{"title":"A general approach for evaluating stepwise testing strategies.","authors":"A P Worth, J H Fentem","doi":"10.1177/026119299902700115","DOIUrl":"https://doi.org/10.1177/026119299902700115","url":null,"abstract":"A stepwise (hierarchical) testing strategy is an approach to hazard evaluation based on the sequential application of one or more alternative methods prior to the use of any animal tests which are considered necessary. The purpose of a stepwise testing strategy is to reduce and refine the use of animals in toxicity testing without compromising human safety. An example of such a strategy is the proposed OECD testing and evaluation strategy for eye irritation/corrosion (1), which is based on a proposal made at the OECD Workshop on Harmonization of Validation and Acceptance Criteria for Alternative Toxicological Test Methods, held in Solna, Sweden, in January 1996 (2). A common motif in recent proposals for stepwise testing strategies (including the proposed OECD testing strategy for eye irritation/corrosion) is the sequential application of three steps based on alternative methods. These steps are based on the use of: a) structure-activity relationships (SARs), where available; b) physicochemical methods (for example, measurements of pH [acidity/alkalinity] and acid/alkali reserve [buffering capacity]); and c) in vitro tests (Figure 1). The basic principle is that these steps will be applied in sequence before any animal tests are conducted. If any one of the alternative methods predicts the chemical of interest to be toxic, a classification is assigned and testing is stopped. Otherwise, testing continues to the next step. The purpose of the tiered approach is that toxic chemicals will be screened out by the alternative methods, so that the animal test(s) conducted in the final step will merely confirm the predictions of non-toxicity made in previous steps. In this way, the tiered approach is expected to reduce and refine the use of animals in toxicity testing. The purpose of this study was to illustrate a general approach to the evaluation of stepwise testing strategies by focusing on the basic design described above. Thus, the three steps (SAR, physicochemical and in vitro) were applied both on their own and as a sequence (Figure 1) to the chemicals used in the European Commission/ British Home Office (EC/HO) validation study (3). There was a need to compare the predictivities of nine in vitro tests, but there were no prediction models (PMs) available for converting the in vitro test results into predictions of eye irritation potential (irritant [I]/non-irritant [NI]). Therefore, a method was devised (which we have termed the “percentile method”) for deriving PMs which would be of comparable sensitivity, but which would be distinguishable in terms of their specificities (or false positive rates). A similar approach for evaluating stepwise testing strategies has also been applied to the proposed OECD testing strategy for skin corrosion (4).","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"161-77"},"PeriodicalIF":2.7,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/026119299902700115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32836431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Development and Characterisation of a Structure-activity Relationship Model of the Draize Eye Irritation Test.","authors":"H S Rosenkranz, Y P Zhang, G Klopman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A structure-activity relationship (SAR) model based on the results of 297 chemicals tested in the Draize eye irritation assay was developed. The SAR model displayed a predictivity of 74% for chemicals not included in the model. The SAR analysis indicated that chemical reactivity was not a requirement for eye irritation. The major structural determinants included hydrophilicity, alkalinity (i.e. primary, secondary and tertiary amines), acidity (for example, the carboxylic acid moiety), and putative lipophobic 4.5-5.4Å receptor-binding ligands. The analysis revealed that, while there were significant structural overlaps between the SAR models of ocular irritation, allergic contact dermatitis and respiratory hypersensitivity, there was much less overlap between ocular irritation and cell toxicity. This decreased overlap must be considered in developing strategies to replace the Draize test with in vitro cellular toxicity assays. </p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"779-809"},"PeriodicalIF":2.7,"publicationDate":"1998-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33361073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L H Bruner, O de Silva, L K Earl, D L Easty, W Pape, H Spielmann
