Mothers and children are related, even in exposure to chemicals present in common consumer products.

BACKGROUND: Phthalates, bisphenol A (BPA) and triclosan (TCS) are detectable in the vast majority of people. Most humans are continuously exposed to these chemicals due to their presence in food or in everyday consumer products. The measurement of these compounds in family members may help to explore the impact of major lifestyle factors on exposure. Mothers and (young) children are especially interesting to study, as they mostly share considerable parts of daily life together. MATERIALS AND METHODS: Phthalate metabolites, bisphenol A (BPA) and triclosan (TCS) were measured in first morning void urine, collected in mother-child pairs (n = 129) on the same day. The mothers (27-45y) and their children (6-11y) were recruited in the Brussels agglomeration and rural areas of Belgium in the context of the European COPHES-DEMOCOPHES human biomonitoring project. Face-to-face questionnaires gathered information on major exposure sources and lifestyle factors. Exposure determinants were assessed by multiple linear regression analysis. RESULTS: The investigated compounds were detectable in nearly all mothers (92.8-100%) and all children (95.2-100%). The range (P90 vs. P10) of differences in urinary concentrations within each age group was for most compounds around 10-20 fold, and was very high for TCS up to 35 and 350-fold in children and mothers respectively. Some participants exceeded the tolerable daily intake guidelines as far as they were available from the European Food Safety Authority (EFSA). Overall, for BPA, the urinary concentrations were similar among both age groups. Most urinary phthalate metabolites were higher in children compared to the mothers, except for monoethyl phthalate (MEP). TCS levels were generally higher in the mothers. Despite the difference in mothers' and children's urinary concentrations, the creatinine-corrected levels were correlated for all biomarkers (Spearman rank r = 0.32 to 0.66, p < 0.001). Furthermore, for phthalates, similar home and lifestyle factors were associated with the urinary concentrations in both age groups: home renovation during last two years or redecoration during the last year for di-ethyl phthalate (DEP); PVC in home for di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP) and butyl benzyl phthalate (BBzP), and personal care products use for DiBP and DnBP. Based on questionnaire information on general food type consumption patterns, the exposure variability could not be explained. However, comparing the phthalate intake from the current study with earlier assessed Belgian food intake calculations for both ages, food in general was estimated to be the major intake source for di-ethyl hexyl phthalate (DEHP), with diminishing importance for BBzP, DiBP and DnBP. CONCLUSION: Our results confirm, that children and their mothers, sharing diets and home environments, also share exposure in common consumer products related chemicals. By collecting morning urine levels on the same day, and using basic questionnaires, suspected exposure routes could be unraveled.

Mercury analysis in hair: Comparability and quality assessment within the transnational COPHES/DEMOCOPHES project.

Human biomonitoring (HBM) is an effective tool for assessing actual exposure to chemicals that takes into account all routes of intake. Although hair analysis is considered to be an optimal biomarker for assessing mercury exposure, the lack of harmonization as regards sampling and analytical procedures has often limited the comparison of data at national and international level. The European-funded projects COPHES and DEMOCOPHES developed and tested a harmonized European approach to Human Biomonitoring in response to the European Environment and Health Action Plan. Herein we describe the quality assurance program (QAP) for assessing mercury levels in hair samples from more than 1800 mother-child pairs recruited in 17 European countries. To ensure the comparability of the results, standard operating procedures (SOPs) for sampling and for mercury analysis were drafted and distributed to participating laboratories. Training sessions were organized for field workers and four external quality-assessment exercises (ICI/EQUAS), followed by the corresponding web conferences, were organized between March 2011 and February 2012. ICI/EQUAS used native hair samples at two mercury concentration ranges (0.20-0.71 and 0.80-1.63) per exercise. The results revealed relative standard deviations of 7.87-13.55% and 4.04-11.31% for the low and high mercury concentration ranges, respectively. A total of 16 out of 18 participating laboratories the QAP requirements and were allowed to analyze samples from the DEMOCOPHES pilot study. Web conferences after each ICI/EQUAS revealed this to be a new and effective tool for improving analytical performance and increasing capacity building. The procedure developed and tested in COPHES/DEMOCOPHES would be optimal for application on a global scale as regards implementation of the Minamata Convention on Mercury.

