Pascal Empereur-Bissonnet

Validity of Biomarkers in Environmental Health Studies: The Case of PAHs and Benzene

Exposure biomarkers, which have long been restricted to the framework of occupational hygiene, currently arouse increasing interest in the field of environmental pollution. To assess their validity, we propose here a conceptual framework that is based on their intrinsic characteristics and on properties related to the procedures for their analysis. The most important criteria are specificity for the toxic substance under consideration and sensitivity, that is, the ability to distinguish contrasted levels of exposure. Their analytic sensitivity and specificity are also important. Fulfilling these criteria is especially important in the context of environmental pollution, because the levels of exposure, and thus the contrasts, are low. This framework is used to assess the validity of some biomarkers for polycyclic aromatic hydrocarbons (1-hydroxypyrene and DNA adducts) and for benzene (urinary and serum benzene, trans,trans muconic acid, and S-phenylmercapturic acid). This evaluation shows that the most relevant biomarkers for estimating individual exposure to environmental pollution are 1-hydroxypyrene for polycyclic aromatic hydrocarbons and urinary benzene and S-phenylmercapturic for benzene.

Urinary 1-hydroxypyrene as a biomarker of polycyclic aromatic hydrocarbons exposure of workers on a contaminated site : Influence of exposure conditions

The aim of the study was to determine the exposure levels of workers to polycyclic aromatic hydrocarbons on gasworks sites by the measurement of urinary 1-hydroxypyrene. Start-shift and end-shift urine samples were taken every day during an entire week (Monday to Friday), once in November and a second time in June. Four groups of workers were selected according to their activity. Increased exposure was only found among volunteers involved in the remediation of a site, 0.16 to 2.31 mumol/mol creatinine in non-smokers. The median of the non-smoker referent group was 0.02 mumol/mol creatinine (95% confidence interval, 0.01 to 0.04). Smokers had greater exposure levels than non-smokers in every group. Within and between variability was around 200%. Assessment of the exposure of persons on contaminated soil is possible, with the condition that the exposed subjects come in direct contact with the soil.

Health Impact of the 2003 Heat-Wave in France

An unprecedented heat-wave struck France in early August 2003, associated to high levels of air pollution. The meteorological event was accompanied by an excess of mortality that started early and rose quickly. Between August 1st and 20th, the excess of deaths reached 14,802 cases in comparison to the average daily mortality in the 2000 – 2002 period. It represents +60 % of mortality for all causes. The observed excess of mortality first affected the elderly (+70 % for 75 years-old and more), but was also severe for the 45 – 74 year olds (+30 %). In all age groups, females mortality was 15 to 20 % higher than male. Almost the whole country was affected by the excess-mortality, however its intensity varied significantly from one region to another and was at a maximum in Paris and suburbs (+142 %). The excess mortality clearly increased with the duration of extreme temperatures. With regard to the location, the highest mortality rate affected nursing homes where the number of deaths observed was twice the expected number. Following the descriptive studies carried out immediately after the heat-wave, two case-control surveys were carried out. The first study was conducted to identify individual risk factors (way of life, medical history, self sufficiency) and environmental factors (housing) in elderly people living at home. The second one was conducted to identify individual risk factors (autonomy/handicap, medical condition, drug consumption) and environmental risk factors (number and quality of personnel available; facility size and characteristics; prevention plans and therapeutic protocols) for elderly residing in a nursing home. This survey was made in two parts: a “facility case-control study” and an “individual case-control study”. High levels of photochemical air pollution were associated to the heat-wave. A study was conducted to estimate the fraction attributable to ozone in the excess risks of mortality jointly related to temperature and ozone, and also to identify a decrease of expected mortality in the weeks following the heat-wave. In cities having experienced the highest excess risk of mortality (Paris, Lyon) the contribution of ozone was minor relative to temperature; the relative part of this air pollutant was higher but variable in cities where the excess risk of mortality was low. The study did not show a harvesting effect within the three weeks following the heat-wave. The French Heat-Wave National Plan, developed immediately after the 2003 event, includes a Heat Health Watch Warning System operating from 2004 and covering the whole country.

