Screening Assessment for the Challenge Hydrazine Chemical Abstracts Service Registry Number 302-01-2 Environment Canada Health Canada January 2011 Screening Assessment CAS RN 302-01-2 Synopsis The Ministers of the Environment and of Health have conducted a screening assessment of hydrazine, Chemical Abstracts Service Registry Number 302-01-2. The substance hydrazine was identified in the categorization of the Domestic Substances List as a high priority for action under the Chemicals Management Plan Challenge initiative. Hydrazine was identified as a high priority as it was considered to pose an intermediate potential for exposure of individuals in Canada and is classified by other agencies on the basis of carcinogenicity. The substance did not meet the ecological categorization criteria for persistence or bioaccumulation potential, but it did meet the criteria for inherent toxicity to aquatic organisms. Most hydrazine is imported into Canada in aqueous solutions, the form of the product commonly found on the market. In aqueous solution, all the hydrazine is invariably present as the hydrate. This chemical species has a molecule of water loosely attached to an electronegative nitrogen atom by a weak hydrogen bond. The hydrated form is not considered to be chemically different from the anhydrous substance, and can be considered to represent a mixture of the substance with water. Therefore, this assessment considers that hydrazine and hydrazine hydrate are effectively the same substance. Only minor differences in physical-chemical properties are observed between these two forms due to the association of hydrazine with water in the hydrated form. According to information submitted under section 71 of CEPA 1999, hydrazine was not manufactured by any company in Canada in the calendar year 2006 above the 100 kg reporting threshold. However, 10 000–100 000 kg of hydrazine was reported to have been imported in 2006. The major use of hydrazine is as a corrosion inhibitor in boiler water used at power generating plants. Releases of hydrazine to the environment from these sources do occur. However, exposure of the general population of Canada to hydrazine is expected to be low. Based principally on the weight-of-evidence-based assessments of international or other national agencies, a critical effect for characterization of risk to human health for hydrazine is carcinogenicity. Increased incidences of bronchial tumours in male and female rats, thyroid tumours in male rats, and nasal tumours in hamsters were observed after inhalation exposure. Increased incidences of lung tumours were observed in mice of both sexes after oral exposure. Genotoxicity was observed in both in vivo and in vitro assays with hydrazine. Based on tumours observed in multiple sites in experimental rodents for which modes of induction have not been fully elucidated, it cannot be precluded that hydrazine induces tumours via a mode of action involving direct interaction with genetic materials. Repeated-dose studies based on inhalation exposure showed effects on the respiratory systems and systemic effects in multiple sites of male rats. Except for increased mortality, no other effects were observed from repeated-dose studies based on oral exposure to hydrazine. Increased incidence of bile duct proliferations was observed in male rats exposed to hydrazine hydrate. Margins of exposure (MOE) were derived for inhalation ii Screening Assessment CAS RN 302-01-2 and oral exposures and these margins were considered adequate to account for uncertainties in the exposure and health effects dataset for non-cancer effects. However, based on the observed genotoxicity and carcinogenicity, for which there may be a probability of harm at any level of exposure, it is concluded that hydrazine may be 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. Hydrazine has high aquatic toxicity but does not meet the criteria defined for persistence or bioaccumulation potential set out in the Persistence and Bioaccumulation Regulations of CEPA 1999. Given its use particularly in power generating plants, this substance tends to be dispersed widely in the Canadian environment. The National Pollutant Release Inventory reported sustained relatively high quantities of hydrazine released to the environment over a six-year period. In some cases, concentrations in surface water near nuclear and fossil-fuel power generating plants across Canada, estimated based on measured and modelled concentrations in effluent outfalls, are higher than or close to the estimated no-effect levels. Based on this information, it is concluded that hydrazine is 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. It is therefore concluded that hydrazine meets one or more of the criteria under section 64 of CEPA 1999. This substance will be considered for inclusion in the Domestic Substances List inventory update initiative. In addition and where relevant, research and monitoring will support verification of assumptions used during the screening assessment and, where appropriate, the performance of potential control measures identified during the risk management phase. iii Screening Assessment CAS RN 302-01-2 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 hydrazine was identified as a high priority for assessment of human health risk because it was considered to present an intermediate potential for exposure and had been classified by other agencies on the basis of carcinogenicity. The Challenge for this substance was published in the Canada Gazette on June 20, 2009 (Canada 2009a). 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. Although hydrazine was determined to be a high priority for assessment with respect to human health, it did not meet the ecological categorization criteria for persistence or bioaccumulation in the Persistence and Bioaccumulation Regulations but it did meet the criteria for toxicity to aquatic organisms. Screening assessments focus on information critical to determining whether a substance meets the criteria as set out in section 64 of CEPA 1999. Screening assessments examine 1 Screening Assessment CAS RN 302-01-2 scientific information and develop conclusions by incorporating a weight-of-evidence approach and precaution1. This screening assessment includes consideration of information on chemical properties, hazards, uses and exposure, including the additional information submitted under the Challenge. Data relevant to the screening assessment of this substance were identified in original literature, review and assessment documents, stakeholder research reports and from recent literature searches, up to October 2010 for the human and ecological sections of the document. Key studies were critically evaluated; modelling results may have been used to reach conclusions. Evaluation of risk to human health involves the consideration of data relevant to estimation of exposure (non-occupational) of the general population, as well as information on health hazards (based principally on the weight-of-evidence assessments of other agencies that were used to prioritize the substance). Decisions for human health are based on the nature of the critical effect and/or margins between conservative effect levels and estimates of exposure, taking into account confidence in the completeness of the identified databases on both exposure and effects, within a screening context. The screening assessment does not represent an exhaustive or critical review of all available data. Rather, it presents a summary of the critical information upon which the conclusion