Canada Gazette, Part I, Volume 155, Number 10: Order Adding a Toxic Substance to Schedule 1 to the Canadian Environmental Protection Act, 1999
March 6, 2021
Canadian Environmental Protection Act, 1999
Department of the Environment
Department of Health
REGULATORY IMPACT ANALYSIS STATEMENT
(This statement is not part of the Order.)
Chlorhexidine and its salts meet the ecological criterion for a toxic substance, as set out in paragraph 64(a) of the Canadian Environmental Protection Act, 1999 (CEPA or "the Act"). Therefore, in accordance with subsection 90(1) of CEPA, the Minister of the Environment and the Minister of Health (the ministers) are recommending to the Administrator in Council to make an order adding chlorhexidine and its salts to Schedule 1 (i.e. List of Toxic Substances) of the Act. The conclusions for this assessment are considered to cover chlorhexidine and its salts, which include, but are not limited to, the four substances in the Table 1 below.
|CAS RN table a1 note a
|DSL table a1 note b name or chemical name
|2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-, diacetate
|2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-, dihydrochloride
|D-Gluconic acid, compound with N,N''-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide
Table a1 note(s)
The Chemicals Management Plan (CMP) is a federal program that assesses and manages chemical substances and microorganisms that may be harmful to the environment or human health in Canada. The ministers assessed chlorhexidine and its salts in accordance with sections 68 and 74 of CEPA as part of the CMP. The substances listed in Table 1 were identified as priorities for assessment, and the information obtained on these substances was used to assess the risk from all chlorhexidine salts.
Description, uses and sources of release
Chlorhexidine and its salts do not occur naturally in the environment. Mandatory surveys issued under section 71 of CEPA for chlorhexidine (reporting year 2011), chlorhexidine diacetate (reporting years 2005, 2006, and 2011), chlorhexidine digluconate (reporting year 2011), and chlorhexidine dihydrochloride (reporting year 2015), along with voluntary information submitted for chlorhexidine dihydrochloride in 2013, indicate that these substances were not reported to be manufactured in Canada above the 100 kilograms (kg) reporting threshold, though they were reported to be imported in the following quantities per year:
- chlorhexidine: no imports reported above reporting threshold of 100 kg (2011);
- chlorhexidine diacetate: 100 kg to 1 000 kg (2005, 2006, and 2011);
- chlorhexidine digluconate: 10 000 kg to 100 000 kg (2011); and
- chlorhexidine dihydrochloride: 100 kg to 1 000 kg (2013); 1 000 kg to 10 000 kg (2015).
In Canada, chlorhexidine and its salts are used as broad-spectrum antiseptics and antimicrobial preservatives in products, such as cosmetics, natural health products, prescription and non-prescription drugs for human and veterinary uses, and hard-surface disinfectants.
The quantity of chlorhexidine and its salts imported into Canada, along with information on their uses, indicate potential for both periodic and continual releases into the Canadian environment. Releases of these substances come from consumer use and the formulation of chlorhexidine-based products, mainly through the municipal and industrial wastewater, as treatment technologies may only partially remove chlorhexidine. Chlorhexidine salts dissociate in water releasing chlorhexidine, the moiety of toxicological concern. In the aquatic environment, chlorhexidine will have an affinity for dissolved and suspended solids, and bed sediment. Chlorhexidine may also be released to soil through the application of biosolids from wastewater treatment systemsfootnote 1 (WWTSs) to agricultural and pasture lands.
Canadian risk management activities
The transportation of chlorhexidine substances is subject to the Transportation of Dangerous Goods Act, 1992 and the Transportation of Dangerous Goods Regulations as well as to the Export and Import of Hazardous Waste and Hazardous Recyclable Material Regulations and the Interprovincial Movement of Hazardous Waste Regulations. A number of regulatory and non-regulatory instruments also exist under the Food and Drugs Act, administered by the Department of Health, to limit the presence of chlorhexidine and its salts found in prescription and non-prescription drugs, natural health products and cosmetics.
Summary of the screening assessment
In June 2019, the ministers published a screening assessment on chlorhexidine and its salts on the Canada.ca (Chemical Substances) website. The screening assessment was conducted to determine whether chlorhexidine and its salts meet one or more of the criteria for a toxic substance as set out in section 64 of CEPA (i.e. to determine if the substances may be harmful to the environment or human health in Canada).
