Alternative Approaches and Tests in Ecotoxicology: A Review of the Present Position and the Prospects for Change, Taking into Account ECVAM's Duties, Topic Selection and Test Criteria

1998 ◽  
Vol 26 (5) ◽  
pp. 649-677 ◽  
Author(s):  
Colin H. Walker
Keyword(s):  
Alternative Methods ◽  
In Vitro Assays ◽  
Toxicity Tests ◽  
The European Union ◽  
Present Position ◽  
Industrial Chemicals ◽  
Discussion Section ◽  
Recommendations For Action ◽  
Ecotoxicity Testing

The objectives of this review are to summarise the present position concerning the use of vertebrates in ecotoxicity testing, giving particular attention to tests that cause suffering, and to discuss in some detail, alternatives to them, and the prospects for change. The report has been written with the objectives of the European Centre for the Validation of Alternative Methods (ECVAM) in mind, and some recommendations for action have been made at the end of the discussion section. The first section of the review describes the present requirements within the European Union for the ecotoxicity testing of industrial chemicals in general, and for pesticides in particular, and the very limited documentation of the tests that are actually carried out. The next four sections describe the many different assays and systems used to evaluate the harmful effects of chemicals on free-living organisms and natural populations, and the extent to which they might be suitable alternatives to vertebrate toxicity tests that cause suffering. Attention is drawn to certain assays and strategies that can already be used as satisfactory alternatives, and thus provide the basis for short-term change. Included here are nondestructive assays on vertebrates which are available for certain types of chemicals, and which provide a direct and relatively uncomplicated approach to the problem. Other approaches are described which still require development, but hold considerable promise in the longer term. The growth of knowledge in the broad field of biochemical toxicology and the development of related technologies should lead to the development of better and more-sophisticated alternatives in the future. In vitro assays employing vertebrate cell systems are of particular interest here. The last section of the review deals with conclusions and recommendations. The recommendations are made with a view to the activities and responsibilities of ECVAM.

scholarly journals Efficacy, toxicity, and lethality of plants with potential anthelmintic activity in small ruminants in Brazil

2019 ◽  
Vol 20 ◽  
Author(s):  
Vanessa Daniele Mottin ◽  
Jurandir Ferreira da Cruz ◽  
Milton Resende Teixeira Neto ◽  
Gabriele Marisco ◽  
Jennifer Souza Figueredo ◽  
...  
Keyword(s):  
Small Ruminants ◽  
Anthelmintic Activity ◽  
Production Costs ◽  
Alternative Methods ◽  
In Vitro Assays ◽  
Toxicity Tests ◽  
Action Preparation ◽  
Chemical Inputs

SUMMARY The use of medicinal plants as a therapeutic method in the control of diseases has been increasing in animal production. In the case of small ruminants, the endoparasitic disease is a major concern, since they are considered the greater sanitary problem, especially when considering the phenomenon of parasite resistance to the medicines used. Therefore, the development of alternative methods of endoparasitary control in goats and sheep has become a pressing need. The use of plants to control endoparasites can reduce the use of chemical inputs, making more environmentally sustainable livestock, minimizing the occurrence of parasitic resistance to conventional medicines and contributing to the reduction of production costs. In this sense, several studies have been carried out in order to evaluate the in vitro and in vivo activity of plants with anthelmintic potential. However, despite the potentiality found in many studies, the results are sometimes contradictory or do not replicate in vivo the same efficacy obtained in the in vitro assays. Another relevant aspect is the low utilization of the lethality and toxicity tests, which are indispensable so that the knowledge can be spread and applied by the producers in their herds. Thus, this review aims to provide the results from studies carried out in Brazil with extract of plants with potential for control of parasitic disease in goats and sheep, describing the main evaluated plants species, mechanisms of action, preparation forms and tests of efficacy, toxicity, and lethality.

Integrated Decision-tree Testing Strategies for Acute Systemic Toxicity and Toxicokinetics with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1_suppl) ◽  
pp. 91-109 ◽  
Author(s):  
Robert Combes ◽  
Christina Grindon ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Decision Tree ◽  
Systemic Toxicity ◽  
Toxicity Tests ◽  
In Vitro Tests ◽  
The European Union ◽  
Animal Testing ◽  
Pbpk Modelling ◽  
Joint Research Project ◽  
The Eu

Liverpool John Moores University and FRAME conducted a joint 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 REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for acute systemic toxicity and toxicokinetic testing. The paper reviews in vitro tests based on basal cytotoxicity and target organ toxicity, along with QSAR models and expert systems available for this endpoint. The use of PBPK modelling for the prediction of ADME properties is also discussed. These tests are then incorporated into a decision-tree style, integrated testing strategy, which also includes the use of refined in vivo acute toxicity tests, as a last resort. The implementation of the strategy is intended to minimise the use of animals in the testing of acute systemic toxicity and toxicokinetics, whilst satisfying the scientific and logistical demands of the EU REACH legislation.

