Proposed prioritization approach for nanoscale forms of substances on the Domestic substances list


July 2016


1.0 Introduction

1.1 Objective of this consultation

Environment and Climate Change Canada (ECCC) and Health Canada (HC) are currently developing an approach to address certain nanomaterials under the Canadian Environmental Protection Act, 1999 (CEPA). This approach was broadly described in the 2015 consultation document entitled “Proposed Approach to Address Nanoscale Forms of Substances on the Domestic Substances List”.

The current consultation document further details the approach proposed for prioritization of nanoscale forms of substances on the Domestic Substance List (DSL). It is intended to inform stakeholders and solicit feedback on the approach described herein.


1.2 Consultation process

This consultation document will be posted on the Government of Canada’s Chemical Substances website and will be distributed by email to Canadian stakeholders involved in the Chemicals Management Plan (CMP) and/or nanomaterials, including representatives from other federal departments and agencies, provincial and territorial governments, industry, academia, and non-governmental organizations. International stakeholders are also being consulted.

ECCC and HC welcome broad participation in this consultation, for example through the distribution of this consultation document to other potential stakeholders. There will be on-going opportunities for stakeholders to participate and provide input as this approach is developed and implemented (e.g., consultation documents and workshops).

Stakeholders may provide their written comments on this consultation document by mail, fax or email via the contact information provided in Section 4.0. ECCC and HC will review all written comments received during the consultation period. Feedback will be considered in the finalization of the approach.

2.0 Context

2.1 Canada’s Chemicals management plan (CMP)

The CMP is a comprehensive Government of Canada initiative aimed at reducing the risks posed by substances to Canadians and their environment. The plan includes measures to assess and manage new and existing substances, integrate government activities involving different laws governing chemicals, provide government accountability and support industry’s role in proactively identifying and safely managing the substances they produce and use.

Since its launch in 2006, the first two phases of the CMP have made significant progress in addressing over 2700 existing substances, as well as assessing some additional 4500 notifications for new substances prior to their introduction into the Canadian market. The third phase of the CMP will focus on addressing the remaining substances on the DSL (approximately 1550) as well as the nanoscale forms of some existing substances, and will pursue actions required to manage some substances assessed under the first two phases. For more information on the CMP, please visit the Chemical Substances website

The government of Canada plans to build on the successes and lessons learned from the first 2 phases of the CMP in incorporating an approach to prioritize nanomaterials on the DSL for risk assessment.


2.2 The Canada-US Regulatory Cooperation Council (RCC) Nanotechnology Work Plan

In Spring 2015 Canada and the US completed work under the Canada-US RCC nanotechnology work plan (RCC Nano). This work aimed at improving Canada-United States bilateral cooperation and consistency in regulatory approaches for nanomaterials. The cornerstone of this work was the development of a common set of policy principles that inform the regulatory oversight of nanomaterials moving forward in both countries. These principles have now been accepted and endorsed by both Canada and the US and will continue to guide Canada’s proposed approach for nanoscale forms of substances on the DSL. The policy principles can be found on Nanoportal website. Other technical documents developed under the RCC Nano are also considered and referenced in this proposed approach.


2.3 The Domestic Substances List (DSL) and Nanomaterials

Industrial chemical substances in Canada are regulated under CEPA; however, they may also be regulated under different legislative acts, depending on their end use. For example, feeds, fertilizers and pesticides are regulated under the Feeds Act, Fertilizers Act and Pest Control Products Act, respectively. Consumer products are regulated under the Canada Consumer Product Safety Act while novel foods, drugs, medical devices, veterinary drugs and cosmetics are regulated under the Food and Drugs Act.

Under CEPA, substances may be considered as being in Canadian commerce (“existing”) or not yet in Canadian commerce (“new”). If a substance is on the Domestic Substances List (DSL) it is considered in commerce in Canada, and if it is not on the DSL, it is new to the Canadian market. Nanomaterials meet the definition of substances under CEPA. In October of 2011, Health Canada published a working definition on nanomaterials. This definition is used as the basis to characterize nanomaterials under CEPA, and defines nanomaterials by their size (1-100 nm) and/or the presence of unique properties.

