Draft screening assessment - Substances identified as being of low concern using the ecological risk classification of inorganic substances and three human health science approaches

Official title: Draft screening assessment - Substances identified as being of low concern using the ecological risk classification of inorganic substances and three human health science approaches

Environment and Climate Change Canada

Health Canada

April 2019

Synopsis

Pursuant to sections 68 or 74 of the Canadian Environmental Protection Act, 1999 (CEPA), the Minister of the Environment and the Minister of Health have conducted a screening assessment of 21 substances. These substances were identified as priorities for assessment as they met categorization criteria under subsection 73(1) of CEPA or were considered a priority on the basis of other human health concerns. The Chemical Abstracts Service Registry Numbers (CAS RN^{Footnote 1}) and their Domestic Substances List (DSL) names are listed in the table below.

^a This substance was not identified under subsection 73(1) of CEPA but was included in this assessment as it was considered a priority on the basis of human health concerns.

^b This CAS RN is a UVCB (unknown or variable composition, complex reaction products, or biological materials).

The 21 substances in this assessment were evaluated for ecological risk and human health risk using four different science approaches (i.e., one ecological and three human health). This draft screening assessment proposes conclusions on those substances that were identified as having a low likelihood of causing harm to human health and the environment through these streamlined approaches.

The ecological risks of the substances in this assessment were characterized using the Ecological Risk Classification of inorganic substances (ERC-I). The ERC-I is a risk-based approach that employs multiple metrics considering both hazard and exposure in a weight of evidence. Hazard characterization in ERC-I included a survey of past predicted no-effect concentrations (PNEC) and water quality guidelines, and the derivation of new PNEC values when required. Exposure profiling considered two approaches: predictive modelling using a generic near-field exposure model for each substance, and an analysis of measured concentrations collected by federal and provincial water quality monitoring programs using these concentrations as a conservative indicator of exposure for individual substances. Modelled and measured predicted environmental concentrations (PECs) were compared to PNECs, and multiple statistical metrics were computed and compared to decision criteria to classify the potential to cause harm to the environment. The ERC-I identified the 21 substances in this assessment as having low ecological concern.

The human health risks of the substances in this assessment were characterized using one of three science approaches: Biomonitoring-based Approach 1, Biomonitoring-based Approach 2, or the Low Human Health Hazard Potential Approach. Biomonitoring-based Approach 1 is a qualitative science approach used to identify substances with limited exposure based on substances or moieties measured in the Canadian population at very low frequencies. Biomonitoring-based Approach 2 compares human biomonitoring data (exposure) against biomonitoring guidance values (health effects), such as biomonitoring equivalents (BEs), to identify substances with low concern for human health. The Low Human Health Hazard Potential Approach is used to identify substances with low inherent repeat-dose toxicity.

When the results of ERC-I and the three human health science approaches are considered together, a subset of 21 substances are identified as being of low concern to both human health and the environment. Conclusions on the remaining substances (i.e., those identified as being either of low concern to the environment through the ERC-I or of low concern to human health through one of the three streamlined human health based approaches, but not both) will be made in other assessments.

Considering all available lines of evidence presented in this draft screening assessment, there is low risk of harm to the environment from the 21 substances in this assessment. It is proposed to conclude that these substances do not meet the criteria under paragraphs 64(a) or (b) of CEPA as they are 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.

On the basis of the information presented in this draft screening assessment, it is proposed to conclude that the 21 substances in this assessment do not meet the criteria under paragraph 64(c) of CEPA as they are 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.

It is therefore proposed to conclude that these 21 substances do not meet any of the criteria set out in section 64 of CEPA.

1. Introduction

Pursuant to sections 68 or 74 of the Canadian Environmental Protection Act, 1999 (CEPA) (Canada 1999), the Minister of the Environment and the Minister of Health have conducted a screening assessment of 21 substances to determine whether these substances present or may present a risk to the environment or to human health. The substances were identified as priorities for assessment as they met categorization criteria under subsection 73(1) of CEPA or were considered a priority on the basis of other human health concerns (ECCC, HC [modified 2017]).

The 21 substances in this assessment were evaluated for ecological risk and human health risk using four different science approaches. The four science approaches, Ecological Risk Classification of Inorganic Substances (ERC-I) (ECCC [modified 2018]), Biomonitoring-based Approach 1 (HC 2016a), Biomonitoring-based Approach 2 (HC 2016b), and Substances with Low Human Health Potential (HC 2019), were published between 2016 and 2018, inclusively. This draft screening assessment proposes conclusions on 21 substances that were identified as having a low likelihood of causing harm to human health and the environment through these approaches.