Under section 64 of CEPA, a substance is considered toxic if it is entering or may enter the environment in a quantity or concentration or under conditions that
- (a) have or may have an immediate or long-term harmful effect on the environment or its biological diversity;
- (b) constitute or may constitute a danger to the environment on which life depends; or
- (c) constitute or may constitute a danger in Canada to human life or health.
The Department of the Environment and the Department of Health (the Departments) generated and collected information from modelling, monitoring and surveillance, literature reviews, database searches, and mandatory surveys issued under section 71 of CEPA to inform the screening assessment conclusion. The ecological and human health portions of this assessment have undergone external written peer review and consultation with academics and other relevant stakeholders.
The screening assessment concluded that chlorhexidine and its salts meet the ecological criterion for a toxic substance as set out in paragraph 64(a) of CEPA, and thus, constitute a risk to the environment in Canada.
Ecological assessment summary
The ecological assessment found that chlorhexidine and its salts, at low concentrations, have the potential to cause adverse effects, such as reduced growth and increased mortality in aquatic and benthic organisms, with algae being particularly sensitive to the effects of chlorhexidine. Available studies on biodegradation of chlorhexidine indicate that chlorhexidine has a low potential to bioaccumulate in aquatic organisms, but that it tends to persist in water, sediment, and soil, resulting in a potential prolonged exposure to chlorhexidine both near and far from points of discharge to the environment.
As this assessment identified no data on measured chlorhexidine concentrations in environmental media in Canada, environmental concentrations were estimated from limited data collected through monitoring and surveillance of specific WWTSs and available information on quantities of chlorhexidine and its salts imported and consumed in Canada. The exposure assessment focused on the releases of chlorhexidine and its salts from the industrial formulation of chlorhexidine-based products and the down-the-drain releases resulting from the consumer use of such products. To determine if these scenarios may pose an ecological risk, a risk quotient was calculated as the ratio between predicted environmental concentrations (PECs) for these substances and predicted no-effect concentrations (PNEC). When PEC values are greater than PNEC values, there is a potential for ecological harm. The results of this analysis indicate that at current levels of use, chlorhexidine and its salts pose a risk to aquatic and benthic organisms when released from industrial use, but not from the use of products containing these substances (down-the-drain releases).
The screening assessment concluded that chlorhexidine and its salts meet the ecological criterion for a toxic substance set out in paragraph 64(a) of CEPA, but does not meet the criterion set out in paragraph 64(b). The assessment also determined that the chlorhexidine moiety meets the persistence criteria, but not the bioaccumulation criteria as set out in the Persistence and Bioaccumulation Regulations of CEPA.
Human health assessment summary
No evidence for carcinogenicityfootnote 2 or genotoxicityfootnote 3 was observed in the available empirical data for chlorhexidine and its salts. Therefore, characterization of risk in the screening assessment was based on non-cancer effects.
Dietary exposure resulting from the use of chlorhexidine digluconate and chlorhexidine diacetate as components in incidental additives (e.g. cleaning products) used in food processing establishments is not expected. Exposure to chlorhexidine through consumption of potentially contaminated drinking water is estimated to be negligible. Therefore, the risk to human health from drinking water is considered to be low at current levels of exposure.
Exposure of the general population to chlorhexidine and its salts occurs predominantly through the use of cosmetics and natural health products that are applied to the skin. For cosmetics and natural health products that are used either daily or on an infrequent basis, comparisons of dermal exposure estimates with the critical effect levelfootnote 4 showed that the risk to human health from the use of these products is considered to be low. Although concurrent or consecutive use of products containing chlorhexidine and its salts may occur, simultaneous exposures from a number of products containing these substances would not be of concern based on the conservative nature of this exposure scenario and the very low dermal absorption of chlorhexidine that has been observed experimentally.
Exposure to chlorhexidine and its salts can also occur orally from the use of a limited number of cosmetics such as lipsticks and lip balms, as well as natural health products such as mouthwashes. Given the limited number of products available and the small market share of these products, exposure of the general population by mouth to these substances is limited. The assessment concluded that the risk to human health from oral exposures to lipsticks, lip balms and mouthwashes is expected to be low at current levels of exposure.
As the risk to human health from chlorhexidine and its salts is considered to be low at current levels of exposure, the screening assessment concluded that these substances do not meet the human health criterion for a toxic substance as set out under paragraph 64(c) of CEPA.
