P.T.J. Scheepers

Smoking and dietary intake of polycyclic aromatic hydrocarbons as sources of interindividual variability in the baseline excretion of 1-hydroxypyrene in urine.

SummarySeventy-six male volunteers, who were not occupationally exposed to polycyclic aromatic hydrocarbons (PAHs), participated in a study on the effect of tobacco smoking, alcohol consumption, dietary PAH intake, age, and body fat content on the baseline excretion of 1-hydroxypyrene in urine. Major determinants of urinary 1-hydroxypyrene excretion were smoking, dietary PAH intake, and age. The mean 1-hydroxypyrene concentrations in the urine of the volunteers in this study ranged between 0.05 and 0.79 μmol/mol creatinine. Smokers excreted on average 0.25 μmol/mol creatinine (range: 0.10–0.79 μmol/mol creatinine), and nonsmokers on average 0.12 μmol/mol creatinine (range: 0.04–0.29 μmol/mol creatinine). The average number of cigarettes smoked per day correlated well with urinary 1-hydroxypyrene concentrations (rs = 0.67, P < 0.001). The consumption of PAH-containing food products and active smoking account for 99% of total pyrene intake. The effect of age on 1-hydroxypyrene excretion is probably caused by a lower creatinine excretion in the elderly. Passive smoking and fat content had a statistically significant, but negligible effect on urinary 1-hydroxypyrene excretion. Passive smoking and the inhalation of ambient air are relatively inimportant for total pyrene intake (both account for less than 1%). Neither the consumption of alcohol nor the inhalation of ambient air significantly affected urinary 1-hydroxypyrene excretion. It is concluded that when urinary 1-OH-pyrene excretion is used in the assessment of PAH exposure, one should particularly be aware of the interindividual variability of the baseline excretion of PAH metabolites due to tobacco smoking and dietary PAH intake.

Pesticide exposure: the hormonal function of the female reproductive system disrupted?

Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation: 1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity, it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both in toxicological and epidemiological settings.

Usage patterns of personal care products: Important factors for exposure assessment

Complete information regarding the use of personal care products (PCPs) by consumers is limited, but such information is crucial for realistic consumer exposure assessment. To fill this gap, a database was created with person-oriented information regarding usage patterns and circumstances of use for 32 different PCPs. Out of 2700 potential participants from the Netherlands, 516 men and women completed a digital questionnaire. The prevalence of use varied by gender, age, level of education and skin type. A high frequency of use was observed for some products (e.g. lip care products), while toothpaste, deodorant and day cream were generally used once or twice a day. The frequency of use for other PCPs varied over a wide range. The amounts of use varied largely between and within different product groups. Body lotion, sunscreen and after sun lotion were often applied on adjacent body parts. The majority of PCPs were applied in the morning, but some products, such as night cream and after sun, were predominantly applied in the evening or night. As expected, the participants used several PCPs simultaneously. The database yields important personalized exposure factors which can be used in aggregate consumer exposure assessment for substances that are components of PCPs.

Gas chromatographic-mass spectrometric determination of nitro polycyclic aromatic hydrocarbons in airborne particulate matter from workplace atmosphere

Abstract A method is described for the determination of 1-nitropyrene and 2-nitrofluorene in low volume ambient air samples (1–150 m3). This method is bas

Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA)

The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substances potential to cause or not cause cancer in humans. For Monograph 112,2 17 expert scientists evaluated the carcinogenic hazard for four insecticides and the herbicide glyphosate.3 The WG concluded that the data for glyphosate meet the criteria for classification as a probable human carcinogen . The European Food Safety Authority (EFSA) is the primary agency of the European Union for risk assessments regarding food safety. In October 2015, EFSA reported4 on their evaluation of the Renewal Assessment Report5 (RAR) for glyphosate that was prepared by the Rapporteur Member State, the German Federal Institute for Risk Assessment (BfR). EFSA concluded that ‘glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential’. Addendum 1 (the BfR Addendum) of the RAR5 discusses the scientific rationale for differing from the IARC WG conclusion. Serious flaws in the scientific evaluation in the RAR incorrectly characterise the potential for a carcinogenic hazard from exposure to glyphosate. Since the RAR is the basis for the European Food Safety Agency (EFSA) conclusion,4 it is critical that these shortcomings are corrected. EFSA concluded ‘that there is very limited evidence for an association between glyphosate-based formulations …

BIOMarkers for occupational diesel exhaust exposure monitoring (BIOMODEM)--a study in underground mining.

Methods for the assessment of exposures to diesel exhaust were evaluated, including various biomarkers of internal exposure and early biological effects. The impact of possible biomarkers of susceptibility was also explored. Underground workers (drivers of diesel-powered excavators) at an oil shale mine in Estonia were compared with surface workers. Personal exposures to particle-associated 1-nitropyrene (NP) were some eight times higher underground than on the surface. Underground miners were also occupationally exposed to benzene and polycyclic aromatic hydrocarbons, as indicated by excretion of urinary metabolites of benzene and pyrene. In addition, increased O(6)-alkylguanine DNA adducts were detected in the white blood cells of underground workers, suggesting higher exposure to nitroso-compounds. However, no differences between underground and surface workers were observed in the levels of other bulky DNA adducts determined by 32P-postlabelling, or in DNA damage. The study indicated that smoking, diet and residential indoor air pollution are important non-occupational factors to consider when interpreting biomonitoring results.

Determination of exposure to benzene, toluene and xylenes in Turkish primary school children by analysis of breath and by environmental passive sampling.

