Toxicokinetic and toxicodynamic model for diazinon toxicity—mechanistic explanation of differences in the sensitivity of Daphnia magna and Gammarus pulex

A mechanistic toxicokinetic and toxicodynamic model for acute toxic effects (immobilization, mortality) of the organothiophosphate insecticide diazinon in Daphnia magna is presented. The model was parameterized using measured external and internal (whole-body) concentrations of diazinon, its toxic metabolite diazoxon, and the inactive metabolite 2-isopropyl-6-methyl-4-pyrimidinol, plus acetylcholinesterase (AChE) activity measured during exposure to diazinon in vivo. The toxicokinetic and toxicodynamic model provides a coherent picture from exposure to the resulting toxic effect on an organism level through internally formed metabolites and the effect on a molecular scale. A very fast reaction of diazoxon with AChE (pseudo first-order inhibition rate constant k(i) = 3.3 h(-1)) compared with a slow formation of diazoxon (activation rate constant k(act) = 0.014 h(-1)) was responsible for the high sensitivity of D. magna toward diazinon. Recovery of AChE activity from inhibition was slow and rate-determining (99% recovery within 16 d), compared with a fast elimination of diazinon (99% elimination within 17 h). The obtained model parameters were compared with toxicokinetic and toxicodynamic parameters of Gammarus pulex exposed to diazinon from previous work. This comparison revealed that G. pulex is less sensitive because of a six times faster detoxification of diazinon and diazoxon and an approximately 400 times lower rate for damage accrual. These differences overcompensate the two times faster activation of diazinon to diazoxon in G. pulex compared to D. magna. The present study substantiates theoretical considerations that mechanistically based effect models are helpful to explain sensitivity differences among different aquatic invertebrates.

[1]  C. Pope,et al.  Pharmacology and toxicology of cholinesterase inhibitors: uses and misuses of a common mechanism of action. , 2005, Environmental toxicology and pharmacology.

[2]  C. Barata,et al.  Biochemical mechanisms of resistance in Daphnia magna exposed to the insecticide fenitrothion. , 2007, Chemosphere.

[3]  J. R. Kemp,et al.  Species specificity in the chemical mechanisms of organophosphorus anticholinesterase activity. , 1991, Chemical research in toxicology.

[4]  A. Baun,et al.  Acute and chronic effects of pulse exposure of Daphnia magna to dimethoate and pirimicarb , 2006, Environmental toxicology and chemistry.

[5]  J. Hermens,et al.  Pattern analysis of the variation in the sensitivity of aquatic species to toxicants. , 1997, Chemosphere.

[6]  S. Duquesne.  Effects of an organophosphate on Daphnia magna at suborganismal and organismal levels: implications for population dynamics. , 2006, Ecotoxicology and environmental safety.

[7]  Tjalling Jager,et al.  Modeling receptor kinetics in the analysis of survival data for organophosphorus pesticides. , 2005, Environmental science & technology.

[8]  Roman Ashauer,et al.  Mechanistic toxicodynamic model for receptor-mediated toxicity of diazoxon, the active metabolite of diazinon, in Daphnia magna. , 2011, Environmental science & technology.

[9]  S. Klaine,et al.  Effect of pulse frequency and interval on the toxicity of chlorpyrifos to Daphnia magna. , 2001, Chemosphere.

[10]  Roman Ashauer,et al.  Toxicokinetic variation in 15 freshwater arthropod species exposed to the insecticide chlorpyrifos , 2010, Environmental toxicology and chemistry.

[11]  Y. Takimoto,et al.  Comparative metabolism of fenitrothion in aquatic organisms. III. Metabolism in the crustaceans, Daphnia pulex and Palaemon paucidens. , 1987, Ecotoxicology and environmental safety.

[12]  Richard E. Sweeney,et al.  Acetylcholinesterase inhibition: does it explain the toxicity of organophosphorus compounds? , 2006, Archives of Toxicology.

[13]  Roman Ashauer,et al.  Toxicokinetic model describing bioconcentration and biotransformation of diazinon in Daphnia magna. , 2011, Environmental Science and Technology.

[14]  J. Johnson,et al.  Species-related differences in the inhibition of brain acetylcholinesterase by paraoxon and malaoxon. , 1987, Toxicology and applied pharmacology.

[15]  G. D'agostino,et al.  The importance of biotransformation in the toxicity of xenobiotics to fish. I. Toxicity and bioaccumulation of diazinon in guppy (Poecilia reticulata) and zebra fish (Brachydanio rerio) , 1991 .

