Launched more than a decade ago, the European Chemical Industry Council’s (Cefic) long-range research initiative (LRI) sponsors independent, high-quality research into the interaction between chemicals, health and the environment.

According to Cefic, the LRI aims to identify and fill gaps in our understanding of the hazards posed by chemicals and to improve the methods available for assessing the associated risks.

As such, it aims to provide sound scientific advice on which industry and regulatory bodies will draw to respond more quickly and accurately to the public’s concerns.

LRI is one of the major voluntary initiatives of the European chemical industry to support its competitiveness and innovation potential. It has recently stepped up its research programme with a renewed focus on high priority topics: human biomonitoring, endocrine disruption, persistent bioaccumulative toxic substances (PBTs), the development of intelligent testing strategies as alternatives for animal testing and the acceptance of new products and technologies.

In particular, the latest research being funded by the LRI focuses on four specific areas:

• Eco-relevance/environmental fate of chemicals. There are three major projects in this section: ‘establishing relationships of biotransformations across organisms’, ‘population dynamics modelling for ecotoxicology’, and ‘investigating the environmental relevance of laboratory bioconcentrations tests’.

This last project, for example, starts at the end of this year and runs for three years with funding of E350000 from the LRI.

When addressing the safety of chemicals, exposure of organisms, including man, via the food-chain is a key part of the assessment. This assessment is a tiered process and starts with the measurement of a chemical’s bioaccumulation potential using the fish bioconcentration factor (BCF) test (for example OECD305) and an assessment of potential toxicity derived from a previously conducted test on a mammalian or avian species.

Using the output from a BCF test, transfer up the food-chain is modelled and those modelled concentrations are compared to an extrapolated no effect concentration derived from the toxicity test. It has become a standard part of such assessments to assume that chemicals with BCFs of over 2000 are of particular concern and require special treatment. The standard tests conducted in the laboratory to address uptake by aquatic organisms are based on relatively simple protocols that are not designed to replicate environmental conditions. Among factors that make extrapolation of laboratory derived data to field conditions difficult are the presence of dissolved and particulate organic matter, temperature, animal growth and species differences.

The object of this project is to investigate how the physical-chemical parameters in a laboratory test impact the test data and their extrapolation to field behaviour of chemicals.

• Toxicogenomics. The main project in this category is ‘male reproductive health and endocrine toxicity: application of toxicogenomic technologies to develop a mechanistic-based risk assessment’.

Over the past 10 years or more, LRI has supported research to better understand the health impact of hormone active agents and help develop internationally approved and validated screening and testing methods at the OECD.

In November 2006 a joint Cefic LRI and ECETOC workshop was convened to explore opportunities for using genomic technologies to advance research on hormone active substances – in particular those causing male reproductive toxicity.

A priority topic identified at the workshop is how to apply data from genomic research into toxicological risk assessment practices, in particular how toxicogenomics might be applied to recognise, and differentiate between, adverse and non-adverse effects in toxicological studies.

Uncertainties about the application of toxicogenomics to develop dose response relationships applies not only to studies of male reproductive health but presents a generic challenge on how to integrate the new technologies into toxicological risk assessment.

A specific challenge is agreeing how toxicogenomics should be used to accurately identify thresholds of toxicity for regulatory decisions.

Currently a major component of toxicological investigations is to identify the highest exposure level, (dose or concentration), that does not cause a treatment-related toxicological effect believed to be relevant for human health.

Over the years a generic, structured approach for evaluating data generated in toxicology studies has been developed using the concepts of thresholds of toxicity which differentiates between an adverse effect and adaptive change(s) in the experimental animal which although related to treatment are not considered to be adverse.

A similar robust and scientifically acceptable framework is required when using data from genomic technologies to identify and differentiate between adverse and non-adverse effects.

Assuming toxicogenomic thresholds can be established, it should be possible to integrate toxicogenomics with traditional quantitative outcomes of toxicity studies.

So this project has been developed based on the priority topics for research identified during the workshop and includes investigations to determine: if toxicogenomic responses produced by exposures to hormone active agents are predictive of sub-chronic or chronic toxicological effects, and if there are ‘toxicogenomic thresholds’ which must be exceeded to progress from a normal state to an adaptive state and subsequently to an adverse /toxic state.

This project is funded to the tune of E1.3million, and runs for three years from the end of this year.

• Endocrine disruption. The main project in this category is ‘support of a tiered approach to evaluate the endocrine effects in aquatic organisms’.

A large number of tests in fish, invertebrates and amphibians have been proposed to explore (potential) endocrine activity in aquatic organisms. Some of these tests have already been incorporated in new and/or existing regulatory requirements. However, since no agreed testing strategy exists, it is unclear how these tests will be used in the overall evaluation of a substance.

This project aims to generate knowledge to promote a tiered approach and support the optimisation of assays and a testing strategy to investigate potential endocrine activity.

This includes: considering the likelihood of exposure in the environment; maximising available information whilst minimising resource required (animals, endpoints and cost) and avoiding redundant testing; and providing data on the natural variability of proposed parameters.

This E450000 project runs over two years from the end of the year.

• v Human biomonitoring (HBM). In particular, the LRI is keen to find out more on the role of biological guidance values (BGVs) in the interpretation of HBM data; the use of computational tools for the derivation of biomonitoring guidance values; the use of computational tools for the derivation of BGVs; and structured data acquisition via in vitro metabolism screens to enhance computational tools.