EUROTOX 2014 – Predictive Toxicology, Endocrine Disruption, and Wonky Dose Response Curves

Computational and IT-based approaches to toxicology have now become firmly established in the field, and have many significant applications. Rusty Thomas, director of the EPA’s National Centre for Computational Toxicology, provided an overview of their activities and discussed how they are using computational approaches for high-throughput screening of chemicals in safety assessments. Other topics touched on using biological data sources for toxicity prediction, omics data, and the Assuring Safety without the Animal Testing (ASAT) concept. The last topic has become very relevant for the cosmetics industry, where in Europe an outright ban on animal testing was introduced in 2013. 

2014 opening reception in Edinburugh 

On the Monday of the conference my colleague Dr. Damien Comiskey and I presented posters on our models and software for assessing exposure to fragrances and other substances present in personal care products and cosmetics. The poster sessions in EUROTOX are always busy affairs and we were pleased to learn we had a lot of interest in our work – and a lot of traffic jams in the narrow viewing areas! These posters are available for download at the end of this blog. 

Cian O'Mahony, Head of Expert Modelling & Statistics at Creme Global 

The “wonky” dose-response curves in the blog title refers to Non-Monotonic Dose Response curves (NMDRs). These are substances which exhibit toxic effects at both high and low doses, in stark contrast to the traditional sigmoidal curves generally observed in toxicology. The usual principle is that “the dose makes the poison”, with toxic effects observed at the higher ranges of exposure. Recently, however, a number of studies on endocrine disrupting substances have indicated that toxic effects may be present at much lower doses too, with a range of exposure between low and high at which no toxic effects are observed. This is a headache for exposure assessors like myself who are used to working with the basic principle that once exposure is below the hazard level the risk is low – a concept now being challenged by these low-dose effects. 

Dr. Damien Comiskey, Expert Modelling & Statistics at Creme Global 

I was therefore somewhat relieved to see this is a headache for the toxicologists too. This year’s Society of Toxicology/EUROTOX debate was titled “Are non-monotonic dose responses at low dose levels toxicologically relevant”, with James Lamb from Exponent and Dieter Schrenk from the Technical University of Kaiserlautern taking opposing views on the topic. This is the second time they have debated the topic, but this time they swapped sides on the motion! 

To their credit, no evidence of their previous positions on the topic was evident from the presentations. In the end we all voted on the motion, however I won’t tell you which side won! Suffice to say, there are plenty of open questions still in toxicology. In risk assessment, exposure assessment is the next step after the toxicology, meaning a host of new questions await for us exposure assessors too. 

Posters are available to download here: 

Poster 1: Aggregate Exposure to Existing and Novel Fragrances in Consumer Product (O'Mahony et al.) 

Poster 2: Combining Databases to Estimate Population Exposure to Cosmetics and Personal Care Products (Comiskey et al.) 

Written by Creme Global on September 19 2014

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