden of the general population. As representative and up-to-date information is missing for Germany, we have analysed a large dataset generated in studies on potential exposure to lower chlorinated PCBs to fill this gap for the levels of HCB, DDE as well as PCB 138, PCB 153 and PCB 180. We have investigated n=2750 plasma samples of persons of the general population living in North Rhine-Westfalia and Hesse aged 6-65 years and sampled between September 2010 and March 2014. For evaluation of the age-dependent accumulation in the general population we have generated seven age groups in the collective. Our laboratory used a validated and quality controlled procedure using GC/MS for quantification of the organochlorine compounds in plasma (LOQ: 0.01μg/L). The median (95th percentile) levels for ∑ PCB 138+PCB 153+PCB 180 were 0.14 (0.73); 0.30 (0.82); 0.38 (0.88); 0.50 (1.14); 0.92; 1.58 (3.54) and 2.41 (4.82)μg/L plasma in the age groups 6-10 years (n=102), 11-17 years (n=499), 18-25 years (n=157), 26-35 years (n=710), 36-45 years (n=400), 46-55 years (n=525) and 56-65 years (n=357), respectively. Similarly, the median (95th percentile) levels of p,p'-DDE were 0.18 (1.24); 0.18 (0.74); 0.24 (0.85); 0.30 (1.20); 0.45 (1.74); 0.64 (3.25) and 0.94 (4.7)μg/L plasma. Finally, the median (95th percentile) of HCB in plasma in these age groups was 0.05 (0.10); 0.06 (0.11); 0.08 (0.15); 0.08 (0.15); 0.11 (0.22); 0.14 (0.42) and 0.20 (0.68)μg/L plasma. Our results prove an overall substantial reduction in the body burden to organochlorine compounds in Germany compared to earlier studies. However, 15% and 3.6% of the examined collective exceeded the HBM-I- and HBM-II-values for PCBs established by the German Human Biomonitoring Commission. Due to a large sample size and a collection period from 2010 to 2014, our data might be suitable for the evaluation of additional exposures to these POPs and may serve as reference values.

Evaluation of Biomonitoring Data from the CDC National Exposure Report in a Risk Assessment Context: Perspectives across Chemicals

Background: Biomonitoring data reported in the National Report on Human Exposure to Environmental Chemicals [NER; Centers for Disease Control and Prevention (2012)] provide information on the presence and concentrations of > 400 chemicals in human blood and urine. Biomonitoring Equivalents (BEs) and other risk assessment–based values now allow interpretation of these biomonitoring data in a public health risk context.Objectives: We compared the measured biomarker concentrations in the NER with BEs and similar risk assessment values to provide an across-chemical risk assessment perspective on the measured levels for approximately 130 analytes in the NER.Methods: We identified available risk assessment–based biomarker screening values, including BEs and Human Biomonitoring-I (HBM-I) values from the German Human Biomonitoring Commission. Geometric mean and 95th percentile population biomarker concentrations from the NER were compared to the available screening values to generate chemical-specific hazard quotients (HQs) or cancer risk estimates.Conclusions: Most analytes in the NER show HQ values of < 1; however, some (including acrylamide, dioxin-like chemicals, benzene, xylene, several metals, di-2(ethylhexyl)phthalate, and some legacy organochlorine pesticides) approach or exceed HQ values of 1 or cancer risks of > 1 × 10–4 at the geometric mean or 95th percentile, suggesting exposure levels may exceed published human health benchmarks. This analysis provides for the first time a means for examining population biomonitoring data for multiple environmental chemicals in the context of the risk assessments for those chemicals. The results of these comparisons can be used to focus more detailed chemical-specific examination of the data and inform priorities for chemical risk management and research.

Reprint of “Update of the reference and HBM values derived by the German Human Biomonitoring Commission”

In 2007, we reviewed the working principles and working procedures of the German Human Biomonitoring Commission together with the reference values and human biomonitoring (HBM) values derived up to that time. Since then, the Commission has decided to derive additionally HBM I values on the basis of tolerable daily intakes and has used and evaluated this new approach on the metabolites of (2-ethylhexyl) phthalate (DEHP) in urine. Furthermore, the Commission has derived a HBM I value for thallium in urine, has recinded the HBM values for lead in blood, and has updated the HBM values for cadmium in urine. Based on the representative data of the German Environmental Survey on Children from 2003 to 2006 (GerES IV), the Commission has updated the reference values for a large number of environmental pollutants in urine and blood of children in Germany. Since 2007, the Commission has derived new and updated reference values for PFOS and PFOA in human plasma, for thallium in urine, for aromatic amines in urine, for a comprehensive number of phthalate metabolites in urine, and for organochlorine pesticides in human breast milk. Furthermore, the Commission has evaluated background exposure levels for two naphthalene metabolites and acrylamide (using acrylamide-haemoglobin adduct) for the general population. This paper reports the new values, including those already published, in order to provide an updated overview.

