Daily Rules, Proposed Rules, and Notices of the Federal Government
In a Notice of Proposed Rulemaking (NPRM) (73 FR 22294) published April 25, 2008, the DEA proposed the classification of three steroids as schedule III anabolic steroids under the CSA. These three steroids included boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione. With the publication of this Final Rule, DEA classifies these three steroids as schedule III anabolic steroids. Background information in support of this Final Rule is provided below.
On November 29, 1990, the President signed into law the Anabolic Steroids Control Act of 1990 (Title XIX of Pub. L. 101-647), which became effective February 27, 1991. This law established and regulated anabolic steroids as a class of drugs under schedule III of the CSA. As a result, a new anabolic steroid is not scheduled according to the procedures set out in 21 U.S.C. 811, but can be administratively classified as an anabolic steroid through the rulemaking process by adding the steroid to the regulatory definition of an anabolic steroid in 21 CFR 1300.01(b)(4).
On October 22, 2004, the President signed into law the Anabolic Steroid Control Act of 2004 (Pub. L. 108-358), which became effective on January 20, 2005. Section 2(a) of the Anabolic Steroid Control Act of 2004 amended 21 U.S.C. 802(41)(A) by replacing the existing definition of “anabolic steroid.” The Anabolic Steroid Control Act of 2004 classifies a drug or hormonal substance as an anabolic steroid if the following four criteria are met: (A) The substance is chemically related to testosterone; (B) the substance is pharmacologically related to testosterone; (C) the substance is not an estrogen, progestin, or a corticosteroid; and (D) the substance is not dehydroepiandrosterone (DHEA). Any substance that meets the criteria is considered an anabolic steroid and must be listed as a schedule III controlled substance. DEA finds that boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione meet this definition of anabolic steroid and is adding them to the list of anabolic steroids in 21 CFR 1300.01(b)(4).
Anabolic steroids are a class of drugs with a basic steroid ring structure that produces anabolic and androgenic effects. The prototypical anabolic steroid is testosterone. Anabolic effects include promoting the growth of muscle. The androgenic effects consist of promoting the development of male secondary sexual characteristics such as facial hair, deepening of the voice, and thickening of the skin.
In the United States, only a small number of anabolic steroids are approved for either human or veterinary use. Approved medical uses for anabolic steroids include treatment of androgen deficiency in hypogonadal males, adjunctive therapy to offset protein catabolism associated with prolonged administration of corticosteroids, treatment of delayed puberty in boys, treatment of metastatic breast cancer in women, and treatment of anemia associated with specific diseases (
Adverse effects are associated with the use or abuse of anabolic steroids. These effects depend on several factors (
With the issuance of this Final Rule, DEA is classifying boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione as anabolic steroids under the definition set forth under 21 U.S.C. 802(41)(A). As noted previously, a drug or hormonal substance is classified as an anabolic steroid by meeting the following four definitional requirements: (A) The substance is chemically related to testosterone; (B) the substance is pharmacologically related to testosterone; (C) the substance is not an estrogen, progestin, or a corticosteroid; and (D) the substance is not DHEA.
To classify a substance as an anabolic steroid, a substance must be chemically related to testosterone. DEA discussed its evaluation of the chemical relationship of boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione in the NPRM published April 25, 2008 (73 FR 22294). A Structure Activity Relationship (SAR) evaluation for each of the substances compared the chemical structure of the steroid to that of testosterone, as substances with a structure similar to that of testosterone are predicted to possess comparable pharmacological and biological activity.
