CEC04-01 Evaluation of non guideline studies as important source of information

The first guideline for toxicokinetic studies was adopted in 1984 by the OECD, and the current version of 2010 still refers to the need for further specification of the recommendations of the responsible agencies. This implies that older toxicokinetic studies are available, particularly for existing chemicals, and that differences in study design and outcome may depend on the existence or non-existence of regulatory recommendations. Furthermore, toxicokinetic studies published in peer-reviewed literature, especially those not conducted for regulatory purposes as well as academic research studies may not be guideline conform.

Non-guideline studies are an important source of information for a wide array of chemical substances. For the structured assessment of toxicity studies criteria checklists are well established and support evaluating the evidence of non-guideline studies.

Currently, the evaluation of toxicokinetic studies is performed as a narrative review which is not supported by a systematic approach to standardize the strength of the evidence obtained from non-guideline toxicokinetic studies for regulatory assessments. In particular, the impact of a single aspect such as purity of the test item, specifications of the analytical methods, or number of animals, to the final rating is important in evaluating the overall reliability of the study.

The transparent way of a systematic review of diverse, non-guidelines studies provides direct evidence of their importance for current risk assessment based on the 3R principles.