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Concept of sustainable training on chemical safety in Serbia
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Abstracts / Toxicology Letters 211S (2012) S43–S216
form (Form I), if scission occurs on one strand (nicking), the supercoil will relax to generate a slower moving open circular form (Form II), if both strands are cleaved, a linear form (Form III) that migrates between Forms I and II will be generated. There is a clear reduction in DNA (form I) and increase in form II and III, by increase in ETU concentration. Thus ETU is able to cleave DNA and it may cause some genotoxicity. doi:10.1016/j.toxlet.2012.03.793
P27-26 A high-throughput bioanalytical method to determine ethylenethiourea in urine Eva Ekman, Margareta Maxe, Christian Lindh Lund University, Sweden Studies show that agricultural workers, and to a limited extent the general population, are exposed to pesticides, their degradation products and metabolites. Ethylenethiourea (ETU) is a metabolite originating from ethylene bisdithiocarbamates (EBDCs), which are commonly used on various crops as fungicides. ETU also exists in the environment as a degradation product of EBDCs. ETU is a concern for human health as animal studies establish that ETU causes major toxicological effects. The adverse effects found in animals are mainly mutagenic, teratogenic, carcinogenic and goitrogenic effects. According to the IARC classification system, the carcinogenicity of ETU is class 3. ETU in urine is still determined with analytical methods needing lengthy, complicated and chemical consuming sample preparation. The aim of this study is to develop a high-throughput liquid chromatography triple quadrupole mass spectrometry (LC–MS/MS) method to determine ETU in urine and evaluate if ETU is conjugated. The method will be applied in a birth cohort study of pesticide exposed pregnant women and children, living near plantations in Costa Rica and in an experimental dermal uptake study. Our method is a user friendly LC–MS/MS method which compromises neither sensitivity nor need of sample volume and increases the throughput of samples 6 times, from 25 to 160 samples a day. After hydrolysation the amount of ETU increases by 30 per cent and the method has a limit of detection of 0.13 ng/mL and limit of quantification of 0.33 ng/mL for ETU. doi:10.1016/j.toxlet.2012.03.794 P29: Regulatory Toxicology
P29-01 Revisiting the value of mouse carcinogenicity bioassays for human safety assessment Richard Billington 1 , Tina Mehta 1 , Richard Lewis 2 , Bennard van Raavenzway 3 , Christian Strupp 4 , Ian Dewhurst 5 Dow AgroSciences, Abingdon, United Kingdom, 2 Syngenta, Bracknell, United Kingdom, 3 BASF, Ludwigshafen, Germany, 4 Makhteshim Agan Europe, Schaffhausen, Switzerland, 5 Health and Safety Executive, York, United Kingdom
1
The value of a second species carcinogenicity study has been in doubt for decades. Recent assessments have focused on the mouse and evaluated the contribution this cancer bioassay makes
from two key regulatory perspectives: (1) human health-based risk assessments and (2) cancer classification. Evaluation of the outcomes for 202 pesticides from the EU review programme under Directive 91/414/EEC indicated that the mouse study made little to no difference to the derivation of the acceptable daily intake (ADI) – the dose used to determine chronic risk to humans – or to the cancer classification of these substances. Only one ADI was based on mouse tumours, and the complete absence of the mouse study would have made no difference to the risk assessment (or Annex I listing) for any of the reviewed pesticides. From a hazard perspective, the mouse data alone resulted in cancer classification for only three (1.5%) of these substances, none of which had relevance to human safety. Finally, carcinogenicity data in two species did not increase the severity (i.e., R40 to R45) of cancer classification for any pesticide. A follow-up review of almost 100 additional EU pesticide evaluations published in EFSA Conclusion reports confirmed the findings of the original review that the mouse study had negligible impact on risk assessment or cancer classification for humans. The conclusions from these 300 pesticide reviews provide compelling support for harmonization of data requirements for pesticides with those for chemicals regulated under REACH by removal of the mouse carcinogenicity study. doi:10.1016/j.toxlet.2012.03.636
P29-02 Concept of sustainable training on chemical safety in Serbia Vesna Milovanovic 1 , Marija Arandjelovic 1 , Jasminka Randjelovic 1 , Biljana Antonijevic 2 Serbian Chemicals Agency, Belgrade, Serbia, 2 Faculty of Pharmacy, Belgrade, Serbia
1
The Serbian Chemicals Agency (SHemA), as competent authority for chemicals management, plays a crucial role in the establishment and enforcement of the legal framework in this field. The successful implementation of newly adopted national legislation on chemicals management requires activities on intensive education of the competent authorities, stakeholders and general public. The education strategy was developed based on analysis of the current state of knowledge related to chemical safety. Identified target groups were: SHemA employees, inspectors, local governments, industry, academia, chemical teachers, and consumer organizations. Delivering of trainings for SHemA’s staff and trainers for chemical advisers has been provided within the IPA 2008 Twinning project and the project implemented by Swedish Chemicals Agency. Three courses for inspectors were organized. In terms of approach, lectures with practical exercises were held and learning-by-doing will be the next step. Awareness-raising campaign related to classification, labelling and packaging of chemicals will be launched in 2012. After intensive trainings related to (eco)toxicology, risk assessment and management methodologies, the capacity of SHemA’s staff, trainers for chemical advisers and inspectors has been strengthened, improving thus level of competence, important prerequisite for consistent implementation of national legislation. The institution of trainers for chemical advisers has been established. In order to create modern interdisciplinary universities’ programs related to chemical safety and risk assessment in line with the best EU practices, a master-level study program is considered to be introduced. The establishment of sustainable education system will set the base for a long-term improvement of chemical safety in Serbia. doi:10.1016/j.toxlet.2012.03.637
