One-year inhalation toxicity study of chlorine in rhesus monkeys (Macaca mulatta)

Chlorine (Cl2) gas is a potentially lung-damaging irritant which is used in the chemical, plastics, and paper industries. There are no data published using experimental animals on the chronic inhalation toxicity of chlorine. The purpose of this study was to investigate the chronic effects of Cl2 inhalation in Rhesus monkeys (Macaca mulatta). Rhesus monkeys were exposed to concentrations of 0, 0.1, 0.5, or 2.3 ppm Cl2 for 6 hr per day. 5 days per week for 1 year. Pulmonary physiology (pulmonary diffusing capacity and distribution of ventilation), body weights, urinalysis, electrocardiographs, hematology, and clinical chemistry were evaluated monthly during the study. Blood gas evaluations were performed at 3-month intervals during the study. Histopathologic, ophthalmologic, and neurologic parameters were evaluated after the 1-year exposure period. Monkeys exposed to 2.3 ppm Cl2 exhibited signs of ocular irritation during the daily exposures and a superficial conjunctival irritation was present in the 2.3 ppm group after the 1-year exposure regimen. Treatment-induced lesions revealed by histopathology were confined to the respiratory tract. Lesions associated with the nasal parasite Anatrichosoma spp. were present in the region of squamous epithelium of the nasal vestibule and did not interfere with interpretation of Cl2-induced effects. Treatment-induced histopathologic changes were found in the respiratory epithelium of the nasal passages and trachea and were limited to focal, concentration-related epithelial hyperplasia with loss of cilia and decreased numbers of goblet cells in affected areas. These changes in the nose and trachea were focal and mild in monkeys exposed to 2.3 ppm and were not found in all animals in these exposure groups. Tracheal lesions were confined to the 2.3 ppm group. The lesions observed at 2.3 ppm were not present in all animals. At the lower Cl2 concentrations, similar though less prominent respiratory epithelial lesions were observed. The latter changes were very minimal and were confined to the nasal passages of some treated monkeys and one male control animal. The results of this study indicate that 2.3 ppm chlorine acts as an upper respiratory irritant in monkeys, while 0.5 and 0.1 ppm induce changes of questionable clinical significance. Furthermore, the monkey appears to be less sensitive than the rat to chlorine toxicity.