Both the non-nanoscale and nanoscale forms of substances on the DSL are described using the same chemical name and unique identification number (known as the Chemical Abstract Services Registry number, or CASRN). CASRNs do not distinguish between substances with the same chemical composition but made up of particles of different sizes (e.g., non-nanoscale particles versus nanoscale particles), nor do they take into account differences in properties between the nanoscale and the non-nanoscale forms of a substance. Since the DSL lists chemicals according to their CASRN, nanomaterials which have a CASRN on the DSL are considered existing substances in Canada and have not undergone an assessment of risks to human health and the environment. To address this gap, ECCC and HC are undertaking a stepwise approach to address nanoscale forms of substances on the DSL.

3.0 Proposed approach

The following sections describe the proposed approach that will be used to:

  1. Establish a list of existing nanomaterials in Canada for prioritization.

  2. Identify how the information available will be used to inform prioritization of nanomaterials for risk assessment.

  3. Outline the proposed outcomes of the prioritization process.


3.1 Establishment of a list of existing nanomaterials for prioritization

In the original consultation document, a proposed list of existing nanomaterials in Canada was developed based on stakeholder-government discussions under RCC Nano. The outcomes of the RCC Nano included a classification scheme to identify nanomaterials expected to exhibit unique properties, a use matrix identifying commercial nanomaterials in Canada and the US and their corresponding uses, and approaches to improve risk assessments of nanomaterials. The RCC Nano outcomes underpin this prioritization approach. For example, the RCC Nano use matrix formed the basis for establishing the list of existing nanomaterials for prioritization and the classification scheme is being proposed as one possible way to group nanomaterials for prioritization. Detailed RCC Nano reports can be found on the NanoPortal website.

Nanomaterials identified as part of the RCC Nano use matrix on commercially relevant nanomaterials were cross-referenced with chemical names listed on the DSL and relevant CASRNs were extracted. The result was a proposed list of distinct existing substances (CASRNs) that may also exist on the nanoscale. Stakeholder consultation was undertaken in 2015 to solicit feedback on the proposed list of nanomaterials in commerce, additional methods and resources for identifying nanomaterials, as well as prioritization factors and outcomes. Following these consultations, a proposed list of 206 nanomaterials suspected to be in commerce in Canada was developed, which can be found in the mandatory survey issued under Section 71 of CEPA (s.71 survey) on nanomaterials. Published in July 2015, the s.71 survey applied to persons who manufactured or imported any of the 206 nanomaterials at a quantity greater than 100 kg during the 2014 calendar year. Based on the results of the s.71 survey, a list of confirmed existing nanomaterials in Canada will be finalized and will be used for subsequent prioritization.

ECCC and HC are proposing that, where possible, the substances identified via the s.71 survey be rolled up into their broader parent nanomaterial groups for the purposes of prioritization (for example, all titanium dioxide and surface modified titanium dioxides will make up the titanium dioxide group). Twenty-one nanomaterial groups were identified under RCC Nano and are included in the s.71 survey. These may be found in List 1. Rolling the substances up to their parent nanomaterial grouping for prioritization will allow, when possible, for a more robust look at the hazard, volume and use data as appropriate, rather than considering an individual substance-by-substance approach. Further consideration for sub-grouping (such as by use, unique property, or functionalization) may also need to be considered for prioritization and/or risk assessment.

List 1. Possible nanomaterial groupings, based on parent substance

Aluminum oxide
Iron (II)/(II/III) oxide
Modified silica
Bismuth oxide
Magnesium oxide
Silicon oxide
Calcium carbonate
Manganese (II & III) oxide
Silver
Cerium oxide
Nanocellulose
Titanium dioxide
Cobalt (II) oxide
Nanoclays
Yttrium oxide
Copper (II) oxide
Nickel (II) oxide
Zinc oxide
Gold
Quantum dots
Zirconium oxide

 

Charge question 1. The Program is seeking input from stakeholders on possible approaches for grouping nanomaterials for prioritization.


