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RESPIRATORY RESPONSE AND INTERNAL TISSUE DOSE OF INHALED CHLORINE IN THE RESPIRATORY TRACT OF B6C3F1 MICE: SEX AND STRAIN COMPARISONS
Citation:
TEWKSBURY, E. W., O. R. MOSS, M. A. SOCHASKI, C. U. PARKINSON, E. A. GROSS, R. A. JAMES, M. E. ANDERSEN, AND A. M. JARABEK. RESPIRATORY RESPONSE AND INTERNAL TISSUE DOSE OF INHALED CHLORINE IN THE RESPIRATORY TRACT OF B6C3F1 MICE: SEX AND STRAIN COMPARISONS . Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Chlorine (Cl2) is a high-production volume ambient air pollutant and an established respiratory irritant for which reactive airways disease or hyper-reactivity has been noted after high-concentration exposures in the occupational arena. We conducted a study to characterize the sensory apnic response and the respiratory dose associated with a 50% reduction in ventilation frequency (RD50) in both sexes of B6C3F1 mice, the strain used in a 2-year bioassay (CIIT, 1993; Wolf et al., 1995, Fundam. Appl. Toxicol. 24, 111). Respiratory frequency and tidal volume were determined by both whole-body and double-chamber plethysmography for comparison (DeLorme and Moss, 2002, J. Pharmacol. Toxicol. Methods, 47, 1) using a Buxco® system (Buxco, Inc., Stamford, CT). The American Society for Testing and Materials (ASTM, 2000) protocol was modified to extend the exposure period to 120 minutes to ensure a maximal plateau in the ventilatory response was achieved (Gagnaire et al., 1994, J. Appl. Toxicol. 14(6), 405). Eight mice were exposed per concentration across a range from 0 to 15 ppm. Mice were sacrificed 1 hr after exposure to harvest tissues for use in biochemical assays to measure indicators of internal Cl2 dose, specifically its hydrolysis product, hypochlorous acid (HOCl). Soluble antioxidants and chlorotyrosines (3-chlorotyrosine and 3,5-dichlorotyrosine) were measured from samples in 4 locations in the nose and the lower left lung lobe. Results indicate that the RD50 is lower than previously reported at CIIT (Jiang et al., 1983, Toxicol. Appl. Pharmacol. 71, 225) and may be due to the longer period of exposure or differences in the plethysmography system employed. The differences between the B6C3F1 strain and other strains tested (Morris et al., 2005, Toxicol. Sci. 83, 380; Gagnaire et al., 1994, J. Appl. Toxicol. 14(6), 405) confirm differences postulated to be due to airway architecture (Moss and Oldham, 2006, J. Aerosol Medicine, In Press). Females have a slightly higher RD50 (approximately 2-fold) than males that may provide some insight on the increased response of females observed in various toxicological studies. The biochemical data will be used to verify dosimetry model predictions of tissue reactions for use in risk assessment. (This abstract does not reflect Agency policy).