Validation of multimedia models assessing exposure to PAHs--the SOLEX study.

Polluted soils have become a public health problem. While population exposure to soil pollutants is generally quantified using multimedia models, their estimations have not been validated, and studies that attempted to do so are scarce. The objective of the SOLEX study was to compare the predictions of pyrene exposure levels (converted into 1 hydroxypyrene) computed by several models with the results of urinary 1-hydropyrene (1-HOP) assays among 110 employees working at three sites polluted during their past use as manufactured gas plants. Four models were used: AERIS (Canada), CalTOX (California, USA), CLEA (UK), and HESP (The Netherlands). Three occupational exposure scenarios--with office, mixed, and outdoor workers--were constructed, based upon job activities during two measurement campaigns, one in winter and one in summer. The exposure levels estimated by the four models could differ markedly (from 7 up to 80 times) according to the exposure scenario. Also, the predominant exposure routes differed according to the model (direct soil ingestion for HESP and CalTOX, inhalation for AERIS, and dermal absorption for CLEA). The predictions of CalTOX are consistent with the 1-HOP measurements for all the scenarios. For HESP, the consistency is observed for the scenarios, office and mixed, for which the pyrene level in the soil is low. AERIS and CLEA yield results that are systematically above the 1-HOP measurements. This study confirms that validation of the models is crucial and points out to the need to proceed to assess components of the models that are the most influential using appropriate statistical analysis in combination with true field data.

Risk of cancer in the vicinity of municipal solid waste incinerators: importance of using a flexible modelling strategy.

BackgroundWe conducted an ecological study in four French administrative departments and highlighted an excess risk in cancer morbidity for residents around municipal solid waste incinerators. The aim of this paper is to show how important are advanced tools and statistical techniques to better assess weak associations between the risk of cancer and past environmental exposures.MethodsThe steps to evaluate the association between the risk of cancer and the exposure to incinerators, from the assessment of exposure to the definition of the confounding variables and the statistical analysis carried out are detailed and discussed. Dispersion modelling was used to assess exposure to sixteen incinerators. A geographical information system was developed to define an index of exposure at the IRIS level that is the geographical unit we considered.Population density, rural/urban status, socio-economic deprivation, exposure to air pollution from traffic and from other industries were considered as potential confounding factors and defined at the IRIS level. Generalized additive models and Bayesian hierarchical models were used to estimate the association between the risk of cancer and the index of exposure to incinerators accounting for the confounding factors.ResultsModelling to assess the exposure to municipal solid waste incinerators allowed accounting for factors known to influence the exposure (meteorological data, point source characteristics, topography). The statistical models defined allowed modelling extra-Poisson variability and also non-linear relationships between the risk of cancer and the exposure to incinerators and the confounders.ConclusionIn most epidemiological studies distance is still used as a proxy for exposure. This can lead to significant exposure misclassification. Additionally, in geographical correlation studies the non-linear relationships are usually not accounted for in the statistical analysis. In studies of weak associations it is important to use advanced methods to better assess dose-response relationships with disease risk.

The French approach to deriving toxicity reference values: An example using reprotoxic effects

Following the French health and environment action plan, the French Agency for Environmental and Occupational Health and Safety set up a workgroup to standardise a method of deriving toxicity reference values (TRVs). Over the last few decades, there has been increasing concern about the effect of exposure to chemicals on reproductive function, leading the group to take an interest in reprotoxic effects. This article presents the recommendations of the workgroup regarding specific reprotoxic effects. Abnormal development of foetuses and infants, together with impairment of reproduction were considered to be critical effects. Where critical windows of exposure were concerned, quantitative analysis suggested the need for several types of toxicity reference value, as a function of exposure duration: reprotoxic effects may result from acute or chronic exposure at any time of life, whilst developmental effects may occur after exposure during the pregnancy or during the lactation period. The choice of a critical study is based on epidemiological or toxicological quality criteria. The working group recommends the use of the benchmark dose approach in estimating the critical dose. Finally, the working group considered the application of uncertainty factors typically used to take into account the variability between animal and human, between different individuals, and the availability of the data.