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Comparative Pharmacology and Toxicology of Pharmaceuticals in the Environment: Diphenhydramine Protection of Diazinon Toxicity in Danio rerio but Not Daphnia magna

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  • Theme: Pharmaceuticals and Personal Care Products in the Environment
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Abstract

Pharmaceuticals and other contaminants of emerging concern present unique challenges to environmental risk assessment and management. Fortunately, mammalian pharmacology and toxicology safety data are more readily available for pharmaceuticals than other environmental contaminants. Identifying approaches to read-across such pharmaceutical safety information to non-target species represents a major research need to assess environmental hazards. Here, we tested a biological read-across hypothesis from emergency medicine with common aquatic invertebrate and vertebrate models. In mammals, the antihistamine diphenhydramine (DPH) confers protection from poisoning by acetylcholinesterase inhibition because DPH blocks the acetylcholine receptor. We employed standardized toxicity methods to examine individual and mixture toxicity of DPH and the acetylcholinesterase inhibitor diazinon (DZN) in Daphnia magna (an invertebrate) and Danio rerio (zebrafish, a vertebrate). Though the standardized Fish Embryo Toxicity method evaluates early life stage toxicity of zebrafish (0–3 days post fertilization, dpf), we further evaluated DPH, DZN, and their equipotent mixture during three development stages (0–3, 3–6, 7–10 dpf) in zebrafish embryos. Independent action and concentration addition mixture models and fish plasma modeling were used to assist interpretation of mixture toxicity experiments. Though our primary hypothesis was not confirmed in acute studies with Daphnia magna, DPH conferred a protective effect for acute DZN toxicity to zebrafish when DPH plasma levels were expected to be greater than mammalian therapeutic, but lower than acutely lethal, internal doses. We further observed that timing of developmental exposure influenced the magnitude of DZN and DPH toxicity to zebrafish, which suggests that future zebrafish toxicity studies with pharmaceuticals and pesticides should examine exposure during developmental stages.

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Acknowledgments

This work was supported by the C. Gus Glasscock, Jr. Endowed Fund for Excellence in Environmental Sciences grant to LAK, the SETAC/EA Jeff Black Fellowship Award to LAK, and the Department of Environmental Science at Baylor University. We also thank SP Haddad, KA Connors, GN Saari, and WC Scott for laboratory assistance, and Dr. Jone Corrales for comments on an earlier draft of this manuscript. Please contact the corresponding author for raw data from this study.

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Author notes

  1. Jason P. Berninger

    Present address: U.S. Environmental Protection Agency, Duluth, Minnesota, USA

Authors and Affiliations

  1. Department of Environmental Science, Waco, Texas, USA

    Lauren A. Kristofco, Bowen Du, Jason P. Berninger & Bryan W. Brooks

  2. Center for Reservoir and Aquatic Systems Research, The Institute of Ecological, Earth, and Environmental Science, Baylor University, Waco, Texas, USA

    Lauren A. Kristofco, Bowen Du, C. Kevin Chambliss & Bryan W. Brooks

  3. Department of Chemistry and Biochemistry, Baylor University, Waco, Texas, USA

    C. Kevin Chambliss

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  1. Lauren A. Kristofco
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  2. Bowen Du
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Correspondence to Bryan W. Brooks.

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Guest Editors: James P. Laurenson, Raanan A. Bloom, and Nakissa Sadrieh

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Kristofco, L.A., Du, B., Chambliss, C.K. et al. Comparative Pharmacology and Toxicology of Pharmaceuticals in the Environment: Diphenhydramine Protection of Diazinon Toxicity in Danio rerio but Not Daphnia magna . AAPS J 17, 175–183 (2015). https://doi.org/10.1208/s12248-014-9677-5

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