Acute-to-chronic species sensitivity distribution extrapolation.

Seeking to make greater use of available data for risk assessment of substances, we constructed, for the situation in which chronic data are limited or even nonexistent but acute data are relatively large, an acute to chronic transformation (ACT) methodology based on the concept of species sensitivity distributions (SSDs). This ACT methodology uses a comparison of acute and chronic SSDs, separately for vertebrate data (with 22 substances) and for invertebrate data (with 15 substances). Rather than comparing an acute toxicity value with a chronic value, as when calculating an acute to chronic ratio (ACR), samples of acute and chronic data corresponding to the same category of species were compared. Starting from a sample of acute data, the ACT methodology showed relationships that enable the creation of a sample of predicted chronic values. This sample can then be used to calculate a predicted chronic hazardous concentration potentially affecting 5% of species (HC5%), just as with a sample of real chronic toxicity values. This ACT approach was tested on 11 substances. For each substance, the real chronic HC5% and the predicted chronic HC5% were calculated and compared. The ratio between chronic HC5% and ACT HC5% was, on average, 1.6 and did not exceed 4.4 for the 11 substances studied.

Effects of data manipulation and statistical methods on species sensitivity distributions.

Species sensitivity distribution (SSD) methodology currently is used in environmental risk assessment to determine the predicted no-effect concentration (PNEC) of a substance in cases where a sufficient number of chronic ecotoxicological tests have been carried out on the substance, covering, for the aquatic environment with which we are concerned, three taxonomic groups: algae, invertebrates, and vertebrates. In particular, SSD methodology enables calculation of a hazardous concentration that is assumed to protect 95% of species (HC5). This approach is based on the hypothesis that the species for which results of ecotoxicological tests are known are representative, in terms of sensitivity, of the totality of the species in the environment, which raises a number of questions, both theoretical and practical. In this study, we compared various methods of constructing a species sensitivity-weighted distribution (SSWD). Each method is characterized by a different way of taking into account intraspecies variation and proportions of taxonomic groups (vertebrates, invertebrates, and algae), as well as by the statistical method of calculation of the HC5 and its confidence interval. Those methods are tested on 15 substances by using chronic no-observed-effect concentration data available in the literature. The choice of data (intraspecies variation and proportions between taxonomic groups) was found to have more effect on the value of the HC5 than the statistical method used to construct the distribution. The weight of each taxonomic group is the most important parameter for the result of the SSWD and letting literature references decide which proportions of data are used to construct it is not satisfactory.

Evaluation of an in vitro hsp70 induction test for toxicity assessment of complex mixtures: comparison with chemical analyses and ecotoxicity tests.

The aim of this study was to assess the potential of a human cell line containing the hsp70 promoter linked to the chloramphenicol acetyltransferase reporter gene in evaluating the toxic potential of complex mixtures. Cells were exposed to eluates of industrial wastes and the cellular responses were compared with the metal contents of the samples and with standardized aquatic (microalgal growth inhibition, daphnia Immobilization, bacterial luminescence inhibition, Ceriodaphnia dubia reproduction inhibition) and terrestrial (earthworm lethality, plant growth inhibition) tests. The hsp70 promoter was significantly induced by 11 of 14 samples, with different dose-response patterns. Significant correlations of in vitro induction potency with aquatic ecotoxicity, especially with chronic tests, and with the metal contents of the samples were observed. Our study provides new information on the relevance of hsp70 gene induction as a criterion of toxicity and suggests its usefulness for the detection of toxicity associated with metallic pollution in complex mixtures.

Modeling explicitly and mechanistically median lethal concentration as a function of time for risk assessment.

A mechanistic model that explains how toxic effects depend on the duration of exposure has been developed. Derived from the dynamic energy budget (DEB)tox model, it expresses the hazard rate as a function of the toxic concentration in the organism. Using linear approximations in accordance with the general simplifications made in DEBtox, the concentration that induces x% of lethality (LCx) and in particular the lethal concentration 50% (LC50) are expressed explicitly as functions of time. Only three parameters are required: an asymptotic effect concentration, a time constant, and an effect velocity. More sophisticated (but still analytic) models are possible, describing more complex toxicity patterns such as an increase of sensitivity with time or, conversely, an adaptation. These models can be fitted to the common and widespread LC50 endpoints available from the literature for various aquatic species and chemicals. The interpretation of the values assigned to the parameters will help explain the toxicity processes and standardize toxicity values from different sources for comparisons.