Sensory irritation tolerance and cross-tolerance in F-344 rats exposed to chlorine or formaldehyde gas

Inhalation of chlorine (Cl2) or formaldehyde (HCHO) stimulates the trigeminal nerve endings in the nasal mucosa and results in respiratory rate depression in a concentration-dependent manner. To determine tolerance and cross-tolerance, the concentration-response curves of respiratory depression were compared between naive rats and rats pre-exposed to Cl2 or HCHO. Chlorine tolerance development was time and concentration dependent, being significant following a 1-day (6 hr/day), 10 ppm exposure, and reaching the maximum in 4 days. At 2.5 ppm of Cl2, tolerance was significant only after 10 days of exposure. Rats tolerant to Cl2 also showed cross-tolerance to HCHO. Tolerance to HCHO was observed in rats exposed to 28 ppm for 4 days, but not in groups exposed to 15 ppm for 1, 4, or 10 days. However, significant cross-tolerance to Cl2 was evident following a 1-day exposure to 15 ppm HCHO, with greatest effect seen in the group exposed for 10 days. Tolerance was reduced after a 7-day recovery following a 4-day exposure. Cross-tolerance was reduced also, but to a much lesser extent. These results suggest a common mechanism for tolerance and cross-tolerance development, but different reactive sites may exist for Cl2 and HCHO at the trigeminal nerve endings.