In view of the toxic properties of nanoparticles, the authorities require them to be specifically identified and labeled This is in keeping with the spirit of the REACH legislation, which aims to protect consumers from products with inadequately documented risks for human health and the environment. However, the presence of natural nanoparticles in the environment must also be taken into account, together with the fact that, in any mixture of particles, the presence of a fraction of nanometer-sized particles cannot be ruled out, owing to the laws of statistical distribution. Moreover, while all toxic nanoparticles generate oxidative stress, their properties are not due solely to their size but also to their shape, surface texture and composition. Thus, nanoparticle toxicity should be considered specifically for each substance or group of substances, and the notion of intentional manufacture of nano-sized particles should be included in the impact assessment. The conditions of nanoparticle concentration/dilution and persistence, especially in water and sewage sludge, exemplified by silver and titanium oxide, suggest that nanoparticle behavior in the environment should be monitored.

Biomass is an important renewable resource of primary energy. Wood burning is expected to expand in future as a cheap means of residential heating, especially in wood-producing rural areas. The health consequences of wood smoke are taken in account far less actively in Europe than in North America, where stringent limitations have been introduced, such as those of the EPA Burnwise project. Recently, wildfires were estimated to release 2 petagrams of carbon into the atmosphere worldwide, contributing to more than 300 000 deaths annually. More effective measures are thus needed to prevent indoor and outdoor exposure to wood smoke. Ultrafine particles are the biggest concern, but the volatile phase also contains many toxicants. Ultrafine particles are among the most dangerous carbonaceous particles found in polluted atmospheres. They can be identified by using C14, levoglucosan, crystallography and spectrometry. Any expansion of the use of wood as a fuel source should take into account its health impact, which is similar to that of fossil fuels.

La biomasse représente une ressource non négligeable d’énergie primaire. L’utilisation du bois comme moyen de chauffage est attrayante en tant qu’énergie verte et elle a des avantages économiques incontetables en milieu rural. Le renchérissement de l’énergie laisse prévoir son développement. Les conséquences sanitaires des fumées de bois de chauffage sont cependant peu prises en compte en Europe alors qu’elles sont nettement plus encadrées en Amérique du Nord, notamment par l’EPA avec son programme « Burnwise ». Les récents épisodes d’incendies de forêts ont attiré l’attention sur leur danger en chiffrant les décès imputables à plus de 300 000 morts par an correspondant à l’émission dans l’atmosphère de deux milliards de tonnes de carbone. Ce sont les particules ultrafines générées par la combustion qui sont le plus préoccupantes. On peut en déterminer la signature par différents traceurs : lévoglucosane, C14, cristallographie, spectrométrie ; leur toxicité est au moins égale à celle des fines particules carbonées polluant l’atmosphère. De nombreuses substances toxiques volatiles préoccupantes sont également produites lors de la combustion incomplète du bois. Tout développement de cette filière devra prendre en compte les conséquences sanitaires qui ne sont guère différentes de celles de la combustion des combustibles fossiles.

Objective: To perform a quantitative estimate of the proportion of cancers attributable to occupational exposures in France in 2000. Methods: Exposure data for established carcinogens were obtained from a 1994 survey and other sources. Relative risks for 23 exposure-cancer combinations were derived from meta-analyses and pooled analyses. Results: A total of 4335 cases of cancer among men (2.7% of all cancers) and 403 cases among women (0.3% of all cancers) were attributed to occupational exposures. Asbestos, polycyclic aromatic hydrocarbons, and chromium VI were the main occupational carcinogens in men, and asbestos and involuntary smoking were the main carcinogens in women. Corresponding proportions for cancer deaths were 4.0% and 0.6% in men and women, respectively. Lung cancer represented 75% of deaths attributable to occupational exposures. Conclusion: Our estimates are comparable with those obtained for other countries in studies based on similar methodology.

Iodine deficiency is a worldwide issue that has not spared Europe. Its health consequences and especially its adverse effects on the growth and development of fetuses, infants, and children are well known. Perchlorates and nitrates impair iodine uptake in the thyroid gland by competitive inhibition of iodine symporter and thus merit the attention paid to other endocrine disruptors, an attention they have not yet received in France. In the US a reference dose of 0.07 to 0.7 mu g/kg has been proposed for perchlorates, which would result in a safe limit of 1.5 to 15 mu g/L of water, after consideration of a safety factor of 10 for fetus and infants. Because nitrate ions, while 240 times less effective than perchlorates, are more than 1 000 times more abundant, elevated nitrate concentrations in some surface waters are a matter of concern, and some French subpopulations with iodine deficiency may be at risk. Moreover, an inventory of perchlorate exposure should be planned.