Boldione is also known by the following chemical name: Androsta-1,4-diene-3,17-dione. DEA has determined that the chemical structure of boldione is chemically related to that of testosterone. The chemical structure of boldione differs from testosterone by only the following structural features: A ketone group at carbon 17 and a double bond between the carbon 1 and carbon 2. The human body would be expected to metabolize the ketone group at carbon 17 into a hydroxyl group that is present on testosterone (Payne and Hales, 2004; Peltoketo
Desoxymethyltestosterone (DMT) is also known by the following names: 17α-Methyl-5α-androst-2-en-17β-ol; and madol. DEA has determined that the chemical structure of desoxymethyltestosterone is chemically related to testosterone. The chemical structure of desoxymethyltestosterone differs from testosterone by the following four structural features: The lack of a ketone group at the third carbon, a double bond between the second and third carbon, the lack of a double bond between the fourth and fifth carbon, and a methyl group at carbon 17. Each of these four chemical features is known through the scientific literature not to eliminate the anabolic and androgenic activity of the substance (Brueggemeir
19-Nor-4,9(10)-androstadienedione is also known by the following chemical names: 19-Norandrosta-4,9(10)-diene-3,17-dione; and estra-4,9(10)-diene-3,17-dione. DEA has determined that the chemical structure of 19-nor-4,9(10)-androstadienedione is chemically related to testosterone. The chemical structure of 19-nor-4,9(10)-androstadienedione differs from testosterone by the following three structural features: A ketone group at carbon 17, the absence of a methyl group at carbon 19, and a double-bond between carbon 9 and carbon 10. The human body would be expected to metabolize the ketone group at carbon 17 into a hydroxyl group like that present in testosterone (Payne and Hales, 2004; Peltoketo
A substance must also be pharmacologically related to testosterone (
There are several different types of assays used to establish androgen receptor binding and efficacy. In one assay, C3H10T1/2 stem cells express androgen receptors and are used to assess steroids for their ability to bind and activate the androgen receptor (Jasuja
Androgenic and anabolic activity assay results indicate that boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione have similar pharmacological activity as testosterone.
DEA sponsored a study
Desoxymethyltestosterone was administered subcutaneously, orally, or intramuscularly to castrated rats (Dorfman and Kincl, 1963; Kincl and Dorfman, 1964; Nutting
As discussed in the NPRM, DEA sponsored a study
As discussed in the NPRM, DEA has determined that boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione are unrelated to estrogens, progestins, and corticosteroids. DEA evaluated the SAR for each of the substances. The chemical structure of each substance was compared to that of estrogens, progestins, and corticosteroids because the chemical structure can be related to its pharmacological and biological activity. DEA found that the three substances lacked the necessary chemical structures to impart significant estrogenic activity (
Dehydroepiandrosterone, also known as DHEA, is exempt from control as an anabolic steroid by definition (21 U.S.C. 802(41)(A)). Boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione are not dehydroepiandrosterone and are therefore not exempted from control on this basis.
On April 25, 2008, DEA published a NPRM (73 FR 22294) proposing to classify boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione as schedule III anabolic steroids. The proposed rule provided an opportunity for all interested persons to submit their comments on or before June 24, 2008. In response to the NPRM, DEA received one comment from a consulting firm that described itself as “[assisting] dietary supplement companies in understanding governmental regulations while facilitating their growth.” These comments are summarized and responded to below.
In regard to androgenic activity comment, the commenter did not provide the full statement from the report which reads: “The direct androgenic and anabolic activity of 1,4-androstadien-3,17-dione in sham operated rats is less clear because of the measured increases in serum T levels that could mediate the androgenic and anabolic activities of 1,4-androstadien-3,17-dione.” This statement in the report mentioned the possibility that the pharmacological effects (reduction in LH and FSH levels and testes size) of 1,4-androstadien-3,17-dione could result indirectly by metabolism to an active steroid such as testosterone. As noted in the report, it was not possible to determine whether or not 1,4-androstadien-3,17-dione actually metabolized to testosterone or some other substance that cross reacted in the testosterone assay. Regardless of whether 1,4-androstadien-3,17-dione acts directly or serves as a prodrug, it still produced pharmacological effects similar to that of testosterone when administered to rats.
DEA has evaluated the comment received and finds that it does not provide any justification to dispute the determination that boldione, desoxymethyltestosterone and 19-nor-4,9(10)-androstadienedione are anabolic steroids.
Therefore, based on the above, DEA concludes that boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione meet the CSA definition of “anabolic steroid” because each substance is: (A) Chemically related to testosterone; (B) pharmacologically related to testosterone; (C) not an estrogen, progestin, or a corticosteroid; and (D) not DHEA (21 U.S.C. 802(41)(A)). All anabolic steroids are classified as schedule III controlled substances (21 U.S.C. 812(e) schedule III). Once a substance is determined to be an anabolic steroid, DEA has no discretion regarding the scheduling of these substances. As discussed further below, upon the effective date of this Final Rule all requirements pertaining to controlled substances in schedule III pertain to these three substances.
