REEXAMINATION OF RESPIRATORY-TRACT RESPONSES IN RATS, MICE, AND RHESUS-MONKEYS CHRONICALLY EXPOSED TO INHALED CHLORINE

Important data for human risk assessment of inhaled chlorine are provi ded by a recent rodent cancer bioassay (Wolf et al., 1995) and a chron ic inhalation toxicity study in rhesus monkeys (Klonne et al., 1987), To improve interspecies comparisons based upon these data sets, the ti ssues from these studies were reexamined to (a) map the location of re sponses to assess the potential role of local chlorine dosimetry, (b) generate quantitative data on selected endpoints to compliment subject ive scores, and (c) further characterize the responses in relation to interspecies differences and potential human health risks. Chlorine-in duced lesions, which were confined to the respiratory tract, exhibited both similarities and differences among rodents and primates. At equi valent airborne concentrations (similar to 2.5 ppm), chlorine-induced responses were less severe in rhesus monkeys, but extended more distal ly in the respiratory tract to involve the trachea, while treatment-in duced lesions were confined to the nose in rats and mice. Quantitation of septal fenestration, intraepithelial mucus, intraepithelial eosino philic material, eosinophil infiltration (detected during the present study), and olfactory sensory cell loss generally supported previously reported subjective pathology scores and clarified concentration-resp onse relationships. In both rodents and rhesus monkeys, airflow-driven regional dosimetry patterns were considered to play a major role in l esion distribution. The present work highlights the need for understan ding regional respiratory-tract dosimetry and mechanisms of tissue res ponse for inhaled chlorine in laboratory animals and humans.