The AR-CALUX® method was validated by the JRC’s EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) and has now been taken up in an international test guideline by the Organisation of Economic Cooperation and Development (OECD) for the detection of androgen-like chemicals.
The JRC led an OECD project to update test guideline TG 458 which includes the AR-CALUX® method along with two other similar methods. All three methods use genetically engineered cell lines that respond to either activation or blocking of the androgen receptor. Government agencies, industry, and contract research organisations need this type of mechanistic information to identify potential endocrine disruptors.
As described in related OECD guidance, information on androgen activity derived from in vitro methods is typically combined with other information sources, for example within an integrated approach to testing and assessment (IATA), to arrive at a conclusion about the endocrine properties of a chemical.
The validation study
The JRC’s EURL ECVAM validated the AR-CALUX® method through a study involving three test facilities of the European Union Network of Laboratories for the Validation of Alternative Methods (EU-NETVAL): RISE, Covance and Charles River; and the test method developer, BioDetection Systems.
As explained by Anne Milcamps, JRC scientist and coordinator of the validation study: “We looked at the reliability and relevance of the AR-CALUX® method for detecting androgen activity. A reliable method means it can be transferred between laboratories and the results obtained will be reproducible. Relevance is more about the science behind the method being right and demonstrating that it can identify chemicals with androgen activity”.
The results of the validation study underwent independent scientific review by ECVAM’s scientific advisory committee (ESAC). All related documentation, including the validation study report, the ESAC Opinion and the method protocol, are publicly available through EURL ECVAM’s Tracking System for Alternative methods towards Regulatory acceptance (TSAR).
More on endocrine disruptors and related EU policy
Societal concerns about endocrine disruptors stem from the fact that they can adversely affect the health of humans and animals by altering the functioning of the endocrine (hormonal) system. Chemicals with endocrine disrupting properties can come from many different sources, both natural and manmade. Minimising our exposure to endocrine disruptors is important to reduce the risk that they contribute to causing endocrine-mediated diseases, such as some cancers.
Updating of TG 458 is an important step towards achieving the Commission’s goal (Commission Communication 2018) of making more endocrine-specific methods available while at the same time reducing reliance on animal testing. In addition to this, EURL ECVAM is conducting an ambitious validation study comprising 17 in vitro methods to detect chemicals that disrupt thyroid function. The JRC, including its EURL ECVAM, is also collaborating with a cluster of 8 research projects (EURION) funded under Horizon 2020 that are focusing on gaining a deeper scientific understanding of endocrine disruption and the development of novel approaches for testing and assessment.
In addition to supporting the uptake of new test methods, the JRC worked closely with other Commission services and relevant EU agencies in defining scientific criteria for identifying endocrine disruptors for biocides and pesticides and is now leading a fitness check to assess whether the EU chemicals legislation is coherent and effective in protecting human health and the environment. For a comprehensive overview of the European Commission’s activities on endocrine disruptors, visit the Commission’s dedicated information portal.
According to Maurice Whelan, JRC scientist and head of the JRC’s EURL ECVAM: “Significant progress has been made in understanding and regulating endocrine disruptors since the EU adopted its first strategy back in 1999. As JRC and EURL ECVAM, we’ll be continuing our extensive work in this area to ensure that the objectives set out in the Commission’s new Green Deal related to endocrine disruptors are achieved as efficiently and effectively as possible”.
AR-CALUX® test method in the EURL ECVAM’s Tracking System for Alternative methods towards Regulatory acceptance (TSAR)
Validation Study Report: Performance assessment of the AR-CALUX® in vitro method
Statistical report of the AR-CALUX® validation study
Standard Operating Procedure for the AR-CALUX® in vitro test method
ESAC Opinion on the scientific validity of the AR-CALUX® test method
- Publication date
- 9 July 2020