A Putative Adverse Outcome Pathway Relevant to Carcinogenicity Induced by Sulfuric Acid in Strong Inorganic Acid Mists

Based on epidemiological studies, an International Agency for Research on Cancer Working Group determined that strong inorganic acid mists containing sulfuric acid are carcinogenic to human even though, sulfuric acid, per se, is not. Accumulative studies indicate that there is a link between chronic occupational exposure to sulfuric acid mists and an increased risk of laryngeal cancer. Unintended, acute exposure to sulfuric acid mists can cause corrosive damage to target tissues depending on the route of exposure. This review compares the toxicity and carcinogenicity of sulfuric acid mists compared to other strong inorganic acid mists. It also examines the routes and duration of exposure (short-term, prolonged, and long-term). In vivo evidence does not support or refute the carcinogenicity of sulfuric inorganic mists even though its co-carcinogenic or promoting potential has been considered. On the basis of existing evidence on sulfuric acid mist toxicity, we suggested a putative adverse outcome pathway (AOP) relevant to carcinogenicity caused by mists containing sulfuric acid. A possible key factor involved in sulfuric acid mist carcinogenesis is the genotoxic effects of low pH since it can increase instability in chromosomes and DNA. A putative AOP for sulfuric acid mist carcinogenicity would help generate better risk assessments and more accurate predictions regarding the risk of developing cancer due to prolonged exposure. Establishing an AOP would also be useful for future studies examining the carcinogenicity of other strong inorganic mists.

Application of the Adverse Outcome Pathway Framework to Risk Assessment for Predicting Carcinogenicity of Chemicals

As industry develops in modern society, many chemicals are being used. The safety of chemicals is an important issue because humans are constantly exposed to chemicals throughout their daily life. Through a risk assessment, the hazardous human effects of chemicals can be identified. Recently, the adverse outcome pathway (AOP) framework has been used to predict the adverse effects of chemicals. As a conceptual framework for organizing existing biological knowledge, the AOP consists of a molecular initiating event, key events, and an adverse outcome. These independent elements represent biological responses and are connected by key event relationships. This AOP framework provides intuitive hazard identification that can be helpful for carcinogenic risk assessment of chemicals. In this review, we introduce the application of the AOP framework to risk assessment for predicting carcinogenicity of chemicals and illustrate the utility of this approach for cancer prevention.