PFAS levels and determinants of variability in exposure in European teenagers - Results from the HBM4EU aligned studies (2014-2021).

BACKGROUND: Perfluoroalkyl substances (PFAS) are man-made fluorinated chemicals, widely used in various types of consumer products, resulting in their omnipresence in human populations. The aim of this study was to describe current PFAS levels in European teenagers and to investigate the determinants of serum/plasma concentrations in this specific age group. METHODS: PFAS concentrations were determined in serum or plasma samples from 1957 teenagers (12-18 years) from 9 European countries as part of the HBM4EU aligned studies (2014-2021). Questionnaire data were post-harmonized by each study and quality checked centrally. Only PFAS with an overall quantification frequency of at least 60% (PFOS, PFOA, PFHxS and PFNA) were included in the analyses. Sociodemographic and lifestyle factors were analysed together with food consumption frequencies to identify determinants of PFAS exposure. The variables study, sex and the highest educational level of household were included as fixed factors in the multivariable linear regression models for all PFAS and each dietary variable was added to the fixed model one by one and for each PFAS separately. RESULTS: The European exposure values for PFAS were reported as geometric means with 95% confidence intervals (CI): PFOS [2.13 µg/L (1.63-2.78)], PFOA ([0.97 µg/L (0.75-1.26)]), PFNA [0.30 µg/L (0.19-0.45)] and PFHxS [0.41 µg/L (0.33-0.52)]. The estimated geometric mean exposure levels were significantly higher in the North and West versus the South and East of Europe. Boys had significantly higher concentrations of the four PFAS compared to girls and significantly higher PFASs concentrations were found in teenagers from households with a higher education level. Consumption of seafood and fish at least 2 times per week was significantly associated with 21% (95% CI: 12-31%) increase in PFOS concentrations and 20% (95% CI: 10-31%) increase in PFNA concentrations as compared to less frequent consumption of seafood and fish. The same trend was observed for PFOA and PFHxS but not statistically significant. Consumption of eggs at least 2 times per week was associated with 11% (95% CI: 2-22%) and 14% (95% CI: 2-27%) increase in PFOS and PFNA concentrations, respectively, as compared to less frequent consumption of eggs. Significantly higher PFOS concentrations were observed for participants consuming offal (14% (95% CI: 3-26%)), the same trend was observed for the other PFAS but not statistically significant. Local food consumption at least 2 times per week was associated with 40% (95% CI: 19-64%) increase in PFOS levels as compared to those consuming local food less frequently. CONCLUSION: This work provides information about current levels of PFAS in European teenagers and potential dietary sources of exposure to PFAS in European teenagers. These results can be of use for targeted monitoring of PFAS in food.

Impact of physiologically relevant temperatures on dermal absorption of active substances - an ex-vivo study in human skin.

Skin temperature plays a certain role in the dermal absorption of substances, but the extent and mechanisms of skin temperatures-induced modulation in ranges caused by physiological thermoregulation or environmental conditions are largely unknown. The influence of dermal temperature on the absorption of the model lipophilic compound (anisole) and the model hydrophilic compounds (1,4-dioxane, ethanol) through human skin was investigated at three dermal temperatures (25, 32 and 39 °C) in an ex-vivo diffusion cell model. The substances were applied to the skin and transdermal penetration was monitored. All substances showed temperature dependent variations in their penetration behavior (3 h: 25-39 °C: 202-275% increase in cumulative, transdermally penetrated amounts). The relative differences in absorption in relation to temperature were greatest within 45 min after exposure (25-39 °C: 347-653% rise in cumulated penetration), although absolute amounts absorbed were small (45 min vs. 3 h: 4.5-14.5%). Regardless of blood circulation, skin temperature significantly influences the amount and kinetics of dermal absorption. Substance-dependent, temperature-related changes of the lipid layer order or the porous pathway may facilitate penetration. The early-stage modulation of transdermal penetration indicates transappendageal absorption, which may be relevant for short-term exposures. For both, toxicological evaluation and perfusion cell studies, it is important to consider the thermal influence on absorption or to perform the latter at a standardized temperature (32±1 °C).

Evaluation of urinary selenium as a biomarker of human occupational exposure to elemental and inorganic selenium.

