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Background Asphalt workers are exposed to polyaromatic hydrocarbons (PAHs) from hot mix asphalt via both inhalation and dermal absorption. The use of crumb rubber modified (CRM) asphalt may result in higher exposure to PAHs and more adverse effects. Our aim is to assess occupational exposure to PAHs from conventional and CRM asphalt paving by measuring PAH metabolites in urine, and to investigate the effects on mitochondrial DNA copy number (mtDNAcn) and telomere length. Methods We recruited 116 workers paving conventional asphalt, 51 workers paving CRM asphalt and 100 controls in Sweden, all males. A repeated-measures analysis included 31 workers paving both types of asphalt. Urine and blood samples were collected pre-working on Monday morning and post-working on Thursday afternoon after 4 days working. PAH metabolites: 1-hydroxypyrene (1-OH-PYR) and 2-hydroxyphenanthrene (2-OH-PH) were measured in urine by LC-MS/MS. Relative mtDNAcn and telomere length were measured by quantitative PCR. Results Conventional and CRM asphalt workers showed higher 1-OH-PYR and 2-OH-PH than controls (p

Phthalates are used as plasticizers in polyvinyl chloride (PVC) materials and it is known that phthalates may migrate into the surrounding environment and then become a source for human uptake. The aim of the study was to investigate whether residential PVC flooring was related to the urinary levels of phthalate metabolites determined in pregnant women. The data were from the Swedish SELMA study where sampling was conducted during the time period 2007-2010. Spot urine samples from 1674 women at the end of the first trimester were analyzed for 14 metabolites from seven phthalates and one phthalate alternative. Data on flooring material in the kitchen and the parents' bedrooms as well as potential confounders were collected by postal questionnaires at the same time as the urine samples were taken. Multiple regression modeling by least square geometric mean and weighted quantile sum regression was applied to log-transformed and creatinine-adjusted phthalate metabolite concentrations adjusted for potential confounders from questionnaire data. This study has found significantly higher urinary levels of the BBzP metabolite (MBzP) in pregnant women living in homes with PVC flooring as compared to homes with other flooring materials.

BACKGROUND: Maternal smoking during pregnancy has repeatedly been associated with decreased sperm counts in sons. Nevertheless, our team recently detected a lower total sperm count in the sons of smoking fathers as compared to sons of non-smoking fathers. Since paternal and maternal tobacco smoking often coincide, it is difficult to discriminate whether effects are mediated paternally or maternally when using questionnaire- or register-based studies. Therefore, getting an objective measure of the maternal nicotine exposure level during pregnancy might help disentangling the impact of paternally and maternally derived exposure. OBJECTIVES: Our aim was to study how paternal smoking at the time of the pregnancy was associated with semen quality in the sons after adjusting for the maternal levels of nicotine exposure during pregnancy. METHODS: We recruited 104 men (17-20 years old) from the general Swedish population. The participants answered a questionnaire about paternal smoking. Associations between smoking and semen volume, total sperm count, sperm concentration, morphology and motility were adjusted for levels of the nicotine metabolite cotinine in stored maternal serum samples obtained from rubella screening between the 6th and 35th week of pregnancy. We additionally adjusted for the estimated socioeconomic status. RESULTS: After adjusting for the maternal cotinine, the men of smoking fathers had 41% lower sperm concentration and 51% lower total sperm count than the men of non-smoking fathers (p = 0.02 and 0.003, respectively). This was robust to the additional adjustment. CONCLUSIONS: Our results suggest a negative association between paternal smoking and sperm counts in the sons, independent of the level maternal nicotine exposure during the pregnancy. (Less)

BackgroundPerfluoroalkyl substances (PFAS) are used in numerous consumer products. They are persistent, bioaccumulating, and suspected to be endocrine disrupting chemicals (EDCs). A growing body of research has reported the association between PFAS exposure and adverse health effects. Concerns have been raised with special focus in childhood development.MethodsPerfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) were analyzed by LC/MS/MS in serum from 1,616 pregnant women in the Swedish SELMA study. The serum samples were collected in the first trimester (median week 10). Least square geometric means (LSGM) of PFAS were estimated for each year period for, adjusted for potential determinants including parity, fish intake in the family, and mother's age.ResultsSix PFAS (PFNA, PFDA, PFUnDA, PFHxS, PFOA, and PFOS) were detected above levels of detection (LOD) in more than 99% of the SELMA women, while PFHpA, and PFDoDA were detected above LOD in 73.4% and 46.7% respectively. Parity, maternal age, maternal smoking, and fish intake during pregnancy were found to be significantly associated (pConclusionsOur analysis shows that six out of eight PFAS could be identified in serum of more than 99% of SELMA subjects with a significant slightly decreasing trend for five of these compounds. Furthermore, parity, higher fish intake and mothers age are determinants for serum levels of PFAS in pregnant women.

Cross-sectional studies have shown an association between exposure to perfluoroalkyl substances (PFASs) and coronary heart disease (CHD). These findings need to be evaluated in longitudinal settings.To investigate the risk of CHD in relation to PFAS levels in a longitudinal setting among Swedish rural residents.In a population-based prospective cohort of male farmers and rural residents recruited in 1990-1991, all men who received a CHD diagnosis between 1992 and 2009 were identified from national registers (n=253). For each CHD case, one control, matched for age, was chosen randomly from the cohort. For all cases and controls, levels of eight PFASs at baseline were measured in stored blood samples. In addition, for a subsample, PFAS levels were also measured in serum samples collected at a follow-up in 2002-2003.There were no statistically significant associations between levels of seven of the eight PFASs at baseline and risk for developing CHD. There was a significant association between perfluoroheptanoic acid (PFHpA) and CHD (OR=2.72; 95% CI: 1.52, 4.84) for the 3rd quartile and (OR=2.45; 95% CI: 1.40, 4.29) for the 4th quartile compared to the lowest quartile. Changes in levels of PFCs between baseline and follow-up did not differ systematically between cases and controls.This longitudinal study does not lend support to the previously reported cross-sectional relationship between PFAS levels and CHD risk. We found a significant association with PFHpA, but this could be a chance finding, considering its chemical resemblance to other PFASs.

Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to

IRET, CERCH Background: Mancozeb and its main metabolite ethylene thiourea (ETU) may alter thyroid function; thyroid hormones are essential for fetal brain development. In Costa Rica, mancozeb is aerially sprayed at large-scale banana plantations on a weekly basis. Objectives: Our goals were to evaluate urinary ETU concentrations in pregnant women living near large-scale banana plantations, compare their estimated daily intake (EDI) with established reference doses (RfDs), and identify factors that predict their urinary ETU concentrations. Methods: We enrolled 451 pregnant women from Matina County, Costa Rica, which has large-scale banana production. We visited 445 women up to three times during pregnancy to obtain urine samples (n = 872) and information on factors that possibly influence exposure. We determined urinary ETU concentrations using liquid chromatography mass spectrometry. Results: Pregnant women’s median urinary ETU concentrations were more than five times higher than those reported for other general populations. Seventy-two percent of the women had EDIs above the RfD. Women who lived closest (1st quartile, < 48m) to banana plantations on average had a 45% (95% CI: 23, 72%) higher urinary ETU compared with women who lived farthest away (4th quartile, ≥ 565m). Compared with the other women, ETU was also higher in women who washed agricultural work clothes on the day before sampling (11%; 95% CI: 4.9, 17%), women who worked in agriculture during pregnancy (19%; 95% CI: 9.3, 29%), and immigrant women (6.2%; 95% CI: 1.0, 13%). Conclusions: The pregnant women’s urinary ETU concentrations are of concern, and the principal source of exposure is likely to be aerial spraying of mancozeb. The factors predicting ETU provide insight into possibilities for exposure reduction. Antecedentes: el mancozeb y su principal metabolito etilen tiourea (ETU) pueden alterar la función tiroidea; Las hormonas tiroideas son esenciales para el desarrollo del cerebro fetal. En Costa Rica, mancozeb se fumiga por vía aérea en plantaciones de banano a gran escala semanalmente. Objetivos: Nuestros objetivos fueron evaluar las concentraciones urinarias de ETU en mujeres embarazadas que viven cerca de grandes plantaciones de banano, comparar su ingesta diaria estimada (EDI) con las dosis de referencia establecidas (RfD) e identificar factores que predicen sus concentraciones urinarias de ETU. Métodos: Inscribimos a 451 mujeres embarazadas del condado de Matina, Costa Rica, que tiene una producción bananera a gran escala. Visitamos a 445 mujeres hasta tres veces durante el embarazo para obtener muestras de orina (n = 872) e información sobre los factores que posiblemente influyen en la exposición. Determinamos las concentraciones urinarias de ETU mediante cromatografía líquida y espectrometría de masas. Resultados: Las concentraciones medias de ETU en orina de las mujeres embarazadas fueron más de cinco veces más altas que las informadas para otras poblaciones generales. Setenta y dos por ciento de las mujeres tenían EDI por encima de la RfD. Las mujeres que vivían más cerca (1er cuartil

Chemicals such as phthalates, parabens, bisphenol A (BPA) and triclosan (TCS), used in a wide variety of consumer products, are suspected endocrine disrupters although their level of toxicity is thought to be low. Combined exposure may occur through ingestion, inhalation and dermal exposure, and their toxic as well as combined effects are poorly understood. The objective of the study was to estimate the exposure to these chemicals in Swedish mothers and their children (6–11 years old) and investigate potential predictors of the exposure. Urine samples from 98 mother–child couples living in either a rural or an urban area were analyzed for the concentrations of four metabolites of di-(2-ethylhexyl) phthalate (DEHP), three metabolites of di-iso-nonyl phthalate (DiNP), mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP), methylparaben (MetP), ethylparaben (EthP), propylparaben (ProP), butylparaben, benzylparaben, BPA, and TCS. Information on sociodemographics, food consumption habits and use of personal care products, obtained via a questionnaire, was used to investigate the associations between the urinary levels of chemicals and potential exposure factors. There were fairly good correlations of biomarker levels between the mothers and their children. The children had generally higher levels of phthalates (geometric mean ΣDEHP 65.5 μg/L; ΣDiNP 37.8 μg/L; MBzP 19.9 μg/L; MnBP 76.9 μg/L) than the mothers (ΣDEHP 38.4 μg/L; ΣDiNP 33.8 μg/L; MBzP 12.8 μg/L; MnBP 63.0 μg/L). Conversely, the mother's levels of parabens (MetP 37.8 μg/L; ProP 13.9 μg/L) and MEP (43.4 μg/L) were higher than the children's levels of parabens (MetP 6.8 μg/L; ProP 2.1 μg/L) and MEP (28.8 μg/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p =, Highlights • We quantified the levels of phthalates, BPA, parabens and triclosan in urine. • The levels were significantly correlated to certain foods and hygiene products. • Mothers had higher levels of parabens and a phthalate used in hygiene products. • Children had generally higher levels of phthalates present in food.

Thiabendazole (TBZ) is widely used as a pre-planting and post-harvest agricultural fungicide and as an anthelminthic in humans and animals. TBZ is of toxicological concern, since adverse effects including nephrogenic, hepatogenic, teratogenic and neurological effects have been reported in mammals. Occupational exposure can occur among agricultural workers and the general public may be environmentally exposed to TBZ through the diet. The metabolite 5-hydroxythiabendazole (5-OH-TBZ) was chosen as biomarker of exposure to TBZ and a LC/MS/MS method for the quantification of 5-OH-TBZ in human urine was developed. The method includes enzyme hydrolysis, as 5-OH-TBZ is conjugated to glucuronide and sulphate in urine. Sample through put was optimised using 96-well plates for sample handling as well as for solid phase extraction (SPE). The method has excellent, within-run, between-run and between-batch precision between 4 and 9%. The limit of detection (LOD) of 0.05 and a limit of quantification (LOQ) of 0.13ng 5-OH-TBZ/mL urine enable detection in environmentally exposed populations. When applying the method in a general Swedish population, 52% had levels above LOD. The method was also applied in one oral and one dermal human experimental exposure study in two individuals. After oral exposure, the excretion of 5-OH-TBZ in urine was described by a two-compartment model and both the first rapid and the second slower elimination phase followed first-order kinetics, with estimated elimination half-life of 2h and 9–12h. The recoveries in urine were between 21 and 24% of the dose. Dermal exposure was described by a one compartment model and followed first order kinetics, with estimated elimination half-life of 9–18h. The recovery in urine was 1% of the administrated dose of TBZ. Although these studies are limited to two individuals, the data provide new basic information regarding the toxicokinetics of TBZ after oral and dermal exposure.

