232 research outputs found
Genotoxic damage in mine workers exposed to diesel exhaust, and the effects of glutathione transferase genotypes
No full textThis study was performed in an Estonian shale-oil mine with the purpose to develop and apply a number of biomarkers for occupational diesel-exhaust exposure monitoring. Increased breathing-zone exposures to exhaust from operators of diesel-powered trucks in the mine was confirmed in the environmental monitoring part of the study, showing a 7.5-fold higher exposure to particle-associated 1-nitropyrene (1-NP) in 50 underground workers compared with 42 surface workers [P.T.J. Scheepers, D. Coggon, L.E. Knudsen, R. Anzion, H. Autrup, S. Bogovski, R.P. Bos, D. Dahmann, P. Farmer, E.A. Martin, V. Micka, V. Muzyka, H.-G. Neumann, J. Poole, A. Schmidt-Ott, F. Seiler, J. Volf, I. Zwirner-Baier, Biomarkers for occupational diesel exhaust exposure monitoring (BIOMODEM)-a study in underground mining, Toxicol. Lett. 134 (2002) 305-317; P.T.J. Scheepers, V. Micka, V. Muzyka, R. Anzion, D. Dahmann, J. Poole, R.P. Bos, Exposure to dust and particle-associated 1-nitropyrene of drivers of diesel-powered equipment in underground mining, Ann. Occp. Hyg. 47 (2003) 379-388]. Analysis of DNA damage by the Comet assay on frozen blood samples was performed on the total study group and showed significantly higher levels (p=0.003) in underground workers (smokers) driving diesel-powered excavation machines (median 155 on a scale from 0 to 400, among 47 persons), compared with surface workers who smoked (median of 90, among 46 persons). The level of DNA damage in underground smokers was significantly higher (p=0.04) than in non-smokers. Samples from 2 of the 3 sampling weeks had significantly lower DNA damage compared with the third week, probably due to timely processing and freezing. These samples also showed significant differences (p<0.001) between underground workers (median 145, among 41 persons) and surface workers (median 60, among 30 persons). An HPLC method was developed for the analysis of (32)P-postlabelled 1-NP-DNA-adducts, and was applied to a sub-sample of 20 workers. No significant differences between surface and underground workers were found in this sub-sample with respect to the minor, unidentified adducts that had similar chromatographic properties to 1-NP adducts, and smoking did not have any effect on adduct levels. No significant effects of the genotypes of GSTM1, GSTP1 and GSTT1 on DNA-adducts and on DNA damage as measured by the Comet assay were found in the total study group. The study confirms an increased level of DNA damage in workers exposed to exhaust from truck-driving in the mine. However, the results of the environmental and biological monitoring of 1-NP did not correlate, suggesting that inhalation exposure to diesel exhaust is not reflected by an increase in 1-NP-DNA-adduct levels and/or that factors other than occupational exposure to diesel exhaust are primary determinants of these DNA-adduct levels
Toxicological comments to the discussion about REACH
No full textIt is the ultimate goal of the intended REACH process (Registration, Evaluation and Authorization of Chemicals) of the European Union to identify substances of hazardous properties and to evaluate the risks of human and environmental exposure. During the last few months there has been a controversial discussion as to what extent in vitro studies and consideration of structure activity relationship provide sufficient information to waive repeated exposure studies. Industry as well as certain regulatory agencies or NGOs support this approach and propose that repeated dose studies may only be required beyond 100 t/a. From a toxicological point of view it has to be stressed that this discussion primarily considers the cost reduction and protection of animals, whereas protection of human health and the environment are secondary. In vitro studies only allow identification of specific hazardous properties which can be detected by the specific test system. Moreover, appropriate information on the dose response of adverse effects, identification of thresholds and NOELs that are essential for risk characterization cannot be obtained from these studies. Consequently, identification of all relevant hazardous properties and endpoints of adverse effects can only be determined in the intact animal by repeated dose studies such as 28-day or 90-day studies. In the absence of such information the hazard identification is incomplete and there is no basis for appropriate risk assessment of human exposure. Thus, any waiving of repeated dose studies in animals bears the probability of unforeseen effects in case of acute or continuous human exposure. From this the undersigning European Toxicologists conclude: 1. The intention of REACH is to identify hazardous properties in order that a reliable risk assessment can be made and measures taken to deal with chemicals posing a significant risk. 2. The recent debate has centered on ways in which the well established in vivo methods for risk assessment can be bypassed. 