PURPOSE: Selenium (Se) is an essential trace element, which however, exhibits a narrow safe range of intake. Selenium also occurs at several workplaces, which results in an inhalative selenium exposure of the employees. Thus, an efficient exposure assessment strategy is demanded. The most established parameter, selenium in plasma, mostly consists of protein-bound selenium. This study aimed to investigate urinary total selenium (Se-U) as an additional biomarker of recent human occupational exposure to elemental and inorganic selenium. METHODS: Pre- and post-shift urine samples from employees with exposure to selenium-containing dust were analyzed to total selenium and compared with Se levels in urine samples from controls without occupational exposure to selenium as well as correlated with the recent ambient Se exposure by personal air monitoring. RESULTS: Se-U in post-shift samples was considerably increased compared to the levels in pre-shift samples as well as to the controls. However, Se-U in pre-shift urine was elevated compared to the Se-U in controls too. Se-U in post-shift urine and even better the shift increment in Se-U correlated with the air exposure of the present shift. A rough estimation by Se-U shift increment and external exposure accounted for an inhalative resorption rate of about 1%. CONCLUSION: Our data indicate that Se-U can display the exposure. Pre-shift Se-U levels may be based on previous exposure and indicate a slow urinary elimination kinetics. The results hint for a rather low resorption rate of selenium and inorganic selenium compounds via the lung.

Urinary concentrations of organophosphate and carbamate pesticides in residents of a vegetarian community.

Few population studies have measured urinary levels of pesticides in individuals with vegan, vegetarian, or organic diets. The objectives of this study were to evaluate whether a vegan/vegetarian diet was associated with increased exposure to organophosphate and carbamate pesticides, and to evaluate the impact of organic consumption on pesticide exposure in vegans and vegetarians. In the current pilot study conducted in 2013-2014, we collected spot urine samples and detailed 24h recall dietary data in 42 adult residents of Amirim, a vegetarian community in Northern Israel. We measured urinary levels of non-specific organophosphate pesticide metabolites (dialkylphosphates, (DAPs)) and specific metabolites of the current-use pesticides chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPy)), propoxur (-isopropoxyphenol (IPPX)), and carbaryl (1-naphthol). Six DAP metabolites were detected in between 67 and 100% of urine samples, with highest geometric mean concentrations for dimethylphosphate (19.2µg/g). Creatinine-adjusted median concentrations of total DAPs and of TCPy were significantly higher in Amirim residents compared to the general Jewish population in Israel (0.29µmol/g compared to 0.16, p<0.05 for DAPs and 4.32µg/g compared to 2.34µg/g, p<0.05 for TCPy). Within Amirim residents, we observed a positive association between vegetable intake and urinary TCPy levels (rho=0.47, p<0.05) and lower median total dimethyl phosphate levels in individuals reporting that >25% of the produce they consume is organic (0.065µmol/L compared to 0.22, p<0.05). Results from this pilot study indicate relatively high levels of urinary organophosphate pesticide metabolite concentrations in residents of a vegetarian community, a positive association between vegetable intake and urinary levels of a chlorpyrifos specific metabolite, and lower levels of total dimethyl phosphate in individuals reporting higher intake of organic produce. Results suggest that consumption of organic produce may offer some protection from increased exposure to organophosphate pesticide residues in vegetarians.

Short-term health effects in the general population following a major train accident with acrylonitrile in Belgium.

BACKGROUND: Following a train derailment, several tons of acrylonitrile (ACN) exploded, inflamed and part of the ACN ended up in the sewage system of the village of Wetteren. More than 2000 residents living in the close vicinity of the accident and along the sewage system were evacuated. A human biomonitoring study of the adduct N-2-cyanoethylvaline (CEV) was carried out days 14-21 after the accident. OBJECTIVES: (1) To describe the short-term health effects that were reported by the evacuated residents following the train accident, and (2) to explore the association between the CEV concentrations, extrapolated at the time of the accident, and the self-reported short-term health effects. METHODS: Short-term health effects were reported in a questionnaire (n=191). An omnibus test of independence was used to investigate the association between the CEV concentrations and the symptoms. Dose-response relationships were quantified by Generalized Additive Models (GAMs). RESULTS: The most frequently reported symptoms were local symptoms of irritation. In non-smokers, dose-dependency was observed between the CEV levels and the self-reporting of irritation (p=0.007) and nausea (p=0.007). Almost all non-smokers with CEV concentrations above 100pmol/g globin reported irritation symptoms. Both absence and presence of symptoms was reported by non-smokers with CEV concentrations below the reference value and up to 10 times the reference value. Residents who visited the emergency services reported more symptoms. This trend was seen for the whole range of CEV concentrations, and thus independently of the dose. DISCUSSION AND CONCLUSION: The present study is one of the first to relate exposure levels to a chemical released during a chemical incident to short-term (self-reported) health effects. A dose-response relation was observed between the CEV concentrations and the reporting of short-term health effects in the non-smokers. Overall, the value of self-reported symptoms to assess exposure showed to be limited. The results of this study confirm that a critical view should be taken when considering self-reported health complaints and that ideally biomarkers are monitored to allow an objective assessment of exposure.