The ecological risks of the substances in this assessment were characterized using the ERC-I (ECCC [modified 2018]). The ERC-I is a risk-based approach that employs multiple metrics considering both hazard and exposure in a weight of evidence. Hazard characterization in ERC-I included a survey of past predicted no-effect concentrations (PNEC) and water quality guidelines, or the derivation of a new PNEC value when required. Exposure profiling considered two approaches: predictive modelling using a generic near-field exposure model for each substance and an analysis of measured concentrations collected by federal and provincial water quality monitoring programs using metal concentrations as a conservative indicator of exposure for individual substances. Modelled and measured predicted environmental concentrations (PECs) were compared to PNECs, and multiple statistical metrics were computed and compared to decision criteria to classify the potential for causing harm to the environment.

The human health risks of the substances in this assessment were characterized using one of three science approaches: Biomonitoring-based Approach 1, Biomonitoring-based Approach 2, or the Low Human Health Hazard Potential Approach. Biomonitoring-based Approach 1 is a qualitative science approach used to identify substances with limited exposure based on substances or moieties measured in the Canadian population at very low frequencies. Biomonitoring-based Approach 2 compares human biomonitoring data (exposure) against biomonitoring guidance values (health effects), such as biomonitoring equivalents (BEs), to identify substances with low concern for human health. The Low Human Health Hazard Potential Approach is used to identify substances with low inherent toxicity.

This draft screening assessment was prepared by staff in the CEPA Risk Assessment Program at Health Canada and Environment and Climate Change Canada and incorporates input from other programs within these departments. The ecological portion of this assessment is based on the ERC-I SciAD (published May 12, 2018), which was externally peer-reviewed and subject to a 60-day public comment period. The health portion of this assessment is based on the Biomonitoring-based Approach 1 SciAD (published September 3, 2016), the Biomonitoring-based Approach 2 SciAD (published December 9, 2016), and the Substances with Low Human Health Hazard Potential SciAD (published December 16, 2017), which were each subject to a 60-day public comment period. Additionally, the Biomonitoring-based Approach 2 SciAD and the Substances with Low Human Health Hazard Potential SciAD were both externally peer-reviewed. External peer-review comments on the Biomonitoring-based approach 2 SciAD were received from Lynne Haber and Andrew Maier from Toxicology Excellence for Risk Assessment (TERA) and Judy LaKind from LaKind Associates. External peer-review comments on the Substances with Low Human Health Hazard Potential Approach SciAD were received from Gary Drendel and Katherine Super from Tetra Tech. External peer-review comments on the technical portions of the ERC-I SciAD were received from Dr. Peter Campbell (L’Institut national de la recherche scientifique, INRS), Mr. Geoff Granville (GCGranville Consulting Corp.), Dr. Carrie Rickwood (Natural Resources Canada), and Dr. Kevin Wilkinson (Université de Montréal). Public comments were received on the ERC-I SciAD, the Biomonitoring Approach 2 SciAD and the Low Human Health Hazard Potential SciAD and an updated Low Human Health Hazard Potential SciAD was published (April 2019)[KM1] . While external comments were taken into consideration, the final content and outcome of the screening assessment remain the responsibility of Health Canada and Environment and Climate Change Canada.

This draft screening assessment focuses on information critical to determining whether substances meet the criteria as set out in section 64 of CEPA by examining scientific information and incorporating a weight of evidence approach and precaution^{Footnote 2}. The draft screening assessment presents the critical information and considerations on which the proposed conclusions are based.

2. Approach

2.1 Potential to cause ecological harm

The ecological risks of substances in this assessment were characterized using the ERC-I (ECCC [modified 2018]). The ERC-I is a risk-based approach that employs multiple metrics that consider both hazard and exposure in a weight of evidence. A summary of the approach is outlined below; the approach is described in detail in the ERC-I science approach document (ECCC [modified 2018]).

Hazard characterization in ERC-I included a survey of past domestic and international assessment predicted no-effect concentrations (PNEC) and water quality guidelines. When no suitable existing PNEC or water quality guideline was found, hazard endpoint data were collected from multiple sources including comprehensive literature searches for specific groups, targeted searches of the ECOTOX database (2016) and European Chemicals Agency (ECHA) registration dossiers (2016). In the absence of more recent information, the assumptions used in the 2006 categorization of the DSL were also considered (ECCC, HC [modified 2017]). Dependent on data availability, either a species sensitivity distribution (SSD) or an assessment factor (AF) approach was taken to derive a new PNEC value.