Fish consumption patterns and hair mercury levels in children and their mothers in 17 EU countries.

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 µg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 µg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements.

Exposure determinants of cadmium in European mothers and their children.

The metal cadmium (Cd) is a widespread environmental pollutant with documented adverse effects on the kidneys and bones from long-term environmental exposure, but with insufficiently elucidated public health consequences such as risk of cardiovascular disease, hormone-related cancer in adults and developmental effects in children. This study is the first pan-European human biomonitoring project that succeeded in performing harmonized measurements of Cd in urine in a comparable way in mother-child couples from 16 European countries. The aim of the study was to evaluate the overall Cd exposure and significant determinants of Cd exposure. A study population of 1632 women (24-52 years of age), and 1689 children (5-12 years of age), from 32 rural and urban areas, was examined within a core period of 6 months in 2011-2012. Women were stratified as smokers and non-smokers. As expected, smoking mothers had higher geometric mean (gm) urinary cadmium (UCd; 0.24 µg/g crea; n=360) than non-smoking mothers (gm 0.18 µg/g crea; n=1272; p<0.0001), and children had lower UCd (gm 0.065 µg/g crea; n=1689) than their mothers at the country level. Non-smoking women exposed to environmental tobacco smoke (ETS) at home had 14% (95% CI 1-28%) higher UCd than those who were not exposed to ETS at home (p=0.04). No influence of ETS at home or other places on UCd levels was detected in children. Smoking women with primary education as the highest educational level of the household had 48% (95% CI 18-86%) higher UCd than those with tertiary education (p=0.0008). The same observation was seen in non-smoking women and in children; however they were not statistically significant. In children, living in a rural area was associated with 7% (95% CI 1-13%) higher UCd (p=0.03) compared to living in an urban area. Children, 9-12 years had 7% (95% CI 1-13%) higher UCd (p=0.04) than children 5-8 years. About 1% of the mothers, and 0.06% of the children, exceeded the tolerable weekly intake (TWI) appointed by EFSA, corresponding to 1.0 µg Cd/g crea in urine. Poland had the highest UCd in comparison between the 16 countries, while Denmark had the lowest. Whether the differences between countries are related to differences in the degree of environmental Cd contamination or to differences in lifestyle, socioeconomic status or dietary patterns is not clear.

[Why bother with regression models?]. / Warum wir uns mit mathematischen Modellen herumplagen müssen. Hazard-Ratio, Hazard-Funktion und Cox-Regression.

In the last article, you learned about the interpretation of survival curves. This article is about the comparison of "survival" - or the time to any defined event. Two survival curves can be summarized with the hazard ratio, which is discussed in more detail in this article. In order to compare the "survival"of two treatment groups - particularly in non-randomised studies - additional variables (potential confounders) must be taken into account. This is done using a regression model, the so-called Cox-regression. After reading this article, hopefully these terms are more familiar to you.

[Painting by number--Survival curves and Kaplan-Meier method]. / Malen nach Zahlen. Von Uberlebenszeit-Analysen und Kaplan-Meier-Kurven.

Survival curves plot percent survival as a function of time. Results of clinical trials are often presented as survival curves. However, the purpose of survival analysis is not, as the name suggests, limited to "survival". Rather, it can concern the time to any defined event, desired or undesired. The me- thod behind these curves may be tricky; "reading" of the curves, however, is simple and intuitive. And with a few basic skills misinterpretations can usually be avoided.