3.2 Prioritization

An overview of the proposed process of prioritization is depicted in Figure 1.

Prioritizing nanomaterials involves the consideration of multiple sources of information, including volume and use pattern information from the s.71 survey, routes of exposure, and scientific information on hazard. The overall priority rankings are intended to be qualitative in nature, and will serve to designate the priority for further action. This process is not meant to be a surrogate for a risk assessment, and the overall priority ranking of the nanomaterials may not necessarily reflect potential human health or environmental health risks.

Information from other sources may also inform prioritization. These include:

  • Input from stakeholder engagement,
  • Information received from voluntary s.71 survey responses,
  • Other Government of Canada initiatives (e.g., conventional chemical risk assessments under the CMP), and
  • International activities (e.g., the Organisation for Economic Co-operation and Development Working Party on Manufactured Nanomaterials (OECD WPMN)), and/or substances identified through research.


Figure 1. Proposed prioritization strategy for DSL nanomaterials

x (see long description below).

Description of Figure 1

The image provides a graphical description of proposed prioritization strategy for DSL nanomaterials. The strategy begins with 206 DSL substances, followed by consideration of the s.71 results. If the volume reported by the s.71 survey is < 100 kg/yr, the prioritization decision is No further action at this time. If the volume reported by the s.71 survey is ≥100 kg/yr, the substance is considered to be in commerce in Canada. Results from additional information gathering (e.g., other substances based on declarations of stakeholder interest/engagement with stakeholders and additional substances of interest) can also inform the list of substances considered in commerce in Canada. In commerce nanomaterials are then grouped by parent nanomaterial, and prioritization factors for human health and environmental considerations are applied. These factors consider Volume and Use, which inform the Exposure prioritization factor, as well as Nanomaterial properties and toxicity, which inform the Hazard prioritization factor. The prioritization decision, resulting from this proposed prioritization strategy include Prioritized list of nanomaterials for assessment, Additional information required to prioritize, and No further action at this time.


3.2.1 Exposure Considerations

Human and ecological exposure will be determined separately using information obtained from the s.71 survey such as information on volume, sector (based on reported North American Industry Classification System or NAICS codes) and use (based on reported substance function code).

Manufacture/import volume information obtained from the s.71 survey results will also be considered when determining the extent of exposure for each nanomaterial grouping. Nanomaterials that were not reported under the survey, and received no voluntary submissions of information will be considered as not in commerce in Canada and no further action will be taken on these substances at this time, as a result of prioritization. Nanomaterials that are manufactured or imported at a volume of ≥ 100 kg/year will be ranked according to volume and this information will be considered when determining a priority for further action based on exposure.


Charge question 2. The program is seeking input from stakeholders on the proposed approach for ranking ecological and human exposure. The program is also seeking any additional information that would further quantify potential sources of release/exposure.

Human exposure considerations

The proposed ranking scheme for human exposure considerations is outlined in Figure 2. This approach considers direct exposure scenarios via industrial, commercial and consumer uses. Indirect exposure (e.g., via contaminated drinking water as a result of consumer product disposal into municipal wastewater or via environmental releases from industrial/commercial activities) will be considered if the import/manufacture volumes are considered high and the information is available.

In general, direct human exposure will be ranked as Low, Moderate or High as follows:

Low: substances with only industrial and/or commercial applications (i.e., no consumer use) or substances contained in manufactured items, but not subject to leaching

Moderate: substances contained in manufactured items subject to possible leaching during normal use

High: substances directly used by consumers, contained in consumer products, or in manufactured items intended for use by or for children


Figure 2. Proposed scheme for determining priority ranking for human exposure, based on direct use pattern (L = low; M = moderate; H = high).


x (see long description below).

Description of Figure 2

The image provides a graphical description of the proposed scheme for determining the priority ranking for human exposure, based on direct use pattern. It begins with the determination of the type of use, and is split industrial/commercial or consumer use.

