Request for Comments on Proposed Listing of “Estrogens, Steroidal” as Known to Cause Cancer

Jun 24, 2005

The California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) is the lead agency for the implementation of the Safe Drinking Water and Toxic Enforcement Act of 1986 (Health and Safety Code section 25249.5 et seq., Proposition 65). OEHHA is proposing to include “estrogens, steroidal” on the list of chemicals known to the state to cause cancer, for the purposes of Proposition 65.

Health and Safety Code section 25249.8(a) requires that certain substances identified by the International Agency for Research on Cancer (IARC) or the National Toxicology Program (NTP), as described in Labor Code section 6382(b)(1) and (d), be included on the Proposition 65 list. Labor Code section 6382(b)(1) references substances identified as human or animal carcinogens by IARC, and Labor Code section 6382(d) references substances identified as carcinogens or potential carcinogens by IARC or NTP. Steroidal estrogens were identified by the NTP as known to be human carcinogens.

In 2002, the NTP published the Tenth Report on Carcinogens. In this report, the NTP concluded “Steroidal estrogens are known to be human carcinogens based on sufficient evidence of carcinogenicity in humans, which indicates a causal relationship between exposure to steroidal estrogens and human cancer.” The NTP had previously listed conjugated estrogens as known to be human carcinogens and some individual non-conjugated steroidal estrogens (i.e., estradiol-17b, estrone, ethinylestradiol and mestranol) as reasonably anticipated to be human carcinogens, beginning in the Fourth Annual Report on Carcinogens (1985). In the Tenth Report on Carcinogens, NTP states, “This listing of steroidal estrogens supersedes the previous listing of specific estrogens in the Report on Carcinogens and applies to all chemicals of this steroid class.”

Some steroidal estrogens are already listed under Proposition 65. “Conjugated estrogens” were added to the Proposition 65 list on February 27, 1987, through Labor Code sections 6382(b)(1) and (d), based on designations by NTP and the International Agency for Research on Cancer (IARC) that conjugated estrogens are causally related to human cancer. On January 1, 1988, based on findings of the state’s qualified experts (at that time, the “Scientific Advisory Panel”), 17b-estradiol, estrone, and ethinylestradiol were added to the Proposition 65 list. On April 1, 1988, mestranol was added to the Proposition 65 list based on findings of the state’s qualified experts. Although this notice of June 24, 2005 proposes the listing of steroidal estrogens as a class, the effective listing dates for the specific steroidal estrogens already listed as causing cancer under Proposition 65 remain unchanged. For clarity, these compounds are listed in the table below.

Chemical	CAS No.	Effective Proposition 65 Listing Date
Conjugated estrogens	-------	February 27, 1987
Estradiol 17 b -	50282	January 1, 1988
Estrone	53167	January 1, 1988
Ethinylestradiol	57636	January 1, 1988
Mestranol	72333	April 1, 1988

Pursuant to state law, NTP’s designation of steroidal estrogens as known to be human carcinogens means that “estrogens, steroidal” must be included on the Proposition 65 list (Labor Code section 6382(d)). Therefore, OEHHA proposes to add “estrogens, steroidal” to the Proposition 65 list of chemicals known to cause cancer. Anyone wishing to provide comments as to whether these chemicals meet the requirements for listing as causing cancer specified in Health and Safety Code section 25249.8(a), by reference to Labor Code section 6382(d), should send written comments in triplicate, along with any supporting documentations, by mail or by fax to:

Ms. Cynthia Oshita
Office of Environmental Health Hazard Assessment
Street Address: 1001 I Street
Sacramento, California 95814

Mailing Address: P.O. Box 4010
Sacramento, California 95812-4010

Fax No.: (916) 323-8803
Telephone: (916) 445-6900

Comments may also be delivered in person or by courier to the above address. It is requested, but not required, that written comments and supporting documentation by transmitted via email addressed to: coshita@oehha.ca.gov. In order to be considered, comments must be postmarked (if sent by mail) or received at OEHHA (if hand-delivered, sent by FAX, or transmitted electronically) by 5:00 p.m. on July 25, 2005.