An Evaluation of the Proposed OECD Testing Strategy for Skin Corrosion

1998 ◽  
Vol 26 (5) ◽  
pp. 709-720 ◽  
Author(s):  
Andrew P. Worth ◽  
Julia H. Fentem ◽  
Michael Balls ◽  
Philip A. Botham ◽  
Rodger D. Curren ◽  
...  
Keyword(s):  
Skin Irritation ◽  
Alternative Methods ◽  
Advisory Group ◽  
Chemical Toxicity ◽  
Testing Strategy ◽  
Animal Testing ◽  
Ph Measurements ◽  
Testing Strategies

The use of testing strategies which incorporate a range of alternative methods and which use animals only as a last resort is widely considered to provide a reliable way of predicting chemical toxicity while minimising animal testing. The widespread concern over the severity of the Draize rabbit test for assessing skin irritation and corrosion led to the proposal of a stepwise testing strategy at an OECD workshop in January 1996. Subsequently, the proposed testing strategy was adopted, with minor modifications, by the OECD Advisory Group on Harmonization of Classification and Labelling. This article reports an evaluation of the proposed OECD testing strategy as it relates to the classification of skin corrosives. By using a set of 60 chemicals, an assessment was made of the effect of applying three steps in the strategy, taken both individually and in sequence. The results indicate that chemicals can be classified as corrosive (C) or non-corrosive (NC) with sufficient reliability by the sequential application of three alternative methods, i.e., structure-activity relationships (where available), pH measurements, and a single in vitro method (either the rat skin transcutaneous electrical resistance (TER) assay or the EPISKIN™ assay). It is concluded that the proposed OECD strategy for skin corrosion can be simplified without compromising its predictivity. For example, it does not appear necessary to measure acid/alkali reserve (buffering capacity) in addition to pH for the classification of pure chemicals.

Integrated Decision-tree Testing Strategies for Skin Corrosion and Irritation with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1_suppl) ◽  
pp. 65-74
Author(s):  
Christina Grindon ◽  
Robert Combes ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Alternative Methods ◽  
The European Union ◽  
Testing Strategy ◽  
Animal Testing ◽  
Safety Testing ◽  
Alternatives To Animal Testing ◽  
Testing Strategies ◽  
The Status ◽  
The Eu

Liverpool John Moores University and FRAME recently conducted a research project, sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This report focuses on how to maximise the use of alternative methods (both in vitro and in silico) for skin corrosion and irritation testing within a tiered testing strategy. It considers the latest developments in in vitro testing, with particular reference to the reconstituted skin models which have now been now been successfully validated and independently endorsed as suitable for both skin corrosivity and irritancy testing within the EU.

Integrated Decision-tree Testing Strategies for Environmental Toxicity with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1_suppl) ◽  
pp. 29-42 ◽  
Author(s):  
Christina Grindon ◽  
Robert Combes ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Risk Assessment ◽  
Decision Tree ◽  
Aquatic Toxicity ◽  
Toxicity Testing ◽  
Threshold Concentration ◽  
Alternative Methods ◽  
The European Union ◽  
Animal Testing ◽  
Testing Strategies

Liverpool John Moores University and FRAME recently conducted a research project sponsored by Defra on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This paper focuses on the prospects for using alternative methods (both in vitro and in silico) for environmental (aquatic) toxicity testing. The manuscript reviews tests based on fish cells and cell lines, fish embryos, lower organisms, and the many expert systems and QSARs for aquatic toxicity testing. Ways in which reduction and refinement measures can be used are also discussed, including the Upper Threshold Concentration — Step Down (UTC) approach, which has recently been retrospectively validated by ECVAM and subsequently endorsed by the ECVAM Scientific Advisory Committee (ESAC). It is hoped that the application of this approach could reduce the number of fish used in acute toxicity studies by around 65–70%. Decision-tree style integrated testing strategies are also proposed for acute aquatic toxicity and chronic toxicity (including bioaccumulation), followed by a number of recommendations for the future facilitation of aquatic toxicity testing with respect to environmental risk assessment.

scholarly journals STopTox: An In-Silico Alternative to Animal Testing for Acute Systemic and TOPical TOXicity

2020 ◽  
Author(s):  
Joyce V. V. B. Borba ◽  
Vinicius Alves ◽  
Rodolpho Braga ◽  
Daniel Korn ◽  
Kirsten Overdahl ◽  
...  
Keyword(s):  
Skin Irritation ◽  
Alternative Methods ◽  
Toxicity Tests ◽  
Inhalation Toxicity ◽  
Chemical Toxicity ◽  
Animal Testing ◽  
Oral Toxicity ◽  
Qsar Models ◽  
Us Epa ◽  
Acute Toxicity Tests