The left side of the image describes the priority ranking scheme for industrial/commercial use. If there is a release to the environment, indirect exposure must be considered (not described in this figure). If there is no release to the environment, the use is ranked as Low priority.

The right side of the image describes the priority ranking scheme for consumer use. If there is use by or for children, the use is ranked as High priority. If there is no use by or for children, an additional consideration of whether the substance is contained in manufactured items or used directly in consumer products is required. If the substance is contained in manufactured items, a final determination is made in regard to whether it leaches. If there is leaching, the use is ranked as Moderate priority. If there is no leaching, the use is ranked as Low priority. If the substance is directly used in consumer products, the use is considered High priority. If the substance is used in consumer products and is released down the drain, it is considered an environmental release and requires a consideration of indirect exposure (not described in this figure).


Ecological exposure considerations

Prioritization for ecological exposure will be based on information reported through the s.71 survey including consideration of the volumes used in Canada, and on three possible types of environmental exposures scenarios:

  1. manufacturing of the nanomaterial;
  2. manufacturing the final end-use product; and/or
  3. use of the end-use product.

Manufacturing of the nanomaterial and final end-use product (exposure scenarios 1 and 2, above) may be associated with releases from point-sources, and will therefore be considered as having higher potential for environmental exposure. Ranking these exposures will be based primarily on the volume being used, direct and/or indirect releases from the manufacturing process, and the likely removal efficiency from municipal wastewater treatment (when relevant/available). Nanomaterials used at a high volume at a single site are expected to result in high ecological exposures, while nanomaterials used at a high volume but in a fully-contained process will result in low ecological exposures.

When the use of a product may result in 100% of the nanomaterial being released directly to the environment (e.g., used as part of drilling fluids for oil/gas extraction), its environmental exposure potential will be considered as a high. Indirect releases of an end-use product will be considered as having moderate potential for exposure (e.g., releases from leaching from coatings via ultra-violet degradation).

3.2.2 Hazard considerations

In order to rank the potential hazards to human health and the environment, information from a variety of sources will be considered including peer-reviewed literature, information available from other government of Canada activities (e.g., CMP) and international reports and activities (e.g., OECD dossiers).


Charge question 3. The program is seeking input from stakeholders on the proposed approach for ranking human health and ecological hazard.

Human health hazard considerations

Human health hazard will be ranked by considering the properties of the nanomaterial as well as any available information on toxicological effects of the nanomaterial itself (e.g., outcomes of available toxicological studies).

It is anticipated that, for many substances, there will be a paucity of toxicological information. In the absence of toxicological information for a nanomaterial grouping, information on properties of the nanomaterial alone may form the basis for determining a priority ranking for human health hazard.

It is also possible that information on nanomaterial properties or toxicity may be used to create subgroupings within a parent nanomaterial grouping.

Nanomaterial Properties

It has been established that changes in a particle’s physical/chemical properties can influence its toxicological properties. Characteristics that have been shown to govern the toxicity of nanomaterials include: aspect ratio, size, shape, surface area, chemical composition and crystalline structure and surface coatingsFootnote 1. System-dependent properties also influence toxicity; these include properties such as surface reactivity, dissolution rate and dispersibilityFootnote 2. These system-dependent properties govern the bio-physical interactions of particles in their environment. Together, physical-chemical and system-dependent properties will form the basis for informing the potential for human health hazard.

The scheme proposed for ranking human health hazard according to nanomaterial properties is modelled after the DF4nanogrouping approachFootnote 2, which groups nanomaterials according to their specific mode of action that may result in a toxicological effect. The approach considers both physical-chemical properties and system-dependent properties. This approach is also aligned with the approaches put forth by the RCC NanoFootnote 3, Footnote 4, which establishes key criteria for identifying key characteristics of nanomaterials, and presents a framework for assessing and identifying testing requirements for nanoparticles.

In considering the potential for human health hazard, based on nanomaterial properties, both particle effects and effects due to the chemical composition of the nanomaterial must be considered. Particle effects that drive toxicity include biopersistence (i.e., dissolution rate), particle shape and size. Chemical-specific effects are driven by factors such as surface coatings and reactivity, as well as effects inherent to the bulk material.

