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Pulmonary inflammation and fibrosis in rats after intratracheal instillation of adipic acid and adipic acid mixtures.
Hubbs AF; Ma JYC; Frazer D; Goldsmith WT; Barger M; Battelli LA; Robinson VA; Porter DW; Castranova V; Vallyathan V; Cocalis J
Toxicologist 1998 Mar; 42(1-S):251
Adipic acid is an aliphatic dicarboxylic acid which can be added to food in small quantities and is used for several other commercial purposes. During me production of polymers and in the sheet glass industry, respiratory exposures occur. There is no OSHA PEL for adipic acid and it has little or no odor. We have investigated the hypothesis that respiratory exposures to adipic acid are non-toxic. We conducted intratracheal instillation exposures to adipic acid and adipic acid mixtures at levels which would produce limited disease and no monality with nuisance dusts. Intratracheal instillation of 2.5, 5, or 7 mgs of adipic acid in rats produced acute pulmonary cytotoxicity and inflammation. One day after instillation. lavage protein. LDH, and inflammtory cells were markedly increased. Histopathology confirmed acute pulmonary inflammation. Four weeks after exposure, pulmonary alterations persisted and were most pronounced in the rats receiving 7 mgs of adipic acid. Significant changes included bydroxyproline increases, histologic foci of pulmonary fibrosis, and persistent tachypnea. Neutralization of the pH ameliorated the toxicity. These findings suggest that high concentrations of adipic acid can cause persistent pulmonary structural and functional alterations. The proposed mechanism is the acidity and lipid solubility of this organic acid. Inhalation studies are planned.
Dicarboxylic-acids; Respiratory-irritants; Respiratory-infections; Respiratory-system-disorders; Animal-studies; Animals; Pulmonary-system; Pulmonary-system-disorders; Pulmonary-disorders; Histopathology; Organic-acids; Laboratory-animals
The Toxicologist. Society of Toxicology 37th Annual Meeting, March 1-5,1998, Seattle, Washington