Frédéric Dor

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.

Exposure of City Residents to Carbon Monoxide and Monocyclic Aromatic Hydrocarbons during Commuting Trips in the Paris Metropolitan Area

Abstract A study was conducted from October 1991 to September 1992 in the Paris metropolitan area to assess the exposure of city-dwellers who are directly or indirectly exposed to car exhaust fumes...

Air Pollution and Health: Correlation or Causality? The Case of the Relationship between Exposure to Particles and Cardiopulmonary Mortality

ABSTRACT William Dab (M.D., Ph.D.) was responsible for the project as the general representative of the APPA. Claire Ségala (M.D., MPH, SEPIA) was the main researcher. The other members of the working group are Frédéric Dor (Ph.D., Institut de Veille Sanitaire), Bernard Festy (president of the APPA), Philippe Lameloise (AIRPARIF), Yvon Le Moullec (Laboratoire dHygiène de la Ville de Paris), Alain Le Tertre (MSc, Institut de Veille Sanitaire), Sylvia Médina (M.D., MSc, Institut de Veille Sanitaire), Philippe Quénel (M.D., Ph.D., Institut de Veille Sanitaire), Benoît Wallaert (PU-PH, Faculté de Médecine de Lille) and Denis Zmirou (M.D., Ph.D., MCU-PH Faculté de Médecine de Grenoble). Many epidemiologic studies have observed, in different contexts, a slight short-term relationship between particles in air and cardiopulmonary mortality, even when air quality standards were respected. The causality of this relationship is important to public health because of the number of people exposed. Our aim was to make a critical assessment of the arguments used in 15 reviews of published studies. We explain the importance of distinguishing validity from causality, and we systematically analyze the various criteria of judgment within the context of ecologic time studies. Our conclusion is that the observed relationship is valid and that most of the causality criteria are respected. It is hoped that the level of exposure of populations to these particles be reduced. In Europe, acting at the root of the problem, in particular on diesel emissions, will also enable the reduction of levels of other pollutants that can have an impact on health. In the United States, the situation is more complicated, as particles are mainly secondary. It is also essential to continue with research to become better acquainted with the determinants of personal global exposures and to better understand the toxic role of the various physicochemical factors of the particles.

Urinary arsenic concentrations and speciation in residents living in an area with naturally contaminated soils

A cross sectional study was carried out to evaluate arsenic exposure of residents living in an area with a soil naturally rich in arsenic (As), through urinary measurements. During the summer of 2007, 322 people aged over 7 years and resident in the study area for at least 4 days prior to the investigation were recruited. The sum of urinary inorganic arsenic and metabolites (iAs+MMA+DMA) and speciation were determined by graphite furnace atomic absorption spectrometry and high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry, respectively. Geometric means levels of iAs+MMA+DMA were 3.6 microg/L or 4.4 microg/g creatinine. The percent of DMA, As(III) and MMA contribution to urinary arsenic concentrations was respectively 84.2%, 12% and 3.7%. We found significant associations between urinary arsenic concentrations and the consumption of seafood (p=0.03), the consumption of wine (p=0.03) and beer (p=0.001), respectively 3 and 4 days before the investigation. When we focus on the various species, As(V) was rarely detected and DMA is the predominant metabolite composing the majority of measurable inorganic-related As in the urine. Considering the percent of DMA contribution to iAs+MMA+DMA urinary concentrations, almost half of the subjects had 100% of DMA contribution whatever the concentration of urinary As whereas the others had a lower DMA contribution, between 39 and 90%. Arsenic levels reported in this original study in France were between 2 and 4 times lower than in other studies dealing with iAs+MMA+DMA levels associated with soil arsenic exposure. Arsenic levels were similar to those observed in unexposed individuals in European countries, although 10% were above the French guideline values for the general population.

Feasibility of assessing dermal exposure to PAHs of workers on gaswork sites--the SOLEX study.

Population exposure to pollutants in soil is an important public health concern. Difficult to measure, it is usually estimated using multimedia models. Modeling data predict that the skin surface is a predominant exposure route in roughly 15% of the US Superfund sites. Nonetheless, no study has confirmed these predictions. The SOLEX study was an opportunity to study the feasibility of estimating the cutaneous polycyclic aromatic hydrocarbons (PAHs: all 16 of the United States Environmental Protection Agency list) load of workers at three former manufactured gas sites, one of those being under remediation. Over two measurement periods (November 1997 and June 1998), 30 and 28 volunteers, respectively, were equipped for a single day work with five pads that collected soil particles and were placed at the neck, shoulder, wrist, groin, and ankle. Pad contamination was observed for six of the nine workers on the site being remediated but not on other sites. The wrist pad was most often affected, followed by the neck pad, these are, the exposed regions of the body. The PAHs most frequently identified were anthracene, fluoranthene, naphthalene, phenanthrene, and pyrene, at concentrations relatively high. In conclusion, this study showed that estimating skin exposure to soil pollutants is feasible. Secondly, it suggested that only subjects in close contact with the soil had a detectable exposure to PAHs. Extension of this approach to other exposure settings is warranted, especially among children playing in polluted public or private gardens, because their games lead to frequent contact with the soil.

