Ecotoxicity prediction methods

Interpretation of ecotoxicity is still more of an art than a science. Perhaps the greatest advances in this area will come from increasing nnderstanding of the structure-activity correlations for chemicals. However, at the present time, further effort is necessary to integrate the wide range of different types of assessment currently employed, which range over almost every scientific discipline. In the strictest sense, the laboratory methods described can permit only comparative evalnation of chemicals under the test conditions. Extrapolation from laboratory results to predict what will happen when chemicals enter the natural environment must be improved. 

The USEPA Office of Pollution Prevention and Toxics (OPPT) (Q)SAR Analysis Methods Branch assesses the model domain for ecotoxicity (Q)SAR determined by structural attributes used to predict toxicity. For example, the domain for molecular... 

When the REACH system is introduced, it is possible that additional human health and ecotox-icological information could be required for up to 30,000 existing chemicals, which are currently marketed in volumes greater than 1 t/year (t.p.a.). Therefore, QSAR and other computer-based methods for predicting toxicity are expected to play an increasingly important role, not only for the priority setting of chemicals that need further assessment, but also for hazard assessment purposes. As yet no formal procedures have been put in place for the use of QSAR in the REACH system. 

Usable methods for measuring ecotoxicity are necessary for the development of efficient strategies for bioremediation. The toxicity of soils to animals, however, cannot always be predicted by knowing only the contaminants and their concentrations (Charrois et al., 2001). There is a need for methods that will determine the risk due to contaminants that are actually bioavailable, so that the environment can be protected without unacceptably high clean-up costs. Future regulations should consider not... 

Ecotoxicity can only be measured by the application of biological methods, whereas chemical analysis determines concentrations of defined chemicals that may be used to deduce toxic effects. All concentration levels such as screening values, guideline values, threshold concentrations, benchmark concentrations and trigger values used for the assessment of contaminated media (water, soil, sediments, etc.) should ideally be derived from the observation of biological effects. Comparing pollutant concentrations with these usually conservative standard values is a common practice in the preliminary assessment of contaminated sites. The integration of further information, such as ecotoxicity data from the site, can improve the risk assessment process and enable a more reliable prediction of environmental threats. 

Abstract While a large hody of information is available on the environmental effects of parent chemicals, we know much less about the effects of transformation products. However, transformation products may be more toxic, more persistent and more mobile than their parent compound. An understanding of the ecotoxicity of transformation products is therefore essential if we are to accmately assess the environmental risks of synthetic chemicals. This chapter therefore uses data on pesticides and their transformation products to explore the relationships between parent and transformation product ecotoxicity to aquatic and terrestrial organisms and describes the potential reasons why a transformation product may be more toxic than its parent compound. As it is not feasible to experimentally assess the ecotoxicity of each and every transformation product, this chapter also describes and evaluates the use of expert systems, read-across methods and quantitative structme activity relationships for estimating transformation product ecotoxicity based on chemical structme. Finally, experimental and predicted ecotoxicity data are used alongside monitoring data for parent pesticides and their transformation products to illustrate how the risks of parent and transformation product mixtiu es can be assessed. 

In another approach, with an aim to offer a realistic motive towards handling millions of databases and hundreds of descriptors for a fruitful structure-activity relationship (SAR), Putz and coworkers have proposed a unique QSAR model called spectral-SAR (S-SAR) [220], which considers the spectral norm in quantifying toxicity and reactivity with molecular structure. A handful of applications of the S-SAR algorithm in dealing with ecotoxicity, enzyme activity, and anticancer bioactivity are well established [221-227]. The S-SAR model coupled with Element Specific Influence Parameter (ESIP) formulations [228] are also utilized for predicting ecotoxicity measures. QSAR studies on the anti-HIV-1 activity of HEPT (l-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine) [229] and further studies involving the minimum topological difference (MTD) method [230, 231] are also reported [232]. 

ADME and molecular mechanics descriptors can be calculated using Accelerys program. Their TOPKAT moditle is an established in silico method for assessing toxicity prediction of organic compoimds [50]. TOPKAT can help assess envirorunental fate, ecotoxicity, toxicity, mntagenicity, and reprodnctive/developmental toxicity of chemicals. TOPKAT technology is currently used to optimize therapeutic ratios of... 

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