Outdoor air pollution and health : despite the overall reduction in air pollution over the years, with the noteworthy exception of carbon dioxide, scientists agree that there remain plausible statistical relations between different atmospheric pollutants and the short-term and long-term risk of certain respiratory and cardiovascular diseases. Although the relative risks are weak, the universal nature of the exposure can incur considerable medical costs. The frequently expressed fear of synergy among pollutants appears unfounded, as the current marginal risk already results from an extremely complex mixture of pollutants whose concentrations have been decreasing for more than 30 years. Attention is currently focusing on the roles of ozone and fine particles. Better knowledge of fine particle origin, composition, size and potential toxic mechanisms is needed. Indoor air pollution and health : the possible medical consequences of exposure to the pollutants of room air is an emerging issue. Domestic exposure combines pollutants contained in outdoor air with those of the habitat itself Exposure can occur for up to 80 % of the day Recent investigations suggest that 9 % of homes are highly polluted and that 45 % are only slightly polluted, but epidemiological studies are still too rare to draw conclusions, except in the case of allergens, tobacco smoke, radon, and asbestos. Based on the intrinsic properties of toxins present in room air, one might expect irritant, immunotoxic, neurotoxic, carcinogenic and reprotoxic effects. Reference values are needed to assess associated health risks but are likely to be highly controversial.

Air extérieur et santé : malgré la réduction globale de la pollution atmosphérique, à l’exception du dioxyde de carbone, il y a consensus parmi les scientifiques pour admettre qu’il demeure une relation statistique plausible, entre les différents constituants de la pollution atmosphérique d’une part, et certaines maladies respiratoires et cardio-vasculaires à court et long terme d’autre part. Bien que les risques relatifs mis en évidence soient faibles, la prévalence universelle de l’exposition entraîne un coût sanitaire non négligeable. Par contre, la crainte fréquemment exprimée d’effets imprévisibles dus à des effets synergiques de polluants paraît infondée, tant la situation sanitaire présente, caractérisée par un risque marginal, est déjà le résultat d’un mélange extrêmement complexe de polluants dont la concentration ne fait que décroître depuis plus de trente ans. L’attention se focalise actuellement sur le rôle de l’ozone et des fines particules. Une meilleure caractérisation de l’origine des particules, de leur composition, de leur taille et de leur mécanisme potentiel d’action toxique est nécessaire. Air intérieur et santé : les conséquences sanitaires possibles de l’exposition aux polluants de l’air intérieur constituent un problème émergent. En termes de risques, l’exposition domestique cumule les polluants de l’air extérieur et ceux propres à l’habitat en nombre élevé et dangerosité variable, pour une durée d’exposition représentant 80 % du temps ; à partir d’enquêtes récentes, 9 % de l’habitat apparaît très pollué alors que 45 % ne l’est que peu, cependant les études épidémiologiques sont encore trop rares pour dresser un bilan sanitaire, à l’exception des allergènes, de la fumée de tabac du radon et de l’amiante. Sur la base des propriétés intrinsèques des toxiques de l’air intérieur, les pathologies qui pourraient résulter de ces expositions sont multiples : irritatives, immunotoxiques, neurotoxiques, cancérogènes et reprotoxiques, ce qui nécessiterait qu’on définisse des valeurs guide pour éviter le danger, qu’à défaut d’indicateur pratique de risque, soient extrapolés, des risques virtuels qui deviendront source de contentieux inextricables.

Executive Summary The assessment of carcinogenic risks associated with doses of ionizing radiation from 0.2 Sv to 5 Sv is based on numerous epidemiological data. However, the doses which are delivered during medical X-ray examinations are much lower (from 0.1 mSv to 20 mSv). Doses close to or slightly higher than, these can be received by workers or by populations in regions of high natural background irradiation. Epidemiological studies have been carried out to determine the possible carcinogenic risk of doses lower than 100 mSv, and they have not been able to detect statistically significant risks even on large cohorts or populations. Therefore, these risks are at worse low since the highest limit of the confidence interval is relatively low. It is highly unlikely that putative carcinogenic risks could be estimated or even established for such doses through case-control studies or the follow-up of cohorts. Even for several hundred thousands of subjects, the power of such epidemiological studies would not be sufficient to demonstrate the existence of a very small excess in cancer incidence or mortality adding to the natural cancer incidence which, in non-irradiated populations, is already very high and fluctuates according to lifestyle. Only comparisons between geographical regions with high and low natural irradiation and with similar living conditions could provide valuable information for this range of doses and dose rates. The results from the ongoing studies in Kerala (India) and China need to be carefully analyzed. Because of these epidemiological limitations, the only method for estimating the possible risks of low doses (< 100 mSv) is extrapolation from carcinogenic effects observed between 0.2 and 3 Sv. A linear no-threshold relationship (LNT) describes well the relation between the dose and the carcinogenic effect in this dose range where it could be tested. However, the use of this relationship to assess by extrapolation the risk of low and very low doses deserves great caution. Recent radiobiological data undermine the validity of estimations based on LNT in the range of doses lower than a few dozen mSv which leads to the questioning of the hypotheses on which LNT is implicitly based: 1) constancy of the probability of mutation (per unit dose) whatever the dose or dose rate, 2) independence of the carcinogenic process which after the initiation of a cell evolves similarly whatever the number of lesions present in neighboring cells and the tissue.