We thank The Research Pools of Rigshospitalet and the EU Interregional Project ReproUnion for funding this study. Background: Perfluoroalkyl substances (PFASs) are bio-accumulative pollutants, and prenatal exposure to PFASs is believed to impact human foetal development and may have long-term adverse health effects later in life. Additionally, maternal cigarette smoking may be associated with PFAS levels. Foetal exposure has previously been estimated from umbilical cord plasma, but the actual concentration in foetal organs has never been measured. Objectives: The concentrations of 5 PFASs and cotinine – the primary metabolite of nicotine – were measured in human foetuses, placentas, and maternal plasma to evaluate to what extent these compounds were transferred from mother to foetus and to determine if the PFAS concentrations were associated with maternal cigarette smoking. Methods: Thirty-nine Danish women who underwent legal termination of pregnancy before gestational week 12 were included; 24 maternal blood samples were obtained together with 34 placental samples and 108 foetal organs. PFASs and cotinine were assayed by liquid chromatography/triple quadrupole mass spectrometry. Results: In foetal organs, the average concentrations of perfluorooctanesulphonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDa), and perfluorodecanoic acid (PFDA) were 0.6 ng/g, 0.2 ng/g, 0.1 ng/g, 0.1 ng/g, and 0.1 ng/g, respectively. A significant positive correlation was found between the exposure duration, defined as foetal age, and foetal to maternal ratio for all five PFASs and cotinine. Smokers presented 99 ng/g cotinine in plasma, 108 ng/g in placenta, and 61 ng/g in foetal organs. No correlation between the maternal cotinine concentrations and PFAS concentrations was found. Conclusions: PFASs were transferred from mother to foetus, however, with different efficiencies. The concentrations of PFOS, PFOA, PFNA, PFUnDA, and PFDA in foetal organs were much lower than the maternal concentrations. Furthermore, a significant correlation between the exposure duration and all of the evaluated PFASs was found. The health-compromising concentrations of these substances during foetal development are unknown. Postprint

Occupational exposure to soot, rich in polycyclic aromatic hydrocarbons (PAH), has been associated with increased risk of cardiovascular disease (CVD). However, our knowledge about PAH exposure and early markers of CVD remains limited. In this cross-sectional study of 151 chimney sweeps and 152 controls, we investigated occupational exposure to PAH and early markers of CVD. Blood pressure (BP) (chimney sweeps only), urinary PAH metabolites and serum biomarkers were measured (C-reactive protein, homocysteine, gamma-glutamyltransferase, cholesterol, HDL, LDL, and triglycerides). Chimney sweeps had up to 7 times higher concentrations of PAH metabolites in urine than controls (P β = 3.4 µmol/L, 0.43 mmol/L, and 0.13 mmol/L, respectively, P ≤ 0.003, adjusted for age, BMI, and smoking). In chimney sweeps, PAH metabolites correlated positively with the percentage of soot sweeping (P P

The general population is exposed to phthalates, a group of chemicals with strong evidence for endocrine disrupting properties, commonly used in a large number of consumer products. Based on published research and evidence compiled by environmental agencies, certain phthalate applications and products have become restricted, leading to an increasing number of "new generation compounds" coming onto the market during recent years replacing older phthalates. Some examples of such newer compounds are di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP), and most recently di-isononyl-cyclohexane-1,2-dicarboxylate (DiNCH).In order to evaluate temporal trends in phthalate exposure, first trimester urinary biomarkers of phthalates were measured in the Swedish SELMA study over a period of 2.5 years (2007-2010).We collected first morning void urine samples around week 10 of pregnancy from 1651 pregnant women. Spot samples were analyzed for 13 phthalate metabolites and one phthalate replacement and least square geometric mean (LSGM) levels of the metabolites were compared between the sampling years when adjusted for potential confounders.All 14 metabolites were detectable in more than 99% of the SELMA subjects. The levels were generally comparable to other studies, but the SELMA subjects showed slightly higher exposure to butyl-benzyl phthalate (BBzP) and di-butyl phthalate (DBP). Di-ethyl-hexyl phthalate (DEHP) metabolites levels decreased while DiNP, DiDP/di-2-propylheptyl phthalate (DPHP), and DiNCH metabolites levels increased during the sampling period.Urinary metabolite levels of the older phthalates and more recently introduced phthalate replacement compound changed during the short sampling period in this Swedish pregnancy cohort. Our results indicate that replacement of phthalates can make an impact on human exposure to these chemicals. During this particularly vulnerable stage of life, phthalate exposures are of particular concern as the impacts, though not immediately noticeable, may increase the risk for health effects later in life.

Introduction and objective. Low levels of serum vitamin D have been associated with increased occurrence of ischemic heart disease (IHD), but findings are inconsistent, e.g. seasonal variation is not always considered in the analyses. The aim of this study was to investigate whether vitamin D is associated with IHD among rural middle-aged men in Sweden when seasonal variation is taken into account. Materials and method. A nested case-control study was performed within a population-based cohort of Swedish farmers and rural residents followed for 20 years. Outcomes were from national health registers. For 276 cases (IHD at any time during follow-up), and for 276 aged-matched controls free of cardiovascular diseases or diabetes, serum levels of vitamin D (25-hydroxyvitamin D-3) were analyzed with liquid chromatography/tandem mass spectrometry (LC/MS/MS), in stored blood samples drawn at the baseline survey in 1990-91. The odds ratio (OR) with 95% confidence intervals (CI) of IHD for vitamin D-quartiles (based on measured as well as adjusted for month of sampling) was evaluated in logistic regression models; potential confounders were taken into account. Results. The measured mean vitamin D levels were 27.6 ng/ml(standard deviation (sd) 8.2 ng/ml) and 28.8 ng/ml (sd 9.0) among cases and controls, respectively. Compared to the quartile with the lowest month-adjusted vitamin D levels, the risk of IHD was significantly lower in the highest quartile (OR=0.46, 95% CI 0.25-0.84, p=0.012) in the fully-adjusted model. Conclusion. Rural Swedish men in the highest quartile of serum vitamin D had halved relative risk of IHD, compared to those in the lowest quartile.

