title: Impact of non-constant concentration exposure on lethality of inhaled hydrogen cyanide.
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 conditions, with the exception of the median lethality of very brief, high concentration, discontinuous exposures.
authors: * Henry M. Jackson Foundation for the Advancement of Military Medicine, Naval Medical Research Unit Dayton, Wright-Patterson AFB, OH 45433;
authors: Lisa M
authors: LM
authors: Sweeney
authors: Douglas R
authors: DR
authors: Sommerville
authors: Stephen R
authors: SR
authors: Channel
mesh_terms: D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006856:Hydrogen Cyanide / Q000633:toxicity*; D019570:Inhalation Exposure / Q000032:analysis*; D007928:Lethal Dose 50; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D023382:Toxicity Tests, Acute
chemical_list: D002619:Chemical Warfare Agents; D006856:Hydrogen Cyanide
keywords: acute lethality; hydrogen cyanide; non-constant concentrations; nose-only inhalation; pulsed exposures; ten Berge model.; toxic load model