There is no evidence of pathogenic effects in human groups exposed to less than 100 mSv at low dose-rate. The attributed effects are therefore the result of extrapolations from higher doses. The validity of such extrapolations is discussed from the point of view of epidemiology as well as cellular and molecular biology. The Chernobyl accident resulted in large excess of thyroid cancers in children; it also raised the point that some actual sanitary effects among distressed populations might be a direct consequence of low doses. Studies under the control of UN have not confirmed this point identifying no dose-effect relationship and "severe socio-economic and psychological pressures... poverty, poor diet and living conditions, and lifestyle factors" as the main cause for depressed health. Some hypothesis are considered for explaining the dose-dependence and high prevalence of non-cancer causes of death among human groups exposed to more than 300 mSv. (C) 2002 Academie des sciences/Editions scientifiques et medicales Elsevier SAS.

Everyone is exposed to radiation from natural, man-made and medical sources, and world-wide average annual exposure can be set at about 3.5 mSv. Exposure to natural sources is characterised by very large fluctuations, not excluding a range covering two orders of magnitude. Millions of inhabitants are continuously exposed to external doses as high as 10 mSv per year, delivered at low dose rates, very few workers are exposed above the legal limit of 50 mSv/year, and referring to accidental exposures, only 5% of the 116,000 people evacuated following the Chernobyl disaster encountered doses above 100 mSv. Epidemiological survey of accidentally, occupationally or medically exposed groups have revealed radio-induced cancers, mostly following high dose-rate exposure levels, only above 100 mSv. Risk coefficients were derived from these studies and projected into linear models of risk (linear non-threshold hypothesis: LNT), for the purpose of risk management following exposures at low doses and low dose-rates. The legitimacy of this approach has been questioned, by the Academy of sciences and the Academy of medicine in France, arguing: that LNT was not supported by Hiroshima and Nagasaki studies when neutron dose was revisited; that linear modelling failed to explain why so many site-related cancers were obviously non-linearly related to the dose, and especially when theory predicted they ought to be; that no evidence could be found of radio-induced cancers related to natural exposures or to low exposures at the work place; and that no evidence of genetic disease could be shown from any of the exposed groups. Arguments were provided from cellular and molecular biology helping to solve this issue, all resulting in dismissing the LNT hypothesis. These arguments included: different mechanisms of DNA repair at high and low dose rate; influence of inducible stress responses modifying mutagenesis and lethality; bystander effects allowing it to be considered that individual cellular responses reflected in fact the results of multiple cellular interactions. Following the conclusion of the French Academy of medicine, LNT modelling resulted in public anxiety by changing an hypothetical residual risk at low doses into a real one, calling on regulators, continuously, for a more and more severe control of tiny sources which may result in considerable collective doses when considered as being exposed to billions of people for hundreds of years. Examples were provided that showed that the perception of risk of radioactive sources was not related to the severity of the risk itself but to the importance attributed to the situation by the media. In some instances, such as those resulting from the loss of gammagraphy sources, it resulted in a dangerous underestimate of the necessary remedial actions.

