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Risk Assessment/Management

Appendices

APPENDIX A- Comparative Analysis of Regulatory Frameworks in Canada and the United States for the Risk Management of Nanomaterials (2013)

[AVAILABLE UPON REQUEST]

APPENDIX B- Stakeholder Call for Nominations

http://content.govdelivery.com/attachments/USAEPA/2012/10/10/file_attachments/166590/RCC%2BNano%2BWebinar%2BInvitation%2B10%2B2012.pdf

 

APPENDIX C- Material Selection Criteria

Definitions of Criteria used in the Nomination of Candidate Nanomaterials

Nanomaterials have been widely developed and are commercially available. They are used in a variety of products and applications such as medicine, energy, electronics, cosmetics, packaging, environmental decontamination, and many other fields. Both the U.S. and Canada are in the process of developing approaches to inform government oversight and strengthen regulatory decision making activities. Conducting a comparative analysis of current risk assessment and management approaches to nanomaterials in Canada (e.g., under Canadian Environmental Protection Act, 1999) and in the U.S. (e.g., under Toxic Substances Control Act) through case studies will aid and assist the relevant regulatory bodies with identifying common approaches/practices and helping to develop a joint framework to ensure consistency for evaluating potential risks to consumers and industries within and between both countries.

The following criteria have been developed to assist in the selection of an appropriate nanomaterial for the purposes of conducting a comparative analysis of current risk assessment approaches. These criteria have been broadly classified into the following five categories:

NOTE: Nomination/identification of a nanomaterial for the purposes of this comparative analysis does not itself constitute a finding that the nanomaterial presents a risk to human health or the environment.

Commercialization and market availability

Nanomaterials that are already in the stream of commerce will be given the highest priority, especially high production volume compounds.  Product capacity will reflect the market size in the near future and will aid with selecting nanomaterials.  With increasing quantity/volume/mass of nanomaterial(s) used, the prices will be expected to decrease and will aid with identifying specific, market-accessible HPV nanomaterials.

Substance composition/ production

Well-characterized and consistently-produced nanomaterials will ensure the least uncertainty with regard to composition and potential toxicity, based on available data, for new substances undergoing risk assessments.

Information availability- Exposure

The risk assessments of nanomaterials will be greatly aided by more complete databases on potential exposure pathways, which include those that occur during manufacture, transport and use, and ultimately end of life.  The availability of this information will aid regulators in Canada and the US in determining the quality, reliability, relevancy of these data for use in robust risk assessments and subsequent peer reviews.

Information availability- Hazard

Information on hazard will be evaluated in conjunction with available exposure information.  As with exposure information, these types of data will be assessed with regard to quality, reliability, and relevancy for use in risk assessments and subsequent peer reviews.

Relevance to the Canadian and US Regulatory Cooperation Council (RCC)

Evaluating materials that have already gone through the regulatory processes in Canada and the US will allow the RCC to identify the similarities and differences by which Canada and US assess risk(s) for nanomaterials, and ultimately aid with harmonizing and streamlining future new nanomaterial submissions in these jurisdictions.

Proposed Material: Short tangled multi-wall carbon nanotubes obtained by catalytical chemical vapour deposition

Market/Commercialization availabilityY or N
Is the material manufactured in Canada and/or the U.S.?N
Is the material capable of being used across many product types (wide application)?Y
Are high volumes of the material being/anticipated to be imported or manufactured?Y
Is there an industry demand for the product now or in the near future?Y
Substance features/production 
Is the material well defined and characterized (e.g. size, shape, surface area, surface chemistry, surface charge, agglomeration/aggregation)?Y
Is the material being manufactured on a commercial scale?Y
Is the production of the material under QA/QC control?Y
Can the material be produced in a consistent manner (e.g. batch to batch consistency)??
Information availability- ExposureY/N
Have the physical/chemical properties and environmental fate of the substance been studied?Y
Is there potential for consumer exposure?Y
Is there anticipated to be environmental release?Y
Are there models available to predict environmental fate and exposure?N
Information availability- Hazard 
Has the standard suite* of toxicity test for industrial substances been conducted?Y
Were the tests conducted according to GLP and acceptable protocols (e.g. OECD, and/or OPPTS Harmonized Test Guidelines)?Y
Have bulk version(s) of the material been tested for, or have any known, toxicity?N
Has characterization of the material 'as dosed' been conducted?Y
Have different sizes/morphology of analogous materials been tested for toxicity?Y
Relevance to Canada/U.S. regulatory co-operation 
Has the material been notified under CEPA (1999)?Y
Has the material been notified under TSCA?Y
Have risk management measures been proposed by the Government of Canada?Y
Have risk management measures been proposed by the US EPA??
Is the material listed on the TSCA inventory?N
Is the material listed on the Canadian DSL?N
Will the notifier allow sharing of CBI across the respective organizations?Y
Total17

