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UPTAKE AND INTERNAL DOSIMETRY OF INHALED CHLORINE IN THE ISOLATED UPPER RESPIRATORY TRACT (URT) OF F344 RATS.
Citation:
ROBERTS, K. C., O. R. MOSS, M. SOCHASKI, R. A. JAMES, E. A. GROSS, M. E. ANDERSEN, AND A. M. JARABEK. UPTAKE AND INTERNAL DOSIMETRY OF INHALED CHLORINE IN THE ISOLATED UPPER RESPIRATORY TRACT (URT) OF F344 RATS. . Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Due to large-volume commercial uses as an intermediate and for water disinfection, chlorine (Cl2) is an important hazardous air pollutant (HAP). Inhaled Cl2 causes irritant effects in the respiratory tract. We conducted studies to characterize determinants of its mass transfer and tissue extraction in the URT. Extraction efficiency in the URT was determined as the percentage of inhaled Cl2 retained in the surgically isolated URT of anesthetized rats (both sexes) exposed by unidirectional delivery (Morris, 1999, Inhal. Toxicol., 11, 943.). Cl2 analysis was done using a thermoionic analyzer previously used in human studies (Nodelman et al., 1998, Rev. Sci. Instrum. 69, 3978), modified to accommodate the lower flow rates and volumes in rodents. Exposure sets consisted of 5 animals exposed to a single concentration and flow rate. The flow rates (100, 200, or 400 ml/min) used correspond to the minute ventilation for rats of the size used, and one half and double that flow rate. The three concentrations (0.5, 1.0, or 2.5 ppm) correspond to a 2-year bioassay (CIIT, 1993; Wolf et al., 1995, Fundam. Appl. Toxicol. 24, 111.). The experimental design also compared uptake in live animals versus in animals killed 2 hours prior to exposure to evaluate the role of blood flow and mucus production. Internal tissue dose of Cl2, specifically its hydrolysis product, hypochlorous acid (HOCl), that reacts with various tissue constituents, was measured by an assay of chlorotyrosines (3-chlorotyrosine and 3,5-dichlorotyrosine, Cl-Tyr). Cl-Tyr are specific and stable products of protein treated with HOCl and proven useful biomarkers for production of HOCl in vivo (Chapman et al., 2000. Arch. Biochem. Biophys. 377, 95). Cl-Tyr was measured in samples from 4 locations in the URT representing respiratory and olfactory tissues in the septal and lateral airstreams. High levels of extraction (>90%) were seen in all exposure sets, consistent with mice (Morris et al., 2005, Toxicol. Sci. 83, 380) and humans (Nodelman et al., 1998, J. Appl. Physiol. 87, 2073). Flow- and concentration-dependencies were also apparent, but the responses as percent conversion to the biomarkers were complex. These data will be used to verify mass transfer coefficients and aid development of dosimetry models for Cl2 for use in risk assessment. (This abstract does not reflect Agency policy).