Mitotane – information sheet

Benzene, 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]-
CAS Registry Number 53-19-0

Publications summarized:

Final Screening Assessment for Mitotane (published on October 28, 2017). Public comments received on the draft screening assessment were considered and a summary was published.
Risk management actions were taken.
Associated notice: Canada Gazette, Part I: Vol. 151, No. 43 - October 28, 2017

The Government of Canada conducts risk assessments of substances under the Canadian Environmental Protection Act, 1999 (CEPA 1999) to determine whether they present or may present a risk to human health or to the environment.
- The risks posed by a substance are determined both by its hazardous properties (potential to cause adverse human health or ecological effects) and the amount or extent of exposure to people and the environment.
- When needed, the Government implements risk management measures under CEPA 1999 and other federal acts to help prevent or reduce potential harm.
The Government concluded that mitotane is harmful to the environment, but not to human health, at levels of exposure considered in the assessment. The preventative actions and risk reduction section below provides links on where to find updates on risk management activities.

The screening assessment focused on the substance benzene, 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]-, also referred to as mitotane. This substance was assessed as part of Batch 12 of the Challenge initiative of the Chemicals Management Plan (CMP).
Mitotane may be formed upon the degradation of dichlorodiphenyltrichloroethane (DDT), including the degradation of DDT present as an impurity in the pesticide dicofol. Although these pesticides are no longer used in Canada, mitotane may be found in the environment from historical pesticide uses.
According to information gathered by the Government, at the time of the assessment, mitotane was used in Canada as an active ingredient in prescription medication as a therapeutic cancer drug for the treatment of adrenal cancer.
The use of mitotane as a drug is regulated under the Food and Drugs Act and is registered in Health Canada's Drug Product Database.

The screening assessment indicated that Canadians may be exposed to mitotane through its use as a therapeutic cancer drug; this type of exposure is addressed under the Food and Drugs Act.
At the time of the assessment, the potential source of exposure for Canadians from non-drug use of mitotane was through the environment as a result of historical pesticide use; however, this exposure was expected to be low.
Mitotane was found to have the potential to be released in small quantities to the aquatic environment through wastewater treatment system effluent following its use as a therapeutic cancer drug.
It is also released to the environment from degradation of DDT, as a result of its historical use.
Mitotane has the potential to remain in the environment for a long time.

The critical effects identified for characterizing the risk to human health from mitotane were effects on the endocrine system.
Mitotane is hazardous to aquatic organisms at low concentrations and has the potential to accumulate in aquatic organisms.

Based upon a comparison of levels to which Canadians may be exposed to mitotane and levels associated with critical health effects, it was determined that the risk to human health from this substance is low.
Based upon a comparison of estimated levels of mitotane released to the aquatic environment from its use as a therapeutic cancer drug and concentrations that may be harmful to the environment, it was determined that the quantity of mitotane that may be released to the environment has the potential to harm aquatic organisms.
Considering all information presented, it was determined that there is risk of harm to the environment from mitotane.

The Government concluded that mitotane is not harmful to human health at levels of exposure considered in the assessment.
The Government concluded that mitotane is entering the environment at levels that are harmful.
Mitotane has been determined to meet both the persistence and bioaccumulation criteria as set out in the Persistence and Bioaccumulation Regulations of CEPA 1999.

The Government published a Risk Management Approach for Mitotane on October 28, 2017 for a 60 day public comment period.
On October 28, 2020, mitotane was added to Schedule 1 of CEPA 1999, also called the List of Toxic Substances. Adding a substance to the list does not restrict its use, manufacture or import. Rather, it enables the Government to take risk management actions under CEPA 1999.
Mitotane is subject to Significant New Activity (SNAc) provisions of CEPA 1999. This requires that the Government be notified of certain proposed new activities related to mitotane, and that the new activity be assessed for potential risks to human health and the environment before being undertaken.
The order for the SNAc provisions outlines the definition of a significant new activity in relation to mitotane, as well as the information that needs to be provided to the Government for assessment before the new activity is undertaken.
No risk management actions are being proposed to limit the use of mitotane as a therapeutic product in Canada.

Updates on risk management actions for mitotane can be found on the timeline for Batch 12 substances. Information on SNAc provisions applied to substances, where applicable, is found in the SNAc publications dataset.
Additional information on the risk management of substances addressed under the CMP is available.
Use the Substances Search tool to find substances that are referenced in certain legislative or regulatory instruments or on Government of Canada websites.

Mitotane may be found in certain prescription medication to treat cancer. Canadians are encouraged to dispose of unused and expired medication in an environmentally safe manner. Pharmaceutical take-back programs exist in many provinces and territories. For more information about pharmaceutical take-back programs, please speak with your local pharmacy.
The screening assessment focused on potential risks from exposure of the general population of Canada, rather than occupational exposure. Hazards related to chemicals used in the workplace are defined within the Workplace Hazardous Materials Information System (WHMIS). For information concerning workplace health and safety and what steps to take in the workplace, Canadians should consult their employer and/or the Occupational Health and Safety Regulator in their jurisdiction.