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Notice of Intent to List Teriparatide

The California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) intends to list teriparatide as known to the state to cause cancer under the Safe Drinking Water and Toxic Enforcement Act of 19861. This action is being proposed under the “Formally Required to Be Labeled or Identified” listing mechanism2.

Chemical

CAS No.

Toxicological Endpoint

Reference

Teriparatide

52232-67-4

Cancer

FDA (2013)

Background on listing via the formally required to be labeled or identified mechanism: A chemical must be listed under Proposition 653 and its implementing regulations (Section 259024) when a state or federal agency has formally required it to be labeled or identified as causing cancer or reproductive toxicity.

OEHHA is the lead agency for Proposition 65 implementation, and evaluates whether listing under Proposition 65 is required pursuant to the definitions set out in Section 25902. 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
  • “As 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’s determination: Teriparatide has been identified and labeled to communicate a risk of cancer (FDA, 2013) in accordance with formal requirements by the US Food and Drug Administration (FDA). The FDA-approved label indicates that teriparatide therapy in patients with osteoporosis increases the risk of developing osteosarcoma (a malignant bone tumor). The label also references FORTEO®, which is a trade name of teriparatide.
Language from the FDA-approved product label which meets the requirements of Section 25902 is quoted below:

Teriparatide [rDNA origin]

Cancer Endpoint
FDA-approved label Reference ID 3366073 (FDA, 2013)

Under BOXED WARNING: “WARNING: POTENTIAL RISK OF OSTEOSARCOMA. In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. The effect was observed at systemic exposures to teriparatide ranging from 3 to 60 times the exposure in humans given a 20-mcg dose. Because of the uncertain relevance of the rat osteosarcoma finding to humans, prescribe FORTEO ® only for patients for whom the potential benefits are considered to outweigh the potential risk. FORTEO should not be prescribed for patients who are at increased baseline risk for osteosarcoma (including those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, or prior external beam or implant radiation therapy involving the skeleton) [see Warnings and Precautions (5.1), Adverse Reactions (6.2), and Nonclinical Toxicology (13.1)].”

Under WARNINGS AND PRECAUTIONS:
“5.1 Osteosarcoma. In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration [see Boxed Warning and Nonclinical Toxicology (13.1)]. FORTEO should not be prescribed for patients at increased baseline risk of osteosarcoma.
These include:

  • Paget’s disease of bone. Unexplained elevations of alkaline phosphatase may indicate Paget’s disease of bone.
  • Pediatric and young adult patients with open epiphyses.
  • Prior external beam or implant radiation therapy involving the skeleton.”

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 this is a ministerial listing, comments should be limited to whether FDA requires that teriparatide be labeled to communicate a risk of cancer or tumors. 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, July 20, 2015. 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 “teriparatide” in the subject line. Comments submitted in paper form may be mailed, faxed, or delivered in person to the address below.

Mailing Address: Esther Barajas-Ochoa
Office of Environmental Health Hazard Assessment
P.O. Box 4010, MS-12B
Sacramento, California 95812-4010
Fax: (916) 323-2265
Street Address: 1001 I Street
Sacramento, California 95814

Comments received during the public comment period will be posted on the OEHHA web site after the close of the comment period.

If you have any questions, please contact Esther Barajas-Ochoa at Esther.barajas-ochoa@oehha.ca.gov or (916) 445-6900.

Footnotes and References

References

Food and Drug Administration (FDA, 2013). FDA approved drug label, Reference ID 3366073, approved 8-30-2013. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021318s036lbl.pdf

 

1 Commonly 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.

2 See Health and Safety Code section 25249.8(b) and Title 27, Cal. Code of Regs., section 25902.

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

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