Exposure profiling considered two approaches: predictive modelling using a generic near-field exposure model and an analysis of measured concentrations collected by federal and provincial water quality monitoring programs. The generic near-field exposure model used Canadian import and manufacture volumes and associated use information of the substances collected from the DSL Inventory Update (DSL-IU) Phase 1 and Phase 2 section 71 surveys (Environment Canada 2009, Environment Canada 2013). As an additional line of evidence, and to address substances where DSL-IU information was unavailable, trade merchandise import data were obtained for relevant harmonized system (HS) codes (CBSA 2016). Additionally, third-party market research reports were used to complement data from other sources and to fill gaps for substances not included to date in a DSL-IU. Volume data from DSL-IU, CBSA, and market research were used in a conservative near-field exposure scenario similar to that used in previous rapid screening approaches (EC, HC 2013; EC, HC 2014; ECCC, HC 2016) and as further detailed in ECCC [modified 2018] to generate PECs.

In addition to using import, manufacture, and use information to model releases to the aquatic environment, reported releases data were also available from the National Pollutant Release Inventory (NPRI) for certain substances or groups of substances. NPRI data for groups of substances (e.g. vanadium, except when in an alloy, and its compounds) were conservatively considered applicable to the subsets of CAS RNs that are remaining priorities. A similar near-field risk-based evaluation was performed using NPRI reported release data for the last five years available at the time of preparation (2011 to 2015).

Water quality monitoring data for surface freshwaters were collected for each substance or group of substances, where available, from multiple federal and provincial programs and repositories covering a number of ecoregions in Canada were collected, as described in ECCC [modified 2018]. Measured concentrations were obtained for the period 2005 to 2015. For some substance groups, measured concentrations in waterbodies exposed to metal mining activities and corresponding reference waterbodies were available from Environmental Effects Monitoring (EEM) studies conducted under the Metals Mining Effluent Regulations (MMER).

Modelled and measured PECs were compared to PNECs, and statistical metrics considering both the frequency and magnitude of exceedances were computed and compared to decision criteria to classify the potential for ecological risk of substances. Critical data and considerations used to create substance-specific ecological profiles and classifications associated with ecological risk, as well as identification of potential need for tracking of future use patterns, are presented in ECCC [modified 2018]. The ERC-I classifications specific to these 21 substances are presented in Table A-2.

2.2 Potential to cause harm to human health

The human health risks of the substances in this assessment were characterized using one of the three human health based approaches: the Biomonitoring-based Approach 1(HC 2016a), the Biomonitoring-based Approach 2 (HC 2016b), and the Low Hazard-based Approach (HC 2019).

Biomonitoring-based approach 1

This science approach is a qualitative biomonitoring-based approach to identify substances of low concern for human health which were identified as priorities for assessment as they met categorization criteria under subsection 73(1) of CEPA.

This biomonitoring-based approach considers available Canadian and U.S. biomonitoring data based on the analysis of the substance or moiety in whole blood, serum, and/or urine. Total concentrations of a substance (or moiety) in blood or urine may provide a biologically-relevant, integrated measure of exposures that may occur across multiple routes (e.g., oral, dermal and inhalation) and sources (including environmental media, diet, and frequent or daily use products to which they were exposed). When biomonitoring data indicate that general population exposure is limited or unlikely, substances or moieties are considered to be of low concern with respect to human health. To determine if exposure is limited or unlikely, a number of metrics are taken into consideration, including the prevalence of exposure across the population (substances or moieties with limited biomarker^{Footnote 3} detection frequency in the population are considered to have limited exposure), the magnitude of the biomarker concentration (if detected at the upper tails of the exposure distribution), the toxicokinetic properties of the substance or moiety, and the use pattern of the substance.

Uncertainties associated with this approach have been outlined in the science approach document (HC 2016a).

Critical data and considerations used in the biomonitoring-based approach 1 are presented in the SciAD (HC 2016a). The magnitude and prevalence of exposure (based on biomonitoring data) for the substances addressed by this approach are summarized in Table A-3.

Biomonitoring-based approach 2

This science approach incorporates biomonitoring data from large population level biomonitoring programs with a human biomonitoring guidance value (e.g., biomonitoring equivalents (BEs), German human biomonitoring values) to identify substances of low concern for human health.