Exposure to 27 polychlorinated biphenyls in the indoor environment of a workplace: a controlled bio-monitoring study.

PURPOSE: To assess the exposure to a broad-spectrum of polychlorinated biphenyl congeners (PCBs) from the indoor environment through bio-monitoring of people working in a building with PCB-containing materials and elevated PCB levels in the indoor air. METHODS: A cross-sectional study comparing the plasma concentration of 27 PCB congeners in 15 people working in a PCB-contaminated building and 30 matched controls. RESULTS: Median concentration of eight low-chlorinated PCB congeners was significantly higher in the exposed than in the control group. The sum of median concentrations of tri + tetra-chlorinated PCB was almost ten times higher in the exposed group than in the unexposed, and sums of dioxin-like and non-dioxin-like PCB were both relatively increased by 60 % in the exposed group. CONCLUSIONS: The occupational indoor environment may significantly add to PCB exposure, especially to the lower-chlorinated congeners. Health effect from this little-acknowledged exposure has not yet been documented, but data supporting lack of effect are sparse and research generating information on effect of exposure to specific congeners including at levels relevant for the indoor environment should be encouraged.

Acrylonitrile exposure in the general population following a major train accident in Belgium: a human biomonitoring study.

BACKGROUND: On Saturday May 4, 2013, a train transporting chemicals derailed in the village of Wetteren (Belgium) and caused a leak of acrylonitrile (ACN). OBJECTIVES: To assess the human exposure to acrylonitrile in the local population with the highest suspected exposure. METHODS: Between May 18-25, 242 residents participated in the study. N-2-cyanoethylvaline (CEV), a biomarker that is highly specific for ACN exposure, was measured in the blood. To account for potential influence by smoking, cotinine was determined in the urine. Participants also filled in a short questionnaire. RESULTS: In the evacuated zone, 37.3% of the non-smokers and 40.0% of the smokers had CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively, at the time of the train accident. Spatial mapping of the CEV concentrations depending on the residential address showed a distribution pattern following the sewage system. DISCUSSION AND CONCLUSION: The train derailment resulted in a highly atypical sequence-of-events. In addition to exposure in the direct vicinity of the site of the train derailment, exposure also occurred via the sewage system, into which acrylonitrile had entered shortly after the accident.

Acrylonitrile exposure assessment in the emergency responders of a major train accident in Belgium: a human biomonitoring study.

BACKGROUND: On May 4, 2013, a train transporting chemicals derailed in Wetteren, Belgium. Several tanks loaded with acrylonitrile (ACN) exploded, resulting in a fire and a leakage of ACN. OBJECTIVES: To determine exposure to ACN and to assess discriminating factors for ACN exposure in the emergency responders involved in the on-site management of the train accident. METHODS: The study population consisted of 841 emergency responders. Between May 21 and June 28, they gave blood for the determination of N-2-cyanoethylvaline (CEV) hemoglobin adducts and urine for the measurement of cotinine. They also filled in a short questionnaire. RESULTS: 163 (26%) non-smokers and 55 (27%) smokers showed CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively. The 95th percentile in the non-smokers was 73 pmol/g globin and the maximum was 452 pmol/g globin. ACN exposure among the non-smokers was predicted by (1) the distance to the accident, (2) the duration of exposure, and (3) the occupational function. DISCUSSION AND CONCLUSION: Emergency responders involved in the on-site management of the train accident were clearly exposed to ACN from the accident. However, the extent of exposure remained relatively moderate with CEV concentrations staying within the ranges described in literature as background for a smoking population. Moreover, the exposure was less pronounced in the emergency responders as compared to that in the local population.

