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PHOSGENE AS AN EXAMPLE OF THE C X T TOXICITY PRINCIPLE: THE ROLE OF ADAPTATION
Citation:
Hatch, G. E. PHOSGENE AS AN EXAMPLE OF THE C X T TOXICITY PRINCIPLE: THE ROLE OF ADAPTATION. Presented at Theories and Practices in Toxicology and Risk Assessment, Cincinnati, OH, April 17, 2002.
Description:
Phosgene as an example of the C x T toxicity principle: the role of adaptation
Name/Title : Dr. Gary E. Hatch
Organization: Pulmonary Toxicology Branch, Experimental Toxicology Division, NHEERL, EPA, RTP
Mailing Address: Mail Drop 82, US EPA, Res. Tri. Park, NC 27711
Phone/Fax: 919-541-2658, Fax 919-541-0026
E-mail address: Hatch.Gary@epa.gov
Abstract
Recent studies of respiratory irritants suggest that traditional subchronic or chronic exposures cause animals to become adapted to toxic effects, such that toxicity readings taken at the end of these studies could underestimate risk when extrapolated to other exposure scenarios using traditional C x T methods. This is shown by inhalation exposures of rats to phosgene in which acute (single day) exposure produces toxic effects that are ten times higher than effects observed after repeated exposures to the same concentration. Moreover, repeated exposures to high concentrations of phosgene was found to yield the greatest and most irreversible long-term effects -- not exposure to high C x T products.
A conceptual framework is presented in which acute injury accumulates over time to produce chronic injury. The phenomenon of "adaptation" plays a key role in this framework because it determines how much repeated injury actually occurs, and it explains why the C x T product becomes invalid in longer-term and episodic exposure scenarios. A better understanding of adaptation to respiratory irritants is needed prior to generation of dose response models.
This abstract is a proposed presentation and does not necessarily reflect EPA policy.