Similar to biomonitoring-based approach 1, biomonitoring-based approach 2 considers available Canadian and U.S. biomonitoring data based on the analysis of the substance or moiety in whole blood, serum, and/or urine. Total concentrations of a substance in blood or urine may provide a biologically relevant, integrated measure of exposures that may occur across multiple routes (e.g., oral, dermal and inhalation) and sources (including environmental media, diet, and frequent or daily use products to which they were exposed). The biomonitoring-approach 2 also incorporates health effects data relevant to humans in the assessment of risk. Human biomonitoring reference values are typically derived from existing health-based exposure guidance values such as a reference dose (RfD) or Tolerable Daily Intake (TDI) and/or pharmacokinetic data. In some cases the human biomonitoring guidance values are based on human studies or epidemiology data.

A thorough review of available toxicokinetic data is an integral part of Biomonitoring Approach 2. Biomonitoring Approach 2 is only recommended for use if the biomarker (chemical concentration in whole blood, plasma, serum or urine) is considered adequate to quantify the exposure in the general population.

If exposures (on the basis of biomonitoring data from large-scale studies) are below the human biomonitoring guidance value (on the basis of an RfD, TDI or other critical health effects), then the substance or metal moiety is considered to be of low concern with respect to human health at current levels of exposure.

Uncertainties associated with this approach have been outlined in the science approach document (HC 2016b).

The BE values or human biomonitoring values (HBM-I) do not represent diagnostic criteria for health assessment at the individual level, but they are useful tools to interpret population-level biomonitoring data. The BE values should only be used for the interpretation of exposure in the general population and should not be used for occupational exposure or for individuals (LaKind et al. 2008). The HBM-I value can be used in the interpretation of exposure in the general population (Angerer et al. 2011).

Critical data and considerations used in the biomonitoring-based approach 2 are presented in the SciAD (HC 2016b). The biomonitoring data and human biomonitoring guidance values for the substances addressed by this approach are summarized in Table A-4. In addition, critical data and considerations used for five iodine-containing substances are presented in Hays et al. 2018.

Substances with low human health hazard potential

This approach is a hazard based screening approach that considers available toxicological data based on human and/or animal studies (HC 2019). It focuses on the inherent toxicity of a substance. When toxicological data shows that health effects are unlikely up to the limit dose of 1000 mg/kg-bw/day (by the oral or dermal route as defined by the OECD), or are limited to recoverable or localized effects above 100 mg/kg-bw/day, in repeated dose studies of high quality and sufficient duration, the substances or moieties are considered to be of low concern with respect to human health. The relevant route of exposure and high hazard flags (i.e., potential for carcinogenicity, mutagenicity/genotoxicity, and reproductive/developmental toxicity) are considered in the process as well.

Substances are first screened regarding the potential for carcinogenicity, mutagenicity/genotoxicity, and reproductive/developmental (CMR) toxicity. This includes assessment of all health effects of a given substance based on a weight of evidence approach and taking into account the totality of the findings including structure-activity relationship, knowledge of mode of action, toxicokinetics and the acknowledgement of limitations of the available data. It also includes a requirement for adequate repeat-dose studies relevant to the primary route of exposure as part of this approach. Only substances not identified as having carcinogenic, genotoxic or reproductive/developmental toxic properties are considered candidates for the low hazard-based approach, and are considered further. Following that, an assessment of the dose level at which health effects are observed is conducted and characterization of the severity or seriousness of those effects is addressed. If there are no health effects documented up to 1000 mg/kg-bw/day, or health effects between 100 and 1000 mg/kg bw/day are limited to site of contact effects, considered reversible, compensatory effects and not serious in nature, the substance is considered as having low concern for human health and no further risk characterization is warranted.

Uncertainties associated with this approach have been outlined in the science approach document (HC 2019).

Critical data and considerations used in the low human health hazard potential approach are presented in the SciAD (HC 2019). The decision points and supporting data for the substances addressed by this approach are summarized in Table A-5. In addition, critical data and considerations used for two iron-containing substances are presented in Appendix B.

3. Summary of screening assessment results

Combining the results from ERC-I and the three streamlined human health approaches, 21 substances were identified to be of low concern for human health and ecological risk and are listed in Table A-1. Given the low ecological and human health concern associated with these 21 substances, there is low risk of harm to organisms and the broader integrity of the environment from these substances and the potential risk to human health is considered to be low.

