Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Speciation of PM₁₀ sources of airborne non-ferrous metals within the 3-km zone of lead/zinc smelters

The purpose of this study was to estimate the speciation of PM10 sources of airborne Pb, Zn, and Cd metals (PM10 is an aerosol standard of aerodynamic diameter less than 10 m.) in the atmosphere of a 3 km zone surrounding lead/zinc facilities in operation for a century. Many powdered samples were collected in stacks of working units (grilling, furnace, and refinery), outdoor storages (ores, recycled materials), surrounding waste slag (4 Mt), and polluted topsoils (3 km). PM10 samples were generated from the raw powders by using artificial resuspension and collection devices. The bulk PM10 multielemental analyses were determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES). The proportions in mass of Pb (50%), Zn (40%), and Cd (1%) contents and associated metals (traces) reach the proportions of corresponding raw powdered samples of ores, recycled materials, and fume-size emissions of plants without specific enrichment. In contrast, Pb (8%) and Zn (15%) contents of PM10 of slag deposit were found to be markedly higher than those of raw dust, Pb (4%), and Zn (9%), respectively. In the same way, Pb (0.18%), Zn (0.20%), and Cd (0.004%) were enriched by 1.7, 2.1, and 2.3 times, respectively, in PM10 as compared with raw top-soil corresponding values. X-ray wavelength dispersive electron-microprobe (EM-WDS) microanalysis did not indicate well-defined phases or simple stoichiometries of all the PM10 samples at the level of the spatial resolution (1 m3). X-ray photoelectron spectroscopy (XPS) indicated that minor elements such as Cd, Hg, and C are more concentrated on the particle surface than in the bulk of PM10 generated by the smelting processes. (XPS) provided also the average speciation of the surface of PM10; Pb is mainly represented as PbSO4, Zn as ZnS, and Cd as CdS or CdSO4, and small amounts of coke were also detected. The speciation of bulk PM10 crystallized compounds was deduced from XRD diffractograms with a raw estimation of the relative quantities. PbS and ZnS were found to be the major phases in PM10 generated by the smelting facilities with PbSO4, PbSO4·PbO, PbSO4·4PbO, Pb metal, and ZnO as minor phases. The slag waste PM10 was found to contain some amounts of PbCO3, PbSO4·PbO, and ZnFe2O4 phases. The large heterogeneity at the level of the individual particle generates severe overlap of chemical information even at the m scale using electron microprobe (WDS) and Raman microprobe techniques. Fortunately, scanning Raman microspectrometry combined with SIMPle-to-use Interactive Self-modeling Mixture Analysis (SIMPLISMA) performed the PM10 speciation at the level of individual particles. The speciation of major Pb, Zn, and Cd compounds of PM10 stack emissions and wind blown dust of ores and recycled materials were found to be PbSO4, PbSO4·PbO, PbSO4·4PbO, PbO, metallic Pb, ZnS, ZnO, and CdS. The PM10 dust of slag waste was found to contain PbCO3, Pb(OH)2·2PbCO3, PbSO4·PbO, and ZnS, while PM10-bound Pb, Zn of the top-soils contain Pb5(PO4)3Cl, ZnFe2O4 as well as Pb(II) and Zn(II) compounds adsorbed on Fe(III) oxides and in association with clays

Wideband TLM Modeling of Planar Antennas on Saturated Ferrite Substrate

International audienc

Absorption et régénération de l'azote dans le système brassé de la Manche : productions nouvelle et régénérée

Nitrate and ammonium uptake rates were measured in spring and summer in deep and shallow well-mixed waters of the English Channel during different cruises between 1986 and 1994. In the deep waters, nitrate uptake was relatively low during phytoplankton development and ammonium uptake represented more than 70 % of the total uptake irrespective of the season. In the shallow waters, nitrate uptake during spring phytoplankton growth was high and represented about 75 % of the total uptake. Ammonium uptake became substantial towards the end of spring and summer. The high contribution of ammonium to the nitrogenous nutrition of phytoplankton over the whole of the well-mixed waters is related to a high rate of recycling of nitrogen in the water column. Ammonium regeneration by microheterotrophs can satisfy between 62 % and the totality of the phytoplankton nitrogen requirements. The high primary production in deep well-mixed waters is not supported by allochthonous nitrogen supply but by an intense in situ regeneration of nitrogen. The situation is similar in shallow well-mixed waters, except during the spring bloom.L'absorption du nitrate et de l'ammonium a été étudiée au printemps et en été dans les systèmes brassés profond et peu profond de la Manche. Les travaux ont été réalisés lors de différentes campagnes à la mer menées entre 1986 et 1994. Dans le système brassé profond, le nitrate est peu utilisé durant la période de développement du phytoplancton et l'absorption de l'ammonium représente, quel que soit le secteur, plus de 70 % de l'absorption totale. Dans le système brassé peu profond, l'absorption du nitrate s'avère élevée en période de floraison du phytoplancton. Elle représente alors 75 % de l'absorption totale. La contribution de l'ammonium à la nutrition azotée du phytoplancton est marquée à la fin de la floraison printanière et en période estivale. Cette contribution élevée de l'ammonium est liée, dans l'ensemble du système brassé, à un recyclage rapide de l'azote dans la colonne d'eau. La régénération de l'ammonium par les microhétérotrophes permet de satisfaire entre 62 % et la totalité des besoins du phytoplancton. Les valeurs élevées de production primaire dans le système brassé profond ne résultent pas d'apports nouveaux en azote mais correspondent à de fortes productions régénérées. En dehors de la floraison printanière du phytoplancton, la situation est similaire dans le système brassé peu profond