Related Experiment Videos
Validation of in vitro and in vivo methods for assessing endocrine disrupting chemicals
1Zeneca Central Toxicology Laboratory, Cheshire, United Kingdom. John.Ashby@CTL.Zeneca.com
Abstract:
The concepts that require validation in terms of the subject of endocrine disruption are listed and discussed. The main mechanisms by which endocrine disruption can occur are identified, and the assays required for the detection of adverse endocrine disruption toxicities associated with these mechanisms are discussed. The process of assay validation is considered. The validation of structure-activity relationships, the need for reference chemicals, and the problems recently encountered when attempting to reproduce endocrine disruption data are also explored. The most important conclusions derived from this analysis are that given the immature state of research into endocrine disruption toxicity, testing strategies and the types of assay employed should be kept under constant review; inevitably researchers need to accept the fact that future revision of each assay will be required. Second, given the current absence of any chemical that is universally accepted to be devoid of endocrine toxicity, assay specificity will be difficult to assess, and that imposes the need for alternative objective criteria for assessing the value of individual assays.
Insights
Research into endocrine disruption requires ongoing validation of testing strategies and assays. Due to the lack of a universal reference chemical, assessing assay specificity for endocrine disruptors is challenging, necessitating alternative evaluation criteria.
Area of Science:
- Endocrinology
- Toxicology
- Chemical Safety Assessment
Background:
- Endocrine disruption is a complex toxicological endpoint requiring robust validation of detection methods.
- Current research faces challenges in assay validation and reproducibility of endocrine disruption data.
Purpose of the Study:
- To discuss concepts requiring validation for endocrine disruption assessment.
- To identify mechanisms of endocrine disruption and associated assays.
- To explore assay validation, structure-activity relationships, and reference chemical needs.
Main Methods:
- Review of existing concepts and mechanisms of endocrine disruption.
- Discussion of assays for detecting adverse endocrine disruption toxicities.
- Consideration of assay validation processes and challenges.
Main Results:
- Immature state of endocrine disruption research necessitates continuous review of testing strategies and assays.
- Difficulty in assessing assay specificity due to the absence of a universally accepted non-endocrine toxicant reference chemical.
Conclusions:
- Assays for endocrine disruption will require future revisions.
- Alternative objective criteria are needed to assess the value of individual assays for endocrine disruptors.