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Impact of non-constant concentration exposure on lethality of inhaled hydrogen cyanide

The ten Berge model, also known as the toxic load model, is an empirical approach in hazard assessment modeling for estimating the relationship between the inhalation toxicity of a chemical and the exposure duration. The toxic load (TL) is normally expressed as a function of vapor concentration (C)...

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Published in:Toxicological sciences 2014-03, Vol.138 (1), p.205-216
Main Authors: Sweeney, Lisa M, Sommerville, Douglas R, Channel, Stephen R
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Language:English
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description The ten Berge model, also known as the toxic load model, is an empirical approach in hazard assessment modeling for estimating the relationship between the inhalation toxicity of a chemical and the exposure duration. The toxic load (TL) is normally expressed as a function of vapor concentration (C) and duration (t), with TL equaling C(n) × t being a typical form. Hypothetically, any combination of concentration and time that yields the same "toxic load" will give a constant biological response. These formulas have been developed and tested using controlled, constant concentration animal studies, but the validity of applying these assumptions to time-varying concentration profiles has not been tested. Experiments were designed to test the validity of the model under conditions of non-constant acute exposure. Male Sprague-Dawley rats inhaled constant or pulsed concentrations of hydrogen cyanide (HCN) generated in a nose-only exposure system for 5, 15, or 30 min. The observed lethality of HCN for the 11 different C versus t profiles was used to evaluate the ability of the model to adequately describe the lethality of HCN under the conditions of non-constant inhalation exposure. The model was found to be applicable under the tested conditions, with the exception of the median lethality of very brief, high concentration, discontinuous exposures.
doi_str_mv 10.1093/toxsci/kft277
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source Oxford Journals Online; Free Full-Text Journals in Chemistry
subjects Animals
Chemical Warfare Agents - toxicity
Dose-Response Relationship, Drug
Hydrogen Cyanide - toxicity
Inhalation Exposure - analysis
Lethal Dose 50
Male
Models, Biological
Rats
Rats, Sprague-Dawley
Time Factors
Toxicity Tests, Acute
title Impact of non-constant concentration exposure on lethality of inhaled hydrogen cyanide
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