The objective of the proposed Order Adding a Toxic Substance to Schedule 1 to the Canadian Environmental Protection Act, 1999 (the proposed Order) is to add chlorhexidine and its salts to Schedule 1 (List of Toxic Substances) of CEPA, which would enable the ministers to propose risk management measures for chlorhexidine and its salts, under section 91 of CEPA to manage potential environmental risks associated with these substances.
The proposed Order would add chlorhexidine and its salts to Schedule 1 (List of Toxic Substances) to CEPA.
On August 19, 2017, the ministers published a summary of the draft screening assessment of chlorhexidine and its salts (which included a link to the complete draft assessment) in the Canada Gazette, Part I, for a 60-day public comment period. Comments were received from four industry stakeholders. These comments were considered in the development of the final screening assessment report, but did not change the conclusion that chlorhexidine and its salts meet the criterion for a toxic substance set out under paragraph 64(a) of CEPA. A table summarizing the complete set of comments received and the response to these comments is available on the Canada.ca (Chemical Substances) website.
Industry stakeholders provided information on the usage and the sources of releases of these substances. Industry stakeholders also provided comments regarding current risk management practices for chlorhexidine within their respective business activities. Officials acknowledged the information provided by all of the stakeholders. Those comments were generally in line with the information already considered in the screening assessment. Stakeholders also pointed out that certain aspects of the risk characterization could be revised to minimize uncertainty or results bias in the screening assessment. Officials responded by providing justifications for the methodological choices or the information presented in the screening assessment.
On June 29, 2019, the ministers also published a risk management approach document on the Canada.ca (Chemical Substances) website to continue discussions with stakeholders on the proposed risk management options for these substances. In particular, the Government of Canada is considering implementing a code of practice and an environmental performance agreement (EPA) to reduce the release of chlorhexidine and its salts to the environment from the industrial use of these substances. The comments related to the proposed risk management options under consideration outlined in the risk management approach for chlorhexidine and its salts will be considered during the development of any risk management instruments. The development of any such measures would also be subject to its own consultation process.
Modern treaty obligations and Indigenous engagement and consultation
An assessment of modern treaty implications must be made in accordance with the Cabinet Directive on the Federal Approach to Modern Treaty Implementation. It is concluded that orders adding substances to Schedule 1 (List of Toxic Substances) to CEPA do not impose any regulatory or administrative burdens and therefore do not result in any impact on modern treaty rights or obligations. It is also concluded that the making of an order under section 90 of the Act does not require specific engagement and consultation with Indigenous peoples.
When a substance meets one or more of the criteria for a toxic substance as set out in section 64 of CEPA, the ministers shall propose one of the following measures under subsection 77(2) of the Act:
- (a) taking no further action in respect to the substance;
- (b) adding the substance to the Priority Substances List (unless the substance is already on the Priority Substances List); or
- (c) recommending that the substance be added to Schedule 1 to CEPA (List of Toxic Substances), and, where applicable, recommending the implementation of virtual eliminationfootnote 5 under subsection 65(3) of CEPA.
The implementation of virtual elimination is applicable if
- the substance met one of the criteria for a toxic substance in section 64 of CEPA;
- the substance was found to be persistent and bioaccumulative in accordance with the Persistence and Bioaccumulation Regulations;
- the presence of the substance in the environment resulted primarily from human activity; and
- the substance was not a naturally occurring inorganic substance.
The implementation of virtual elimination does not apply to chlorhexidine and its salts, as these substances were found to be persistent but not bioaccumulative in accordance with the Persistence and Bioaccumulation Regulations. Based on the available evidence, which includes data received from industry and the conclusions of the screening assessment, the ministers determined that choosing paragraph 77(2)(a) or (b) of the Act is not appropriate to manage the potential environmental risks associated with chlorhexidine and its salts in Canada. Therefore, the ministers are choosing the option under paragraph 77(2)(c) of CEPA and thus are recommending to the Administrator in Council to add chlorhexidine and its salts to Schedule 1 to CEPA (List of Toxic Substances). An order is the only available instrument to implement this recommendation.
Benefits and costs
The addition of chlorhexidine and its salts to Schedule 1 (List of Toxic substances) to CEPA would have no impacts (benefits or costs). The proposed Order would address the screening assessment conclusion for chlorhexidine and its salts, which determined that these substances meet the ecological criterion for a toxic substance as set out in paragraph 64(a) of CEPA. The proposed Order would enable the ministers to propose risk management measures for a toxic substance under section 91 of CEPA to manage potential ecological risks associated with chlorhexidine and its salts. During the development of risk management measures, the ministers would assess potential benefits and costs and consult with the public and other interested parties.