<p><a>Since 2009, animal testing for cosmetic products has been prohibited in Europe, and in 2016, US EPA announced their intent to modernize the so-called "6-pack" of acute toxicity tests (acute oral toxicity, acute dermal toxicity, acute inhalation toxicity, skin irritation and corrosion, eye irritation and corrosion, and skin sensitization) and expand acceptance of alternative methods to reduce animal testing of pesticides. We have compiled, curated, and integrated the largest publicly available dataset and developed an ensemble of QSAR models for all six endpoints. All models were validated according to the OECD QSAR principles and tested using newly identified data on compounds not included in the training sets. We have established a publicly accessible Systemic and Topical chemical Toxicity (STopTox) web portal (https://stoptox.mml.unc.edu/) integrating all developed models for “6-pack” assays. This portal can be used by scientists and regulators to identify putative toxicants or non-toxicants in chemical libraries of interest.</a></p>

scholarly journals STopTox: An In-Silico Alternative to Animal Testing for Acute Systemic and TOPical TOXicity

2020 ◽  
Author(s):  
Joyce V. V. B. Borba ◽  
Vinicius Alves ◽  
Rodolpho Braga ◽  
Daniel Korn ◽  
Kirsten Overdahl ◽  
...  
Keyword(s):  
Skin Irritation ◽  
Alternative Methods ◽  
Toxicity Tests ◽  
Inhalation Toxicity ◽  
Chemical Toxicity ◽  
Animal Testing ◽  
Oral Toxicity ◽  
Qsar Models ◽  
Us Epa ◽  
Acute Toxicity Tests

<p><a>Since 2009, animal testing for cosmetic products has been prohibited in Europe, and in 2016, US EPA announced their intent to modernize the so-called "6-pack" of acute toxicity tests (acute oral toxicity, acute dermal toxicity, acute inhalation toxicity, skin irritation and corrosion, eye irritation and corrosion, and skin sensitization) and expand acceptance of alternative methods to reduce animal testing of pesticides. We have compiled, curated, and integrated the largest publicly available dataset and developed an ensemble of QSAR models for all six endpoints. All models were validated according to the OECD QSAR principles and tested using newly identified data on compounds not included in the training sets. We have established a publicly accessible Systemic and Topical chemical Toxicity (STopTox) web portal (https://stoptox.mml.unc.edu/) integrating all developed models for “6-pack” assays. This portal can be used by scientists and regulators to identify putative toxicants or non-toxicants in chemical libraries of interest.</a></p>

Integrated Decision-tree Testing Strategies for Developmental and Reproductive Toxicity with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1) ◽  
pp. 65-80 ◽  
Author(s):  
Christina Grindon ◽  
Robert Combes ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Risk Assessment ◽  
Decision Tree ◽  
Endocrine Disruption ◽  
Reproductive Toxicity ◽  
Toxicity Testing ◽  
Alternative Methods ◽  
The European Union ◽  
Animal Testing ◽  
Testing Strategies

Liverpool John Moores University and FRAME conducted a research project, sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This paper focuses on the prospects for the use of alternative methods (both in vitro and in silico) in developmental and reproductive toxicity testing. It considers many tests based on primary cells and cell lines, and the available expert systems and QSARs for developmental and reproductive toxicity, and also covers tests for endocrine disruption. Ways in which reduction and refinement measures can be used are also discussed, particularly the use of an enhanced one-generation reproductive study, which could potentially replace the two-generation study, and therefore considerably reduce the number of animals required in reproductive toxicity. Decision-tree style integrated testing strategies are also proposed for developmental and reproductive toxicity and for endocrine disruption, followed by a number of recommendations for the future facilitation of developmental and reproductive toxicity testing, with respect to human risk assessment.

Integrated Decision-tree Testing Strategies for Developmental and Reproductive Toxicity with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1_suppl) ◽  
pp. 123-138 ◽  
Author(s):  
Christina Grindon ◽  
Robert Combes ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Risk Assessment ◽  
Decision Tree ◽  
Endocrine Disruption ◽  
Reproductive Toxicity ◽  
Toxicity Testing ◽  
Alternative Methods ◽  
The European Union ◽  
Animal Testing ◽  
Testing Strategies

Liverpool John Moores University and FRAME conducted a research project, sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This paper focuses on the prospects for the use of alternative methods (both in vitro and in silico) in developmental and reproductive toxicity testing. It considers many tests based on primary cells and cell lines, and the available expert systems and QSARs for developmental and reproductive toxicity, and also covers tests for endocrine disruption. Ways in which reduction and refinement measures can be used are also discussed, particularly the use of an enhanced one-generation reproductive study, which could potentially replace the two-generation study, and therefore considerably reduce the number of animals required in reproductive toxicity. Decision-tree style integrated testing strategies are also proposed for developmental and reproductive toxicity and for endocrine disruption, followed by a number of recommendations for the future facilitation of developmental and reproductive toxicity testing, with respect to human risk assessment.

