A simple mechanistic model to interpret the effects of narcotics

Baas, J.; Spurgeon, D. ORCID: https://orcid.org/0000-0003-3264-8760; Broerse, M.. 2015 A simple mechanistic model to interpret the effects of narcotics. SAR and QSAR in Environmental Research, 26 (3). 165-180. https://doi.org/10.1080/1062936X.2015.1018940

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Official URL: http://dx.doi.org/10.1080/1062936X.2015.1018940

Abstract/Summary

In this research we will show the advantages of using a time-independent dose metric in a mechanistic model to evaluate toxic effects for different narcotic compounds on different species. We will show how different already existing QSARs can be combined within a mechanistic framework to 1) make predictions of lethal thresholds; 2) show some limitations in the use of existing QSARs; 3) show how a mechanistic framework solves some conceptual problems in current approaches and 4) show how such a framework can be used to be of aid in an experimental setup in predicting the outcome of a survival experiment. The approach we chose is based on the simplest mechanistic model available, a scaled one-compartment model to describe uptake and elimination and hazard model to link the exposure to effects on survival. Within this theoretical framework a prediction for an internal threshold for effects on survival of 3 mmol/kg bw can be made, which should be similar for different species and independent of the partitioning characteristics of the toxicant. To demonstrate this, a threshold for 51 different species was derived, which indeed appeared to lie in a relatively small range, typically between 1 and 10 mmol/kg bw.

Item Type:	Publication - Article
Digital Object Identifier (DOI):	https://doi.org/10.1080/1062936X.2015.1018940
UKCEH and CEH Sections/Science Areas:	Acreman
ISSN:	1062-936X
Additional Keywords:	mechanistic modelling, no effect concentration, critical body residue, narcotics, QSAR, time
NORA Subject Terms:	Ecology and Environment Biology and Microbiology Chemistry
Date made live:	17 Jun 2015 11:17 +0 (UTC)
URI:	https://nora.nerc.ac.uk/id/eprint/511070

Item Type:

Publication - Article

Digital Object Identifier (DOI):

https://doi.org/10.1080/1062936X.2015.1018940

UKCEH and CEH Sections/Science Areas:

Acreman

ISSN:

1062-936X

Additional Keywords:

mechanistic modelling, no effect concentration, critical body residue, narcotics, QSAR, time

NORA Subject Terms:

Ecology and Environment
Biology and Microbiology
Chemistry