[16]  Joop L. M. Hermens,et al.  Uptake and elimination kinetics of organophosphorous pesticides in the guppy (poecilia reticulata): Correlations with the octanol/water partition coefficient , 1991 .

[17]  Carola A. Schriever,et al.  The footprint of pesticide stress in communities--species traits reveal community effects of toxicants. , 2008, The Science of the total environment.

[18]  M. D. Corbett,et al.  The uptake and in vivo metabolism of the organophosphate insecticide fenitrothion by the blue crab, Callinectes sapidus. , 1986, Toxicology and applied pharmacology.

[19]  J. Hermens,et al.  Analysis of the Time-Dependent Acute Aquatic Toxicity of Organophosphorus Pesticides: The Critical Target Occupation Model , 1999 .

[20]  Roman Ashauer,et al.  General unified threshold model of survival--a toxicokinetic-toxicodynamic framework for ecotoxicology. , 2011, Environmental science & technology.

[21]  J. Pedersen,et al.  Organophosphorus insecticides in agricultural and residential runoff: field observations and implications for total maximum daily load development. , 2006, Environmental science & technology.

[22]  Sebastiaan A L M Kooijman,et al.  Making Sense of Ecotoxicological Test Results: Towards Application of Process-based Models , 2006, Ecotoxicology.

[23]  D. Baird,et al.  Biochemical factors contributing to response variation among resistant and sensitive clones of Daphnia magna Ssraus exposed to ethyl parathion. , 2001, Ecotoxicology and environmental safety.

[24]  J. R. Kemp,et al.  Molecular determinants of the species-selective inhibition of brain acetylcholinesterase. , 1990, Toxicology and applied pharmacology.

[25]  A. Callaghan,et al.  A comparative study on the relationship between acetylcholinesterase activity and acute toxicity in Daphnia magna exposed to anticholinesterase insecticides , 2004, Environmental toxicology and chemistry.

[26]  G. D'agostino,et al.  Enzymological differences of AChE and diazinon hepatic metabolism: correlation of in vitro data with the selective toxicity of diazinon to fish species. , 1995, The Science of the total environment.

[27]  F. Sánchez‐Bayo.  Comparative acute toxicity of organic pollutants and reference values for crustaceans. I. Branchiopoda, Copepoda and Ostracoda. , 2006, Environmental pollution.

[28]  J. Hermens,et al.  Variation in the sensitivity of aquatic species in relation to the classification of environmental pollutants. , 1997, Chemosphere.

[29]  M. Lydy,et al.  Toxicokinetics of Organic Contaminants in Hyalella azteca , 2003, Archives of environmental contamination and toxicology.

[30]  Roman Ashauer,et al.  Toxicokinetic and toxicodynamic modeling explains carry-over toxicity from exposure to diazinon by slow organism recovery. , 2010, Environmental science & technology.

[31]  C. Stamm,et al.  Significance of urban and agricultural land use for biocide and pesticide dynamics in surface waters. , 2010, Water research.

[32]  Donald J Baird,et al.  A new method for ranking mode‐specific sensitivity of freshwater arthropods to insecticides and its relationship to biological traits , 2010, Environmental toxicology and chemistry.

[33]  Roman Ashauer,et al.  Advantages of toxicokinetic and toxicodynamic modelling in aquatic ecotoxicology and risk assessment. , 2010, Journal of environmental monitoring : JEM.

[34]  H. Chambers.  1 – Organophosphorus Compounds: An Overview , 1992 .

[35]  Roman Ashauer,et al.  Acute toxicity of organic chemicals to Gammarus pulex correlates with sensitivity of Daphnia magna across most modes of action. , 2011, Aquatic toxicology.

[36]  R. Holmes,et al.  Monitoring of Diazinon Concentrations and Loadings, and Identification of Geographic Origins Consequent to Stormwater Runoff from Orchards in the Sacramento River Watershed, U.S.A. , 2003, Environmental monitoring and assessment.

[37]  Roman Ashauer,et al.  New ecotoxicological model to simulate survival of aquatic invertebrates after exposure to fluctuating and sequential pulses of pesticides. , 2007, Environmental science & technology.

[38]  Hartmut Derendorf,et al.  Modeling of Pharmacokinetic/Pharmacodynamic (PK/PD) Relationships: Concepts and Perspectives , 1999, Pharmaceutical Research.