{"title":"Report on the COLIPA Workshop on Mechanisms of Eye Irritation.","authors":"L H Bruner, O de Silva, L K Earl, D L Easty, W Pape, H Spielmann","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This report summarises the discussions of a workshop sponsored by the European Cosmetics, Toiletries and Perfumery Association (COLIPA). The workshop discussed the state-of-the-art of eye irritancy testing, and made recommendations as to the best ways in which to validate alternatives to the Draize eye irritation test. The importance of understanding the mechanisms of eye irritation, particularly when attempting to improve in vitro prediction of in vivo eye irritancy, was also emphasised. </p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"811-20"},"PeriodicalIF":2.7,"publicationDate":"1998-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33361074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C Hendriksen, J M Spieser, A Akkermans, M Balls, L Bruckner, K Cussler, A Daas, J Descamps, R Dobbelaer, J Fentem, M Halder, M van der Kamp, R Lucken, J Milstien, D Sesardic, D Straughan, A Valadares
{"title":"Validation of alternative methods for the potency testing of vaccines.","authors":"C Hendriksen, J M Spieser, A Akkermans, M Balls, L Bruckner, K Cussler, A Daas, J Descamps, R Dobbelaer, J Fentem, M Halder, M van der Kamp, R Lucken, J Milstien, D Sesardic, D Straughan, A Valadares","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"747-61"},"PeriodicalIF":2.7,"publicationDate":"1998-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33359120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In vitro models of the blood-brain barrier.","authors":"P Garberg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In this literature review on in vitro models of the blood-brain barrier (BBB), it is concluded that there is a need to identify a unified in vitro model for the BBB. The best evaluated model at present is based on the use of primary cultures of bovine brain endothelial cells. Primary cell cultures are usually shown to retain several BBB characteristics, but are time-consuming and difficult to establish. To make a unified in vitro model for the BBB more generally available, it is strongly suggested that such a model should be based on the use of an established cell line. To identify the best in vitro model, an evaluation of the most promising immortalised BBB-derived endothelial cell lines, as well as other established cell lines presently used as BBB models, is highly recommended. An evaluation of possible species variation is also important, in order to establish the most relevant species to be used. Furthermore, it is also suggested that the specific properties of in vitro BBB models, as compared to models for the \"intestinal barrier\", for example, should be evaluated. Finally, it is recommended that an evaluation of available computer models is performed, to further improve early predictions for drug candidates with regard to BBB permeability. </p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"821-47"},"PeriodicalIF":2.7,"publicationDate":"1998-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33361076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Co-occurring Words: Finding Information About Alternatives to Animal Testing.","authors":"J Huggins","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A collection of co-occurring words has been gathered from a small database of abstracts about alternatives to skin irritation testing by using Boolean logic. Words were selected according to a strategy based on methodology. Such words and their co-occurrences may be considered an archival code by which data that describe alternatives to skin irritation testing can be more readily recognised. As such, they can be used to enhance the efficiency with which information about this area of alternatives to animal testing is found in journal articles, databases and Web sites. </p>","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"849-56"},"PeriodicalIF":2.7,"publicationDate":"1998-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33361077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Screening for endocrine disruptors - time for more science and less politics.","authors":"R D Combes","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"735-9"},"PeriodicalIF":2.7,"publicationDate":"1998-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33359119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Todd, B Garthoff, W Bernhardt, G Bodé, S Farr, R Kolar, C Lumley, M Pieters, G Bodé, V Rogiers, U Sauer, H Spielmann, J Straus, L Warngard
{"title":"Issues relating to the release of proprietary information and data for use in the validation of alternative methods.","authors":"M Todd, B Garthoff, W Bernhardt, G Bodé, S Farr, R Kolar, C Lumley, M Pieters, G Bodé, V Rogiers, U Sauer, H Spielmann, J Straus, L Warngard","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"13-20"},"PeriodicalIF":2.7,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33240871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Neutral Red Uptake Assay: Comments on the Results of the Istituto Superiore di Sanità in the EC/HO Validation Study.","authors":"A Stammati, F Zampaglioni, C Zanetti","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":520549,"journal":{"name":"Alternatives to laboratory animals : ATLA","volume":" ","pages":"61-8"},"PeriodicalIF":2.7,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33240873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}