Screening Assessment for the Challenge Antimony trioxide (Antimony oxide) Chemical Abstracts Service Registry Number 1309-64-4 Environment Canada Health Canada September 2010 Screening Assessment CAS RN 1309-64-4 Synopsis Pursuant to section 74 of the Canadian Environmental Protection Act, 1999 (CEPA 1999), the Ministers of the Environment and of Health have conducted a screening assessment of antimony trioxide, Chemical Abstracts Service Registry Number 1309-64- 4. The substance antimony trioxide was identified in the categorization of the Domestic Substances List (DSL) as a high priority for action under the Challenge. Antimony trioxide was identified as a high priority as it was considered to pose greatest potential for exposure of individuals in Canada and is classified by other agencies on the basis of carcinogenicity. In addition, this substance met the ecological categorization criteria for persistence and inherent toxicity to non-human organisms. The focus of this assessment of antimony trioxide relates to both human health and ecological risks. According to information reported under section 71 of CEPA 1999, between 1 000 000 and 10 000 000 kg of antimony trioxide was manufactured in Canada in 2006. In addition, Canadian companies reported importing over 1 850 000 kg and using approximately 3 270 000 kg in that year. Between 1 000 to 10 000 kg of antimony trioxide was released into the environment in 2006, with the majority disposed of in landfill sites. In Canada, antimony trioxide is used primarily as a plastic catalyst in manufacturing polyethylene terephthalate and as a synergist with halogenated compounds to provide flame retardancy properties. Flame retardants are used in a variety of household items including furniture upholstery, carpets, mattress covers and other textiles. Based on available information on concentrations of antimony in environmental media (soil, drinking water, ambient air) and food, as well as results for antimony trioxide from a survey conducted under section 71 of CEPA 1999, the general population is expected to be exposed to antimony trioxide primarily from household items containing flame retardants. However, the total exposure level to antimony trioxide resulting from household products and environmental media identified in this screening assessment is expected to be low. As antimony trioxide was classified on the basis of carcinogenicity by international regulatory agencies, carcinogenicity was a key focus for this screening assessment. Lung tumours were observed in female but not male rats exposed to the highest concentrations of antimony trioxide tested in 1-year inhalation bioassays. No evidence was available to suggest carcinogenic potential for antimony trioxide via the oral route. Collective evidence from genotoxicity studies suggests that antimony trioxide is not likely to be mutagenic but may exert some clastogenic effects in vitro. The mode of action for induction of tumours proposed by other regulatory agencies links to local inflammatory response and pulmonary overload. Although the mode of induction of tumours is not fully elucidated, the tumours observed are not considered to have resulted from direct ii Screening Assessment CAS RN 1309-64-4 interaction with genetic material. Therefore, a threshold approach is used to characterize risk to human health. There was some evidence for adverse effects on fertility in limited developmental and reproductive toxicity studies in experimental animals, as well as in epidemiological studies. The critical effect concentration for non-cancer effects was based on an increase in lung weight, pulmonary changes and no significant increase in the incidence of lung tumours in female rats exposed by inhalation to antimony trioxide for a year. For the oral route, the critical effect level was based on histopathological changes in the liver and an increase of aspartate transaminase (serum glutamic oxaloacetic transaminase) activity in male rats administered antimony trioxide for 24 weeks. The critical effect levels were also below the levels at which reproductive and developmental toxicity may occur. The margins between upper-bounding estimates of exposure to antimony trioxide from environmental media (based on antimony) and from use of household items and levels associated with effects in experimental animals are considered to be adequately protective to account for uncertainties in the health effects and exposure databases. On the basis of the adequacy of the margins between conservative estimates of exposure to antimony trioxide and critical effect levels in experimental animals, it is concluded that antimony trioxide is not entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health. Antimony trioxide is released into the Canadian environment mainly as a result of its use as a synergistic flame retardant and as atmospheric emissions from fossil fuel combustion and non-ferrous metal production. Antimony trioxide emitted to air is then deposited onto surrounding terrestrial and aquatic ecosystems. Because antimony trioxide has some solubility in water, it will dissolve in contact with moisture once in these ecosystems and yield a variety of dissolved antimony species, depending on the environmental conditions. Antimony has been demonstrated to have a moderate potential to cause harm to aquatic, soil and sediment organisms. Site-specific industrial scenarios based on monitoring data were developed for the most important sources of releases of antimony trioxide to the environment. Modelled exposure concentrations in the aquatic environment were also estimated, mainly for the plastics industry from the use of antimony trioxide as a flame retardant. Based on a risk quotient analysis, harm to aquatic and terrestrial organisms resulting from exposure to antimony trioxide is unlikely. Hence, it is concluded that the substance is not entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity or that constitute or may constitute a danger to the environment on which life depends. Antimony trioxide meets the criteria for persistence but does not meet the criteria for bioaccumulation potential as set out in the Persistence and Bioaccumulation Regulations of CEPA 1999. Based on the information available, it is concluded that antimony trioxide does not meet the criteria set out in section 64 of CEPA 1999. iii Screening Assessment CAS RN 1309-64-4 This substance will be considered for inclusion in the DSL inventory update initiative. In addition and where relevant, research and monitoring will support verification of assumptions used during the screening assessment. iv Screening Assessment CAS RN 1309-64-4 Introduction The Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada 1999) requires the Minister of the Environment and the Minister of Health to conduct screening assessments of substances that have met the categorization criteria set out in the Act to determine whether these substances present or may present a risk to the environment or to human health. Based on the information obtained through the categorization process, the Ministers identified a number of substances as high priorities for action. These include substances that • met all of the ecological categorization criteria, including persistence (P), bioaccumulation potential (B) and inherent toxicity to aquatic organisms (iT), and were believed to be in commerce in Canada; and/or • met the categorization criteria for greatest potential for exposure (GPE) or presented an intermediate potential for exposure (IPE) and had been identified as posing a high hazard to human health based on classifications by other national or international agencies for carcinogenicity, genotoxicity, developmental toxicity or reproductive toxicity. The Ministers therefore published a notice of intent in the Canada Gazette, Part I, on December 9, 2006 (Canada 2006), that challenged industry and other interested stakeholders to submit, within specified timelines, specific information that may be used to inform risk assessment, and to develop and benchmark best practices for the risk management and product stewardship of those substances identified as high priorities. The substance antimony oxide, referred to in this assessment as antimony trioxide, was identified as a high priority for assessment of human health risk because it was considered to present GPE and had been classified by other agencies on the basis of carcinogenicity. The Challenge for this substance was published in the Canada Gazette on March 14, 2009 (Canada 2009). A substance profile was released at the same time. The substance profile presented the technical information available prior to December 2005 that formed the basis for categorization of this substance. As a result of the Challenge, submissions of information pertaining to the substance were received (Environment Canada 2009). Although antimony trioxide was categorized as a high priority for assessment with respect to human health, it also met the ecological categorization criteria for persistence and inherent toxicity to aquatic organisms. Therefore this assessment of antimony trioxide considers both human health and ecological risks. Screening assessments focus on information critical to determining whether a substance meets the criteria set out in section 64