For the purposes of determining the potential for human health hazard, DF4nanogrouping approach classifies nanomaterials into the following four groups, depending on their physical-chemical and system-dependent properties:

Soluble nanomaterials. Soluble nanomaterials (water solubility > 100 mg/L) are not expected to exhibit unique nanomaterial properties, and their toxicity will be largely dependent on their chemical composition (i.e., properties of the bulk material, surface reactivity etc.). Soluble nanomaterials may also include those that are not water soluble, but are soluble in biological media; these nanomaterials may exhibit an increased potential for human health hazard due to their ability to translocate from the site of contact, possibly resulting in toxic effects in the body.

Passive nanomaterials. Passive nanomaterials are biopersistent and non-fibrous (i.e., dissolution rate < 100 mg/L, aspect ratio < 3:1), but do not have surface reactivity and do not elicit cellular effects. As such, the toxicity of passive nanomaterials is largely driven by particle effects, rather than chemical-specific effects. Passive nanomaterials are not expected to be biodistributed from the site of contact and are not expected to elicit toxic effects. They may exhibit effects due to their particulate nature (e.g., dust effects upon inhalation).

Active nanomaterials. Active nanomaterials are biopersistent and non-fibrous (i.e., dissolution rate < 100 mg/L, aspect ratio < 3:1), but are considered to have a hazard potential due to factors such as chemical composition, dissolution rate, surface reactivity, dispersibility or cellular effects. As such, their toxicity is driven by their chemical-specific effects, and they may exhibit toxic effects at low doses.

Fibrous nanomaterials.These nanomaterials are biopersistent and fibrous (i.e., dissolution rate < 100 mg/L; aspect ratio > 3:1). It is recognized that, once inhaled, these nanomaterials may deposit deep in the lung and may be difficult to remove. Nanomaterials in this grouping are expected to have a high potential for human health hazard due to their fibrous nature; however, they may also exhibit toxicity due to chemical-specific effects.

Toxicological information

Should toxicological information be available, it may be used to further inform the potential for human health hazard. This information will be particularly useful for those nanomaterials whose toxicity is governed by chemical-specific effects (versus particle effects), i.e., for soluble and active nanomaterials.

Table 1 describes a proposed scheme in which toxicological information may be used to inform the potential for human health hazard. This scheme parallels that currently used by Health Canada for assessing the toxicity of new chemical substances. Consideration may also be given to toxicological information obtained from alternative testing methods (e.g., in vitro test methods, toxicogenomics studies etc.), if available.

 

Table 1. Proposed guidance on ranking human health hazard using toxicological studies
Low Hazard FlagModerate Hazard FlagHigh Hazard Flag
  • Low acute or repeat-dose toxicity
  • Nanomaterial does not have a moderate or high hazard flag
  • Moderate acute or repeat-dose toxicity
  • Genotoxicity (in vitro)
  • Sensitization
  • Eye/skin irritation
  • High acute or repeat-dose toxicity
  • Reproductive/developmental toxicity Genotoxicity (in vivo) Carcinogenicity
  • Endocrine disruption

 

Ecological hazard considerations

Ecological hazard ranking of nanomaterials for prioritization will be done by looking at the most sensitive endpoint (LC50 or EC50) across all compartments (e.g., soil, sediment, air, water), species and exposure durations, using studies which conform to standardized and accepted test guidelines. Table 2 below is the proposed ranking for ecotoxicological studies.

