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Experts urge revision to pesticide guidelines following toxicity study

The new study below shows yet another reason why pesticide risk assessment as practised today is inadequate: it does not assess the effects of exposure sequences, nor are these tested in the standardized studies performed by industry to justify a pesticide’s release onto the market.
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Experts urge revision to pesticide guidelines following toxicity study

University of York, 21 February 2017
https://www.york.ac.uk/news-and-events/news/2017/research/pesticide-toxicity-study/

Scientists at the University of York have discovered for the first time that the sequence of exposure to pesticides and pollutants – not just the dosage - significantly affects the levels of toxicity for surrounding wildlife.

Previously, it was always assumed that "the dose makes the poison", in terms of chemicals causing detrimental health effects on organisms. Yet it has now been found that when organisms are exposed to two toxicants in sequence, the toxicity can differ if their order is reversed.

This is due to the fact that some chemicals cause lingering damage to organisms’ systems, causing a slow recovery time, resulting in "carry over toxicity" which then compounds the effects of a second pollutant.

Exposure sequences

Exposing freshwater shrimp (Gammarus pulex) to different toxicants, it was found that more damage was caused when pollutants producing a slow recovery time were dispensed first, followed by chemicals that organisms recover quickly from. This is in contrast to the sequence being reversed, when a toxicant with a fast recovery time, followed by a slow, was administered.

Even when toxicant exposure was days apart, and the toxicants dispensed were for different actions (i.e. different pesticides that use separate mechanisms for distinctive targets), researchers found shrimp mortality exceeded predicted expectations in the former sequence.

This shows that current chemical risk assessment guidelines could severely underestimate the risks associated with differing exposure sequences.

Health effects

Dr Roman Ashauer, Senior Lecturer in York’s Environment Department and lead author of the study, said, “This research proves for the first time that toxicants interact, even if exposure is days apart and the toxicants have a different chemical make-up, resulting in a build-up of toxicodynamic damage in organisms.

“The sequence effect and carry-over toxicity is currently not considered in environmental risk assessment, so this has wide-reaching implications. Guidelines for allowing chemicals such as pesticides to go on the market must be revised to look at mixtures over time, e.g. different sequences of pesticides.

“We have developed a successful model for predicting the sequence effect of toxicants, and we hope that agencies such as the European Food Safety Authority look closely at this to inform their work. Exposure to multiple toxicants, in highly variable sequences, is a real-life scenario for humans as well as all other organisms, so it is vital that we pay attention to possible detrimental health effects.”

Toxic Mixtures in Time – the sequence makes the poison is published in the journal Environmental Science and Technology. To read, visit: http://dx.doi.org/10.1021/acs.est.6b06163

Toxic Mixtures in Time — The Sequence Makes the Poison

Roman Ashauer, Isabel O’Connor, and Beate I. Escher
Environ. Sci. Technol.
DOI: 10.1021/acs.est.6b06163
Publication Date (Web): February 8, 2017
http://pubs.acs.org/doi/abs/10.1021/acs.est.6b06163

Abstract

“The dose makes the poison”. This principle assumes that once a chemical is cleared out of the organism (toxicokinetic recovery), it no longer has any effect. However, it overlooks the other process of re-establishing homeostasis, toxicodynamic recovery, which can be fast or slow depending on the chemical. Therefore, when organisms are exposed to two toxicants in sequence, the toxicity can differ if their order is reversed. We test this hypothesis with the freshwater crustacean Gammarus pulex and four toxicants that act on different targets (diazinon, propiconazole, 4,6-dinitro-o-cresol, 4-nitrobenzyl chloride). We found clearly different toxicity when the exposure order of two toxicants was reversed, while maintaining the same dose. Slow toxicodynamic recovery caused carry-over toxicity in subsequent exposures, thereby resulting in a sequence effect – but only when toxicodynamic recovery was slow relative to the interval between exposures. This suggests that carry-over toxicity is a useful proxy for organism fitness and that risk assessment methods should be revised as they currently could underestimate risk. We provide the first evidence that carry-over toxicity occurs among chemicals acting on different targets and when exposure is several days apart. It is therefore not only the dose that makes the poison but also the exposure sequence.