[Instructions for aggregated evidence: Systematic reviews and meta-analyses (part 1)]. / Gebrauchsanweisung für konzentrierte Evidenz. Von Reviews, systematischen Übersichtsarbeiten und Metaanalysen (Teil 1).

High-quality, up-to-date, systematic reviews comprehensively summarize the evidence from clinical studies for a focused clinical question. A meta-analyses is a quantitative summary of results from individual studies and often part of a systematic review. Important features of a systematic review are a focused research question, a comprehensive, reproducible search for primary studies, selection of studies using clear and transparent eligibility criteria, and a standardized critical appraisal of the methodological quality of included studies.

[Instructions for aggregated evidence: About reviews, systematic reviews and meta-analyses (part 2)]. / Gebrauchsanweisung für konzentrierte Evidenz. Von Reviews, systematischen Übersichtsarbeiten und Metaanalysen (Teil 2).

Valid systematic reviews are essential for a safe navigation through the existing literature on a specific clinical topic. In the second part of our training to "Reviews, systematic reviews and meta-analyses", we explain how the results of systematic reviews and meta-analyses should be presented and how they should be interpreted. We describe the forest plot, with which you can get a quick overview of the results of numerous studies, the funnel plot, which can be useful for identifying a publication bias, and report on sensitivity and subgroup analyses, which are of great importance to discover the source of heterogeneity between individual studies. Finally, at the end of our article series, we hopefully convinced you of the importance to make up your own mind about the interpretation of the results of aggregated evidence.

[Evidence-based pharmacy - Assessement of quality and clinical relevance of study results]. / Qualitätsbewertung klinischer Studien. Ergebnisqualität: Wie man die Spreu vom Weizen trennt (Teil 2).

The critical appraisal of a study publication includes several steps: quality inspection of the study methodology, examination of the results, assessments of benefit and harm for the individual patient. If the first step of the "critical appraisal" determines, that different sources of bias were successfully eliminated or minimized in the study conduct, it is worthwhile to work through the article completely. In the second step, the size and confidence of the study results have to be examined in detail. Different outcome measures are used to describe the effect of an intervention in clinical trials. However, not all endpoints studied, or differences that are found between treatment groups, are important for the decision making of a patient. In the last step, the study results are interpreted for the individual patient in terms of the expected ben- efits and possible harms. While the control of methodical quality and the effect size of study outcomes may be based on formal criteria, professional value judgement is necessary for the transfer of study results to an individual patient, by which a recommendation can be made, adapted to the individual circumstances, needs and expectations of the patient.

[Evidence-based pharmacy--assessment of study quality]. / Qualitätsbewertung klinischer Studien. Wie man die Spreu vom Weizen trennt.

After having identified relevant studies through a literature search for a specific question, it is now necessary to consider the trustworthiness of the publications found. This article deals with the quality assessment of the raw material "information". The focus is based on the following questions: (a) Why is the randomized controlled trial (RCT) the gold standard for proving a cause-effect relationship? (b) What types of biases exist? To identify the risk of bias, it is necessary to become familiar with some terms. The aim of the current paper is to clarify and explain the key points for the assessment of internal validity of RCTs. The underlying question is: Can I trust the results of this study at all? And: Is it worthwhile to read further? In addition, an example of how to structure a "critical appraisal" will be shown. For this purpose, checklists are helpful to systematize and document the procedure.

[Navigation aid through the information overload]. / Navigationshilfe durch die Informationsfluten.

We live in the modern information society. "To be informed" has a crucial impact on the personal, professional, economic and social development. The knowledge of things and their relationships is essential for acute decisions as well as for long-term planning. And at no time it was easier to get the information required within shorter time periods--no matter to whatsoever. The offer of information of the World Wide Web is inexhaustible. This also applies to information about all possible therapeutic and pharmaceutical issues. But is the information found reliable, too? And are easily accessible sources credible? Can we deal with the information overload at these days or do we actually risk paddling only on the surface of the "information-sea", without ever perceiving the actual information depth and width, less to use it? How can we protect being taken in by marketing strategies? The present article describes a structured proceed when seeking literature to find useful medical and pharmaceutical information in a time saving manner.