Everyone is exposed to radiation from natural, man-made and medical sources, and world-wide average annual exposure can be set at about 3.5 mSv. Exposure to natural sources is characterised by very large fluctuations, not excluding a range covering two orders of magnitude, Millions of inhabitants are continuously exposed to external doses as high as 10 mSv per year, delivered at low dose rates, very few workers are exposed above the legal limit of 50 mSv/year, and referring to accidental exposures, only 5 % of the 116 000 people evacuated following the Chernobyl disaster encountered doses above 100 mSv, Epidemiological survey of accidentally, occupationally or medically exposed groups have revealed radio-induced cancers, mostly following high dose-rate exposure levels, only above 100 mSv. Risk coefficients were derived from these studies and projected into linear models of risk (linear non-threshold hypothesis: LNT), for the purpose of risk management following exposures at low doses and low dose-rates. The: legitimacy of this approach has been questioned, by the Academy of sciences and the Academy of medicine in France, arguing: that LNT was not supported by Hiroshima and Nagasaki studies when neutron dose was revisited; that linear modelling failed to explain why so many site-related cancers were obviously non-linearly related to the dose, and especially when theory predicted they ought to be; that no evidence could be found of radio-induced cancers related to natural exposures or to low exposures at the work place; and that no evidence of genetic disease could be shown from any of the exposed groups. Arguments were provided from cellular and molecular biology helping to solve this issue, all resulting in dismissing the LNT hypothesis. These arguments included: different mechanisms of DNA repair at high and low dose rate; influence of inducible stress responses modifying mutagenesis and lethality; bystander effects allowing it to be considered that individual cellular responses reflected in fact the results of multiple cellular interactions. Following the conclusion of the French Academy of medicine, LNT modelling resulted in public anxiety by changing an hypothetical residual risk at low doses into a real one, calling on regulators, continuously, for a more and more severe control of tiny sources which may result in considerable collective doses when considered as being exposed to billions of people fur hundreds of years. Examples were provided that showed that the perception of risk of radioactive sources was not related to the severity of the risk itself but to the importance attributed to the situation by the media. In some instances, such as those resulting from the loss of gammagraphy sources, it resulted in a dangerous underestimate of the necessary remedial actions. (C) 2000 Academie des sciences/Editions scientifiques ct medicales Elsevier SAS.

This work describes quantitative MRI assessment of primate brain maturation. Nine young baboons were followed from the age of one to 30 months. Assessment of myelination was based on the gray/white matter contrast on MR images and the evolution of T2 relaxation time respectively. The brain maturation began in the posterior fossa and progressed to the olfactory bulbs corresponding to decreasing white matter T2 values. Relaxation parameters provide new opportunities to trace the myelination process in vivo.

Purpose: Using magnetic resonance (MR) and isotopic imaging to investigate the cerebral alterations after high-dose single-fraction irradiation on a pig model. We assessed the nuclear magnetic resonance (NMR) relaxation times as early markers of radiation injury to the healthy brain.Methods and Materials: A total of 17 animals was studied; 15 irradiated and 2 unirradiated controls. Pigs were irradiated with a 12 MeV electron beam at a rate of 2 Gy/min. Ten animals received 40 Gy at the 90% isodose, five animals received 60 Gy, and two animals were unirradiated. The follow-up intervals ranged from 2 days to 6 months. T-1-weighted scans, T-2-weighted scans, and scintigrams were performed on all animals to study neurological abnormalities, cerebral blood flow, and blood-brain barrier (BBB) integrity. T-1 and T-2 relaxation times were measured in selected regions of interest (ROIs) within the irradiated and contralateral hemispheres. A ratio T-1 after irradiation/T-1 before irradiation, and a ratio T-2 after irradiation/T-2 before irradiation, were calculated, pooled for each dose group, and followed as a function of time after irradiation.Results: Scintigraphy visualized the brain perfusion defect and BBB disruption in all irradiated brains. The ratio T-2 after irradiation/T-2 before irradiation was proportional to the effective dose received. The T-2 ratio kinetics could be analyzed in three phases: an immediate and transient phase, two long-lasting phases, which preceded compression of the irradiated lateral ventricle, and edema and necrosis at later stages of radiation injury, respectively. The magnetic resonance imaging (MRI) observations correlated well with histological analysis.Conclusion: The results show that quantitative imaging is a sensitive in vivo method for early detection of cerebral radiation injury. The reliability and dose dependence of T-2 relaxation time may offer new opportunities to detect and understand brain pathophysiology after high-dose single-fraction irradiation.