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.

Demographic and dietary predictors of urinary bisphenol A concentrations in adults in Israel.

BACKGROUND: To date, there is scarce data on levels of exposure to bisphenol A (BPA) in the general population in Israel and the region. The goal of the current study was to measure urinary levels of BPA in the general adult population in Israel and to determine the demographic and dietary predictors of exposure. METHODS: We recruited 249 individuals (ages 20-74) from five different regions in Israel. We collected urine samples and questionnaire data including detailed dietary data and analyzed urine samples for BPA concentrations. RESULTS: Eighty nine percent of the study population had urinary BPA concentrations equal to or above the level of quantification (0.3 µg/L). Median creatinine adjusted BPA urinary concentrations in the study population (2.3 µg/g) were slightly higher than those reported for the general population in the US (1.76 µg/g) and Canada (1.47 µg/g), and were comparable to those reported for the general population in Belgium (2.25 µg/g) and Korea (2.09 µg/g). BPA concentrations were higher in Jews compared to Arab and Druze (prevalence ratio (PR)=2.34; 95%CI 1.56-3.49), in individuals with higher education (PR=1.70, 1.11-2.62), in individuals consuming mushrooms (PR=2.08, 1.07-4.05), and in smokers (PR=1.43, 1.00-2.05). CONCLUSIONS: We found that the general adult population in Israel is widely exposed to BPA. Our findings on higher BPA levels in Jews compared to Arabs and Druze and in individuals with higher education highlights the fact that predictors of BPA exposure vary across populations.

Urinary concentrations of organophosphate pesticide metabolites in adults in Israel: demographic and dietary predictors.

Exposure to organophosphate pesticides (OPs) in agricultural and urban populations has been associated with a range of adverse health effects. The purpose of the current study was to estimate exposure to OPs in the general adult population in Israel and to determine dietary and demographic predictors of exposure. We measured six non-specific organophosphate pesticide metabolites (dialkyl phosphates) in urine samples collected from 247 Israeli adults from the general population. We collected detailed demographic and dietary data from these individuals, and explored associations between demographic and dietary characteristics and urinary dialkyl phosphate concentrations. OP metabolites were detectable in all urine samples. Concentrations of several dialkyl phosphate metabolites (dimethylphosphate, dimethylthiophosphate, diethylphosphate) were high in our study population relative to the general populations in the US and Canada and were comparable to those reported in 2010 in France. Total dialkyl phosphates were higher in individuals with fruit consumption above the 75th percentile. In a multivariate analysis, total molar dialkyl phosphate concentration increased with age and was higher in individuals with high income compared to individuals with the lowest income. Total diethyl metabolite concentrations were higher in females and in study participants whose fruit consumption was above the 75th percentile. In conclusion, we found that levels of exposure to OP pesticides were high in our study population compared to the general population in the US and Canada and that intake of fruits is an important source of exposure.

Urinary concentrations of environmental contaminants and phytoestrogens in adults in Israel.

BACKGROUND: The Ministry of Health Biomonitoring Study estimated exposure of individuals in the Israeli population to bisphenol A (BPA), organophosphate (OP) pesticides, phthalates, cotinine, polycyclic aromatic hydrocarbons (PAHs), and the phytoestrogenic compounds genistein and daidzein. METHODS: In 2011, 250 individuals (ages 20-74) were recruited from five different regions in Israel. Urine samples were collected and questionnaire data were obtained, including detailed dietary data (food frequency questionnaire and 24hour recall). Urinary samples were analyzed for BPA, OP metabolites (dialkyl phosphates), phthalate metabolites, cotinine, PAH metabolites, genistein, and daidzein. RESULTS AND DISCUSSION: BPA urinary concentrations were above the limit of quantification (LOQ) in 89% of the samples whereas urinary concentrations of phthalate metabolites were above the LOQ in 92-100% of the samples. PAH metabolites were above the LOQ in 63-99% of the samples whereas OP metabolites were above the LOQ in 44-100% of the samples. All non-smoking participants had detectable levels of cotinine in their urine; 63% had levels above the LOQ, and the rate of quantification was high compared to the general non-smoking population in Canada. Median creatinine adjusted concentrations of several OP metabolites (dimethyl phosphate, dimethyl thiophosphate) were high in our study population compared to the general US and Canadian populations. Median creatinine adjusted urinary BPA concentrations in the study population were comparable to those in Belgium and Korea; higher than those reported for the general US, German, and Canadian populations; and very low compared to health-based threshold values. Phthalate concentrations were higher in our study population compared to the general US population but values were very low compared to health-based threshold values. Median creatinine adjusted PAH concentrations were generally comparable to those reported for the general US population; median creatinine adjusted daidzein concentrations were high in our population compared to the general US population whereas genistein concentrations were comparable. CONCLUSIONS: We interpreted observed urinary contaminant levels observed in our study by comparing values with health-based threshold values and/or values from international human biomonitoring studies. Using this data interpretation scheme, we identified two contaminants as being of potential public health concern and high priority for public health policy intervention: environmental tobacco smoke (ETS) and OP pesticides. We used the data collected in this study to support public health policy interventions. We plan to conduct a follow-up biomonitoring study in 2015 to measure ETS and OP exposure in the general population in Israel, to evaluate the effectiveness of relevant policy interventions.