3. The evidence that the available alternatives would support such replacement is weak. Progress to improve their value for risk assessment purposes is bound to be slow because the issues are very complex. As a group of European Toxicologists we strongly support the need for more research support in these areas, but we believe that over claims for progress is damaging their development. 4. Under the circumstances only two options are available: to reduce very substantially the estimation of hazard and risk with inevitable adverse consequences for human health and environmental protection, or to continue the existing methods until properly validated new methods are available
Scientific Committee on Healthand Environmental Risks opinion on: New evidence of air pollution effects on human health and the environment
No full textAdopted by the SCHER during the 4th plenary of 18 March 2005Members of Working Group of SCHERby alphabetical order: H. Autrup (Rapporteur), P.Fischer (external expert), P. Karlsson (external expert), H Kumulainen, O. Ladefoged, S. Medina (external expert), J. Sokal, A. Steenhout.http://ec.europa.eu/health/scientific_committees/environmental_risks/scher_04-09/index_en.htmhttp://ec.europa.eu/health/scientific_committees/environmental_risks/opinions/scher_opinions_en.htmhttp://ec.europa.eu/health/archive/ph_risk/committees/04_scher/docs/scher_o_009.pdfAir Qualityinfo:eu-repo/semantics/publishe
Scientific Committee on Healthand Environmental Risks opinion on: Effectiveness of vapour retardants in reducing risks to human health from paint strippers containing dichloromethane ETVREAD Final Report 01 April 2004
No full textAdopted by the SCHER during the 4th plenary of 18 March 2005Member of Working Group by alphabetical order: H. Autrup, W. Hanke, B. Jansson (rapporteur), A. Steenhouthttp://ec.europa.eu/health/scientific_committees/environmental_risks/scher_04-09/index_en.htmhttp://ec.europa.eu/health/scientific_committees/environmental_risks/opinions/scher_opinions_en.htmhttp://ec.europa.eu/health/archive/ph_risk/committees/04_scher/docs/scher_o_006.pdfIndustrial/Professional use in Productsinfo:eu-repo/semantics/publishe
Scientific Committee on Health and Environmental Risks opinion on: Research priorities for the 7th Framework Program - Human Health and the Environment
No full textMembers of Working Group of SCHER by alphabetical order: H. Autrup (Rapporteur), W. Dekant, W.Hanke, B. Jansson, C. Janssen, I. Mansgeldorf, A.Steenhout,M. Vilukselahttp://ec.europa.eu/health/scientific_committees/environmental_risks/scher_04-09/index_en.htmhttp://ec.europa.eu/health/scientific_committees/environmental_risks/opinions/scher_opinions_en.htmhttp://ec.europa.eu/health/archive/ph_risk/committees/04_scher/docs/scher_o_044.pdfOthersinfo:eu-repo/semantics/publishe
Animal burdens versus human benefits:how should the ethical limits be drawn for use of animals as models in toxicology?
No full textReview of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment.
No full textThis review examines the large body of toxicological and epidemiological information on human exposures to chlorpyrifos, with an emphasis on the controversial potential for chlorpyrifos to induce neurodevelopmental effects at low doses. The results of this review demonstrate that the use of urinary 3,5,6-trichlorpyridinol (TCPy), a metabolite of chlorpyrifos as a biomarker of nonoccupational exposure is problematic and may overestimate nonoccupational exposures to chlorpyrifos by 10-to 20-fold because of the widespread presence of both TCPy and chlorpyrifos-methyl in the food supply. Current background (nonoccupational) levels of exposure to chlorpyrifos are several orders of magnitude lower than those required to inhibit plasma cholinesterase activity, which is a more sensitive target than nervous system cholinesterase. However, several in vitro studies have identified putative neurodevelopmental mechanisms that are altered at concentrations of chlorpyrifos below those that inhibit cholinesterases. Although one human cohort study reported an association between maternal and cord blood chlorpyrifos levels and several measures of neurodevelopment, two other cohort studies that utilized urinary TCPy as a surrogate for chlorpyrifos exposure did not demonstrate an association. Although the weight of the scientific evidence demonstrates that current levels of chlorpyrifos exposure will not have any adverse effects on neurodevelopment that might result from inhibition of nervous system cholinesterases, several recent studies propose alternative mechanisms. Thus, further in vivo investigation on neurodevelopment in an appropriate animal model is needed; additional epidemiological studies may be warranted if a suitable, chlorpyrifos-exposed cohort can be identified and more rigorous measures of exposure are utilized
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