Dermal chemical exposure is common in many professions. The filaggrin protein is important for the skin barrier and variations in the filaggrin gene (FLG) may influence the uptake of chemicals via the skin, and consequently, the degree of systemic effects. The aim of this study was to investigate, in chimney sweeps with occupational exposure to polycyclic aromatic hydrocarbons (PAH) from soot, the influence of variation in FLG on internal PAH dose and DNA alterations, including epigenetic, previously linked to cancer and cardiovascular disease. We used TaqMan PCR to genotype 151 chimney sweeps and 152 controls for four FLG null variants (R501X, R2447X, S3247X and 2282del4) which cause impaired skin barrier, and FLG copy number variation (12th repeat, CNV12) which potentially is beneficial for the skin barrier. The internal dose of PAH was represented by urinary PAH metabolites (e.g. 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene) that we measured by LC-MS/MS. We measured epigenetic alterations (methylation of AHRR and F2RL3) in blood by pyrosequencing; and DNA alterations (telomere length and mitochondrial DNA copy number) by real-time PCR. Hypomethylation of AHRR or F2RL3 is a risk factor for lung cancer and shorter telomere length a risk factor for cardiovascular disease. The frequencies of FLG null were 8.6 and 11.8% (p = 0.35), and CNV12 27.8 and 19.7% (p = 0.09) in chimney sweeps and controls, respectively. We found that among chimney sweeps working predominately with soot sweeping (high PAH exposure), CNV12 carriers had lower concentrations of PAH metabolites in urine compared with non-carriers (median 1-hydroxypyrene = 0.37 vs 0.86 μg/g creatinine respectively; p = 0.025 by linear regression models adjusted for age, BMI and smoking) compared to sweeps not carrying CNV12. Further, FLG null was associated with approximately 2.5% higher methylation of F2RL3 (cg03636183, p = 0.019 after adjustment for exposure group, age, BMI and smoking). FLG null was associated with approximately 7% shorter telomere length (p = 0.015, adjusted model). Our results suggest that FLG variations may influence the dose of PAH in highly exposed workers, possibly via dermal uptake. It also suggests that FLG variation may influence the degree of (epi)genotoxicity in the body. FLG variation is common in the working population and should be considered in risk assessment.

Importance: Prenatal exposure to phthalates has been associated with neurodevelopmental outcomes, but little is known about the association with language development. Objective: To examine the asso ...

Phthalate esters are suspected endocrine disruptors that are found in a wide range of applications. The aim of this study was to determine the excretion of urinary metabolites in 16 individuals after inhalation and/or dermal exposure to 100&ndash, 300 &micro, g/m3 of deuterium-labelled diethyl phthalate (D4-DEP) and bis(2-ethylhexyl) phthalate (D4-DEHP). Dermal exposure in this study represents a case with clean clothing acting as a barrier. After inhalation, D4-DEP and D4-DEHP metabolites were excreted rapidly, though inter-individual variation was high. D4-DEP excretion peaked 3.3 h (T&frac12, of 2.1 h) after combined inhalation and dermal exposure, with total excreted metabolite levels ranging from 0.055 to 2.351 nmol/nmol/m3 (nmol of urinary metabolites per phthalates air concentration in (nmol/m3)). After dermal exposure to D4-DEP, metabolite excretion peaked 4.6 h (T&frac12, of 2.7 h) after exposure, with excreted metabolite levels in between 0.017 and 0.223 nmol/nmol/m3. After combined inhalation and dermal exposure to D4-DEHP, the excretion of all five analysed metabolites peaked after 4.7 h on average (T&frac12, of 4.8 h), and metabolite levels ranged from 0.072 to 1.105 nmol/nmol/m3 between participants. No dermal uptake of particle phase D4-DEHP was observed. In conclusion, the average excreted levels of metabolites after combined inhalation and dermal exposure to D4-DEP was three times higher than after combined exposure to D4-DEHP, and nine times higher than after dermal exposure of D4-DEP. This study was made possible due to the use of novel approaches, i.e., the use of labelled phthalate esters to avoid the background concentration, and innovative technique of phthalate generation, both in the particle and the gas phase.

Ethylenethiourea (ETU) is of major toxicological concern, since in experimental animal studies, ETU has shown a large spectrum of adverse effects. High occupational exposure can be found among agricultural workers or during manufacturing of ethylenbisdithiocarbamates (EBDC). For the general public, sources of environmental exposure may be residues of ETU in commercial products, food and beverages. For the determination of ETU in human urine we present a high-throughput online on-column extraction liquid chromatography triple quadrupole mass spectrometry method using direct injection of hydrolysed urine samples. This method is simple, user- and environmentally friendly and all sample preparation is performed in 96-well plates. A labelled ETU internal standard was used for quantification. The method showed a good sensitivity with a limit of quantification (LOQ) of 0.5ng ETU/mL urine and the calibration curve was linear in the range 0.25–200ng ETU/mL urine. The within-run, between-run and between-batch precision was between 6% and 13%. Alkaline hydrolysis considerably increased the levels of ETU indicating a potential conjugate. The method was applied in an experimental dermal exposure study in humans, with sample concentrations ranging from 0.4 to 5.0ng ETU/mL urine. The excretion in urine was 10% of the applied dose. The elimination profile seemed to differ between the two individuals. The results show an estimated half-life of ETU between 34 and 72h. Although the experiment is limited to two individuals, the data provide valuable and new information regarding the toxicokinetics of ETU after dermal exposure.