This study was designed to compare the translocation from lung of the Pu contained in the pure and mixed industrial oxides PuO2 and (U,Pu)O2. The latter had a Pu content of 20% w/w. For this purpose, young adult male rats and male and female baboons were exposed to a single inhalation of these oxides. Two baboons were exposed to the reference PuO2, i.e. 239PuO2. Rats were killed under anaesthesia 1, 15, 30, 90 and 180 days after exposure, and baboons, also under anaesthesia, 1 year thereafter. The results indicate that lung retention of Pu was independent of the oxide inhaled, but was smaller in rat (12-15% of the initial pulmonary burden, 6 months after exposure) than in baboon (56-80% of this burden, 1 year after exposure). In rat, Pu translocation kinetics were similar for the two industrial oxides, but as from day 15 after inhalation until 6 months thereafter, measurement of Pu deposits in the liver and skeleton showed that translocation of Pu from the mixed oxide was 2-3 times greater than that from the industrial Pu oxide. In baboon, the largest amounts of Pu were retained in the lung and thoracic lymph nodes for the three oxides inhaled. Pu translocation to the liver, skeleton and kidneys, and also urinary Pu excretion, were greater after inhalation of the mixed oxide than after inhalation of the industrial and reference Pu oxides. Nevertheless, the amount of mixed oxide Pu translocated to these sites and excreted in urine remained under 3% of the initial pulmonary burden.

Preliminary results are given on a comparative study of kidney and liver toxicity induced by the administration of DTPA or 3,4,3-LIHOPO to baboons. The chelating agents were administered intravenously on day 0 and then intramuscularly on days 3, 6, 9, 16, 20, 23 and 26. Individual animals were administered with 30 µmol.kg-1 DTPA, 3 or 30 µmol.kg-1 3,4,3-LIHOPO. Two untreated baboons were used as controls. Animals were housed in individual metabolic cages for 24h before treatment and 7 d after treatment in order to collect urine and blood for measurements of biochemical parameters. Kidney and liver biopsies were performed 8 d after the treatment. The tissue samples were examined by light and electron microscopy. The results obtained suggest that the different chelate treatments did not alter the function and cytology of the kidney and liver in the baboons.

L'ozone est un polluant atmospherique dont les concentrations sont liees a celles des oxydes d'azote et donc aux activites humaines. Par ailleurs, des concentrations de radon importantes sont observees dans plus de 5 % de l'habitat francais. Les donnees de la litterature sur le risque cancerogene ou cocancerogene potentiel de l'ozone sont actuellement parcellaires et contradictoires. Cependant les travaux de l'equipe de C. Borek suggerent la possibilite d'effets synergiques entre l'irradiation et l'exposition a l'ozone. Nous nous sommes proposes d'evaluer le pouvoir cancerogene ou cocancerogene potentiel de l'ozone chez le rat dans un modele experimentai associant a l'inhalation d'ozone une irradiation locale pulmonaire par inhalation de radon 222 et de ses descendants (emetteurs alpha). En effet, il a ete demontre experimentalement qu'un effet cocancerogene se traduisait par une augmentation de l'incidence des tumeurs induites apres administration combinee des agents potentiellement cancerogenes. Le but de ces experimentations est d'evaluer chez le rat le pouvoir cancerogene potentiel de l'ozone, agissant : - soit seul, comme un cancerogene complet, - soit comme un promoteur, apres une initiation par irradiation locale pulmonaire par le radon. Ces experimentations ont porte sur 3 groupes d'animaux : groupe 1 : 50 rats exposes au radon a la dose de 1 000 WLM dont il a ete demontre qu'elle induisait une incidence de 20 a 22 % de cancers du poumon ; groupe 2 : 50 rats exposes au radon a la dose de 1 000 WLM, puis 1 mois apres la fin de l'inhalation de radon a de l'ozone a la concentration de 0,2 ppm , 6 heures par jour, 5 jours par semaine, pendant 6 mois ; - groupe 3 : 50 rats exposes a l'ozone seul , a la concentration de 0,2 ppm , 6 heures par jour, 5 jours par semaine pendant 6 mois. La concentration de 0,2 ppm d'ozone correspond aux concentrations moyennes observees dans les periodes de pollution liees aux episodes de brouillard photochimique. Les resultats de cette etude sont compares en ce qui concerne l'incidence tumorale et les temps de survie a ceux observes dans un groupe historique de 1287 rats temoins non exposes. Une autopsie complete a ete pratiquee sur tous les animaux. L'etude histopathologique est actuellement en cours, mais l'incidence des tumeurs pulmonaires a pu etre evaluee sur la base des lesions macroscopiques. Elle est de 20 % dans le groupe 1, 40 % dans le groupe 2 et 6 % dans le groupe 3, comparee a 0,9 % chez les temoins. Sous reserve de confirmation du diagnostic histopathologique, ces resultats preliminaires suggerent un effet cancerogene ou cocancerogene potentiel de l'ozone chez le rat pour des niveaux d'exposition correspondant a ceux rencontres durant les episodes aigus de pollution urbaine.