Notice of Intent to Change the Basis for Listing as Known to the State of California to Cause Cancer: Actinomycin D

The California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) intends to change the basis for the listing of actinomycin D as known to the state to cause cancer under the Safe Drinking Water and Toxic Enforcement Act of 1986¹. Actinomycin D was originally added to the Proposition 65 list as causing cancer on October 1, 1989 via the Labor Code mechanism². OEHHA intends to change the basis to the “formally required to be labeled or identified” listing mechanism³. OEHHA intends to take this action pursuant to a recent decision by the Third District Court of Appeal in the Styrene Information and Research Council v. The Office of Environmental Health Hazard Assessment case⁴.  (See also OEHHA’s Notice to Interested Parties Regarding Certain IARC 2B Chemicals).  

Background on listing via the formally required to be labeled or identified mechanism:  A chemical must be listed under the Proposition 65⁵ and its implementing regulations (Section 25902⁶) when a state or federal agency has formally required it to be labeled or identified as causing cancer or reproductive toxicity. 

According to Section 25902(b):

• “‘[F]ormally required’ means that a mandatory instruction, order, condition, or similar command, has been issued in accordance with established policies and procedures of an agency of the state or federal government to a person or legal entity outside of the agency.  The action of such agency may be directed at one or more persons or legal entities and may include formal requirements of general application;”
• “‘[L]abeled’ means that a warning message about the carcinogenicity or reproductive toxicity of a chemical is printed, stamped, written, or in any other manner placed upon the container in which the chemical is present or its outer or inner packaging including any material inserted with, attached to, or otherwise accompanying such a chemical;”
• “‘[I]dentified’ means that a required message about the carcinogenicity or reproductive toxicity of the chemical is to be disclosed in any manner to a person or legal entity other than the person or legal entity who is required to make such disclosure”; and
• “[A]s causing cancer” means:  “For chemicals that cause cancer, the required label or identification uses any words or phrases intended to communicate a risk of cancer or tumors.”

OEHHA is the lead agency for Proposition 65 implementation.  After a state or federal agency has required that a chemical be labeled or identified as causing cancer or reproductive toxicity, OEHHA evaluates whether listing under Proposition 65 is required pursuant to the definitions set out in Section 25902.

OEHHA’s determination:  Actinomycin D has been identified or labeled to communicate a risk of cancer in accordance with formal requirements by the U.S. Food and Drug Administration (FDA). 

Language from the FDA-approved product label which meets the requirements of Section 25902 is quoted below:

Actinomycin D
Cancer Endpoint (Under boxed WARNING and WARNINGS)
Under boxed WARNING:  “Due to the toxic properties of dactinomycin [actinomycin D] (e.g., corrosivity, carcinogenicity, mutagenicity, teratogenicity), special handling procedures should be reviewed prior to handling and followed diligently.”
Under WARNINGS:  “Reports indicate an increased incidence of second primary tumors (including leukemia) following treatment with radiation and anti-neoplastic agents, such as COSMEGEN [actinomycin D].  Multi-modal therapy creates the need for careful, long-term observation of cancer survivors.”

Request for comments: OEHHA is requesting comments as to whether this chemical meets the criteria set forth in the Proposition 65 regulations for listings via the formally required to be labeled or identified mechanism (Section 25902). Because these are ministerial listings, comments should be limited to whether FDA requires that Actinomycin D be labeled to communicate a risk of cancer or reproductive harm. OEHHA cannot consider scientific arguments concerning the weight or quality of the evidence considered by FDA when it established the labeling requirement and will not respond to such comments if they are submitted.

In order to be considered, OEHHA must receive comments by 5:00 p.m. on MONDAY, FEBRUARY 4, 2013.  We encourage you to submit comments in electronic form, rather than in paper form.  Comments transmitted by e-mail should be addressed to P65Public.comments@oehha.ca.gov. Please include “actinomycin D” in the subject line. Comments submitted in paper form may be mailed, faxed, or delivered in person to the address below.

Mailing Address:   
Office of Environmental Health Hazard Assessment
P.O. Box 4010, MS-19B
Sacramento, California 95812-4010
Fax: (916)323-8803
Street Address:1001 I Street
Sacramento, California 95814

Any public comments received will be posted after the close of the comment period.  If you have any questions, please contact Sam Delson at sam.delson@oehha.ca.gov or at (916) 445-6900.

Comment Period

• Comment Period - Notice of Intent to Change the Basis for Listing as Known to the State of California to Cause Cancer: Actinomycin D

Link to Public Comments

Chemical Reference

• Actinomycin D

Related Notices

• Regarding Certain IARC (International Agency For Research On Cancer) 2B Chemicals

  Jan 4, 2013

Footnotes and References

Food and Drug Administration (FDA, 2012).  FDA approved labeling for the drug Actinomycin D.  Approved by FDA in February 2012 and available at URL: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050682s029s030lbl.pdf.

¹Commonly known as Proposition 65, the Safe Drinking Water and Toxic Enforcement Act of 1986 is codified in Health and Safety Code section 25249.5 et seq.

²Actinomycin D was listed as causing cancer on October 1, 1989 pursuant to Labor Code Section 6382(d) which is incorporated by reference as a Proposition 65 listing mechanism by Health and Safety Code Section 25249.8(a), based on its identification by the International Agency for Research on Cancer (IARC) as a “Group 2B” carcinogen with less than sufficient animal and human evidence at the time of listing. 

³See Health and Safety Code section 25249.8(b) and Title 27, Cal. Code of Regs., section 25902.  All further references are to sections of Title 27, unless indicated otherwise.

⁴SIRC v OEHHA (Nov. 15, 2012) Westlaw No. 5834844 

⁵See Health and Safety Code section 25249.8(b).

⁶All referenced sections are from Title 27 of the Cal. Code of Regulations.