Using the Go3R Search Engine to Collect Toxicological Data and Three Rs-relevant Information for REACH Registration Dossiers

The European REACH Regulation No. 1907/2006 on the Registration, Evaluation and Authorisationof Chemicals obliges companies to register all chemicals manufactured or imported inquantities above 1 tonne per year. Since detailed information on the intrinsic properties of chemicalsubstances has to be provided in the registration dossiers, comprehensive collection of allexisting relevant data serves to avoid animal testing. Also, when new data have to be compiledto obtain hazard information, testing on vertebrates may only be undertaken as a last resort.Hence, meeting the challenges of the REACH legislation further requires the continuous updatingof the information on newly-developed test methods that replace, reduce and refine animaltesting. The knowledge-based search engine Go3R (www.Go3R.org) has been designed to assistscientists from industry and regulatory authorities in accomplishing both tasks. Analysing the22 million documents of the PubMed and Toxicology Data Network (TOXNET) databases, Go3Rmakes use of expert knowledge on Three Rs methods and regulatory toxicology, laid down in anetwork of concepts, terms and synonyms, to recognise the contents of documents. Searchresults are automatically sorted into a table of contents, which is displayed alongside the list ofdocuments retrieved. By clicking onto different sections of the table of contents, the user canquickly filter the set of documents by topics of interest. Documents containing hazard informationare automatically assigned to the IUCLID5 toxicological information section of the table ofcontents that follows the endpoint-specific IUCLID5 categorisation required for REACH registrationdossiers. To enable Go3R to sort documents by the toxicological endpoint being investigated,complex endpoint-specific search queries were compiled and integrated into the searchengine. Dependent upon the endpoint, up to 100% of relevant documents containing either invitro or in vivo hazard information were correctly sorted into the respective IUCLID5 category.Since Go3R can be customised to search in different databases, the IUCLID5 categorisation isalso applicable to the screening and sorting of unpublished in-house data, and it can also be usedto group substances. The Three Rs specific searches section of the table of contents recognisesThree Rs-relevant documents and sorts these by Three Rs-specific information. The table of contentsprovides an overview on available test methods that replace, reduce or refine animal testing\ sorted by area of use, types of cells or tissues used in in vitro systems, in vitro endpointsand in vitro endpoint detection methods. Since important information on Three Rs alternativesis published not only in scientific journals, but also on dedicated internet sites, Go3R furtherallows searching the entire world-wide-web employing a Google-based search tool with priorrankingof information from Three Rs relevant websites. This option supports the retrieval ofinformation on the status of validation and regulatory acceptance of specific test methods or theirStandard Operating Procedure. The presentation will provide examples on how to use Go3R toretrieve substance-specific toxicological data and Three Rs relevant documents and will discussthe ongoing evaluation of the Go3R search engine

Using the Go3R Search Engine to Collect Toxicological Data and Three Rs-relevant Information for REACH Registration Dossiers

The European REACH Regulation No. 1907/2006 on the Registration, Evaluation and Authorisationof Chemicals obliges companies to register all chemicals manufactured or imported inquantities above 1 tonne per year. Since detailed information on the intrinsic properties of chemicalsubstances has to be provided in the registration dossiers, comprehensive collection of allexisting relevant data serves to avoid animal testing. Also, when new data have to be compiledto obtain hazard information, testing on vertebrates may only be undertaken as a last resort.Hence, meeting the challenges of the REACH legislation further requires the continuous updatingof the information on newly-developed test methods that replace, reduce and refine animaltesting. The knowledge-based search engine Go3R (www.Go3R.org) has been designed to assistscientists from industry and regulatory authorities in accomplishing both tasks. Analysing the22 million documents of the PubMed and Toxicology Data Network (TOXNET) databases, Go3Rmakes use of expert knowledge on Three Rs methods and regulatory toxicology, laid down in anetwork of concepts, terms and synonyms, to recognise the contents of documents. Searchresults are automatically sorted into a table of contents, which is displayed alongside the list ofdocuments retrieved. By clicking onto different sections of the table of contents, the user canquickly filter the set of documents by topics of interest. Documents containing hazard informationare automatically assigned to the IUCLID5 toxicological information section of the table ofcontents that follows the endpoint-specific IUCLID5 categorisation required for REACH registrationdossiers. To enable Go3R to sort documents by the toxicological endpoint being investigated,complex endpoint-specific search queries were compiled and integrated into the searchengine. Dependent upon the endpoint, up to 100% of relevant documents containing either invitro or in vivo hazard information were correctly sorted into the respective IUCLID5 category.Since Go3R can be customised to search in different databases, the IUCLID5 categorisation isalso applicable to the screening and sorting of unpublished in-house data, and it can also be usedto group substances. The Three Rs specific searches section of the table of contents recognisesThree Rs-relevant documents and sorts these by Three Rs-specific information. The table of contentsprovides an overview on available test methods that replace, reduce or refine animal testing\ sorted by area of use, types of cells or tissues used in in vitro systems, in vitro endpointsand in vitro endpoint detection methods. Since important information on Three Rs alternativesis published not only in scientific journals, but also on dedicated internet sites, Go3R furtherallows searching the entire world-wide-web employing a Google-based search tool with priorrankingof information from Three Rs relevant websites. This option supports the retrieval ofinformation on the status of validation and regulatory acceptance of specific test methods or theirStandard Operating Procedure. The presentation will provide examples on how to use Go3R toretrieve substance-specific toxicological data and Three Rs relevant documents and will discussthe ongoing evaluation of the Go3R search engine