scholarly journals Review of skin irritation/corrosion hazards on the basis of human data: a regulatory perspective

2012 ◽  
Vol 5 (2) ◽  
pp. 98-104 ◽  
Author(s):  
David Basketter ◽  
Dagmar Jírova ◽  
Helena Kandárová
Keyword(s):  
Patch Test ◽  
Skin Irritation ◽  
Alternative Methods ◽  
Test Protocol ◽  
Rabbit Skin ◽  
Irritation Test ◽  
Skin Irritation Test

Abstract Regulatory classification of skin irritation has historically been based on rabbit data, however current toxicology processes are transitioning to in vitro alternatives. The in vitro assays have to provide sufficient level of sensitivity as well as specificity to be accepted as replacement methods for the existing in vivo assays. This is usually achieved by comparing the in vitro results to classifications obtained in animals. Significant drawback of this approach is that neither in vivo nor in vitro methods are calibrated against human hazard data and results obtained in these assays may not correspond to situation in human. The main objective of this review was to establish an extended database of substances classified according to their human hazard to serve for further development of alternative methods relevant to human health as well as resource for improved regulatory classification. The literature has been reviewed to assemble all the available information on the testing of substances in the human 4 h human patch test, which is the only standardized protocol in humans matching the exposure conditions of the regulatory accepted in vivo rabbit skin irritation test. A total of 81 substances tested according to the defined 4 h human patch test protocol were found and collated into a dataset together with their existing in vivo classifications published in the literature. While about 50% of the substances in the database are classified as irritating based on the rabbit skin test, on using the 4 h HPT test, less than 20% were identified as acutely irritant to human skin. Based on the presented data, it can be concluded that the rabbit skin irritation test largely over-predicts human responses for the evaluated chemicals. Correct classification of the acute skin irritation hazard will only be possible if newly developed in vitro toxicology methods will be calibrated to produce results relevant to man.

scholarly journals Commentary on ‘‘Toxicity Testing in the 21st Century: A vision and a Strategy’’

2010 ◽  
Vol 29 (1) ◽  
pp. 11-14 ◽  
Author(s):  
Robert F Phalen
Keyword(s):  
21St Century ◽  
Toxicity Testing ◽  
In Vitro Testing ◽  
Chemical Toxicity ◽  
Animal Testing ◽  
In Vitro Techniques ◽  
Human Monitoring ◽  
Animal Tests ◽  
In Silico Methods

Toxicity Testing in the 21st Century: A Vision and a Strategy (NRC, 2007) presents a bold plan for chemical toxicity testing that replaces whole-animal tests with cell-culture, genetic, other in-vitro techniques, computational methods, and human monitoring. Although the proposed vision is eloquently described, and recent advances in in-vitro and in-silico methods are impressive, it is difficult believe that replacing in-vitro testing is either practical or wise. It is not clear that the toxicity-related events that occur in whole animals can be adequately replicated using the proposed methods. Protecting public health is a serious endeavor that should not be limited by denying animal testing. Toxicologists and regulators are encouraged to read the report, carefully consider its implications, and share their thoughts. The vision is for too important to ignore.

scholarly journals A fast and reliable method for monitoring genomic instability in the model organism Caenorhabditis elegans

2021 ◽  
Author(s):  
Merle Marie Nicolai ◽  
Barbara Witt ◽  
Andrea Hartwig ◽  
Tanja Schwerdtle ◽  
Julia Bornhorst
Keyword(s):  
Caenorhabditis Elegans ◽  
Animal Experiments ◽  
Model Organism ◽  
Animal Testing ◽  
C Elegans ◽  
Testing Strategies ◽  
Genotoxic Agents ◽  
Genotoxicity Testing

AbstractThe identification of genotoxic agents and their potential for genotoxic alterations in an organism is crucial for risk assessment and approval procedures of the chemical and pharmaceutical industry. Classically, testing strategies for DNA or chromosomal damage focus on in vitro and in vivo (mainly rodent) investigations. In cell culture systems, the alkaline unwinding (AU) assay is one of the well-established methods for detecting the percentage of double-stranded DNA (dsDNA). By establishing a reliable lysis protocol, and further optimization of the AU assay for the model organism Caenorhabditis elegans (C. elegans), we provided a new tool for genotoxicity testing in the niche between in vitro and rodent experiments. The method is intended to complement existing testing strategies by a multicellular organism, which allows higher predictability of genotoxic potential compared to in vitro cell line or bacterial investigations, before utilizing in vivo (rodent) investigations. This also allows working within the 3R concept (reduction, refinement, and replacement of animal experiments), by reducing and possibly replacing animal testing. Validation with known genotoxic agents (bleomycin (BLM) and tert-butyl hydroperoxide (tBOOH)) proved the method to be meaningful, reproducible, and feasible for high-throughput genotoxicity testing, and especially preliminary screening.

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