Article: Pulmonary changes induced in rabbits by long-term exposure to n-hexane

New Zealand male rabbits were exposed in an inhalation chamber to 3,000 ppm of n-hexane 8 h/day, 5 days/week for 24 weeks, resulting in a total of 120 exposures. After a further 120 days in clean air, morphologic examination of lungs by light and transmission electron microscopy (TEM) revealed three important exposure-related lesions. These consisted of air space enlargement centered on respiratory bronchioles and alveolar ducts (centriacinar emphysema), scattered foci of pulmonary fibrosis, and papillary tumors of non-ciliated bronchiolar epithelial cells. At TEM examination these tumors were rather homogeneous and were found to consist of cells showing both small and large electron dense ovoid granules in their cytoplasmic matrix, a feature that has been described for Clara cells. The implications of these findings are discussed.

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References

1.

Fonzi L, Lungarella G . Elastolytic activity in rabbit leukocyte extracts. Effects of the whole leukocyte homogenate on the rabbit lung. Exp Mol Pathol. 1979; 31(3):486-91. DOI: 10.1016/0014-4800(79)90047-9. View

2.

Foa V, Gilioli R, Bulgheroni C, Maroni M, Chiappino G . [Etiology of polyneuritides due to glues : experimental studies on the neurotoxicity of n-hexane]. Med Lav. 1976; 67(2):136-44. View

3.

Spencer P, Schaumburg H, Sabri M, Veronesi B . The enlarging view of hexacarbon neurotoxicity. Crit Rev Toxicol. 1980; 7(4):279-356. DOI: 10.3109/10408448009037489. View

4.

Plopper C, Mariassy A, Hill L . Ultrastructure of the nonciliated bronchiolar epithelial (Clara) cell of mammalian lung: I. A comparison of rabbit, guinea pig, rat, hamster, and mouse. Exp Lung Res. 1980; 1(2):139-54. DOI: 10.3109/01902148009069644. View

5.

Fonzi L, Lungarella G . Correlation between biochemical and morphological repair in rabbit lungs after elastase injury. Lung. 1980; 158(3):165-71. DOI: 10.1007/BF02713719. View

6.

Devereux T, Slaughter S, Wolf C, Philpot R, Fouts J . Identification of cytochrome P-450 isozymes in nonciliated bronchiolar epithelial (Clara) and alveolar type II cells isolated from rabbit lung. Exp Lung Res. 1981; 2(3):221-30. DOI: 10.3109/01902148109052317. View

7.

Perbellini L, Brugnone F, Pavan I . Identification of the metabolites of n-hexane, cyclohexane, and their isomers in men's urine. Toxicol Appl Pharmacol. 1980; 53(2):220-9. DOI: 10.1016/0041-008x(80)90422-6. View

8.

Lungarella G, Fonzi L, Centini F . Respiratory tract lesions induced in rabbits by short-term exposure to N-hexane. Res Commun Chem Pathol Pharmacol. 1980; 29(1):129-39. View

9.

Schnoy N, Schmidt R, Altenkirch H, Wagner H . Ultrastructural alteration of the alveolar epithelium after exposure to organic solvents. Respiration. 1982; 43(3):221-31. DOI: 10.1159/000194487. View

10.

Spencer P, Schaumburg H . Experimental neuropathy produced by 2,5-hexanedione--a major metabolite of the neurotoxic industrial solvent methyl n-butyl ketone. J Neurol Neurosurg Psychiatry. 1975; 38(8):771-5. PMC: 492070. DOI: 10.1136/jnnp.38.8.771. View

11.

Lungarella G, Fonzi L . Response of lung enzyme activities in rabbits following short-term exposure to n-hexane: correlation between morphological and biochemical changes. Agents Actions. 1982; 12(5-6):737-42. DOI: 10.1007/BF01965095. View

Pulmonary Changes Induced in Rabbits by Long-term Exposure to N-hexane