WOS: 000319871200001, PubMed ID: 23198723, Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended., ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5:"Food Quality and Safety" [FOOD-CT-2005-513943]; ECNIS2, a coordination and support action within the European Union FP7 Cooperation Theme 2 Food, Agriculture, Fisheries and Biotechnologies; CISBO; Ingeborg; Leo Dannin Foundation; National Science Council, TaiwanNational Science Council of Taiwan [NSC 97-2314-B-040-015-MY3, NSC 100-2628-B-040-001-MY4]; US NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P30ES009089]; Instituto Carlos III division of the Government for Clinical Research [PI-10/00802, RD06/0045/0006]; Generalitat ValencianaGeneralitat Valenciana [ACOM/2012/238]; Swedish Council for Working Life and Social ResearchSwedish Research CouncilSwedish Research Council for Health Working Life & Welfare (Forte); TUBITAK (Technical and Scientific Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [108Y049]; Grant Agency of the Czech RepublicGrant Agency of the Czech Republic [P503/11/0084]; Sahlgrenska University Hospital, Gothenburg; UK Medical Research Council via a People Exchange Programme Research Leader Fellowship award [G1001808/98136], Some of the authors of this work were partners in, and this work was partly supported by, ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5:"Food Quality and Safety" (Contract No. FOOD-CT-2005-513943), and also ECNIS2, a coordination and support action within the European Union FP7 Cooperation Theme 2 Food, Agriculture, Fisheries and Biotechnologies.; P Moller and S Loft are supported by CISBO and the Ingeborg and Leo Dannin Foundation.; M-R Chao and C-W Hu acknowledge financial support from the National Science Council, Taiwan (Grants NSC 97-2314-B-040-015-MY3 and NSC 100-2628-B-040-001-MY4).; R Santella acknowledges the contribution of Qiao Wang, and support from US NIH P30ES009089.; G Saez and C Cerda acknowledge financial support from the Instituto Carlos III division of the Government for Clinical Research (Grants PI-10/00802 and RD06/0045/0006) and Grant ACOM/2012/238 from Generalitat Valenciana.; K Broberg, C Lindh, and M Hossain acknowledge financial support from the Swedish Council for Working Life and Social Research; H Orhan and N Senduran acknowledge financial support from TUBITAK (Technical and Scientific Research Council of Turkey), grant number 108Y049.; P Rossner, Jr. and RJ Sram acknowledge support from the Grant Agency of the Czech Republic (P503/11/0084).; L Barregard acknowledges financial support from the Sahlgrenska University Hospital, Gothenburg.; MS Cooke acknowledges support from the UK Medical Research Council via a People Exchange Programme Research Leader Fellowship award (G1001808/98136).

Proteomic-based studies of nasal lavage fluid (NLF) may identify molecular pathways associated with disease pathology and new biomarker candidates of upper airway diseases. However, most studies have used rather tedious untargeted MS techniques. Selected reaction monitoring (SRM) is a sensitive and specific technique that can be used with high throughput. In this study, we developed a semiquantitative SRM-based method targeting 244 NLF proteins. The protein set was identified through a literature study in combination with untargeted LC-MS/MS analyses of trypsin-digested NLF samples. The SRM assays were designed using MS/MS data either downloaded from a proteomic data repository or experimentally obtained. Each protein is represented by one to five peptides, resulting in 708 SRM assays. Three to four transitions per assay were used to ensure analyte specificity. The majority (69%) of the assays showed good within-day precision (coefficient of variation ≤ 20%). The accuracy of the method was evaluated by analyzing four samples prepared with varying amounts of four proteins. Peptide and protein ratios were in good agreement with expected ratios. In conclusion, a high throughput screening method for relative quantification of 244 NLF proteins was developed. The method should be of general use in any proteomic study of the upper airways.

Phthalates and phenolic substances were investigated in urine samples from first-time mothers in Uppsala, Sweden, collected between 2009 and 2014. These substances have a comparably fast metabolism and urinary metabolites are predominantly analysed. The main aim was to investigate if measures to decrease production and use of certain phthalates and bisphenol A (BPA) have resulted in decreased human exposure, and to determine if exposures to replacement chemicals have increased. Temporal trends were evaluated for metabolites (n=13) of seven phthalates, a phthalate replacer, four different bisphenols, triclosan, one organophosphate-based flame retardant, and for two pesticides. The results showed downward trends of several phthalates which are in the process of being regulated and phased out. Concomitantly, an increasing trend was seen for a metabolite of the phthalate replacer Di-iso-nonylcyclohexane 1,2-dicarboxylate (DiNCH). Bisphenol A (BPA) showed a downward trend, whereas bisphenol F, identified as one of the substitutes for BPA, showed an increasing trend. The decreasing trend of triclosan is likely due to declining use within the EU. Temporal trend studies of urine samples make it possible to investigate human exposure to rapidly metabolised substances and study how measures taken to regulate and replace problematic chemicals affect human exposure.

Background There is a controversy on exposure and adverse health effects of workers working with road asphalt paving. Furthermore, the increasing usage of crumb rubber modified (CRM) asphalt raises the concern of exposure to CRM asphalt. Objective To assess the exposure of both conventional and CRM asphalt, and to elucidate the health effects regarding airway symptoms, lung function, inflammation response and genotoxic effects on telomere length (TL) and mitochondria DNA copy number (mtDNAcn). Methods We carried out a cross-week study with 116 workers with conventional asphalt, 51 workers with CRM asphalt and 100 controls in Sweden. Personal air sampling was carried out in 60 workers in varied worksites. Symptoms during working week were investigated by standard questionnaires. Lung function test results together with urine and blood samples were collected before work on Monday morning and immediately after work on Thursday afternoon. Results The exposure level for benzothiazol was higher in CRM asphalt (2.2 ± 0.8 µg/m3) than conventional asphalt (0.7 ± 0.8 µg/m3, p Conclusion The results do not indicate that road asphalt paving in open area is an occupation with high exposure or severe health issues. Similarly, the results do not suggest that CRM asphalt is related to more adverse health effects than conventional asphalt. However, the higher concentration of benzothiazole during CRM paving may suggest that crumb rubber is a main source and that benzothiazole may be useful as an indicator of CRM fume exposure.

Introduction: Cholesterol has many important functions in the human body. However, high levels of low-density lipoprotein (LDL) cholesterol are associated with higher risk for cardiovascular diseas...

Background: Mancozeb is a fungicide aerially sprayed in large-scale banana plantations. It is 21% weight manganese (Mn) and its main metabolite is ethylenethiourea (ETU). Data on neurodevelopmental...

Introduction: PFAAs are used in many applications e.g. for water protection in clothes and shoes, impregnation of papers and food containers and in fire-fighting foams. Many PFAAs are highly stable...