[The information flood--a multicomponent mixture. Analytical methods for the extraction of valid information]. / Die Informationsflut--ein Vielstoffgemisch. Die analytischen Methoden zur Extraktion valider Informationen.

Over the centuries some individual scientists have challenged their knowledge, believes and behaviour. The common knowledge developed very fast, but the challenge still remains to ask the question "what do we really know"? And "what is the basis of our decisions and recommendations?" The scattered individual efforts finally advanced to a consolidated methodology--known as "evidence based medicine". This is the first article of a series to get German speaking pharmacists familiar with the basic concepts of evidence based methodology. The series gives some examples how the concept of evidence based medicine can be implemented in pharmaceutical practice.

Occupational exposure of air crews to tricresyl phosphate isomers and organophosphate flame retardants after fume events.

Aircraft cabin air can possibly be contaminated by tricresyl phosphates (TCP) from jet engine oils during fume events. o-TCP, a known neurotoxin, has been addressed to be an agent that might cause the symptoms reported by cabin crews after fume events. A total of 332 urine samples of pilots and cabin crew members in common passenger airplanes, who reported fume/odour during their last flight, were analysed for three isomers of tricresyl phosphate metabolites as well as dialkyl and diaryl phosphate metabolites of four flame retardants. None of the samples contained o-TCP metabolites above the limit of detection (LOD 0.5 µg/l). Only one sample contained metabolites of m- and p-tricresyl phosphates with levels near the LOD. Median metabolite levels of tributyl phosphate (TBP), tris-(2-chloroethyl) phosphate (TCEP) and triphenyl phosphate (TPP) (DBP 0.28 µg/l; BCEP 0.33 µg/l; DPP 1.1 µg/l) were found to be significantly higher than in unexposed persons from the general population. Median tris-(2-chloropropyl) phosphate (TCPP) metabolite levels were significantly not higher in air crews than in controls. Health complaints reported by air crews can hardly be addressed to o-TCP exposure in cabin air. Elevated metabolite levels for TBP, TCEP and TPP in air crews might occur due to traces of hydraulic fluid in cabin air (TBP, TPP) or due to release of commonly used flame retardants from the highly flame protected environment in the airplane. A slight occupational exposure of air crews to organophosphates was shown.

Biomonitoring of exposure to N-methyl-2-pyrrolidone in workers of the automobile industry.

N-methyl-2-pyrrolidone (NMP) is an important organic solvent for varnishes in industry. NMP has been previously shown to be a developmental toxicant in rodents. This study reports current exposures to NMP in the spraying department of an automobile plant using biological monitoring. Two specific metabolites, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methyl-succinimide (2-HMSI), were analyzed in 69 urine samples of 14 workers exposed to NMP and 9 nonexposed controls. Three different working tasks ('loading' and 'cleaning' of the sprayer system and 'wiping/packing' of the sprayed materials) and three sampling times (preshift, postshift, and preshift of the following day) were studied in exposed workers. Median exposures of 5-HNMP and 2-HMSI in postshift urine of exposed workers were 0.91 and 0.52mg g(-1) creatinine, respectively, whereas median levels in controls were below the limit of detection. Decreased levels of 5-HNMP were observed in preshift urine samples on the following day (0.39mg g(-1) creatinine) in exposed workers, while the concentration of 2-HMSI did not change (0.49mg g(-1) creatinine). Highest exposures occurred during sprayer cleaning with a maximum level of 8.31mg g(-1) creatinine of 5-HNMP in postshift urine. In contrast to 'wipers/packers', no decrease in 5-HNMP could be observed in preshift urine samples on day 2 of the 'loaders' and 'cleaners'. Overall, exposure in terms of 5-HNMP postshift and 2-HMSI preshift of the following day were well below the current biological limit values of the European Union (70 and 20mg g(-1) creatinine). Our results provide initial data on NMP exposure in the automobile industry and suggest that the analysis of 5-HNMP in preshift samples also provides essential information, particularly in situations involving direct handling of liquid NMP-containing formulations.