Yes = 1; No = 0
* standard suite of toxicity tests includes- Acute toxicity, irritation, sensitization, repeated dose toxicity, in-vitro gene mutation, in-vitro chromosomal aberration, and in-vivo genotoxicity

 

APPENDIX D- Peer Review Guidance Document

Checklist for Internal Peer Review of Nanomaterial Risk Assessment Reports

Peer Reviewer: _____________________________________________________________

Organization: _______________________________________________________________

Date: ___________________

Substance Identity Comments
Was the particle size/distribution data accurate (were the proper methods used)?

Yes

No

N/A

 
Is the name an accurate reflection of the material?

Yes

No

N/A

 
Are there any impurities?

Yes

No

N/A

 
Was the manufacturing technique of the material described?

Yes

No

N/A

 
Was the shape of the particle described?

Yes

No

N/A

 
Was the agglomeration/aggregation potential of the substance described?

Yes

No

N/A

 
Physical/Chemical Properties Comments
Was the solubility/dispersability of the material addressed?

Yes

No

N/A

 
Was the agglomeration/aggregation potential of the substance described?

Yes

No

N/A

 
Was zeta potential, surface charge or surface density measured?

Yes

No

N/A

 
Were changes in phys/chem parameters considered for the test media?

Yes

No

N/A

 
Were models or measured data used to predict any phys/chem parameter?

Yes

No

N/A

 
Lifecycle Comments
Were current and anticipated production/import quantities considered?

Yes

No

N/A

 
Were all steps in the lifecycle described from material manufacture to material disposal (‘cradle to grave’)?

Yes

No

N/A

 
Were current and potential uses considered?

Yes

No

N/A

 
Environmental Fate and Bioaccumulation Comments
Hydrolysis as a function of pH?

Yes

No

N/A

 
Ready/ultimate biodegradation?

Yes

No

N/A

 
Were persistence and bioaccumulation addressed?

Yes

No

N/A

 
Were all compartments addressed?

Yes

No

N/A

 
Was the stability in each compartment addressed?

Yes

No

N/A

 
Were ‘conservative’ assumption made in absence of compartment specific information?

Yes

No

N/A

 
Environmental Release and Exposure Comments
Was an exposure scenario used? What kind of scenario (provide comment)

Yes

No

N/A

 
Was STP removal considered? If so what percentage and on what basis (literature report etc.)

Yes

No

N/A

 
Was a PEC calculated? If so what assumptions were made (provide comment)

Yes

No

N/A

 
Direct human exposure Comments
Was information on end-use products available/described?

Yes

No

N/A

 

Will the product be used in consumer goods?

Was leaching from the consumer good considered?

Yes

No

N/A

 
Was the physical form of the material in the end-use product considered?

Yes

No

N/A

 
Was 100% bioavailability assumed?  If not, are data available that support an alternate bioavailability assumption?

Yes

No

N/A

 
Indirect Human Exposure Comments
Were releases from all sources identified in the lifecycle analysis addressed?

Yes

No

N/A

 
Were releases from the end-use product considered?

Yes

No

N/A

 
 

Yes

No

N/A

 
Environmental Hazard Assessment (Ecotoxicity) Comments
Were ecotoxicity tests provided (e.g OECD tests methods 211,212, 204, 202, and 201 following GLP guidelines)?

Yes

No

N/A

 
Were analogues identified, if so on what criteria?

Yes

No

N/A

 
Were the concentrations measured in each test? How were they monitored (e.g. UV-Vis)

Yes

No

N/A

 
Were impurities present? How were they measured?

Yes

No

N/A

 
If impurities were present was their effect addressed?

Yes

No

N/A

 
Was the substance or any impurities soluble?

Yes

No

N/A

 
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, surface area etc.)?

Yes

No

N/A

 
Was there sufficient information regarding the testing and methodology?

Yes

No

N/A

 
Were safety factors considered? If so which ones?

Yes

No

N/A

 
Was a PNEC calculated? What was the assessment factor used?

Yes

No

N/A

 
Was an endpoint reported for each test? If not was suitable justification provided?

