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.

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.

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.

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.

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.

Analysis of nitroaromatic compounds in urine by gas chromatography-mass spectrometry for the biological monitoring of explosives.

Organic nitrocompounds are the most frequently used constituents of explosives and some of them have been evaluated to be highly toxic or even carcinogenic. Human contact with explosives may originate from a variety of sources, including occupational exposure during the production of ammunition as well as environmental exposure due to the contamination of soil and ground water reservoirs on former military production sites and training areas. This paper describes two gas chromatography-mass spectrometry-selected ion monitoring methods for the determination of twelve nitroaromatic compounds in urine (nitrobenzene, 1,2-dinitrobenzene, 1,3-dinitrobenzene, 1,3,5-trinitrobenzene, 2-nitrotoluene, 3-nitrotoluene, 4-nitrotoluene, 2,4-dinitrotoluene, 2,6-dinitrotoluene, 2,4,6-trinitrotoluene, 2-amino-4,6-dinitrotoluene, 4-amino-2,6-dinitrotoluene). The analytes are detectable in the lowest microg/l range, with imprecisions of 3-22% within series and 5-29% between series, depending on the compound of interest. Both procedures are rapid and relatively easy to perform and, therefore, are advantageous for the screening of occupationally or environmentally exposed persons. We analysed urine samples obtained from nine workers from an ammunition dismantling workshop and from twelve control persons. 2,4,6-Trinitrotoluene was detected in six samples at concentrations between 4 and 43 microg/l. The main metabolites of 2,4,6-trinitrotoluene, 4-amino-2,6-dinitrotoluene and 2-amino-4,6-dinitrotoluene, were found in a concentration range from 143 to 16,832 microg/l and from 24 to 5787 microg/l, respectively. Nonconjugated aminodinitrotoluenes were present as varying percentages of the total amount. 2,4-Dinitrotoluene and 2,6-dinitrotoluene were found in two samples (2-9 microg/l). Nitroaromatics were not detectable in urine specimens from control persons.

N-methylcarbamoyl adducts at the N-terminal valine of globin in workers exposed to N,N-dimethylformamide.

N,N-dimethylformamide (DMF) is a commonly used industrial solvent. The formation of some metabolites of DMF in humans occurs via N-methyl-carbamoylated species (e.g. N-methylcarbamoylated glutathione). The aim of our study was to investigate whether DMF leads to N-methylcarbamoylated adducts at the N-terminal valine of haemoglobin (Hb). Therefore, Hb adduct levels of ten DMF exposed workers and ten controls were analysed by a specific and sensitive detection method using capillary gas chromatography and a mass selective detector (GC/MS). Using this method we were able to show for the first time that Hb adducts are formed during the metabolism of DMF in humans. The general population, however, shows still unidentified background levels of this adduct which are on average lower by a factor of 50. The pathway for the formation of the investigated DMF-Hb adduct in workers exposed to DMF is still unknown. As identical adducts were also found after exposure to methylisocyanate (MIC), our work indicates the formation of MIC during the metabolism of DMF. The formation of Hb adducts with DMF and its relevance for occupational health is a subject of further research.

Carbon disulphide. II. Investigations on the uptake of CS2 and the excretion of its metabolite 2-thiothiazolidine-4-carboxylic acid after occupational exposure.

The reported investigations on the uptake of carbon disulphide (CS2) and the excretion of its metabolite 2-thiothiazolidine-4-carboxylic acid (TTCA) were based on results from 403 personal air samples (352 passive and 51 active samples) and 362 TTCA determinations in biological material measured during a field study on the adverse effects due to CS2 exposure. The external exposure ranged from below the detection limit (0.2 ppm) to 66 ppm and the urinary TTCA excretion from below the detection limit (0.16 mg./l) to 33.4 mg/l. The excretion of TTCA in postshift urine related to creatinine and volume showed a linear correlation to the CS2 air concentration. On the basis of these results the influence on the internal exposure of physical work load, dermal exposure and individual parameters (age, Brocaindex, disturbed skin barrier) was evaluated. Correlations between the TTCA values in the postshift urine and the individually measured CS2 concentrations were carried out separately for individual departments and persons with and without indications of a disturbed skin barrier. In order to be able to judge the individual internal exposure related to external exposure, a personal quotient was formed from the TTCA level in the urine and the CS2 air concentration measured on the same day (relative internal exposure RIE index = TTCA mg/g creatinine/CS2 in ppm). On investigating interindividual differences, higher relative internal exposures were found in persons with a heavy physical work load and more intensive skin contact. It could be shown for a large group of persons exposed to CS2 that a pathological skin condition leads to an increase in the dermal penetration rate of hazardous substances.(ABSTRACT TRUNCATED AT 250 WORDS)

Mid-peripheral hemorrhages secondary to Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia is a progressive neoplastic syndrome of the reticuloendothelial system and is characterized by the presence of monoclonal IgM paraproteins. The ocular manifestations of macroglobulinemia can include mid-peripheral hemorrhages, sludging of blood in the conjunctival vessels, blurred disc margins, exudates in the fundus and serous retinal detachment. Waldenström's macroglobulinemia and its ocular complications are herein presented.