 

Table 2. Proposed guidance on ranking ecological hazard using toxicological studies
Low Hazard FlagModerate Hazard FlagHigh Hazard Flag
  • LowFootnote a acute or chronic ecotoxicity
  • Low in-vitro ecotoxicity
  • ModerateFootnote b acute or chronic ecotoxicity
  • Moderate in-vitro ecotoxicity
  • HighFootnote c acute or chronic ecotoxicity
  • High in-vitro ecotoxicity
  • Other flags such as endocrine activity

Footnotes

Footnote A

Low = effective concentration >100mg/L;

Return to footnote a

Footnote B

Moderate = effective concentration >1mg/L and <100mg/L)

Return to footnote b

Footnote C

High = effective concentration <1mg/L

Return to footnote c

 


3.3 Outcomes of prioritization for nanomaterials

As a result of prioritization, three ‘bins’ will be created: no further action at this time, nanomaterials prioritized for risk assessment, and nanomaterials that will be set aside for future consideration due to insufficient information. These bins will form the basis for recommendations of additional activity on existing nanomaterials. The following section describes the proposed actions that will be taken as a result of prioritization.

No further action at this time

This bin will include nanomaterials that did not receive any responses from the S. 71 survey, that received no voluntary submission of information, or that were identified as having low potential for exposure and low concern environment and/or human health. Substances in this bin would only be reconsidered for prioritization if new information becomes available at a future date.No further action will be taken on these substances at this time, as a result of prioritization.

Substances prioritized for risk assessment

This bin will include groupings of nanomaterials that will be considered for further assessment work. Scheduling of these nanomaterials for further assessment activities will take several factors into consideration including:

  • Input from stakeholder engagement,
  • Alignment with other assessments under the CMP, and
  • Alignment with international activities (e.g., OECD WPMN) and/or risk assessment decisions by other jurisdictions (such as the European Chemicals Agency Community Rolling Action Plan).

Insufficient information to prioritize at this time

It is likely that some nanomaterials will have insufficient hazard or exposure information to either prioritize them for risk assessment or to determine that no further action is required. These substances will be set aside for prioritization at a later date, once information becomes available.


Charge question 4. The program is seeking input from stakeholders on mechanisms that could be used to fill data gaps for nanomaterials that require additional information to prioritize.

4.0 Timelines and next steps

Stakeholders are invited to submit comments on the content of this consultation document and provide other information that would help inform decision making. Please submit comments to one of the addresses provided below by September 25, 2016. ECCC and HC will respond to comments and adapt the proposed approach based on the feedback received on this document, as described in Section 1.2.

Comments on this consultation document can be submitted to one of the following addresses:

By Mail:
Environment and Climate Change Canada
Substances Management Information Line
Chemicals Management Plan
351 St. Joseph Boulevard
Gatineau, Québec
K1A 0H3

By Email:
eccc.substances.eccc@canada.ca
Please type “Consultation on Prioritization Approach for Nanomaterials” in the subject line of your message.

By Fax:
819-938-5212

Glossary

   Consumer Product
A product, including its components, parts or accessories, that may reasonably be expected to be obtained by an individual to be used for non-commercial purposes, including for domestic, recreational and sports purposes, and includes its packaging.

   Manufactured item

An item that is formed into a specific physical shape or design during manufacture and has, for its final use, a function or functions dependent in whole or in part on its shape or design.

   Nanomaterial

Health Canada considers any manufactured substance or product and any component material, ingredient, device, or structure to be nanomaterial if (i) it is at or within the nanoscale in at least one external dimension, or has internal or surface structure at the nanoscale or (ii) it is smaller or larger than the nanoscale in all dimensions and exhibits one or more nanoscale properties/phenomena.

   Nanoscale

A size range from 1 to 100 nanometres, inclusive, in any one external dimension, or internal or surface structure.

 

Footnotes

Footnote 1

Hristozov DR, Gottardo S, Critto A, Marcomini A. 2012. Risk assessment of engineered nanomaterials: a review of available data and approaches from a regulatory perspective. Nanotoxicology 6(8): 880-898.

Return to footnote 1

Footnote 2

Arts et al. (2015) A decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping). Reg Toxicol Pharmacol. 71: S1-S27.

Return to footnote 2

Footnote 3

Regulatory Cooperation Council (RCC) Nanotechnology Intiative. Work Element 2, Priority Setting: Development of a Joint Nanomaterials Classification Scheme.

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Footnote 4

Regulatory Cooperation Council (RCC) Nanotechnology Intiative. Work Element 3, Risk Assessment/Risk Management.

Return to footnote 4

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