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 Evaluating opportunities for advancing the use of alternative methods in risk assessment through the development of fit-for-purpose in vitro assays

2018 ◽  
Vol 48 ◽  
pp. 310-317 ◽  
Author(s):  
Patrick D. McMullen ◽  
Melvin E. Andersen ◽  
Brian Cholewa ◽  
Harvey J. Clewell ◽  
Katherine M. Dunnick ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Alternative Methods ◽  
In Vitro Assays ◽  
Fit For Purpose

Local Irritation/Corrosion Testing Strategies: Development of a Decision Support System for the Introduction of Alternative Methods

2000 ◽  
Vol 28 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Stephan Zinke ◽  
Ingrid Gerner ◽  
Gabriele Graetschel ◽  
Eva Schlede
Keyword(s):  
Decision Support ◽  
Decision Support System ◽  
Support System ◽  
Chemical Properties ◽  
Alternative Methods ◽  
In Vitro Tests ◽  
The European Union ◽  
Animal Testing ◽  
Property A

The notification procedure for new chemicals of the European Union (EU) requires protocols on physicochemical and toxicological tests for the evaluation of physico-chemical properties and probable toxic effects of each notified substance. In order to reduce the amount of animal testing, alternative methods should be introduced into toxicity testing. Therefore, we have developed a rule-based decision support system (DSS) for the prediction of the local corrosive/irritant properties of new chemicals. To this end, data on more than 1000 substances were examined, which resulted in approximtely 180 “exception-rules” of the kind IF (physicochemical property) A THEN not (toxic) Effect B. In addition, the structural formulae of the chemicals were analysed, which resulted in approximately 160 “structure-rules” of the kind IF Substructure A THEN Effect B. The DSS can predict (based on theoretical structure-activity relationships) whether a chemical produces: a) corrosive effects (i.e. no testing is necessary; b) might have corrosive effects (i.e. no animal testing, in vitro tests are suitable); and c) will produce no effects or only marginal effects (i.e. animal tests are necessary based on current EU legislation for hazard assessment purposes). In addition, the DSS provides reliable data for legal classification and labelling based on a specific result.

Assessment of the Eye Irritating Properties of Chemicals by Applying Alternatives to the Draize Rabbit Eye Test: The Use of QSARs and In Vitro Tests for the Classification of Eye Irritation

2005 ◽  
Vol 33 (3) ◽  
pp. 215-237 ◽  
Author(s):  
Ingrid Gerner ◽  
Manfred Liebsch ◽  
Horst Spielmann
Keyword(s):  
Alternative Methods ◽  
In Vitro Assays ◽  
In Vitro Tests ◽  
Eye Irritation ◽  
Limit Values ◽  
Oecd Principles ◽  
Irritation Test ◽  
Definition Of ◽  
Eye Lesions

Huggins has reported on the current situation relating to the development of alternatives to the Draize eye irritation test with rabbits, and an ECVAM Working Group have reviewed the efforts needed in order to replace this animal test within the next 10 years by using the results of non-animal assessment methods. Our report reviews regulatory experience gained over the last 20 years with the EU chemicals notification procedure with respect to the assessment of eye lesions observed in Draize tests. The nature of eye lesions and their importance for classification and labelling of possible hazards to human eyes are evaluated and discussed, with a view to promoting the development of specific in vitro assays which are able to discriminate between eye damage, moderate eye irritation, and minor irritation effects which are completely reversible within a few days. Structural alerts for the prediction of eye irritation/corrosion hazards to be classified and labelled according to international classification criteria, are presented, which should be validated in accordance with internationally agreed (OECD) principles for (Q)SAR system validation. Physicochemical limit values for prediction of the absence of any eye irritation potential relevant for human health can make available a definition of the applicability domains of alternative methods developed for the replacement of the Draize eye irritation test.

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.

Effect of spice supplementation on in vitro methane production using ground wheat as a substrate

2009 ◽  
Vol 2009 ◽  
pp. 27-27
Author(s):  
M M H Khan ◽  
A S Chaudhry
Keyword(s):  
Fatty Acids ◽  
European Union ◽  
Global Warming ◽  
Economic Benefit ◽  
Energy Use ◽  
Alternative Methods ◽  
The European Union ◽  
Use Efficiency ◽  
Ground Wheat

Ruminants lose about 8 to 12 % of their food energy as methane (CH4). Eructation of CH4 from ruminants may contribute to the climatic change and global warming. Reducing CH4 production can be of direct economic benefit because it coincides with greater energy-use efficiency of feeds by the animal. To reduce CH4, antibiotics have been used in addition to their use for growth and disease prevention. However, the European Union has banned the use of antibiotics in animal feeds from January 2006, so there is a need to find alternative methods to reduce CH4 production. It has been shown that tannin and unsaturated fatty acid can play important roles to reduce CH4 production in ruminants (Patra et al., 2006; Giger-Reverdin et al. 2003). Some spices are high in tannin and others are high in fatty acids. In the present study, the chemical composition of five spices and their role in reducing in vitro CH4 production were assessed. Ground wheat (wheat) is a highly fermentable feed as it can produce large amount of gas, and it was therefore used as a substrate to compare the effects of spices on in vitro rumen fermentation in this study.

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 Acute Systemic Toxicity and Toxicokinetics with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1) ◽  
pp. 45-63 ◽  
Author(s):  
Robert Combes ◽  
Christina Grindon ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Decision Tree ◽  
Systemic Toxicity ◽  
Toxicity Tests ◽  
In Vitro Tests ◽  
The European Union ◽  
Animal Testing ◽  
Pbpk Modelling ◽  
Joint Research Project ◽  
The Eu

Liverpool John Moores University and FRAME conducted a joint 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 REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for acute systemic toxicity and toxicokinetic testing. The paper reviews in vitro tests based on basal cytotoxicity and target organ toxicity, along with QSAR models and expert systems available for this endpoint. The use of PBPK modelling for the prediction of ADME properties is also discussed. These tests are then incorporated into a decision-tree style, integrated testing strategy, which also includes the use of refined in vivo acute toxicity tests, as a last resort. The implementation of the strategy is intended to minimise the use of animals in the testing of acute systemic toxicity and toxicokinetics, whilst satisfying the scientific and logistical demands of the EU REACH legislation.

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