Introduction: Growing evidence suggests that pesticide exposure may disrupt thyroid hormones, but data in humans are limited. We studied the association of pesticide exposure and thyroid hormones i...

Introduction: Children are exposed to phthalates and other plasticizers in their everyday environments, including the preschool environment. As formerly widely used phthalates are subjected to stricter regulations, non-phthalate substitutes have become more common. However, there is limited exposure data for these compounds. The aim of this study is to evaluate the levels and exposure of phthalates and non-phthalate plasticizers in Swedish preschools and identify important exposure predictors in the indoor environment. Methods: Dust samples from 100 preschools and urine samples from 113 preschool children were collected. The samples were analysed for phthalates and non-phthalate plasticizers. Preschool inspections were performed to collect information about potential exposure predictors in the indoor environment. Results: Geometric mean levels of phthalates in dust were highest for DINP (450 μg/g dust) followed by DEHP (266 μg/g dust). Levels of non-phthalate plasticizers in dust were 105 μg/g for DEHT, 7...

INTRODUCTION: Epidemiological studies have found that the general population is exposed to chemicals that may interact with the endocrine system in humans and animals, so called endocrine disruptin...

INTRODUCTION: Epidemiological studies indicate that early life exposure for phthalates could be associated to asthma in children. During infancy transient wheeze is common, making a robust asthma d...

STUDY QUESTION: Is female exposure to phthalate metabolites associated with reduced fecundity, as estimated by prolonged time to pregnancy (TTP)?SUMMARY ANSWER: Female exposure to monoethyl phthalate (MEP) but not monobutyl phthalate (MBP), monobenzyl phthalate (MBzP) and monoethylhexyl phthalate (MEHP) was associated with a longer TTP.WHAT IS KNOWN ALREADY: Male exposure to phthalates is potentially associated with adverse effects on human fecundity in epidemiological studies, but little is known about the potential effects on female reproduction.STUDY DESIGN SIZE AND DURATION: A cohort study with prospective data based on 229 women from a Danish cohort of 430 first pregnancy planning couples enrolled in 1992-1994. In 2009, urinary analyses of phthalate metabolites were performed on stored urine samples from this cohort.PARTICIPANTS/MATERIALS, SETTING AND METHODS: We analyzed MEP, MBP, MBzP and MEHP in female morning spot urine samples collected daily during the first 10 days of menstrual cycles after discontinuation of contraception. The exposure assessment was based on the mean of two measurements from each woman collected in a period of 6 menstrual cycles. We used Cox regression with discrete time to estimate fecundability ratios (FRs) and 95% CI in relation to the average urine metabolite concentration exposure level, controlled for age and BMI, and the time-varying variables smoking and alcohol.MAIN RESULT AND ROLE OF CHANCE: Urinary concentration of MEP was associated with a decreased fecundity (adjusted FR 0.79; 95% CI: 0.63; 0.99) corresponding to a 21% decreased probability of conception for each natural log (ln) unit increase in MEP. No significant association with TTP was found for MBP, MBzP and MEHP.LIMITATIONS REASONS FOR CAUTION: Subfertile women were overrepresented in the study population due to exclusion of 77 high fertile women who became pregnant in the first cycle when urine collection began.WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that female exposure to MEP may have an adverse effect on female fecundity, but these findings need to be replicated in a larger and newer cohort study with sufficient exposure contrast if the use of diethyl phthalate (DEP) and thereby MEP in the future potentially should be regulated in cosmetics and industrial consumer products.STUDY FUNDING/COMPETING INTERESTS: The original data collected were founded by Aarhus University Research Foundation, the Danish Medical Research Council and the Danish Medical Health Insurance Foundation. There are no conflicts of interest to be declared.TRIAL REGISTRATION NUMBER: N/A.

The aims of this study were to quantify salivary concentrations of bisphenol A (BPA) and to assess if presence of dental composite fillings is associated with higher BPA levels in saliva. Twenty individuals with six or more tooth surfaces filled with polymer-based dental materials (composite group) and 20 individuals without any polymer-based materials (control group) were included in the study. Saliva was collected in polypropylene tubes and stored at −80 °C before analysis. Concentration of free (unconjugated) and total bisphenol A was determined by liquid chromatography/mass spectrometry (LC/MS). Values below limit of detection (0.1 ng/mL) were set to one-half of the limit of detection. Mann-Whitney U test (one sided; the Exact Tests Option in IBM-SPSS version 21) was used for the statistical analyses. The concentration of BPA in saliva was very low. In the composite group, 8 of 20 samples had detectable concentrations of BPA. In the control group, 3 of 20 samples had detectable concentrations of BPA. Statistical analysis indicated that the concentration of unconjugated BPA was slightly higher in the composite group (p = 0.044) than in the control group. Presence of dental composites may be associated with slightly higher concentration of unconjugated BPA in saliva. However, additional studies using sensitive analytical methods are needed before firm conclusions can be drawn. Influence from other factors, like food intake and time of the day for saliva sampling, must be considered. The relative contribution of existing polymer-based dental fillings to total BPA exposure seems to be low.

Cohort studies have indicated an association between prenatal smoking exposure and children's motor difficulties. However, results are inconsistent and exposure is most often self-reported. Studies indicate that measurement of serum cotinine can result in a more accurate status of smoking exposure in comparison with self-report.To investigate whether prenatal smoking exposure, measured as maternal serum cotinine, is associated with maternal interview based assessment of motor development in infancy (age at crawling, standing-up and walking) and motor skills at young school age (assessed by the Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07)).In 2002-2004, 1,253 pregnant women from Greenland and Ukraine were included in the INUENDO birth cohort. The participating women filled in questionnaires and 1,177 provided blood samples, which were analyzed for serum cotinine. Smokers were defined as women with a serum cotinine concentration10ng/ml. At follow-up when the offspring were 6-9 years of age 1,026 of the parents from the cohort participated. They completed an interview-based questionnaire including questions about age at motor milestones of their children. In addition, child motor development was assessed using the questionnaire "DCDQ'07". Linear regression analyzes were performed and adjusted for covariates; age of the mother and child, parity, sex, maternal educational level, maternal pre-pregnancy alcohol consumption and duration of breastfeeding. Data were stratified by country.No statistically significant difference in age at motor milestones was found comparing children of smokers with children of non-smokers. Also, there was no statistically significant difference in motor score (Developmental Coordination Disorder Questionnaire Score, DCDQ-score) among five to seven-year-old children. However, in Greenland children of smokers had a lower DCDQ-score than children of non-smokers at eight to nine years (-2.2 DCDQ points, 95% CI: -4.3;-0.1). Supplementary results for the same age group in Greenland showed that children of smokers had higher odds of being classified with motor difficulties in comparison with children of non-smokers (OR=1.9, 95% CI: 1.1;3.3).Maternal serum cotinine was not related to delayed motor development milestones or reduced motor function abilities in children up to 7 years of age. Reduced motor skills observed in 8-9 years old exposed children warrant further study.

