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An LC<sub>50</sub> vs Time Model for the Aquatic Toxicity of Reactive and Receptor-Mediated Compounds. Consequences for Bioconcentration Kinetics and Risk Assessment
57
Citations
9
References
1999
Year
BioconcentrationEcotoxicitySurrogate DoseBioconcentration KineticsDrug ResistanceEnvironmental ChemistryToxicologyBiostatisticsToxicological AspectPublic HealthPredictive ToxicologyBiochemistryReceptor-mediated CompoundsEcotoxicologyChemical PollutionCritical Body ResiduePharmacologyAquatic ToxicityForensic ToxicologyEnvironmental ToxicologyToxicokineticsMedicinePharmacokineticsDrug DiscoveryExposure Time
For aquatic toxicants that act by so-called nonpolar narcosis, it is generally acknowledged that the Critical Body Residue (CBR) at death, as a surrogate dose metric for the amount of target that has interacted with the toxicant, is constant. This constancy is not only maintained across exposure times but also across different (narcosis) compounds as well as species. We present here an alternative model, applicable to reactive and receptor-mediated toxicants, that implies that for these compounds there is no constant CBR. The model also shows that for each single species-compound combination, the Critical Area Under the Curve (CAUC) is constant and independent of exposure time. These findings can have profound consequences for the interpretation of experimental toxicity data (such as 96 h LC50 values) in risk assessment. Among other things, it shows us that for compounds other than nonpolar narcotics, LC50 vs time values may decrease significantly even after bioconcentration steady state has been achieved. Consequently, it also shows us that the incipient LC50 will be severely overestimated (i.e. toxicity underestimated) when using the familiar models based on just bioaccumulation kinetics.
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