INTRODUCTION

Antimony trioxide (SbO) is a synergist in flame retardants, a catalyst in polyethylene terephthalate (PET) production, and a material used in various industrial process and consumer goods. Antimony trioxide is a potential public health concern because of occupational exposure and a suggested association with cancer based on animal studies. The National Toxicology Program (NTP) conducted a cancer hazard assessment of SbO for possible listing in the Report on Carcinogens (RoC), a document mandated by the U.S. Congress to provide information on cancer hazards for people residing in the United States.

METHODS

Using a systematic review approach, NTP evaluated evidences on human exposure, cancer studies in humans and experimental animals, mechanisms, and other relevant information. Studies identified via a systematic literature search of three databases were selected using pre-defined inclusion and exclusion criteria. Using a structured framework, multiple reviewers assessed human and animal cancer studies for the study quality (potential biases and study sensitivity) and utility of informing SbO carcinogenicity. NTP also evaluated mechanistic data, using the 10 key characteristics of carcinogens as a guide, and reviewed other relevant data, such as metabolism and toxicokinetic studies. Because SbO may exert its effects through released trivalent antimony ions, biological effects observed with other compounds containing trivalent antimony were also considered. Conclusions on the level of evidence (e.g., sufficient, limited, or inadequate) of the carcinogenicity of antimony trioxide from cancer studies in experimental animals and humans, and the final listing recommendation (not to list, or ) were reached by applying the RoC listing criteria to the body of evidence.

RESULTS AND DISCUSSION

Among over 5,500 references identified, 256 references were cited in the monograph. This included an evaluation of five cancer studies in experimental animals and four human cancer studies of independent populations. Antimony trioxide administered by inhalation caused lung tumors (i.e., malignant tumors and/or combined benign and malignant tumors) in rats and mice of both sexes and tumors at several other tissue sites (adrenal gland in female rats, skin in male mice, and lymphatic system in female mice). All studies, except one study in which the high dose was too low, reported increase in tumors. In human cancer studies, elevated mortality of lung cancer was seen in all three cohort studies of antimony-exposed smelter workers; however, it is unclear whether the increased risk was due to exposure to antimony or concurrent exposure to other lung carcinogens. An increased risk of stomach cancer was found in one case-control study and only one of two antimony smelter cohort studies. Evidence for antimony-induced biological effects potentially contributing to carcinogenicity include oxidative stress (and consequently oxidative damage) seen in cultured cells treated with SbO or other antimony compounds, and inhibition of DNA repair seen in cultured cells treated with antimony trichloride. Furthermore, trivalent antimony inhibits cell differentiation in cultured skin cells treated with antimony trichloride or antimony potassium tartrate, which also contains trivalent antimony, and consequently increase the potential for tumor development.

CONCLUSIONS

NTP recommends that antimony trioxide is based on evidence of carcinogenicity from studies in experimental animals and supporting evidence from mechanistic studies. The data available from studies in humans are to evaluate the relationship between human cancer and exposure specifically to SbO or antimony in general.