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Toxicity of Ambient Particulate Matter IV: Acute toxicity study in pulmonary hypertensive rats after exposure to model compounds for the secondary aerosol fraction of PM10 - ammonium bisulfate, ferrosulfate and nitrate

Toxiciteit fijn stof deel 4

Synopsis

This (4th) report on the toxicity of ambient particulate matter (PM) presents effects of the model compounds for PM in ambient air - ammonium bisulfate, ammonium ferrosulfate and ammonium nitrate - on healthy rats and rats with monocrotaline-induced pulmonary hypertension (PH). The objective was based on the epidemiological indications that people with cardiopulmonary diseases form a part of the general population sensitive to acute exposure to PM, and that ambient mass concentrations of sulfate and nitrate appear associated with health effects. Concretely, the study would test the hypothesis that secondary aerosols exert pulmonary effects in rats, and that rats with PH are more sensitive to these aerosols than normal healthy animals. Healthy and PH rats were exposed to ultrafine and fine ammonium aerosols for four hours a day for three consecutive days. The two independent studies performed with ammonium bisulfate differed only in the mass concentrations of the aerosol test atmospheres. The animals were sacrificed one day after the last exposure to establish effects on the airways using bronchoalveolar lavage fluid (BALF) analysis, airway reactivity measurements and histopathological microscopical examination. The MCT treatment (to induce pulmonary hypertension accompanied by inflammation and ultimately heart failure) was successful, as seen by medial hypertrophy of muscular pulmonary arteries and neomuscularization of small blood vessels. Histopathological examination did not reveal test-atmosphere-related abnormalities.There were no signs of cytotoxicity due to aerosol exposures (measured with lactate dehydrogenase (LDH), and protein and albumin contents in BALF). Since no changes were observed in N-acetyl glucosaminidase (NAG), macrophages had not been activated due to the MCT treatment or the test atmospheres. Cell differentiation profiles were inconsistent, partly caused by an unavoidable infection with Haemophilus sp. However, despite this, the test atmospheres did not affect cell differentiation or total cell counts.The results suggest that at exposure levels comparable to previous studies in asthmatic mice, ammoniun salt aerosols do not exert marked adverse health effects in either healthy or PH rats.
 

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