Should the scope of human mixture risk assessment span legislative/regulatory silos for chemicals?, Science of The Total Environment, RM Evans, OV Martin, M Faust, A Kortenkamp. Available online 10 November 2015, ScienceDirect (open-access)
Our recently accepted paper discusses whether the scope of a mixture risk assessment needs to include chemicals and/or effects that are subject to different pieces of legislation (which we defined as ‘silos’). We present illustrations of multiple situations in which it is entirely plausible that the risk to human health can only be accurately predicted by considering multiple chemicals across multiple silos – however this is almost never done, and nor is there a legislative framework for doing so. We propose the discussion of various options, ranging from small, incremental changes based on existing legislation and practice, up to larger, more ambitious proposals for new legislation.
We hope to promote discussion and would welcome comments via this blog, through email or via the full text paper.
Evans RM, Scholze M, Kortenkamp A. Examining the feasibility of mixture risk assessment: A case study using a tiered approach with data of 67 pesticides from the Joint FAO/WHO Meeting on Pesticide Residues (JMPR). Food Chem Toxicol. 2015 Oct;84:260-9. doi: 10.1016/j.fct.2015.08.015. Epub 2015 Sep 4. PubMed. Free access on ScienceDirect (until 30th Dec. 2015).
Our recently published paper presents a case study testing a tiered approach to mixture risk assessment (MRA) using data for 67 pesticides. Our main conclusions were:
- The data requirements of a tiered approach can grow dramatically so that low tiers, with lower data requirements, can be completed but higher tiers, with the highest data requirements, cannot.
- This is likely to leave many assessments in ‘limbo’, being unable to conclude that the risk of mixture toxicity is either acceptably low or unacceptably high.
- Nonetheless, tiered approaches may indicate data gaps that, once filled, can allow an assessment to progress; and may provide indications for the best use of resources in managing any risk.
- More systematic data collection, perhaps in high throughout systems, and open access to toxicology data may improve the situation.
The first release of the CREST database is now available for public access.
CREST is a database of Chemical attributes, Regulatory approaches and Experimental STudies from a mixture toxicology perspective.
CREST is freely available online and users can explore the database starting from a published study, a chemical of interest or from a series of datasets that have been incorporated into CREST.
A major design feature of CREST is the use of Standard International Chemical Identifier (InChI) Keys to link disparate data sources, including a unique dataset of over 450 mixture toxicity studies curated from the literature.
User feedback and opinions are very welcome, and can be sent as blog comments, or by contacting us.
Last week, we presented work from the TRI project at the Annual Congress of the British Toxicology Society (BTS) in Solihull, UK. We presented a poster describing:
- the challenge of implementing mixture risk assessment (MRA) as part of routine chemical risk assessment
- the approach we are taking in reviewing the relevant legislation and literature, including the generation of a database, CREST, on which there will be more soon on this blog.
- the case studies we are developing to illustrate the problem and to identify pragmatic solutions to the issue.
Kortenkamp A, Scholze M, Ermler S. Mind the gap: can we explain declining male reproductive health with known antiandrogens? Reproduction. 2014 Mar 2;147(4):515-27. doi: 10.1530/REP-13-0440. Print 2014. PubMed PMID: 24435164
This paper asks the question: can our current understanding of human exposure to chemicals with anti-androgenic properties explain the observed decline in male reproductive health – for example manifesting as cryptorchidism, hypospadias and testicular germ cell cancer (the ‘testicular dysgenesis syndrome’)?
Cumulative Health Risk Assessment: finding new ideas and escaping from the old ones.
Sexton 2014. Human and Ecological Risk Assessment, epub.
In this article, Sexton contrasts effect-based and stressor-based cumulative risk assessment (CRA) approaches, and discusses an alternative vulnerability-based approach (Sexton, 2014). Stressor-based approaches are prospective and useful for chemical regulation, level setting etc, whilst effect-based approaches may come into their own when attempting to explain an observed health effect (retrospectively) and when non-chemical stressors are involved.
The German Federal Environment Agency (UBA) has published a report on the evaluation of the uncertainties of the environmental risk assessment of endocrine disrupting chemicals (EDCs). Titled “Substances of very high concern under REACH – an evaluation of uncertainties in the environmental risk assessment of endocrine active substances”; the project aimed to “identify the most relevant factors increasing the uncertainty of the environmental risk assessment (ERA) of endocrine active substances as compared to baseline toxicants.” Continue reading
A recent paper by Dr Martin (Martin, Scholze and Kortenkamp 2013) addressed the background and use of default uncertainty factors in chemical risk assessment. Mixture Toxicology often identifies issues in single chemical risk assessment that become especially problematic when mixture effects are considered.