Document Detail

Toxicokinetic and toxicodynamic model for diazinon toxicity-mechanistic explanation of differences in the sensitivity of Daphnia magna and Gammarus pulex.
MedLine Citation:
PMID:  22653849     Owner:  NLM     Status:  Publisher    
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 (TKTD) 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) ) in comparison to 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 to 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. Environ. Toxicol. Chem. © 2012 SETAC.
Andreas Kretschmann; Roman Ashauer; Juliane Hollender; Beate I Escher
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-31
Journal Detail:
Title:  Environmental toxicology and chemistry / SETAC     Volume:  -     ISSN:  1552-8618     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-6-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8308958     Medline TA:  Environ Toxicol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 SETAC.
Eawag, Swiss Federal Institute of Aquatic Science and Technology, Dübendorf, Switzerland; Institute of Biogeochemistry and Pollutant Dynamics, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zürich, Switzerland.
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