Abstracts / Toxicology Letters 211S (2012) S43–S216
form (Form I), if scission occurs on one strand (nicking), the supercoil will relax to generate a slower moving open circular form (Form II), if both strands are cleaved, a linear form (Form III) that migrates between Forms I and II will be generated. There is a clear reduction in DNA (form I) and increase in form II and III, by increase in ETU concentration. Thus ETU is able to cleave DNA and it may cause some genotoxicity. doi:10.1016/j.toxlet.2012.03.793
P27-26 A high-throughput bioanalytical method to determine ethylenethiourea in urine Eva Ekman, Margareta Maxe, Christian Lindh Lund University, Sweden Studies show that agricultural workers, and to a limited extent the general population, are exposed to pesticides, their degradation products and metabolites. Ethylenethiourea (ETU) is a metabolite originating from ethylene bisdithiocarbamates (EBDCs), which are commonly used on various crops as fungicides. ETU also exists in the environment as a degradation product of EBDCs. ETU is a concern for human health as animal studies establish that ETU causes major toxicological effects. The adverse effects found in animals are mainly mutagenic, teratogenic, carcinogenic and goitrogenic effects. According to the IARC classification system, the carcinogenicity of ETU is class 3. ETU in urine is still determined with analytical methods needing lengthy, complicated and chemical consuming sample preparation. The aim of this study is to develop a high-throughput liquid chromatography triple quadrupole mass spectrometry (LC–MS/MS) method to determine ETU in urine and evaluate if ETU is conjugated. The method will be applied in a birth cohort study of pesticide exposed pregnant women and children, living near plantations in Costa Rica and in an experimental dermal uptake study. Our method is a user friendly LC–MS/MS method which compromises neither sensitivity nor need of sample volume and increases the throughput of samples 6 times, from 25 to 160 samples a day. After hydrolysation the amount of ETU increases by 30 per cent and the method has a limit of detection of 0.13 ng/mL and limit of quantification of 0.33 ng/mL for ETU. doi:10.1016/j.toxlet.2012.03.794 P29: Regulatory Toxicology
P29-01 Revisiting the value of mouse carcinogenicity bioassays for human safety assessment Richard Billington 1 , Tina Mehta 1 , Richard Lewis 2 , Bennard van Raavenzway 3 , Christian Strupp 4 , Ian Dewhurst 5 Dow AgroSciences, Abingdon, United Kingdom, 2 Syngenta, Bracknell, United Kingdom, 3 BASF, Ludwigshafen, Germany, 4 Makhteshim Agan Europe, Schaffhausen, Switzerland, 5 Health and Safety Executive, York, United Kingdom
1
The value of a second species carcinogenicity study has been in doubt for decades. Recent assessments have focused on the mouse and evaluated the contribution this cancer bioassay makes
from two key regulatory perspectives: (1) human health-based risk assessments and (2) cancer classification. Evaluation of the outcomes for 202 pesticides from the EU review programme under Directive 91/414/EEC indicated that the mouse study made little to no difference to the derivation of the acceptable daily intake (ADI) – the dose used to determine chronic risk to humans – or to the cancer classification of these substances. Only one ADI was based on mouse tumours, and the complete absence of the mouse study would have made no difference to the risk assessment (or Annex I listing) for any of the reviewed pesticides. From a hazard perspective, the mouse data alone resulted in cancer classification for only three (1.5%) of these substances, none of which had relevance to human safety. Finally, carcinogenicity data in two species did not increase the severity (i.e., R40 to R45) of cancer classification for any pesticide. A follow-up review of almost 100 additional EU pesticide evaluations published in EFSA Conclusion reports confirmed the findings of the original review that the mouse study had negligible impact on risk assessment or cancer classification for humans. The conclusions from these 300 pesticide reviews provide compelling support for harmonization of data requirements for pesticides with those for chemicals regulated under REACH by removal of the mouse carcinogenicity study. doi:10.1016/j.toxlet.2012.03.636
P29-02 Concept of sustainable training on chemical safety in Serbia Vesna Milovanovic 1 , Marija Arandjelovic 1 , Jasminka Randjelovic 1 , Biljana Antonijevic 2 Serbian Chemicals Agency, Belgrade, Serbia, 2 Faculty of Pharmacy, Belgrade, Serbia
1
The Serbian Chemicals Agency (SHemA), as competent authority for chemicals management, plays a crucial role in the establishment and enforcement of the legal framework in this field. The successful implementation of newly adopted national legislation on chemicals management requires activities on intensive education of the competent authorities, stakeholders and general public. The education strategy was developed based on analysis of the current state of knowledge related to chemical safety. Identified target groups were: SHemA employees, inspectors, local governments, industry, academia, chemical teachers, and consumer organizations. Delivering of trainings for SHemA’s staff and trainers for chemical advisers has been provided within the IPA 2008 Twinning project and the project implemented by Swedish Chemicals Agency. Three courses for inspectors were organized. In terms of approach, lectures with practical exercises were held and learning-by-doing will be the next step. Awareness-raising campaign related to classification, labelling and packaging of chemicals will be launched in 2012. After intensive trainings related to (eco)toxicology, risk assessment and management methodologies, the capacity of SHemA’s staff, trainers for chemical advisers and inspectors has been strengthened, improving thus level of competence, important prerequisite for consistent implementation of national legislation. The institution of trainers for chemical advisers has been established. In order to create modern interdisciplinary universities’ programs related to chemical safety and risk assessment in line with the best EU practices, a master-level study program is considered to be introduced. The establishment of sustainable education system will set the base for a long-term improvement of chemical safety in Serbia. doi:10.1016/j.toxlet.2012.03.637