Benzene, toluene, m/p-xylene and o-xylene (BTX) are toxic volatile organic compounds and ubiquitous air pollutants. Smoking and consumer products are indoor sources of BTX, whereas traffic and industrial activities are primary sources contributing to outdoor levels of BTX. The aim of this study was to characterize exposure of children to BTX by personal air sampling using diffusive samplers and by analysis of end-exhaled air. For this study, 101 children of 10-11 years of age were recruited from four primary schools in Southern Turkey during the warm season (May 2008). Two schools were situated in a residential area near primary and secondary iron and steel works (Payas) and two schools were located in a non-industrialized city (Iskenderun). The children and their parents were visited at home for an interview and to identify possible sources of BTX in the residence. Median concentrations of benzene determined by diffusive samplers were higher in Payas (4.1 microg/m(3)) than in Iskenderun (2.7 microg/m(3), p<0.001). For toluene, no differences were observed, whereas for xylene isomers air concentrations tended to be lower for children living in Payas. The median end-exhaled air concentrations were 8.2, 29, 3.8, and 5.7 pmol/L for benzene, toluene, m/p-xylene and o-xylene, respectively (Payas), and 6.9, 25, 4.9, and 6.0 pmol/L, respectively (Iskenderun). Concentrations of toluene in end-exhaled air were 50% higher in children living with household members who smoked indoors (p<0.05) and benzene in end-exhaled air was more than 3-fold higher for those children who were exposed to tobacco smoke inside a vehicle (p<0.001). End-exhaled concentrations of benzene were also higher in children living in a residence with an attached garage (p<0.05). These exposure modifying factors were not identified when using the results obtained with diffusive samplers.

Application of biological monitoring for exposure assessment following chemical incidents: a procedure for decision making.

Determination of the level of exposure during and after a chemical incident is crucial for the assessment of public health risks and for appropriate medical treatment, as well as for subsequent health studies that may be part of disaster management. Immediately after such an incident, there is usually no opportunity to collect reliable quantitative information on personal exposures and environmental concentrations may fall below detectable levels shortly after the incident has passed. However, many substances persist longer in biological tissues and thus biological monitoring strategies may have the potential to support exposure assessment, as part of health studies, even after the acute phase of a chemical incident is over. Reported successful applications involve very persistent chemical substances such as protein adducts and include those rare cases in which biological tissues were collected within a few hours after an incident. The persistence of a biomarker in biological tissues, the mechanism of toxicity, and the sensitivity of the analysis of a biomarker were identified as the key parameters to support a decision on the feasibility and usefulness of biological monitoring to be applied after an incident involving the release of hazardous chemicals. These input parameters could be retrieved from published methods on applications of biomarkers. Methods for rapid decision making on the usefulness and feasibility of using biological monitoring are needed. In this contribution, a stepwise procedure for taking such a decision is proposed. The persistence of a biomarker in biological tissues, the mechanism of toxicity, and the sensitivity of the analysis of a biomarker were identified as the key parameters to support such a decision. The procedure proposed for decision making is illustrated by case studies based on two documented chemical incidents in the Netherlands.

Characterisation of exposure to total and hexavalent chromium of welders using biological monitoring

Inhalation exposure to total and hexavalent chromium (TCr and HCr) was assessed by personal air sampling and biological monitoring in 53 welders and 20 references. Median inhalation exposure levels of TCr were 1.3, 6.0, and 5.4 microg/m(3) for welders of mild steel (MS, <5% alloys), high alloy steel (HAS, >5% alloys), and stainless steel (SS, >26% alloys), respectively. The median exposures to HCr compounds were 0.23, 0.20, and 0.08 microg/m(3), respectively. Median concentrations of TCr in urine, blood plasma and erythrocytes were elevated in all welders, compared with the corresponding median concentrations in the reference group (p<0.005). The TCr levels observed in plasma were two-fold higher in welders of SS and HAS than in welders of MS (p<0.01). Exposure to HCr as indicated by median total content of Cr in erythrocytes was 10 microg/L in welders of SS, MS and HAS. Uptake of TCr during the shift was confirmed for welders of SS by a median increase of urinary TCr from pre- to post-shift of 0.30 microg/g creatinine. For welders of MS and HAS as a group TCr was not increased.

The probabilistic aggregate consumer exposure model (PACEM): validation and comparison to a lower-tier assessment for the cyclic siloxane D5

Current practice of chemical risk assessment for consumer product ingredients still rarely exercises the aggregation of multi-source exposure. However, focusing on a single dominant source/pathway combination may lead to a significant underestimation of the risk for substances present in numerous consumer products, which often are used simultaneously. Moreover, in most cases complex multi-route exposure scenarios also need to be accounted for. This paper introduces and evaluates the performance of the Probabilistic Aggregate Consumer Exposure Model (PACEM) applied in the context of a tiered approach to exposure assessment for ingredients in cosmetics and personal care products (C&PCPs) using decamethylcyclopentasiloxane (D5) as a worked example. It is demonstrated that PACEM predicts a more realistic, but still conservative aggregate exposure within the Dutch adult population when compared to a deterministic point estimate obtained in a lower tier screening assessment. An overall validation of PACEM is performed by quantitatively relating and comparing its estimates to currently available human biomonitoring and environmental sampling data. Moderate (by maximum one order of magnitude) overestimation of exposure is observed due to a justified conservatism built into the model structure, resulting in the tool being suitable for risk assessment.