Re-evaluation of animal numbers and costs for in vivo tests to accomplish REACH legislation requirements for chemicals - a report by the Transatlantic Think Tank for Toxicology (t4)

Rovida, Costanza; Hartung, Thomas

doi:10.14573/altex.2009.3.187

Cited by 221 publications

(194 citation statements)

References 16 publications

(22 reference statements)

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“…OECD 421, or 422) produced at more than 10 tons. The costs of this in vitro testing is around 10 times lower than the in vivo testing, which in its cheapest version costs around 55,000 Euro [48]. Expert judgment still is needed in different situations to interpret the outcomes, e.g.…”

Section: Module 4 Data Integration and Risk Assessmentmentioning

confidence: 99%

The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals

Burg

Wedebye

Dietrich

et al. 2015

Reproductive Toxicology

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a b s t r a c tThere is a great need for rapid testing strategies for reproductive toxicity testing, avoiding animal use. The EU Framework program 7 project ChemScreen aimed to fill this gap in a pragmatic manner preferably using validated existing tools and place them in an innovative alternative testing strategy. In our approach we combined knowledge on critical processes affected by reproductive toxicants with knowledge on the mechanistic basis of such effects. We used in silico methods for prescreening chemicals for relevant toxic effects aiming at reduced testing needs. For those chemicals that need testing we have set up an in vitro screening panel that includes mechanistic high throughput methods and lower throughput assays that measure more integrative endpoints. In silico pharmacokinetic modules were developed for rapid exposure predictions via diverse exposure routes. These modules to match in vitro and in vivo exposure levels greatly improved predictivity of the in vitro tests. As a further step, we have generated examples how to predict reproductive toxicity of chemicals using available data. We have executed formal validations of panel constituents and also used more innovative manners to validate the test panel using mechanistic approaches. We are actively engaged in promoting regulatory acceptance of the tools developed as an essential step towards practical application, including case studies for read-across purposes. With this approach, a significant saving in animal use and associated costs seems very feasible.

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Section: Module 4 Data Integration and Risk Assessmentmentioning

confidence: 99%

The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals

Burg

Wedebye

Dietrich

et al. 2015

Reproductive Toxicology

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“…Thus, the gold standard used for the identification of contact sensitizers, the local lymph node assay (LLNA) [2,3], can no longer be used. The EU Chemicals Directive REACh would require a vast numbers of animals for retesting of more than 30,000 chemicals to assess their sensitizing potential [4][5][6][7]. International programmes have been established for the development of in vitro alternatives to animal testing in different areas of toxicology.…”

Section: Replacement Of Animal Testing: T Cells As Tools In Immunotoxmentioning

confidence: 99%

T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

Martin

Esser

Schmucker

et al. 2010

Cell. Mol. Life Sci.

131

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Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an This article is dedicated to the memory of our colleague and friend Reinhard Wanner, died 2 April 2010. Cellular and Molecular Life Sciences overview of the development of the field over the last two decades.

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“…First, skin sensitisation is an economically relevant endpoint because the number of people suffering from ACD has been increasing world-wide for many years (Thyssen et al,Introduction 6 chemicals under REACH suggest 162.8 billion Euros for the total number of chemicals, considering a moderate scenario on the animal tests requirements (Rovida and Hartung, 2009). Under the same moderate scenario, animal tests for skin sensitisation, such as the Local Lymph Node Assay (LLNA) (Kimber et al, 1994;Kimber et al, 2001) described in the OECD TG 429 (OECD, 2010) and guinea pig based tests described in the OECD TG 406 (OECD, 1992), are estimated to require the use of about 823,891 animals in order to meet the requirements of REACH (Rovida and Hartung, 2009).…”

Section: Addressing the Development Of Efficient Toxicity Testing Strmentioning

confidence: 99%

“…Under the same moderate scenario, animal tests for skin sensitisation, such as the Local Lymph Node Assay (LLNA) (Kimber et al, 1994;Kimber et al, 2001) described in the OECD TG 429 (OECD, 2010) and guinea pig based tests described in the OECD TG 406 (OECD, 1992), are estimated to require the use of about 823,891 animals in order to meet the requirements of REACH (Rovida and Hartung, 2009). To achieve cost minimisation in the development of testing strategies, it is important to further study the integration of information about direct testing costs, animal welfare considerations and indirect costs from the increasing occurrence of ACD, the clinically relevant effect of skin sensitisation, in the development of testing strategies for assessing skin sensitisation.…”

Section: Addressing the Development Of Efficient Toxicity Testing Strmentioning

confidence: 99%

“…Furthermore, generating information about the hazardous properties of chemicals is resource consuming (Koch and Ashford, 2006;Bottini and Hartung, 2009). It has been estimated that fulfilling information requirements defined by REACH -if based on existing animal tests -would increase testing costs by several billions of Euros, depending on the toxicological endpoint and the number of chemicals that need to be tested for a given endpoint (Rovida and Hartung, 2009). The need to fill information gaps for large numbers of chemicals at low cost has stimulated research on developing new and efficient approaches to toxicity testing (Schaafsma et al, 2009;Andersen and Krewski, 2010;Hartung, 2010a).…”

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confidence: 99%

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An economic approach to non-animal toxicity testing for skin sensitisation

Leontaridou¹

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Re-evaluation of animal numbers and costs for in vivo tests to accomplish REACH legislation requirements for chemicals - a report by the Transatlantic Think Tank for Toxicology (t4)

Cited by 221 publications

References 16 publications

The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals

The ChemScreen project to design a pragmatic alternative approach to predict reproductive toxicity of chemicals

T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

An economic approach to non-animal toxicity testing for skin sensitisation

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