A Review of the Chronic Toxicity, Carcinogenicity, and Possible Mechanisms of Action of Inorganic Acid Mists in Animals

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Abstract
Occupational exposure to inorganic acid mists containing sulfuric acid has been associated with increased laryngeal cancer. The primary objective of this review was to compile the literature regarding chronic toxicity and carcinogenicity of inorganic acid mists in laboratory animals. Several chronic toxicity studies had exposures of 1 year or longer. Whereas numbers of animals were limited, no evidence of neoplastic or preneoplastic lesions was reported. Two studies evaluated the carcinogenicity of inorganic acid mists in rats; however, one was limited by a short duration of exposure and the other did not achieve a maximum tolerated dose. A large lifetime study in hamsters evaluated the carcinogenicity of 100 mg/M3 sulfuric acid mist, as well as its ability to act as a promoter or co-carcinogen for benzo(a)pyrene. No evidence of carcinogenic potential was shown. Although an increase in papillomas was noted in the benzo(a)pyrene + H2SO4 group, the co-carcinogenic or promoting potential was considered equivocal. Thus, no evidence from experimental animals strongly supports or refutes the induction of cancer by inorganic acid mists. A possible mechanism that could be associated with inorganic acid mist carcinogenicity relates to the genetic consequences of lowering the pH. Reduced pH can induce chromosomal aberrations, enhance depurination, and deamination of cytidine in DNA. This mechanism has not been evaluated in tissues of the respiratory tract.