Pollution Atmosphérique et Santé: Corrélation ou Causalité? Le Cas de la Relation entre l'Exposition aux Particules et la Mortalité Cardio-pulmonaire

De nombreuses études épidémiologiques ont observé dans des contextes différents une faible relation à court terme entre les particules et la mortalité cardio-pulmonaire, même quand les normes de qualité de lair nétaient pas dépassées. La causalité de cette relation est un enjeu de santé publique en raison de limportance de la population exposée. Notre objectif est de faire linventaire critique des arguments utilisés dans 15 revues de la littérature publiées. Nous expliquons limportance de distinguer la validité de la causalité et analysons de façon systématique les différents critères de jugement dans le contexte des études écologiques temporelles. Notre conclusion est que la relation observée est valide et que la plupart des critères de causalité sont respectés. Diminuer le niveau dexposition des populations aux particules est souhaitable. En Europe, en agissant à la source, notamment sur les émissions Diesel, on diminuera aussi dautres polluants qui peuvent jouer un rôle sanitaire. Aux États-Unis, la situation est plus complexe car les particules sont surtout secondaires. Il est également indispensable de poursuivre les recherches pour mieux connaître les déterminants des expositions globales des individus et mieux comprendre le rôle toxique des différents facteurs physico-chimiques des particules.

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.

Does arsenic in soil contribute to arsenic urinary concentrations in a French population living in a naturally arsenic contaminated area

A cross sectional study using environmental and biological samples was implemented to assess the association between arsenic (As) concentrations in the environment and urinary As levels of residents living in an area where the soil is naturally As rich. As was measured in drinking water, atmospheric particulate matter, and soil and a geographic information system was used to assign environmental concentrations closest to the participants dwellings and the sum of inorganic As and metabolites in urine samples. The only potential source of As environmental contamination was from soil with a range of 13-131 mg As/kg of dry matter. As(V) was the only species present among As extracted from the analyzed soil samples. The chemical extraction showed a poor mobility of As soil. There was no difference between child and teenager, and adult urinary As concentrations, though men had higher urinary As concentrations than women (p<0.001). Given the important differences in lifestyle between 7-18 year olds, men, and women, these groups were analyzed separately. Whilst we were unable to find a stable model for the 7-18 year old group, for the adult men group we found that seafood consumption in the 3 days prior to the investigation (p=0.02), and beer (p=0.03) and wine consumption in the 4 days before the study, were associated with As urinary levels (μg/L). In adult women, creatinine was the only variable significantly associated with As urinary concentration (μg/L). The concentrations we measured in soils were variable and although high, only moderately so and no link between As concentrations in the soil and urinary As concentrations could be found for either men or women. Some individual factors explained half of the variability of adult men urinary As levels. The unexplained part of the variability should be searched notably in As mobility in soil and uncharacterized human behavior.

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.

Personal Exposure of Workers to Atmospheric PAHs on Gasworks Sites - The SOLEX Study

The aim of the SOLEX study was to estimate the personal exposure of workers to atmospheric polycyclic aromatic hydrocarbons (PAHs) on former gasworks sites in the Paris metropolitan area. Devices to sample gas and particulate phases for 9 PAHs were carried during one working day of a study week in November 1997 by 24 workers and in June 1998 by 19 workers with contrasted job profiles involving different opportunities for contact with the soil; among these volunteers, some were active in the process of contaminated soil remediation during the November study period. PAH concentrations were measured by high-performance liquid chromatography. Subjects working on the site under remediation were clearly more exposed (684.1 ng/m3 for total PAHs in November 1997) than workers, without close contact with soil, whose PAH exposure was similar to that measured by fixed monitors in the ambient air in Paris. The contrasts were weaker in June 1998, when soil remediation had nearly been completed. Only subjects involved in activities with close contact with the ground were found with exposures exceeding background levels. Further investigations are needed to improve our understanding of the influence of the pollutants present in the soil.