Concentration-response relationships of rat lungs to exposure to oxidant air pollutants: a critical test of Haber's Law for ozone and nitrogen dioxide.
Gelzleichter-TR; Witschi-H; Last-JA
Toxicol Appl Pharmacol 1992 Jan; 112(1):73-80
The relationship between exposure to ozone (10028156) or nitrogen-dioxide (10102440) (NO2) and concentration and duration was investigated in rats. Male Sprague-Dawley-rats were exposed to 0.2 to 0.8 part per million (ppm) ozone and 3.6 to 14.4ppm NO2 for periods of 6 to 24 hours each day for 3 days. Response was measured by lung lavage changes in total protein and specific cell types. Acute lung damage was a function of cumulative dose for the three highest dose rates; inclusion of the lowest dose rates resulted in attenuation of pulmonary response. Rats exposed to a combination of the two gases exhibited lung damage that was a function of peak concentration not cumulative dose. Response was additive when rats were exposed to the mixture at the low dose rate but significantly higher than additive with exposure to the mixture at medium/low, medium/high and high dose rates. The authors attribute deviation from Haber's Law to a synergistic, not additive, response to this ozone/NO2 mixture.
Toxic-gases; Laboratory-animals; Cell-damage; Toxic-effects; Lung-cells; Synergism; Dose-response; Lung-function
Toxicology and Applied Pharmacology
University of California - Davis