Integrated Testing Strategies

Time:

Meeting: 8-10 July 2013

Venue: Hotel Belvedere, Ranco (Varese, Italy)

Overall goal of the workshop:

This workshop aims to bring together experts to discuss about how to make Integrating Testing Strategy (ITS) a practical tool that will help toxicologists in risk assessment of chemicals by using data from different sources.

Workshop set-up:

The workshop will bring together selected experts in the area of toxicology as well computational chemistry.

First day: Introduction into the vision of this workshop and in-depth discussion of possibilities

Second day: Elaboration of collaborative strategies

Third day: Conclusions and preliminary outcome report.

Abstract:

For determination of science-based, high-throughput and human-relevant approaches for safety assessment of chemicals, an objective decision making process needs to be adopted and accepted for regulatory purposes. According to the theory that risk assessment should be ruled by knowledge and not by fear, it is now well recognized that the future of chemical risk assessment will be through a combination of approaches (in vitro, ex vivo, in silico) with distinctive applicability domains, which address functional endpoints relevant to mechanisms underlying the adverse outcome. In spite of this shared awareness, the way toward this goal is still unclear as there are controversies starting from the definition of an ITS, how it can be validated and last, but not least, there are no computational  tools that can be used for this purpose (Hartung et al. 2013).

The principle of ITS is to incorporate multiple data and information, e.g. information from different test methods, test method batteries, tiered test schemes, modeling techniques e.g. (Q)SAR, exposure and epidemiological data into this decision-making process. This way is not straightforward and one of the main challenges is to accommodate the flexibility ITS require, e.g. to respond to varying levels of uncertainty or resolution needed, with the requirement of standardization that is mandatory for regulatory applications.

The aim of this workshop is to lay-out a basis for the construction of transparent, objective and consistent ITS tools that fulfill the needs of risk assessors. It uses the example of skin sensitization, where such integration of the assays recently evaluated and validated is imminent and the mechanistic understanding is advanced. Even though the applicability of ITS is general, this workshop will consider skin sensitization as an example about how ITS can be really applied in practice. Skin sensitization represents a good starting point as the biological mechanism is well known and there are many in vitro methods that are at an advanced state of validation, plus an in vivo method (LLNA) that is the only in vivo method that has been fully validated.

Questions to be addressed:

• What are the selection criteria for in vitro and in silico methods and the combination criteria of the methodologies for the ITS approach?
• How to evaluate the performance of the ITS approach for the regulatory use?
• Which statistical and/or mathematical tools are available for relevant integration of data from different sources?
• Do we need a new dedicated system or can we adopt standard programs for statistical evaluation?
• How to assess the predictive performance of ITS?