Scientific options for avoiding chronic fish testing on the basis of existing data and extrapolation approaches
The assessment of aquatic toxicity is an important component of the environmental hazard and risk assessment of all types of chemicals, and is therefore included in several pieces of EU chemicals legislation. Aquatic toxicity refers to the effects of chemicals on organisms living in the water and is usually determined by testing on organisms representing three trophic levels, i.e. plants (or algae), invertebrates (crustaceans such as Daphnia spp.) and vertebrates (fish). Whereas acute aquatic toxicity testing is a basic requirement in most pieces of EU chemicals legislation, chronic aquatic toxicity testing may be required when the outcome of the acute testing indicates a risk, or in the case that long-term exposure is expected. EU chemicals legislation encourages the use of all available information for hazard and risk assessment before new tests on vertebrates are proposed or conducted. In this context, scientific options for avoiding chronic fish testing on the basis of existing data and extrapolation approaches have been explored.
For the purposes of this work, data on acute and chronic aquatic toxicity (Daphnia and fish) from several databases (US EPA Ecotox database, Aquatic ECETOC, Aquatic OASIS, Aquatic Japan MoE databases and ECHA database as implemented in the OECD QSAR Toolbox Version 2.3) were collated and analysed. Simple linear relationships and interspecies sensitivity ratios were calculated using either acute Daphnia data (48h LC50) or chronic Daphnia data (14 days NOEC) and chronic fish data (>21 days NOEC). Acute to chronic relationships and acute to chronic ratios (ACR) were also calculated based on acute fish data (96h LC50) and chronic fish data. These analyses were carried out on the whole set of chemicals and on subgroups of chemicals classified according to the Verhaar mode of action (MOA) scheme, which attribute general mode of acute aquatic toxic action based on the chemical structure of the molecule. Outliers were identified applying the Robust regression and Outlier removal (ROUT) method.
Our results show that the best fitted relationships for the prediction of chronic fish toxicity are obtained based on acute fish data (r2=0.87) and acute Daphnia data (r2=0.64) when dealing with the whole set of chemicals regardless of the MOA. The quality of the relationships was increased by using the geometric mean (calculated across all the values extracted for a given chemical and a given endpoint) instead of the lowest value for a given endpoint.
When considering the MOA, MOA 3 and MOA 1 chemicals give the strongest acute Daphnia to chronic fish relationship and chronic Daphnia to chronic fish relationship; however the relationships obtained with acute Daphnia data are better (r2= 0.83 and 0.69 for MOA 3 and MOA 1 respectively) than the one obtained with chronic Daphnia data (r2= 0.66 and 0.65 for MOA 1 and 3 respectively). When considering acute fish data, all the MOA classes give strong relationships (r2=0.88 for MOA 3 and MOA 5 chemicals, 0.85 for MOA 4 chemicals and 0.83 for MOA 1 and MOA 2 chemicals). Therefore when acute toxicity data on fish are available, they might give a reliable basis to extrapolate the chronic toxicity on fish as a first tier assessment or within a weight of evidence approach.
There is a correlation between chemicals with high ACR values or interspecies sensitivity ratios and the outliers identified in the above-mentioned relationships. When considering chemicals with a high interspecies sensitivity ratio, Daphnia being more sensitive than fish, several aniline derivatives and pesticides acting through cholinesterase inhibition were identified. When considering high interspecies sensitivity ratio chemicals for which Daphnia is less sensitive than fish, we found pesticides and known endocrine disruptors such as ethynil oestradiol and 17ß-oestradiol. Extreme (i.e. <1 or > 100) interspecies sensitivity ratios were mainly evident for MOA 2, 4 and 5 chemicals. Regarding ACR for fish, around 50% of the chemicals in each MOA class have an ACR within a factor of 10; whereas 100% of MOA 3, 90.9% of MOA 2, 88.3% of MOA 4 and 85.5% of MOA 1 chemicals have an ACR within a factor of 100. Therefore, the safety factor of 100 commonly applied in environmental risk assessment does not seem to be equally protective for every MOA.
KIENZLER Aude;
HALDER Maria Elisabeth;
WORTH Andrew;
2016-05-11
Publications Office of the European Union
JRC101327
978-92-79-58167-0,
1831-9424,
EUR 27907,
OP LB-NA-27907-EN-N,
https://publications.jrc.ec.europa.eu/repository/handle/JRC101327,
10.2788/546221,
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