Effect of cumulative exposure on nasal response to ozone

Toxicology and Applied Pharmacology
R F HendersonJ R Harkema

Abstract

To assess the potential health risks associated with exposure to low levels of ozone, it is essential to know if the ozone-induced responses are dependent on cumulative exposures or on the peak concentrations. To answer this question female F344/N rats, 11-13 weeks of age, were exposed to a matrix of equal concentration x time values that included exposures to 0, 0.12, 0.24, and 0.48 ppm ozone for 3, 6, 12, or 24 hr. the response of the nasal epithelium was measured as induced DNA synthesis determined by the uptake of bromodeoxyuridine (a thymidine analog) into epithelial cells lining the nasal anterior maxilloturbinates. No increased DNA synthesis was observed in rats exposed to 0.12 ppm ozone for any of the time periods. For exposures higher than 0.12 ppm ozone, the response of the nasal epithelium was similar for equal cumulative exposures. The responses, however, were not linearly related to the cumulative (concentration x time) exposures. It appeared that some mitigating factor was present which decreased the responses at the higher cumulative exposures. No frank toxicity or cellular necrosis was observed, indicating that sublethal cell damage was sufficient to induce DNA synthesis. A simple mathematical model was develope...Continue Reading

Citations

Jul 31, 2003·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·L NikasinovicN Seta
May 2, 1998·American Journal of Respiratory Cell and Molecular Biology·S Potter-PerigoT N Wight
Feb 25, 1999·American Journal of Respiratory Cell and Molecular Biology·J R HarkemaC Basbaum
Dec 1, 1994·Environmental Health Perspectives·L Calderon-GarcidueñasL Ramirez
Feb 1, 1996·Environmental Health Perspectives·L Calderon-GarciduenasA Villarreal-Calderon
Jan 1, 1997·Environmental and Molecular Mutagenesis·L Calderón-GarcidueñasA Villarreal-Calderón
Apr 6, 1999·Carcinogenesis·L Calderón-GarcidueñasM C Madden

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