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      Comparison of Toxicities to Vibrio fischeri and Fish Based on Discrimination of Excess Toxicity from Baseline Level

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          Abstract

          Investigations on the relationship of toxicities between species play an important role in the understanding of toxic mechanisms to environmental organisms. In this paper, the toxicity data of 949 chemicals to fish and 1470 chemicals to V. fischeri were used to investigate the modes of action (MOAs) between species. The results show that although there is a positive interspecies correlation, the relationship is poor. Analysis on the excess toxicity calculated from toxic ratios (TR) shows that many chemicals have close toxicities and share the same MOAs between the two species. Linear relationships between the toxicities and octanol/water partition coefficient (log K OW) for baseline and less inert compounds indicate that the internal critical concentrations (CBRs) approach a constant both to fish and V. fischeri for neutral hydrophobic compounds. These compounds share the same toxic mechanisms and bio-uptake processes between species. On the other hand, some hydrophilic compounds exhibit different toxic effects with greatly different log TR values between V. fischeri and fish species. These hydrophilic compounds were identified as reactive MOAs to V. fischeri, but not to fish. The interspecies correlation is improved by adding a hydrophobic descriptor into the correlation equation. This indicates that the differences in the toxic ratios between fish and V. fischeri for these hydrophilic compounds can be partly attributed to the differences of bioconcentration between the two species, rather than the differences of reactivity with the target macromolecules. These hydrophilic compounds may more easily pass through the cell membrane of V. fischeri than the gill and skin of fish, react with the target macromolecules and exhibit excess toxicity. The compounds with log K OW > 7 exhibiting very low toxicity (log TR < –1) to both species indicate that the bioconcentration potential of a chemical plays a very important role in the identification of excess toxicity and MOAs.

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          Most cited references22

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          A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity.

          Several pieces of legislation have led to an increased interest in the use of in silico methods, specifically the formation of chemical categories for the assessment of toxicological endpoints. For a number of endpoints, this requires a detailed knowledge of the electrophilic reaction chemistry that governs the ability of an exogenous chemical to form a covalent adduct. Historically, this chemistry has been defined as compilations of structural alerts without documenting the associated electrophilic chemistry mechanisms. To address this, this article has reviewed the literature defining the structural alerts associated with covalent protein binding and detailed the associated electrophilic reaction chemistry. This information is useful to both toxicologists and regulators when using the chemical category approach to fill data gaps for endpoints involving covalent protein binding. The structural alerts and associated electrophilic reaction chemistry outlined in this review have been incorporated into the OECD (Q)SAR Toolbox, a freely available software tool designed to fill data gaps in a regulatory environment without the need for further animal testing.
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            Measurement and estimation of electrophilic reactivity for predictive toxicology.

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              A conceptual framework for predicting the toxicity of reactive chemicals: modeling soft electrophilicity.

              Although the literature is replete with QSAR models developed for many toxic effects caused by reversible chemical interactions, the development of QSARs for the toxic effects of reactive chemicals lacks a consistent approach. While limitations exit, an appropriate starting-point for modeling reactive toxicity is the applicability of the general rules of organic chemical reactions and the association of these reactions to cellular targets of importance in toxicology. The identification of plausible "molecular initiating events" based on covalent reactions with nucleophiles in proteins and DNA provides the unifying concept for a framework for reactive toxicity. This paper outlines the proposed framework for reactive toxicity. Empirical measures of the chemical reactivity of xenobiotics with a model nucleophile (thiol) are used to simulate the relative rates at which a reactive chemical is likely to bind irreversibly to cellular targets. These measures of intrinsic reactivity serve as correlates to a variety of toxic effects; what's more they appear to be more appropriate endpoints for QSAR modeling than the toxicity endpoints themselves.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 February 2016
                2016
                : 11
                : 2
                : e0150028
                Affiliations
                [001]State Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of Environment, Northeast Normal University, Changchun, Jilin, P. R. China
                Northwest Fisheries Science Center, NOAA Fisheries, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Analyzed the data: XHW YY TH WCQ LMS YHZ. Wrote the paper: XHW YHZ.

                Article
                PONE-D-15-36557
                10.1371/journal.pone.0150028
                4762671
                26901437
                1b83a558-786f-4db4-a3c3-90b2e2926ec7
                © 2016 Wang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 September 2015
                : 8 February 2016
                Page count
                Figures: 3, Tables: 1, Pages: 17
                Funding
                This research was financially supported by the National Natural Science Foundation of China, 21377022,( http://www.nsfc.gov.cn/) to YHZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Toxicology
                Toxicity
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Toxicology
                Toxicity
                Biology and Life Sciences
                Toxicology
                Predictive Toxicology
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Toxicology
                Predictive Toxicology
                Biology and Life Sciences
                Zoology
                Fish Biology
                Fish Physiology
                Biology and Life Sciences
                Zoology
                Animal Physiology
                Vertebrate Physiology
                Fish Physiology
                Physical Sciences
                Chemistry
                Chemical Compounds
                Acids
                Ketones
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Alcohols
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Alcohols
                Physical Sciences
                Chemistry
                Chemical Compounds
                Esters
                Biology and Life Sciences
                Zoology
                Fish Biology
                Physical Sciences
                Chemistry
                Chemical Compounds
                Phenols
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                All relevant data are within the paper and its Supporting Information files.

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