ACUTE PULMONARY TOXICITY OF AEROSOLIZED RESPONSES OF THE PULMONARY SURFACTANT OIL-BASED AMINOCARB INSECTICIDE: EARLY

The pulmonary toxicity of aerosolized oil-formulated aminocarb (Matacil) insecticide was assessed in acutely treated rats in relation to pulmonary surfactant (SF). Time- and dose-dependent changes in biochemical markers [alkaline phosphatase (AKP), acid phosphatase (ACP), j3-N-acetyl glucosaminidase @-NAG) and lactic dehydrogenase (LDH), protein and phospholipid contents] were analyzed in four pulmonary surfactant compartments: (1) the lavaged lung tissue, (2) the cell-free bronchoalveolar lavage (BAL) and its surfactant subfractions obtained by centrifugation, namely, (3) the common myelin figure (CMF) fraction or surfactant proper and (4) the tubular myelin figure VMF) fraction. Air control groups were used for comparison for every treatment time period. Aerosol deposition was estimated by mathematical calculation. First, groups of animals were treated for 1 hr with a high-concentration aerosol (134 mg aminocarb/m3 air; MMAD 3.6 pm; GSD 2.4 pm) and studied at 1,3, and 14 days postexposure. After 1 day, AKP selectively showed high and early increases in lung tissue and extracellular SF compartments (BAL and TMF), suggesting stimulated secretion of surfactant. Early damage to deep lung was also indicated by a higher amount of protein and activity of LDH in BAL. Most enzymatic parameters returned to control values with time. Prominent early increases in phospholipid (PL) also suggested increased synthesis of surfactant. Second, rats were exposed for 1 hr to high, intermediate, and low concentrations of the formulation, respectively 134, 39, and 11 mg aminocarb/m3 air and vehicle only (3153 mg vehicle/m3 air), and studied 3 days after exposure. Lung homogenate AKf: ACf: @-NAG, protein, and PL then demonstrated dose-dependent profiles, while for most parameters in all four compartments, the low concentration appeared to induce no effect. Rats exposed to vehicle only showed the most pronounced changes. AKP uniquely exhibited most significant changes in BAL and to a lesser extent in CMF and TMF subfractions. The biochemical studies were correlated with light and electron microscopic studies of the pulmonary tissues.