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

Toxicological Sciences : an Official Journal of the Society of Toxicology
Lisa M SweeneyStephen R Channel

Abstract

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...Continue Reading

References

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Apr 13, 2013·Nature·Erika Check Hayden

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Citations

Jun 21, 2016·Regulatory Toxicology and Pharmacology : RTP·Lisa M SweeneyStephen R Channel
Oct 30, 2016·Regulatory Toxicology and Pharmacology : RTP·Liesbeth GeraetsWouter Ter Burg
Apr 13, 2019·Regulatory Toxicology and Pharmacology : RTP·Alexander SlawikJeffry T Urban

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