Use of Physical Chemistry and In vivo Exposure to Investigate the Toxicity ofFormaldehyde Bound to Carbonaceous Particles in the Murine Lung

摘要

The research investigated whether exposure to formaldehyde decreases resistanceto respiratory infections through dysfunctions of the alveolar macrophage phagocytic system. The study also explored whether interactions between formaldehyde and respirable carbon black particles alter susceptibility to respiratory infections and impairment of alveolar macrophage phagocytosis by delivering adsorbed formaldehyde to the deep lung with the inhaled particles. Mice were exposed to formaldehyde and to carbon black (Regal GR) plus formaldehyde; increased susceptibility to respiratory infections was quantified by alveolar macrophage-dependant intrapulmonary killing of Staphylococcus aureus. These studies showed that: Fifteen parts per million (ppm) formaldehyde impaired intrapulmonary killing when exposure followed the bacterial challenge. One ppm formaldehyde impaired intrapulmonary killing when exposure preceded and was continued after the bacterial challenge. Coexposures to target concentrations of 3.5 mg/cum carbon black and 2.5 ppm formaldehyde, or 10 mg/cum carbon black and 5 ppm formaldehyde after the bacterial challenge had no effect. Preexposure for four hours per day for four days to target concentrations of 3.5 mg/cum carbon black and 2.5 ppm formaldehyde had no effect on intrapulmonary killing when the assay was performed one day after the cessation of exposure. To determine whether any possible effect was delayed, a surrogate assay for alveolar macrophage phagocytic function, Fc-receptor-mediated phagocytosis, was performed 1, 3, 5, 10, 14, 25, and 40 days after the cessation of exposure.