Background: Animal studies indicate that some phthalate metabolites may harm female reproductive function. Objectives: We assessed the associations between exposure to phthalate metabolites and pregnancy loss. Methods: Using a previously established cohort of couples planning their first pregnancy, we analyzed four primary and two oxidized secondary phthalate metabolites in urine samples collected on day 10 after the first day of the last menstrual period before conception occurred (n = 128) and during the previous cycle (if any, n = 111). Subclinical embryonal loss was identified by repeated measurement of urinary human chorionic gonadotropin, and information on clinical spontaneous abortions was obtained by telephone interview with the mother. Results: Pregnancy loss (n = 48) was increased among women with urinary concentration of monoethylhexyl phthalate (MEHP) in the upper tertile in the conception sample compared with women in the lowest tertile [adjusted odds ratio (OR) = 2.9; 95% confidence interval (CI): 1.1, 7.6]. The corresponding OR for subclinical embryonal loss (n = 32) was 40.7 (95% CI: 4.5, 369.5). Conclusions: The phthalate metabolite MEHP was associated with higher occurrence of pregnancy loss. Because this is the first human study to show this association and the sample size is small, the findings need to be corroborated in independent studies.

Environmental exposure to cadmium (Cd) is known to induce oxidative stress, a state of imbalance between the production of reactive oxygen species (ROS) and the ability to detoxify them, in adults. However, data are lacking on potential effects in early-life. We evaluated urinary concentrations of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a recognized marker of oxidative DNA damage, in relation to Cd exposure in 96 predominantly breast-fed infants (11-17 weeks of age) in rural Bangladesh. Urinary 8-oxodG was measured using liquid chromatography tandem mass spectrometry and Cd in urine and breast milk by inductively coupled plasma mass spectrometry. Median concentration of 8-oxodG was 3.9 nmol/L, urinary Cd 0.30 mu g/L, and breast-milk Cd 0.13 mu g/L. In linear regression analyses, urinary 8-oxodG was positively associated with Cd in both urine (p=0.00067) and breast milk (p=0.0021), and negatively associated with body weight (kg: p=0.0041). Adjustment for age, body weight, socio-economic status, urinary arsenic, as well as magnesium, calcium, and copper in breast milk did not change the association between Cd exposure and urinary 8-oxodG. These findings suggest that early-life low-level exposure to Cd via breast milk induces oxidative stress. Further studies are warranted to elucidate whether this oxidative stress is associated with impaired child health and development. (C) 2011 Elsevier Inc. All rights reserved. (Less)

In this study, a method using liquid chromatography triple quadrupole mass spectrometry (LC/MS/MS) is described for the analysis of the plant growth regulator chlormequat (CCC) in human urine. Analysis was carried out using selected reaction monitoring (SRM) in the positive ion mode. [(2)H(4)] labeled CCC as internal standard (IS) was used for quantification of CCC. The limit of detection (LOD) was determined to 0.1 ng/mL. The method was linear in the range 0.3-800 ng/mL urine and had a within-run precision of 4-9%. The between-run precision was determined at urine levels of 7.0 and 31 ng/mL and found to be 5 and 6% respectively. The reproducibility was 3-6%. To validate CCC as a biomarker of exposure, the method was applied in a human experimental oral exposure to CCC. Two healthy volunteers received 25 μg/kg b.w. CCC in a single oral dose followed by urine sampling for 46 h post-exposure. The CCC was estimated to follow a first order kinetic and a two compartment model with an elimination half-life of 2-3h and 10-14 h respectively. One hundred 24h urine samples were collected from non-occupationally exposed individuals in the general population in southern Sweden. All samples had detectable levels above the LOD 0.1 ng/mL urine. The median levels were 4 ng/mL of CCC in unadjusted urine. The levels found in the population samples are several magnitudes lower than those found in the experimental exposure, which corresponds to an oral exposure of 50% of the ADI for CCC.

Objectives Telomeres are critical to maintain the integrity of the chromosomes, and telomere abnormalities are important features of carcinogenesis. Telomere length differs among individuals due to genetic and environmental factors. Aiming to examine the relationship between DNA-damaging agents and average telomere length in peripheral blood, we conducted a cross-sectional study among 157 workers working in the rubber industry in Sweden. Methods N-nitrosamines were measured in air by personal sampling on Thermosorb/N tubes and analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS) for 60 individuals. Based on a similar working situation, the exposure was estimated for all workers. Polycyclic aromatic hydrocarbons (PAH) were measured as the metabolite 1-hydroxypyrene (1-HP) in urine by LC. Carbon disulphide (CS2) was measured as the metabolite 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine by LC/MS/MS. Toluidines (orto-, meta-, and para-) were measured in urine by gas chromatography (GC)/MS. The average telomere length in peripheral blood was determined by quantitative polymerase chain reaction (PCR). Results There was a reduction in telomere length with increasing exposure to N-nitrosamines in air [measured (N=60) N-nitrosamines β-coefficient= -10, (95% confidence interval [95% CI] -17– -1.9) P=0.016; estimated (N=157) N-nitrosamines β-coefficient = -5.3, (95% CI -9.5– -0.97) P=0.016]. Also, there were negative associations between para-toluidine [β-coefficient= -0.031 (95% CI -0.055– -0.0063) P=0.014], as well as age β-coefficient= -0.005 (95% CI -0.007– -0.002) P=0.001] and telomere length. There were no strong associations between other exposures and telomere length nor did smoking modify the effect. Conclusion N-nitrosamines exposure may lead to telomere shortening.