Exposure of German residents to ethylene and propylene glycol ethers in general and after cleaning scenarios.

Glycol ethers are a class of semi-volatile substances used as solvents in a variety of consumer products like cleaning agents, paints, cosmetics as well as chemical intermediates. We determined 11 metabolites of ethylene and propylene glycol ethers in 44 urine samples of German residents (background level study) and in urine samples of individuals after exposure to glycol ethers during cleaning activities (exposure study). In the study on the background exposure, methoxyacetic acid and phenoxyacetic acid (PhAA) could be detected in each urine sample with median (95th percentile) values of 0.11 mgL(-1) (0.30 mgL(-1)) and 0.80 mgL(-1) (23.6 mgL(-1)), respectively. The other metabolites were found in a limited number of samples or in none. In the exposure study, 5-8 rooms were cleaned with a cleaner containing ethylene glycol monobutyl ether (EGBE), propylene glycol monobutyl ether (PGBE), or ethylene glycol monopropyl ether (EGPE). During cleaning the mean levels in the indoor air were 7.5 mgm(-3) (EGBE), 3.0 mgm(-3) (PGBE), and 3.3 mgm(-3) (EGPE), respectively. The related metabolite levels analysed in the urine of the residents of the rooms at the day of cleaning were 2.4 mgL(-1) for butoxyacetic acid, 0.06 mgL(-1) for 2-butoxypropionic acid, and 2.3 mgL(-1) for n-propoxyacetic acid. Overall, our study indicates that the exposure of the population to glycol ethers is generally low, with the exception of PhAA. Moreover, the results of the cleaning scenarios demonstrate that the use of indoor cleaning agents containing glycol ethers can lead to a detectable internal exposure of residents.

Cardiovascular function of workers exposed to carbon disulphide.

OBJECTIVES: The aim of the study was to verify that exposure to carbon disulphide (CS(2)) up to 10 ppm results in a negative inotropic effect on cardiovascular function. METHODS: In a cross-sectional study a total of 325 workers exposed to CS(2) in the rayon-producing industry and 179 controls from the same plants were examined. The exposure assessment was based on personal air sampling and biological monitoring (2-thiothiazolidine-4-carboxylic acid (TTCA) in urine) for all persons. The examination consisted of a standardised questionnaire, physical examination, assessment of body fat mass, ergometric test with the determination of work capacity at heart rates of 100, 130, 150 and 170 beats/min, and electrocardiography. RESULTS: The mean external exposure was 6.04 ppm CS(2) (range: 0.03-91.08); the mean internal exposure was 1.14 mg TTCA/g creatinine (range: 0.02-11.50). The workers exposed to CS(2) showed better physical fitness. The diameters of the left heart chamber of the exposed persons were not significantly different when compared with occupationally non-exposed workers, but there was a tendency of increasing diameters for the exposed employees. In the multiple linear regression the diameters showed physiologically plausible correlations with the body mass index, body fat mass, alcohol consumption, and physical fitness, but not, however, with the exposure, neither with the exposure group in all persons nor with the internal or external exposure within the exposed workers. CONCLUSIONS: In this study, differences in the heart chamber diameters between exposed persons and controls could not be confirmed. Differences in physical fitness and constitution can explain differences in heart chamber diameters.

Skin strain and its influence on systemic exposure to a glycol ether in offset printing workers.

