Evaluation of pulmonary toxicity of heavy metal compounds

Abstract

The present report describes toxicological approaches to evaluate inflammatory potency of heavy metal compounds deposited in the lung. Although inhalation exposure is a well-accepted method to study effects of pulmonary toxicants, it requires expensive facilities and many man-hours to complete experiments. Intratracheal (i.t.) instillation, an alternative and simple method to expose animals to toxicants via airways, has been proved to be useful to investigate the pulmonary clearance of heavy metals. However, acute inhalation exposure caused more severe inflammatory lung injury than i. t. instillation when the same amount of nickel sulfate was administered in the rat. Among several biochemical inflammatory indices such as some enzyme activities and the protein concentration in bronchoalveolar lavage (BAL) fluid, only lactate dehydrogenase (LDH) activity increased linearly with a wide range of doses of heavy metals. The increase in polymorphonuclear leukocytes (PMN) in BAL fluid, a cytological index of inflammatory responses of the lung, is believed to reflect pulmonary toxicity of heavy metals. However, more extensive study is required to elucidate the mechanism of transpulmonary PMN infiltration upon heavy metal insult. In addition to the linearity between LDH activity in BAL fluid and doses of heavy metals, the increase in this cytosolic enzyme activity is associated with cell lysis in the bronchoalveolar milieu and appears to be the best index to evaluate pulmonary inflammatory potency of heavy metals.