Erratum to “Update of the reference and HBM values derived by the German Human Biomonitoring Commission” [Int. J. Hyg. Environ. Health 215 (1) (2012) 26–35

Erratum to “Update of the reference and HBM values derived by the German Human Biomonitoring Commission” [Int. J. Hyg. Environ. Health 215 (1) (2012) 26–35

Levels of phthalate metabolites in urine among mother–child-pairs – Results from the Duisburg birth cohort study, Germany

Phthalates are used ubiquitously and human exposure is widespread. Some phthalates are anti-androgens and have to be regarded as reproductive and developmental toxicants. In the Duisburg birth cohort study we examine the associations between hormonally active environmental agents and child development. Here we report the concentrations of 21 primary and secondary phthalate metabolites from seven low molecular weight (LMW) phthalates (DMP, DEP, BBzP, DiBP, DnBP, DCHP, DnPeP) and five high-molecular weight (HMW) phthalates (DEHP, DiNP, DiDP, DPHP, DnOP) in 208 urine samples from 104 mothers and their school-aged children. Analysis was performed by multidimensional liquid chromatography coupled to tandem mass spectrometry (LC/LC-MS/MS), using internal isotope-labeled standards. In both children and mothers, 18 out of 21 phthalate metabolites were detected above the limits of quantification (between 0.2 and 1.0 μg/l) in nearly all urine samples. Among the LMW phthalates, the excretion level (geometric mean) of the ΣDiBP metabolites was most prominent in children (103.9 μg/l), followed by ΣDnBP (56.5 μg/l), and MEP (39.1 μg/l). In mothers ΣDiBP (66.6 μg/l) was highest, followed by MEP (50.5 μg/l), and ΣDnBP (36.0 μg/l). Among the HMW phthalates, ΣDEHP was highest in children and mothers (55.7/28.9 μg/l). Compared to reference values derived from the German Human Biomonitoring Commission, children's metabolite concentrations were within background levels, whereas for mothers considerably higher exposure to the LMW phthalates DnBP and DiBP, and the HMW phthalate DEHP was detected (MiBP: 10.7%; MnBP: 11.7%; ΣDEHP: 23.3% of the samples were above the reference values). The LMW metabolites from DMP, DiBP, and DnBP, and the HMW metabolites from DEHP and DiNP were correlated between the mothers and children, probably indicating shared exposure in the immediate surrounding environment. Children showed higher excretion levels for most of the secondary metabolites than mothers, confirming previous findings on higher oxidized metabolite levels in children. The LMW metabolites ΣDiBP, ΣDnBP, and MMP, and the HMW metabolites ΣDEHP were negatively associated with children's age. The LMW metabolites ΣDiBP, ΣDnBP, and MBzP were inversely associated with body mass index of the children. The LMW ΣDiBP metabolites revealed a significant association with nicotine metabolites in urine from both children and mothers. Further analyses are ongoing to study long-term phthalate exposure and the associations with puberty outcome in these children.

Update of the reference and HBM values derived by the German Human Biomonitoring Commission

In 2007, we reviewed the working principles and working procedures of the German Human Biomonitoring Commission together with the reference values and human biomonitoring (HBM) values derived up to that time. Since then, the Commission has decided to derive additionally HBM I values on the basis of tolerable daily intakes and has used and evaluated this new approach on the metabolites of (2-ethylhexyl) phthalate (DEHP) in urine. Furthermore, the Commission has derived a HBM I value for thallium in urine, has recinded the HBM values for lead in blood, and has updated the HBM values for cadmium in urine. Based on the representative data of the German Environmental Survey on Children from 2003 to 2006 (GerES IV), the Commission has updated the reference values for a large number of environmental pollutants in urine and blood of children in Germany. Since 2007, the Commission has derived new and updated reference values for PFOS and PFOA in human plasma, for thallium in urine, for aromatic amines in urine, for a comprehensive number of phthalate metabolites in urine, and for organochlorine pesticides in human breast milk. Furthermore, the Commission has evaluated background exposure levels for two naphthalene metabolites and acrylamide (using acrylamide-haemoglobin adduct) for the general population. This paper reports the new values, including those already published, in order to provide an updated overview.

Human biomonitoring assessment values: Approaches and data requirements

Human biomonitoring (HBM) data is a very useful metric for assessing human's exposures to chemicals in commerce. To assess the potential health risks associated with the presence of chemicals in blood, urine or other biological matrix requires HBM assessment values. While HBM assessment values based on human exposure-response data remain the most highly valuable and interpretable assessment values, enough data exists for such values for very few chemicals. As a consequence, efforts have been undertaken to derive HBM assessment values in which external dose based guidance values such as tolerable daily intakes have been translated into equivalent biomonitoring levels. The development of HBM values by the German HBM Commission and Biomonitoring Equivalents by Summit Toxicology has resulted in conceptually similar assessment values. The review of the development of these values provided here demonstrates examples and approaches that can be used to broaden the range of chemicals for which such assessment values can be derived. Efforts to date have resulted in the publication of HBM assessment values for more than 80 chemicals, and now provide tools that can be used for the evaluation of HBM data across chemicals and populations.