Using the Go3R Search Engine to Collect Toxicological Data and Three Rs-relevant Information for REACH Registration Dossiers

The European REACH Regulation No. 1907/2006 on the Registration, Evaluation and Authorisationof Chemicals obliges companies to register all chemicals manufactured or imported inquantities above 1 tonne per year. Since detailed information on the intrinsic properties of chemicalsubstances has to be provided in the registration dossiers, comprehensive collection of allexisting relevant data serves to avoid animal testing. Also, when new data have to be compiledto obtain hazard information, testing on vertebrates may only be undertaken as a last resort.Hence, meeting the challenges of the REACH legislation further requires the continuous updatingof the information on newly-developed test methods that replace, reduce and refine animaltesting. The knowledge-based search engine Go3R (www.Go3R.org) has been designed to assistscientists from industry and regulatory authorities in accomplishing both tasks. Analysing the22 million documents of the PubMed and Toxicology Data Network (TOXNET) databases, Go3Rmakes use of expert knowledge on Three Rs methods and regulatory toxicology, laid down in anetwork of concepts, terms and synonyms, to recognise the contents of documents. Searchresults are automatically sorted into a table of contents, which is displayed alongside the list ofdocuments retrieved. By clicking onto different sections of the table of contents, the user canquickly filter the set of documents by topics of interest. Documents containing hazard informationare automatically assigned to the IUCLID5 toxicological information section of the table ofcontents that follows the endpoint-specific IUCLID5 categorisation required for REACH registrationdossiers. To enable Go3R to sort documents by the toxicological endpoint being investigated,complex endpoint-specific search queries were compiled and integrated into the searchengine. Dependent upon the endpoint, up to 100% of relevant documents containing either invitro or in vivo hazard information were correctly sorted into the respective IUCLID5 category.Since Go3R can be customised to search in different databases, the IUCLID5 categorisation isalso applicable to the screening and sorting of unpublished in-house data, and it can also be usedto group substances. The Three Rs specific searches section of the table of contents recognisesThree Rs-relevant documents and sorts these by Three Rs-specific information. The table of contentsprovides an overview on available test methods that replace, reduce or refine animal testing\ sorted by area of use, types of cells or tissues used in in vitro systems, in vitro endpointsand in vitro endpoint detection methods. Since important information on Three Rs alternativesis published not only in scientific journals, but also on dedicated internet sites, Go3R furtherallows searching the entire world-wide-web employing a Google-based search tool with priorrankingof information from Three Rs relevant websites. This option supports the retrieval ofinformation on the status of validation and regulatory acceptance of specific test methods or theirStandard Operating Procedure. The presentation will provide examples on how to use Go3R toretrieve substance-specific toxicological data and Three Rhe ongoing evaluation of the Go3R search engine

Single ingestion of di-(2-propylheptyl) phthalate (DPHP) by male volunteers: DPHP in blood and its metabolites in blood and urine.

Di-(2-propylheptyl) phthalate (DPHP) is used as a plasticizer for polyvinyl chloride products. A tolerable daily intake of DPHP of 0.2 mg/kg body weight has been derived from rat data. Because toxicokinetic data of DPHP in humans were not available, it was the aim of the present work to monitor DPHP and selected metabolites in blood and urine of 6 male volunteers over time following ingestion of a single DPHP dose (0.7 mg/kg body weight). Concentration-time courses in blood were obtained up to 24 h for DPHP, mono-(2-propylheptyl) phthalate (MPHP), mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPHP), and mono-(2-propyl-6-oxoheptyl) phthalate (oxo-MPHP); amounts excreted in urine were determined up to 46 h for MPHP, OH-MPHP, oxo-MPHP, and mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP). All curves were characterized by an invasion and an elimination phase the kinetic parameters of which were determined together with the areas under the concentration-time curves in blood (AUCs). AUCs were: DPHP > MPHP > oxo-MPHP > OH-MPHP. The amounts excreted in urine were: oxo-MPHP > OH-MPHP> > cx-MPHP > MPHP. The AUCs of MPHP, oxo-MPHP, or OH-MPHP could be estimated well from the cumulative amounts of urinary OH-MPHP or oxo-MPHP excreted within 22 h after DPHP intake. Not considering possible differences in species-sensitivity towards unconjugated DPHP metabolites, it was concluded from a comparison of their AUCs in DPHP-exposed humans with corresponding earlier data in rats that there is no increased risk of adverse effects associated with the internal exposure of unconjugated DPHP metabolites in humans as compared to rats when receiving the same dose of DPHP per kg body weight