Under workplace conditions, it is difficult to prove the influence of skin lesions on skin penetration by chemical substances. The aim of the present study was to show whether systemic exposure to glycol ether increases due to lesions of the skin in printing workers. 28 male printers, exposed to 2-(2-butoxyethoxy)ethanol (BEE), were interviewed about the workplace exposure by a standardized questionnaire. The systemic exposure in printers was determined by biological monitoring of the main metabolite of BEE butoxyethoxyacetic acid (BEAA) in urine. Furthermore, clinical examination of the skin, transepidermal water loss, capacitance and skin surface pH measurements were carried out. Erythema and scaliness were the most important factors showing an effect on dermal absorption. The mean urinary BEAA excretions for printers with skin lesions on the hands were higher (20.62 mg/l for scaliness and 14.40 mg/l for erythema) compared to that for printers without detectable skin lesions (12.08 mg/l for scaliness and 13.03 mg/l for erythema). Bioengineering measurements to predict skin strain and percutaneous absorption were only supportive. We were able to show that by using a multiple spectrum of methods an enhancement of percutaneous absorption of BEE could be demonstrated in workers with skin lesions.

Exposure assessment and sensitisation in workers exposed to organic acid anhydrides.

OBJECTIVES: To clarify whether the intensity of exposure to organic acid anhydrides (OAAs) is associated with the risk of sensitisation to these allergens. METHODS: The investigations were carried out in three different manufacturing plants (A, B, and C) where OAAs were used in the production of epoxy resins. Methyltetrahydrophthalic acid anhydride (MTHPA) was used in all three plants. The exposure assessment included stationary and ambient air monitoring (OAAs in the air) and biological monitoring (metabolites in urine). In plant A 20, in plant B 86 and in plant C 113 employees were examined by a physician (anamnesis, skin-prick test, specific IgE, spirometry). In plants B and C, the exposure areas were classified as high, medium, and low, without the results of the exposure assessment being known. RESULTS: The ambient air concentrations (in microg/m3) of MTHPA were 37.2 and 58.5 in plant A (number of samples n = 2), ranged from <0.5-26.2 in plant B (n = 5) and from 2.1-57.9 in plant C (n = 3) with stationary air collecting, and from 8-45 (n = 6), from < 4.7-35.7 (n = 3) and from 2-37.8 (n = 3) with personal air collection. The metabolites of OAAs in urine (in nmol/mmol creatinine) ranged from 5.7-645 (median of MTHPA: 346) in plant A, from < 1-213 (median of MTHPA: 10.1) in plant B and from 0.1-830 (median of the sum of the OOA metabolites: 108.6) in plant C. The prevalence of sensitisation was 35% in plant A, 21% in plant B and 29% in plant C. A higher prevalence in the highly exposed areas, however, could not be seen. Levels of IgE specific for conjugates of MTHPA were not associated with the metabolites in the end of shift urine. Levels of IgG specific for conjugates of MTHPA, however, were associated with the metabolites in the end of shift urine. CONCLUSIONS: The data showed that biological monitoring is a useful tool in the exposure assessment of OAAs. Comparing the prevalence of sensitisation and the results of biological monitoring, between the three plants, we found that sensitisation increased with increasing exposure. Within a plant a higher risk of sensitisation in persons working in highly exposed areas at the time of the examination could not be seen, possibly due to frequent job rotation.

Percutaneous penetration studies for risk assessment.

During the last few years the general interest in the percutaneous absorption of chemicals has increased. It is generally accepted that there is very few reliable quantitative and qualitative data on dermal exposure to chemicals in the general population and in occupationally exposed workers. In order to predict the systemic risk of dermally absorbed chemicals and to enable agencies to set safety standards, data is needed on the rates of percutaneous penetration of important chemicals. Standardization of in vitro tests and comparison of their results with the in vivo data could produce internationally accepted penetration rates and/or absorption percentages very useful for regulatory toxicology. The work of the Percutaneous Penetration Subgroup of EC Dermal Exposure Network has been focussed on the standardization and validation of in vitro experiments, necessary to obtain internationally accepted penetration rates for regulatory purposes. The members of the Subgroup analyzed the guidelines on percutaneous penetration in vitro studies presented by various organizations and suggested a standardization of in vitro models for percutaneous penetration taking into account their individual experiences, literature data and guidelines already in existence. During the meetings of Percutaneous Penetration Subgroup they presented a number of short papers of up to date information on the key issues. The objective was to focus the existing knowledge and the gaps in the knowledge in the field of percutaneous penetration. This paper is an outcome of the meetings of the Percutaneous Penetration Subgroup and reports the presentations on the key issues identified throughout the 3-year duration of the Dermal Exposure Network (1997-1999).