While exposures of the general population to these 21 substances are not of concern at current levels, three substances (silicon carbide CAS RN 409-21-2, molybdenum oxide CAS RN 1313-27-5, and beryllium CAS RN 7440-41-7) are considered to have a health effect of concern on the basis of their potential for carcinogenicity if exposure were to increase (see Table A-6 for further details).

Additional substances were identified by the SciADs as having either a low ecological or low human health concern, but not both. Proposed conclusions on these additional substances will be made in other screening assessments conducted under section 68 or 74 of CEPA.  

4. Conclusion

Considering all available lines of evidence presented in this draft screening assessment, there is low risk of harm to the environment from the 21 substances in this assessment. It is proposed to conclude that these substances do not meet the criteria under paragraphs 64(a) or (b) of CEPA as they are 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.

On the basis of the information presented in this draft screening assessment, it is proposed to conclude that the 21 substances in this assessment do not meet the criteria under paragraph 64(c) of CEPA as they are 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.

It is therefore proposed to conclude that these 21 substances do not meet any of the criteria set out in section 64 of CEPA.

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https://www.canada.ca/en/environment-climate-change/services/evaluating-existing-substances/science-approach-substances-low-human-health-hazard-potential.html

Appendix A. ERC-I and streamlined human health approaches for substances addressed in this screening assessment

^a Post-categorization human health concern

^b This CAS RN is a UVCB (unknown or variable composition, complex reaction products, or biological materials)

Abbreviations: N/A, not applicable

^a Post-categorization human health priority

Abbreviations: LOD = limit of detection, ND = Not Detected

^a HC 2016a

^b 97.5^th percentile

^c 1988-1994 US data not included as it is not considered to be representative of current exposure

<LOD = less than the limit of detection (LOD = 0.05 μg/L), N/A= not applicable

^a HC 2016b, Hays et al. 2018

^b 1988-1994 US data not included as it is not considered to be representative of current exposure

Abbreviations:  N/A= Not Applicable, CMR= Carcinogenicity, Mutagenicity, Reproductive/Developmental

^a HC 2019, umber and C.I. Pigment Yellow 42 data presented in Appendix B

^b Identified on the basis of classifications by other national or international agencies for carcinogenicity, genotoxicity, developmental toxicity or reproductive toxicity for the oral route of exposure which is considered to be most relevant for general population exposure

^c Fibrous silicon carbide is a group 2B carcinogen according to IARC. Only non-fibrous sources are currently used in Canada, which does not increase cancer risk.

^a High health hazards were identified on the basis of classifications by other national or international agencies for carcinogenicity, genotoxicity, developmental or reproductive toxicity.

^b Post-categorization human health concern

Appendix B. Results of the low human health hazard potential approach for C.I. Pigment Yellow 42 and umber

Oral intake for the general Canadian population is expected to be the primary route of exposure to C.I. Pigment Yellow 42 (CAS RN 51274-00-1) and umber (CAS RN 12713-03-0). C.I. Pigment Yellow 42 is a hydrated iron (III) oxide with the formula FeO₂H ∙ H₂O, while umber is a UVCB, which contains iron (III) oxide as its major component (40% to 73%) (Fuller 1988). Due to limited empirical health effects data on C.I. Pigment Yellow 42 and umber, a read-across approach using data from the analogue iron oxide (CAS RN 1309-37-1) was used to inform the human health effects assessment of these substances. Iron oxide, a pigment consisting of Fe (III), is a suitable analogue as it contains iron in the same redox state as C.I. Pigment Yellow 42 and presumably umber. The overall weight of evidence indicates that iron oxide is negative for carcinogenicity, mutagenicity and reproductive/developmental toxicity up to the Limit Dose of 1000 mg/kg bw/day (JECFA 1980, 1983, IARC 1987, EFSA 2015). In repeat-dosing studies, there were no health effects of concern below the Limit Dose of 1000 mg/kg bw/day (i.e., Decision point 1 based on the approach for substances with low human health hazard potential, HC 2019) (Yun et al. 2015). Therefore, based on the analogue iron oxide, C.I. Pigment Yellow 42 and umber are considered to be of low concern for human health according to the hazard-based approach.

^a The EFSA panel concluded there was no concern with respect to systemic genotoxicity of orally administered red iron oxide. Although DNA strand breakages were observed in some studies in cultured mammalian cells in vitro, this was not confirmed in other in vitro studies. In addition, red iron oxide was negative for genotoxicity in a thoroughly conducted in vivo study.