A Theoretical Model for Utilizing Mammalian Pharmacology and Safety Data to Prioritize Potential Impacts of Human Pharmaceuticals to Fish

Huggett, Duane B.; Cook, Jon C.; Ericson, Jon F.; Williams, R.

doi:10.1080/714044797

Cited by 278 publications

(288 citation statements)

References 27 publications

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“…If these plasma concentrations in fish are compared with human therapeutic doses (C max ) [26], then L. megalotis plasma levels of diphenhydramine, diltiazem and carbamazepine were 17, 190 and 490 lower than human C max values, respectively (electronic supplementary material, table S5). Huggett et al [26] previously proposed that if pharmaceuticals occur in fish plasma within a factor of 1000 (based on three separate safety factors of 10 for mammalian to non-mammalian species -species differences and human to animal extrapolations) from the human therapeutic dose then these chemicals deserve additional study. Bioaccummulation of diltiazem and carbamazepine was previously reported from a similar study in Sweden [24].…”

Section: Results and Discussion (A) Traditional Water Chemistry Measumentioning

confidence: 99%

Bioaccumulation and trophic dilution of human pharmaceuticals across trophic positions of an effluent-dependent wadeable stream

Haddad

Luek

et al. 2014

Phil. Trans. R. Soc. B

123

114

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Though pharmaceuticals are increasingly observed in a variety of organisms from coastal and inland aquatic systems, trophic transfer of pharmaceuticals in aquatic food webs have not been reported. In this study, bioaccumulation of select pharmaceuticals was investigated in a lower order effluent-dependent stream in central Texas, USA, using isotope dilution liquid chromatography–tandem mass spectrometry (MS). A fish plasma model, initially developed from laboratory studies, was tested to examine observed versus predicted internal dose of select pharmaceuticals. Pharmaceuticals accumulated to higher concentrations in invertebrates relative to fish; elevated concentrations of the antidepressant sertraline and its primary metabolite desmethylsertraline were observed in the Asian clam, Corbicula fluminea , and two unionid mussel species. Trophic positions were determined from stable isotopes (δ 15 N and δ 13 C) collected by isotope ratio-MS; a Bayesian mixing model was then used to estimate diet contributions towards top fish predators. Because diphenhydramine and carbamazepine were the only target compounds detected in all species examined, trophic magnification factors (TMFs) were derived to evaluate potential trophic transfer of both compounds. TMFs for diphenhydramine (0.38) and carbamazepine (1.17) indicated neither compound experienced trophic magnification, which suggests that inhalational and not dietary exposure represented the primary route of uptake by fish in this effluent-dependent stream.

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Section: Results and Discussion (A) Traditional Water Chemistry Measumentioning

confidence: 99%

Bioaccumulation and trophic dilution of human pharmaceuticals across trophic positions of an effluent-dependent wadeable stream

Haddad

Luek

et al. 2014

Phil. Trans. R. Soc. B

123

114

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“…However, for most human and many veterinary drugs, insights as to possible effects in the environment can be gleaned from existing data collected to determine drug efficacy and human-health safety (2,3,25,26). Pharmaceuticals are developed purposely to affect specific biological pathways (and, hopefully, not others) in target species.…”

Section: Testing Pharmaceuticals For Ecological Effectsmentioning

confidence: 99%

Repeating History: Pharmaceuticals in the Environment

Ankley

Brooks²,

Huggett³

et al. 2007

Environ. Sci. Technol.

333

237

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“…The majority of currently available bioaccumulation models specifically developed for IOCs in fish are regression-based [9][10][11][12], although an equilibrium partitioning approach considering the role of sorption to proteins was recently proposed to characterize the bioaccumulation potential of some PFAAs [13]. Generic methods for estimating the tissue-plasma partitioning of IOCs have also been described in the literature [14,15].…”

Section: Introductionmentioning

confidence: 99%

Development and evaluation of a mechanistic bioconcentration model for ionogenic organic chemicals in fish

Armitage

Arnot

Wania

et al. 2012

Enviro Toxic and Chemistry

152

239

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Abstract-A mechanistic mass balance bioconcentration model is developed and parameterized for ionogenic organic chemicals (IOCs) in fish and evaluated against a compilation of empirical bioconcentration factors (BCFs). The model is subsequently applied to a set of perfluoroalkyl acids. Key aspects of model development include revised methods to estimate the chemical absorption efficiency of IOCs at the respiratory surface (E W ) and the use of distribution ratios to characterize the overall sorption capacity of the organism. Membranewater distribution ratios (D MW ) are used to characterize sorption to phospholipids instead of only considering the octanol-water distribution ratio (D OW ). Modeled BCFs are well correlated with the observations (e.g., r 2 ¼ 0.68 and 0.75 for organic acids and bases, respectively) and accurate to within a factor of three on average. Model prediction errors appear to be largely the result of uncertainties in the biotransformation rate constant (k M ) estimates and the generic approaches for estimating sorption capacity (e.g., D MW ). Model performance for the set of perfluoroalkyl acids considered is highly dependent on the input parameters describing hydrophobicity (i.e., log K OW of the neutral form). The model applications broadly support the hypothesis that phospholipids contribute substantially to the sorption capacity of fish, particularly for compounds that exhibit a high degree of ionization at biologically relevant pH. Additional empirical data on biotransformation and sorption to phospholipids and subsequent incorporation into property estimation approaches (e.g., k M , D MW ) are priorities with respect to improving model performance. Environ. Toxicol. Chem. 2013;32:115-128. # 2012 SETAC

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A Theoretical Model for Utilizing Mammalian Pharmacology and Safety Data to Prioritize Potential Impacts of Human Pharmaceuticals to Fish

Cited by 278 publications

References 27 publications

Bioaccumulation and trophic dilution of human pharmaceuticals across trophic positions of an effluent-dependent wadeable stream

Bioaccumulation and trophic dilution of human pharmaceuticals across trophic positions of an effluent-dependent wadeable stream

Repeating History: Pharmaceuticals in the Environment

Development and evaluation of a mechanistic bioconcentration model for ionogenic organic chemicals in fish

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