Biological monitoring of workers exposed to N,N-dimethylformamide in the synthetic fibre industry.

OBJECTIVES: Monitoring of workplace air and biological monitoring of 23 workers exposed to N,N-dimethylformamide (DMF) in the polyacrylic fibre industry was carried out on 4 consecutive days. The main focus of the investigation was to study the relationship between external and internal exposure, the suitability of the metabolites of DMF for biological monitoring and their toxicokinetic behaviour in humans. METHODS: Air samples were collected using personal air samplers. The limit of detection (LOD) for DMF using an analytical method recommended by the Deutsche Forschungsgemeinschaft (DFG) was 0.1 ppm. The urinary metabolites, N-hydroxymethyl-N-methylformamide (HMMF), N-methylformamide (NMF), and N-acetyl-S-(N-methylcarbamoyl)-cysteine (AMCC), were determined in one analytical run by gas chromatography with thermionic sensitive detection (GC/TSD). The total sum of HMMF and NMF was determined in the form of NMF. The LOD was 1.0 mg/l for NMF and 0.5 mg/l for AMCC. RESULTS AND CONCLUSIONS: The external exposure to DMF vapour varied greatly depending on the workplace (median 1.74 ppm, range < 0.1-159.77 ppm). Urinary NMF concentrations were highest in post-shift samples. They also covered a wide range (< 1.0-108.7 mg/l). This variation was probably the result of different concentrations of DMF in the air at different workplaces, dermal absorption and differences in the protective measures implemented by each individual (gloves, gas masks etc.). The urinary NMF concentrations had decreased almost to zero by the beginning of the next shift. The median half-time for NMF was determined to be 5.1 h. The concentrations of AMCC in urine were determined to be in the range from < 0.5 to 204.9 mg/l. Unlike the concentrations of NMF, the AMCC concentrations did not decrease during the intervals between the shifts. For the exposure situation investigated in our study, a steady state was found between the external exposure to DMF and the levels of AMCC excreted in urine about 2 days after the beginning of exposure. AMCC is therefore excreted more slowly than NMF. The half-time for AMCC is more than 16 h. Linear regression analysis for external exposure and urinary excretion of metabolites was carried out for a sub-group of 12 workers. External exposure to 10 ppm DMF in air (the current German MAK value) corresponds to an average NMF concentration of about 27.9 mg/l in post-shift urine from the same day and an average AMCC concentration of 69.2 mg/l in pre-shift urine from the following day. NMF in urine samples therefore represents an index of daily exposure to DMF, while AMCC represents an index of the average exposure over the preceding working days. AMCC is considered to be better suited for biomonitoring purposes because (1) it has a longer half-time than NMF and (2) its formation in humans is more closely related to DMF toxicity.

Musk xylene: analysis, occurrence, kinetics, and toxicology.

1,3-Dimethyl-2,4,6-trinitro-5-tert.-butylbenzene (musk xylene, MX), a synthetic musk, is often used in fragrances and soaps to substitute the natural musk. MX belongs to the common group of nitromusk compounds. The main environmental intake of MX occurs after sewage introduction. The consumption of fish and drinking water as well as the use of body care and perfumed household products could lead to an ingestion of this substance in humans. Although the acute oral and dermal toxicity of MX is low, some hint for the carcinogenic potential of MX was found in one animal experiment. These findings and the high potential of MX as environmental contaminant, it is stable against biological and chemical degradation and it is highly lipophil, raised considerable attention in the field of environmental medicine. Biological monitoring and the toxicology of MX, which previously has been described to occur in human milk, human fat tissue, as well as human blood samples, are of central interest. The aim of this article is to summarize the data on the analysis, occurrence, kinetics, and toxicology of MX. As there is a lack of knowledge on human toxicity and human carcinogenicity of MX, a final evaluation of the toxicological data with regard to public health is still impossible. Nevertheless, in view of the published data about MX, there is no evidence for any substantial human risk at the moment.