Small business lens
The assessment of the small business lens concluded that the proposed Order would not have an impact on small businesses, as it would not impose any new administrative or compliance costs on small businesses.
The assessment of the one-for-one rule concluded that the rule would not apply to the proposed Order, as it would not impose any new administrative or compliance costs on industry.
Regulatory cooperation and alignment
Canada is engaged in several international bilateral and multilateral agreements related to chemicals and chemicals management. The CMP is administered in cooperation and alignment with these agreements.footnote 6
There are no known existing international risk management measures for controlling the releases of chlorhexidine and its salts to the environment. However, the United States Environmental Protection Agency completed a Reregistration Eligibility Decision for chlorhexidine diacetate as a pesticide active ingredient in 1996, and the substance, along with chlorhexidine digluconate, has been under a reregistration review since 2011. Chlorhexidine digluconate has also been registered as part of the Registration, Evaluation, Authorisation and Restriction of Chemicals Regulation in the European Union.
Canadian health legislation generally aligns with the European Union and the United States in terms of restrictions in place for cosmetics and drug products. For example, the maximum concentrations of chlorhexidine and its salts in cosmetics are similar between Canada, the European Union and the United States. However, a recent ruling by the U.S. Food and Drug Administration (FDA) on over-the-counter health care antiseptics resulted in a misalignment with the Canadian health legislation. Based on the lack of data to support human health safety and efficacy, companies can no longer market health care antiseptics containing chlorhexidine digluconate in the United States. Since December 2018, any such products are considered as new drugs requiring the U.S. FDA approval.
Strategic environmental assessment
In accordance with the Cabinet Directive on the Environmental Assessment of Policy, Plan and Program Proposals, a strategic environmental assessment was completed for the CMP, which encompasses orders adding substances to Schedule 1 (List of Toxic Substances) to CEPA. The assessment concluded that the CMP is expected to have a positive effect on the environment and human health.
Gender-based analysis plus
The gender-based analysis plus (GBA+) assessment concluded that the proposed Order would not affect socio-demographic groups based on factors such as gender, sex, age, language, education, geography, culture, ethnicity, income, ability, sexual orientation, or gender identity.
Implementation, compliance and enforcement, and service standards
As no specific risk management instruments are recommended as part of the proposed Order, developing an implementation plan and a compliance and enforcement strategy, as well as establishing service standards, are not necessary.
A complete assessment of these elements would be undertaken during the development of any risk management instruments for chlorhexidine and its salts.
Acting Executive Director
Program Development and Engagement Division
Department of the Environment
Substances Management Information Line:
1‑800‑567‑1999 (toll-free in Canada)
819‑938‑3232 (outside of Canada)
Risk Management Bureau
Department of Health
PROPOSED REGULATORY TEXT
Notice is given, pursuant to subsection 332(1)footnote a of the Canadian Environmental Protection Act, 1999footnote b, that the Administrator in Council, on the recommendation of the Minister of the Environment and the Minister of Health, pursuant to subsection 90(1) of that Act, proposes to make the annexed Order Adding a Toxic Substance to Schedule 1 to the Canadian Environmental Protection Act, 1999.
Any person may, within 60 days after the date of publication of this notice, file with the Minister of the Environment comments with respect to the proposed Order or a notice of objection requesting that a board of review be established under section 333 of that Act and stating the reasons for the objection. All comments and notices must cite the Canada Gazette, Part I, and the date of publication of this notice, and be sent to the Executive Director, Program Development and Engagement Division, Department of the Environment, Gatineau, Quebec K1A 0H3 (email: email@example.com).
A person who provides information to the Minister of the Environment may submit with the information a request for confidentiality under section 313 of that Act.
Ottawa, February 25, 2021
Assistant Clerk of the Privy Council
Order Adding a Toxic Substance to Schedule 1 to the Canadian Environmental Protection Act, 1999
1 Schedule 1 to the Canadian Environmental Protection Act, 1999footnote b is amended by adding the following in numerical order:
- 156 Chlorhexidine, which has the molecular formula C22H30Cl2N10, and its salts
Coming into Force
2 This Order comes into force on the day on which it is registered.