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.

Development of a Decision Support System for the Introduction of Alternative Methods into Local Irritancy/Corrosivity Testing Strategies. Development of a Relational Database

2000 ◽  
Vol 28 (1) ◽  
pp. 11-28 ◽  
Author(s):  
Ingrid Gerner ◽  
Gabriele Graetschel ◽  
Jürgen Kahl ◽  
Eva Schlede
Keyword(s):  
Decision Support ◽  
Decision Support System ◽  
Support System ◽  
Scientific Information ◽  
Alternative Methods ◽  
In Vitro Tests ◽  
Property A ◽  
Chemical Substances ◽  
Testing Strategies ◽  
Structure Activity

For new chemical substances that are notified within the European Union, data sets have to be submitted to the National Competent Authorities. The data submitted have to demonstrate the physicochemical and toxic properties of the new chemical, such as solubility, partition coefficients and spectra, as well as acute toxic properties and the potential to cause local irritant or corrosive effects. In order to minimise testing for notification purposes (for example, animal testing), it is necessary to develop stepwise assessment procedures, including structure-activity considerations, alternative methods (for example, in vitro tests), and computerised structure-activity relationship (SAR) models. An electronic database was developed which contains physicochemical and toxicological data on approximately 1300 chemical substances. It is used for regulatory structure-property relationship (SPR) and SAR considerations, and for the development of rules for a decision support system (DSS) for the introduction of alternative methods into local irritancy/corrosivity testing strategies. The information stored in the database is derived from proprietary data, so it is not possible to publish the data directly. Therefore, the database is evaluated by regulators, and the information derived from the data is used for the development of scientific information about SARs. This information can be published, for example, by means of tables correlating measured physicochemical values and specific toxic effects caused by the measured chemical. This information is introduced to the public by means of a DSS that predicts local irritant/corrosive potential of a chemical by listing so-called exception rules of the kind IF (physicochemical property) A THEN not (toxic) Effect B and so-called structural rules of the kind IF Substructure A THEN Effect B. These DSS rules “translate” proprietary data into scientific knowledge that can be published.

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.

Validation of a decision-support system for blueberry anthracnose and fungicide sensitivity of Colletotrichum gloeosporioides isolates.

Plant Disease ◽  
2020 ◽  
Author(s):  
Andre B Gama ◽  
Leandro Gabriel Cordova ◽  
Carolina Suguinoshita Rebello ◽  
Natalia A. Peres
Keyword(s):  
Decision Support ◽  
Decision Support System ◽  
Support System ◽  
Colletotrichum Gloeosporioides ◽  
Low Frequency ◽  
Fruit Rot ◽  
Fungicide Sensitivity ◽  
Thiophanate Methyl ◽  
Advisory System

Blueberry is an increasingly important crop in Florida. Anthracnose fruit rot (AFR), mostly caused by Colletotrichum gloeosporioides, is favored by long wetness periods and temperatures from 15 to 27oC. Currently, the model in the Strawberry Advisory System (StAS) guides fungicide applications targeting strawberry AFR. Given the similarity between blueberry and strawberry AFR, we hypothesized that the model used in StAS could be used in a decision-support system built for blueberry AFR. There is no information on inhibition posed by fungicides on C. gloeosporioides isolates from blueberry. Our objectives were to demonstrate that the model used in the StAS could be used for blueberry AFR management in Florida, and to assess the sensitivity of isolates to fungicides. Four trials were undertaken in blueberry fields in Florida during two seasons to compare the effectiveness of fungicide applications following the model to the growers’ standard calendar. Sensitivity of blueberry C. gloeosporioides isolates to azoxystrobin, benzovindiflupyr, penthiopyrad, pydiflumetofen, boscalid, thiophanate-methyl, fluazinam, and fludioxonil was evaluated. AFR incidence and yield were compared between treatments. Following recommendations from the model resulted in disease control as effective as the standard program and in some cases with a reduced number of applications. All isolates were sensitive to benzovindiflupyr, penthiopyrad, fluazinam, and fludioxonil. Low frequency of in vitro inhibition of isolates by azoxystrobin, pydiflumetofen, boscalid, and thiophanate-methyl should raise concern for fungicide resistance. Our results indicate that the model used in StAS could be used in a blueberry decision-support system to aid Florida growers to manage AFR.

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.

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