Aquatic toxicity

Aquatic toxicity is a major environmental concern and one of the leading indicators of anthropogenic impacts to natural systems. It is a form of inherent hazard frequently used to assess the ecological effects of chemicals in surface water. To this end, aquatic life toxicants are regulated under the Clean Water Act by US EPA, and under REACH legislature in the European Union.

Using aquatic toxicity data for the fathead minnow, Japanese medaka, D. magna and P. subcapitata, we have identified three design guidelines that can distinguish >90% of the chemicals that have no acute and chronic aquatic toxicity concern, as defined by EPA (1). The method relies on just three computed parameters and does not require prior classification by mode of action. Compounds that meet the three criteria are 10x more likely to have low or no acute and chronic aquatic toxicity. To estimate level of hazard, CADRE's module for aquatic toxicity (CADRE-AT) incorporates discriminant models that assign a chemical to one of the EPA's categories of concern. Accuracy of these predictions is ca. 80-95% depending on the category. Using a broad training set of chemicals and aquatic species,CADRE-AT can be used to reliably predict effects of chemicals to organisms at all trophic levels used for aquatic toxicity testing, i.e. vertebrates (fish), invertebrates (crustaceans) and plants (algae). Additionally, our model provides guidance on how to modify chemical structure so as to retain function and reduce aquatic toxicity. CADRE-AT was developed in collaboration with Yale and Baylor Universities, and extensively validated in partnership with EPA Design for the Environment and the Syracuse Research Corporation.


  1. Kostal J, Voutchkova-Kostal AM, Zimmerman JB&Anastas, P (2014) Computational Approaches for Identifying Chemicals with Minimal Toxicity to the Fathead Minnow. Proc NatAcadSci 112(20):6289-6294. Download pdf
  2. Connors K, Voutchkova-Kostal AM, Kostal J, Anastas P, Zimmerman JB& Brooks B (2014) Reducing Aquatic Hazards of Industrial Chemicals: Probabilistic Assessment of Sustainable Molecular Design Guidelines. Environ ToxicolChem33:1894-1902.
  3. Voutchkova AM, Kostal J, Connors K., Brooks B, Anastas P & Zimmerman JB (2012) Towards Rational Molecular Design for Reduced Chronic Aquatic Toxicity. Green Chem14:1001-1008.
  4. Voutchkova AM, Kostal J,Steinfeld J, Emerson J, Brooks B, Anastas P & Zimmerman, JB (2011) Towards Rational Molecular Design: Derivation of Property Guidelines for Reduced Acute Aquatic Toxicity. Green Chem3:2373-2379. Green Chemistry Top 10 Article (August)

The following endpoints have been developed via the CADRE and/or ToxSpec approaches:

Currently under development:

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ToxFix is a platform for development of predictive tools and design guidelines for reduced toxicity of commercial chemicals. It is managed by DOT (DesigningOutToxicity), a consultancy in Green Chemistry and Toxicology based in Alexandria, Virginia

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