Quantification of four major metabolites of embryotoxic N-methyl- and N-ethyl-2-pyrrolidone in human urine by cooled-injection gas chromatography and isotope dilution mass spectrometry.

N-Methyl- and N-ethyl-2-pyrollidone (NMP and NEP) are frequently used industrial solvents and were shown to be embryotoxic in animal experiments. We developed a sensitive, specific, and robust analytical method based on cooled-injection (CIS) gas chromatography and isotope dilution mass spectrometry to analyze 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI), two newly identified presumed metabolites of NEP, and their corresponding methyl counterparts (5-HNMP, 2-HMSI) in human urine. The urine was spiked with deuterium-labeled analogues of these metabolites. The analytes were separated from urinary matrix by solid-phase extraction and silylated prior to quantification. Validation of this method was carried out by using both, spiked pooled urine samples and urine samples from 56 individuals of the general population with no known occupational exposure to NMP and NEP. Interday and intraday imprecision was better than 8% for all metabolites, while the limits of detection were between 5 and 20 µg/L depending on the analyte. The high sensitivity of the method enables us to quantify NMP and NEP metabolites at current environmental exposures by human biomonitoring.

Determination of 2,3-dihydroxypropionamide, an oxidative metabolite of acrylamide, in human urine by gas chromatography coupled with mass spectrometry.

The general population is exposed to acrylamide (AA) mainly through food and tobacco smoke. AA is classified as probably carcinogenic to humans. Glycidamide (GA), as the primary oxidative metabolite, was identified to be the ultimate genotoxic agent. This warrants full investigation of the oxidative pathway in AA metabolism and the share of the oxidative compared to the reductive pathway. 2,3-Dihydroxy-propionamide (OH-PA) as the direct hydrolysis product of GA has been shown to be a major urinary oxidative metabolite in human AA metabolism. We developed an analytical method to reliably quantify OH-PA in urine by GC-MS after a multistep procedure including "stripping" on a solid phase material, lyophilization, silylation and re-extraction. With a detection limit of 1 µg/L, our method is sensitive enough to quantify OH-PA in all urine samples of the general population. Within and between series precisions were between 1.9% and 8.2% and mean recoveries between 97% and 101%. We applied this method to 30 urine samples from the general population. In all the samples, OH-PA was present in concentrations between 6.8 and 109.4 µg/L (median, 49.7 µg/L) with no difference between smokers and non-smokers. OH-PA concentrations were approximately ten times higher than expected from the metabolism of AA via GA. Currently, we cannot confirm OH-PA to be a specific biomarker of the oxidative pathway of AA metabolism. Other sources than AA respectively GA might need to be considered for the formation of OH-PA.

Excretion of 2,3-dihydroxy-propionamide (OH-PA), the hydrolysis product of glycidamide, in human urine after single oral dose of deuterium-labeled acrylamide.

A dose of 0.99 mg d(3)-acrylamide (d(3)-AA) (13.2 µg/kg body weight) was ingested by a healthy male volunteer. Urine samples were collected over a period of 46 h after the intake and analyzed for the hydrolysis product of glycidamide (GA), 2,3-dihydroxy-propionamide (OH-PA), a metabolite of the toxicologically relevant oxidative AA metabolism pathway; 5.4% of the administered d(3)-AA dose was eliminated as OH-PA within 46 h after ingestion. Therefore, OH-PA represents a major metabolite of the oxidative metabolism pathway. Elimination kinetics of OH-PA is similar to the oxidative metabolites N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA) and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-cysteine (iso-GAMA). The major excretion of d(3)-OH-PA took place between 8 and 22 h with the highest urinary d(3)-OH-PA concentration (c (max)) of 69.3 µg/L urine, 18 h (t (max)) postdose. OH-PA (5.4%), together with the other known urinary metabolites of the oxidative pathway GAMA (4.6%) and iso-GAMA (0.8%), represents 10.8% of the total AA dose. The share of the oxidative pathway metabolites is much smaller than the share of the reductive pathway metabolite N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) that represents 51.7% of the ingested d(3)-AA dose. However, this new quantitative human data on OH-PA together with the previous data on the other oxidative pathway metabolites are of special importance when evaluating the carcinogenic potential of AA and when comparing human data with data from animal studies.

