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RESPIRATORY RESPONSE AND INTERNAL TISSUE DOSE OF INHALED CHLORINE IN THE RESPIRATORY TRACT OF F344 RATS: SEX AND SPECIES COMPARISONS
Citation:
PARKINSON, C. U., O. R. MOSS, M. SOCHASKI, E. W. TEWKSBURY, E. A. GROSS, M. E. ANDERSEN, AND A. M. JARABEK. RESPIRATORY RESPONSE AND INTERNAL TISSUE DOSE OF INHALED CHLORINE IN THE RESPIRATORY TRACT OF F344 RATS: SEX AND SPECIES COMPARISONS. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Inhaled Cl2 causes irritant effects in the respiratory tract. Females of various toxicological studies show more severe effects than males, notably a decrease in survivability observed in rats of a 2-year bioassay (CIIT, 1993; Wolf et al., 1995, Fundam. Appl. Toxicol. 24, 111), which required their exposure be reduced to 3 days / week. We conducted a study to characterize the sensory apnic response and respiratory dose associated with a 50% reduction in ventilation frequency (RD50) in both sexes of F344 rats, the strain used in the bioassay. 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 rats were exposed per concentration across a range from 0 to 60 ppm. Rats 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. The internal dose measures will allow comparison of internal dose after in vivo cyclical breathing versus after a study using unidirectional steady-state exposure in isolated upper respiratory tracts. Results show the RD50 is lower than previously reported at CIIT (Barrow and Steinhagen, 1982; Toxicol. Appl. Pharmacol. 65, 383) and may be due to the longer period of exposure or differences in the plethysmography system employed. Mice are the more sensitive species with an RD50 of approximately 3 to 12 ppm, depending on the strain, versus 20 ppm in F344 rats. Female rats have a higher RD50 (approximately 2-fold) than males which provides some insight on their increased responsiveness. 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).