Pulmonary hyperreactivity in cynomolgus monkeys (Macaca fascicularis) from nose-only inhalation exposure to disodium hexachloroplatinate, Na2PtCl6.
The pulmonary and dermal effects of exposure to Na2PtCl6 were investigated in cynomolgus monkeys (Macaca fascicularis) exposed by the nose-only inhalation and percutaneous routes. Separate inhalation exposures were performed in monkeys at 200 micrograms/m3 and 2 mg/m3 (4 hr/day, biweekly for 12 weeks), while another group of monkeys was percutaneously exposed biweekly by an open patch method. After a 2-week refractory period, serial Na2PtCl6 bronchoprovocation challenges and intradermal Na2PtCl6 sensitivity evaluations were performed. Na2PtCl6 bronchoprovocation in naive control monkeys yielded significant impairments in post-challenge pulmonary mechanics and ventilatory function. These results indicate a pharmacologic or irritant-mediated bronchoconstriction mechanism for acute exposure to this compound. When the post-challenge pulmonary function of animals exposed for the 12-week exposure regimen (across treatments) was compared to pulmonary deficits observed in control animals upon challenge, significantly greater pulmonary deficits were seen in animals exposed at the 200 micrograms/m3 concentration. Exposure at this concentration yielded significant changes in post-challenge average pulmonary flow resistance (RL) and forced expiratory volume in 0.5 sec corrected for vital capacity (FEV0.5/FVC) when compared to control monkey responses. Animals exposed by the percutaneous route or at 2 mg/m3 showed no significant post-challenge pulmonary deficits when compared to control animals. Intradermal Na2PtCl6 sensitivity was found not to be exposure related in the conditions of this experiment.
D000336:Aerosols; D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008252:Macaca fascicularis; D008297:Male; D012129:Respiratory Function Tests; D012882:Skin Tests
D000336:Aerosols; D002945:Cisplatin; C038762:disodium hexachloroplatinate