Yes

No

N/A

 
Human Health Hazard Assessment (mammalian toxicity testing) GENERAL Comments
Acute oral toxicity
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
Acute dermal toxicity
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
Acute inhalation toxicity  
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
Skin irritation
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
Eye irritation
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
Skin Sensitization
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
 Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
Repeated dose toxicity
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
In-vitro genotoxicity (mutation)
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
In-vitro genotoxicity (chromosomal aberration)
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
In-vivo genotoxicity
Was the material characterized (e.g. purity, size, shape, manufacture technique, aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
Other
Was the material characterized (e.g. purity, size, shape, manufacture technique,    aggregation/agglomeration potential, etc…)?

Yes

No

N/A

 
Were the effects of the dosing method on the phys/chem properties of the material investigated?

Yes

No

N/A

 
Was there sufficient information in the summary regarding dose preparation, animals, methodology, etc…?

Yes

No

N/A

 
General
Was all available information considered?

Yes

No

N/A

 
Were analog substances considered? How appropriate were the analogs?

Yes

No

N/A

 
Was information on a bulk counterpart considered?

Yes

No

N/A

 
Were the effects of changing phys/chem parameters (e.g. size, shape, surface chemistry,           agglomeration/aggregation potential, etc…) discussed?

Yes

No

N/A

 
Was a key study identified?

Yes

No

N/A

 
Environmental Risk Assessment Comments
Was a PEC/PNEC ratio calculated?

Yes

No

N/A

 
Were all environmental concerns summarized?

Yes

No

N/A

 
 

Yes

No

N/A

 
Human Health Risk Assessment Comments

Was a quantitative risk assessment conducted?

If yes what safety factors were used?

Yes

No

N/A

 
Were potential uses addressed?

Yes

No

N/A

 
Does the toxicity data match the exposure data (e.g. oral exposure vs oral effect)?

Yes

No

N/A

 
Have all target populations been considered?

Yes

No

N/A

 
Were the uncertainties/gaps/ variability in the risk assessment addressed?

Yes

No

N/A

 

 

APPENDIX E- RCC Task Group Case Study

Availability of this document is being discussed with the sponsor as it contains proprietary information that will require sponsor’s consent for wider distribution.

[AVAILABLE UPON REQUEST]

 

APPENDIX F- Particle Screening Framework

[AVAILABLE UPON REQUEST]


APPENDIX G- List of Participants of TG3

Myriam HILL (Co-Chair)

Nanotechnology Section

New Substances Assessment and Control Bureau

Health Canada

Myriam.Hill@hc-sc.gc.ca

Todd STEDEFORD (Co-Chair)

Risk Assessment Division

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

Stedeford.Todd@epa.gov

Abdul AFGHAN

Nanotechnology Section

New Substances Assessment and Control Bureau

Health Canada

Abdul.Afghan@hc-sc.gc.ca

Jim ALWOOD

Chemical Control Division

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

Alwood.Jim@epamail.epa.gov

Fred ARNOLD

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

Arnold.Fred@epamail.epa.gov

Stéphane BERNATCHEZ

Nanotechnology Section

New Substances Assessment and Control Bureau

Health Canada

Stephane.Bernatchez@hc-sc.gc.ca

Lie CHEN

Nanotechnology Section

New Substances Assessment and Control Bureau

Health Canada

Lie.Chen@hc-sc.gc.ca

Richard FEHIR

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

Fehir.Richard@epamail.epa.gov

Cathy FEHRENBACHER

Exposure Assessment Branch

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

Fehrenbacher.Cathy@epamail.epa.gov

Tariq FRANCIS

Nanotechnology Section

Emerging Priorities Division

Environment Canada

Tariq.Francis@ec.gc.ca

Doug GREEN

New Substances Assessment and Control Bureau

Health Canada

Doug.Green@hc-sc.gc.ca

David LAI

Risk Assessment Division

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

Lai.David@epamail.epa.gov

Kristan MARKEY

Chemical Control Division

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

Markey.Kristan@epamail.epa.gov

Justin ROBERTS

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

Roberts.Justin@epamail.epa.gov


Phil SAYRE

Associate Director, Risk Assessment Division

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

Sayre.Phil@epamail.epa.gov

Yasir SULTAN

Nanotechnology Section

Emerging Priorities Division

Environment Canada

Yasir.Sultan@ec.gc.ca

Eva M. WONG

Exposure Assessment Branch

Office of Pollution Prevention and Toxics

US Environmental Protection Agency

Wong.Eva@epamail.epa.gov

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