Urinary metabolites of polycyclic aromatic hydrocarbons in workers exposed to vapours and aerosols of bitumen.

Urinary hydroxylated metabolites of polycyclic aromatic hydrocarbons (PAH) were investigated as potential biomarkers of bitumen exposure in a cross-shift study in 317 exposed and 117 non-exposed workers. Personal measurements of the airborne concentration of vapours and aerosols of bitumen during a working shift were weakly associated with post-shift concentrations of 1-hydroxypyrene (1-OHP) and 1-, 2+9-, 3- and 4-hydroxyphenanthrenes (further referred to their sum as OHPHE), but not 1- and 2-hydroxynaphthalene (OHNA). Smoking showed a strong influence on the metabolite concentrations, in particular on OHNA. Pre-shift concentrations of 1-OHP and OHPHE did not differ between the study groups (P = 0.16 and P = 0.89, respectively). During shift, PAH metabolite concentrations increased in exposed workers and non-exposed smokers. Statistical modelling of post-shift concentrations revealed a small increase in 1-OHP by a factor of 1.02 per 1 mg/m(3) bitumen (P = 0.02) and 1.04 for OHPHE (P < 0.001). A group difference was observed that was diminished in non-smokers. Exposed non-smokers had a median post-shift 1-OHP concentration of 0.42 µg/l, and non-smoking referents 0.13 µg/l. Although post-shift concentrations of 1-OHP and OHPHE were slightly higher than those in the general population, they were much lower than in coke-oven workers. The small content of PAHs in vapours and aerosols of bitumen, the increasing use of additives to asphalt mixtures, the strong impact of smoking and their weak association with airborne bitumen limit the use of PAH metabolites as specific biomarkers of bitumen exposure.

DNA adducts and strand breaks in workers exposed to vapours and aerosols of bitumen: associations between exposure and effect.

To study the associations between exposure to vapours and aerosols of bitumen and genotoxic effects, a cross-sectional and cross-shift study was conducted in 320 exposed workers and 118 non-exposed construction workers. Ambient air measurements were carried out to assess external exposure to vapours and aerosols of bitumen. Hydroxylated metabolites of naphthalene, phenanthrene and pyrene were measured in urine, whereas (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide ((+)-anti-BPDE), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodGuo) and DNA strand breaks were determined in blood. Significantly higher levels of 8-oxodGuo adducts and DNA strand breaks were found in both pre- and post-shift blood samples of exposed workers compared to those of the referents. No differences between exposed workers and referents were observed for (+)-anti-BPDE. Moreover, no positive associations between DNA damage and magnitude of airborne exposure to vapours and aerosols of bitumen could be observed in our study. Additionally, no relevant association between the urinary metabolites of PAH and the DNA damage in blood was observed. Overall, our results indicate increased oxidative DNA damage in workers exposed to vapours and aerosols of bitumen compared to non-exposed referents at the group level. However, increased DNA strand breaks in bitumen workers were still within the range of those found in non-exposed and healthy persons as reported earlier. Due to the lack of an association between oxidative DNA damage and exposure levels at the workplaces under study, the observed increase in genotoxic effects in bitumen workers cannot be attributed to vapours and aerosols of bitumen.