Acrylates are used in vast quantities, for instance in paints, adhesive glues, molding. They are potent contact allergens and known to cause respiratory hypersensitivity and asthma. Here we study ethyl 2-cyanoacrylate (ECA), methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA). There are only limited possibilities to measure the exposure to acrylates, especially for biological monitoring. The aim of the present study was to investigate the chemical structures of adducts formed after reaction of hemoglobin (Hb) with ECA, MMA, and HEMA. This information may be used to identify adducted Hb peptides for biological monitoring of exposure to acrylates. Hb-conjugates with ECA, MMA, and HEMA were synthesized in vitro. The conjugates were digested by trypsin and pronase E. Adducted peptides were characterized and analyzed by liquid chromatography and nano electro spray/hybrid quadrupole time-of-flight mass spectrometry (MS) as well as tandem quadrupole MS. The search for the adducted peptides was facilitated by visualizing the MS data by different computer programs. The results showed that ECA binds covalently to cysteines at the 104 position in the alpha and the position 112 in the beta-chains in Hb. MMA and HEMA bound to all the cysteines in both chains, Cys(104) in the alpha-chain and Cys(93) and 112 in the beta-chain. The full-length spectra of in un-digested Hb confirmed this binding pattern. There was no reaction with N-acetyl-l-lysine at physiological pH. The adducted peptides were possible to measure using LC/MS/MS in selected reaction monitoring mode. These peptides may be used for biological monitoring of exposure to ECA, MMA and HEMA. (Less)

Hairdressers are frequently exposed to bleaching powder containing persulfates, a group of compounds that may induce hypersensitivity in the airways. The mechanism causing this reaction is not clear. The aim of this study was to identify changes in the nasal lavage fluid proteome after challenge with potassium persulfate in hairdressers with bleaching powder-associated rhinitis. Furthermore, we aimed to compare their response to that of hairdressers without nasal symptoms, and atopic subjects with pollen-associated nasal symptoms. To study the pathogenesis of persulfate-associated rhinitis, the response in protein expression from the upper airway was assessed by time-dependent proteomic expression analysis of nasal lavage fluids. Samples were prepared by pooling nasal lavage fluids from the groups at different time points after challenge. Samples were depleted of high-abundant proteins, labeled with iTRAQ and analyzed by online 2D-nanoLC-MS/MS. Differences in the protein pattern between the three groups were observed. Most proteins with differentially expressed levels were involved in pathways of lipid transportation and antimicrobial activities. The major finding was increased abundance of apolipoprotein A-1, 20 min postchallenge, detected solely in the group of symptomatic hairdressers. Our results suggest there may be differences between the mechanisms responsible for the rhinitis in the symptomatic and atopic group.

Methylhexahydrophthalic anhydride (MHHPA) is a reactive, low molecular weight chemical used in products such as plastics, paints, and electronic components. Exposure to MHHPA may lead to work-related airway diseases such as rhinitis, conjunctivitis, and asthma. Twelve subjects employed at a plant manufacturing electrical capacitors using MHHPA were included in this study. Nasal lavages were collected from subjects before work Monday morning and after work Tuesday afternoon. The levels of MHHPA adducted to serum albumin were analyzed with a straightforward work-up method. The samples were trypsinated before being analyzed with a liquid chromatography-triple quadrupole mass spectrometer. The mass spectrometer was run using selected reaction monitoring for six adducted peptides. Also, some biomarkers of effect (albumin, total protein, eosinophil cationic protein, and tryptase) were analyzed in nasal lavages. Furthermore, the metabolite MHHP acid in urine after work on Tuesday was analyzed by gas chromatography-mass spectrometry. Symptoms from the airways and the eyes and sensitization were registered. The main result of this study is that protein adducts can be analyzed in vivo after low occupational exposures to MHHPA. The results also show a correlation between adducted peptides and albumin in nasal lavage. Furthermore, there may be a difference in the potential to induce hyperresponsiveness between adducts bound to different amino acids.

Previous inconsistent results suggest that menstrual cycles may be disturbed by exposure to polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE).Information on menstrual cycle characteristics were obtained by questionnaires, and PCB and DDE were measured in serum samples from a total of 1494 women from Greenland, Swedish fishermen's wives, and inhabitants of Warsaw in Poland and Kharkiv in Ukraine.No consistent effects of PCB and DDE exposure on menstrual cycle characteristics were observed across populations. Within populations, we observed increased risks of short cycles (or =24 days) among Swedish fishermen's wives exposed to high levels of PCB [odds ratio (OR) 2.5, confidence interval (CI) 1.2-5.1], and increased risk of long cycles (or =32 days) among Polish women exposed to high levels of DDE (OR 3.1, CI 1.1-8.6). However, in Greenland it seemed that high levels of PCB or DDE were protective against long menstrual cycles (OR 0.7 CI 0.5-0.96 and OR 0.7 CI 0.5-0.99, respectively).It is unlikely that exposure to PCB and DDE is a main cause of menstrual disturbances. Genetic differences or dietary factors may be involved in the non-homogenous associations of organochlorine exposure and menstrual cycle between countries.

OBJECTIVES: This study examines associations between prenatal exposure to tobacco smoking and adverse behaviour in the offspring.METHODS: We included 1016 pregnant women from Greenland and Ukraine (526 from Greenland and 490 from Ukraine). Serum cotinine measurements were used to identify smoking pregnant women. When the children were from five to nine years of age, the parents assessed the child's behaviour using the Strength and Difficulties Questionnaire (SDQ).RESULTS: Overall, smoking in pregnancy was not associated with a higher probability of adverse behaviour assessed by the total SDQ score. However, in the crude analysis smoking was associated with a higher mean difference of SDQ-total score. In Greenland the SDQ-total mean difference (MD) was (MD (95% CI)=1.31 points (0.42; 2.19)) and in Ukraine (MD (95% CI)=0.18 points (-1.2; 0.91)), whereas the adjusted mean differences were statistically non-significant.CONCLUSIONS: In utero exposure to tobacco smoking was not associated with a significant higher risk of adverse behaviour in the offspring, but elevated risk of adverse behaviour among children prenatally exposed to smoking cannot be excluded.