The classification of boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione as schedule III anabolic steroids makes these three substances subject to CSA requirements. Any person who manufactures, distributes, dispenses, imports, or exports boldione, desoxymethyltestosterone, or 19-nor-4,9(10)-androstadienedione, or who engages in research or conducts instructional activities with respect to these three substances, must obtain a schedule III registration in accordance with the CSA and its implementing regulations.
As of January 4, 2010, manufacture, import, export, distribution, or sale of boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione, except by DEA registrants, is a violation of the CSA that may result in imprisonment and fines (21 U.S.C. 841 and 960). Possession of these three steroids, unless legally obtained, is also subject to criminal penalties (21 U.S.C. 844).
In addition, under the CSA, these three substances may be imported only
Effective January 4, 2010, boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione are subject to CSA regulatory controls and administrative, civil, and criminal sanctions applicable to the manufacture, distribution, dispensing, importation, and exportation of a schedule III controlled substance, including the following:
Persons who possess substances classified as anabolic steroids and who wish to dispose of them rather than becoming registered to handle them should contact their local DEA Diversion field office for assistance in disposing of these substances legally. DEA Diversion field offices will provide the person with instructions regarding the disposal. A list of local DEA Diversion field offices may be found at
The Deputy Administrator hereby certifies that this rulemaking has been drafted in accordance with the Regulatory Flexibility Act (5
The manufacturers and distributors of the 61 identified dietary supplements purported to contain boldione, desoxymethyltestosterone, or 19-nor-4,9(10)-androstadienedione also sell a variety of other dietary supplements. DEA has identified a substantial number of Internet distributors that sell these dietary supplements. However, these distributors also sell a variety of other nutritional products. DEA did not receive any information regarding the percentage of revenues derived from these dietary supplements. DEA did not receive any comments regarding legitimate uses of these three substances. DEA has not identified any chemical manufacturers that are currently using these substances as intermediates in their manufacturing process(es).
As of August 2008, DEA identified 32 chemical manufacturers and distributors that sell at least one of the three substances. Most of the companies are located in China and sell a variety of steroids. DEA notes that, as the vast majority of entities handling these substances are Internet based, it is virtually impossible to accurately quantify the number of persons handling these substances at any given time. Further, DEA has no information regarding the percentage of revenue these substances constitute for each handler.
DEA has identified five companies based in the U.S. that are DEA registrants that manufacture and/or distribute at least one of these substances as reference products for testing laboratories. DEA notes, upon placement into schedule III, these substances may be used for analytical purposes. These companies are registered with DEA and are already in compliance with the CSA and DEA implementing regulations regarding the handling of schedule III substances.
The Deputy Administrator hereby certifies that this rulemaking has been drafted in accordance with Executive Order 12866 section 1(b). It has been determined that this rule is a significant regulatory action. Therefore, this action has been reviewed by the Office of Management and Budget.
As discussed above, the effect of this rule removes products containing these substances from the over-the-counter marketplace. DEA has no basis for estimating the size of the market for these products. DEA notes, however, that virtually all of the substances are imported. According to U.S. International Trade Commission data, the import value of all anabolic steroids for the first eleven months of 2008 was $2.1 million. These three substances are
The benefit of controlling these substances is to remove from the marketplace substances that have dangerous side effects and no legitimate medical use in treatment in the United States. As discussed in detail above, these substances can produce serious health effects in adolescents and adults. If medical uses for these substances are developed and approved, the drugs will be available as schedule III controlled substances in response to a prescription issued by a medical professional for a legitimate medical purpose. Until that time, however, this action bars the importation, exportation, and sale of these three substances except for legitimate research or industrial uses.
This regulation meets the applicable standards set forth in Sections 3(a) and 3(b)(2) of Executive Order 12988 Civil Justice Reform.
This rulemaking does not preempt or modify any provision of state law; nor does it impose enforcement responsibilities on any state; nor does it diminish the power of any state to enforce its own laws. Accordingly, this rulemaking does not have federalism implications warranting the application of Executive Order 13132.
This rule regulates three anabolic steroids, which are neither approved for medical use in humans nor approved for administration to cattle or other non-humans. Only chemical manufacturers who may use these substances as chemical intermediates for the synthesis of other steroids are required to register with DEA under the CSA. However, DEA has not identified any chemical manufacturers that are currently using these substances as intermediates in their manufacturing process(es). Thus, DEA does not expect this rule to impose any additional paperwork burden on the regulated industry.
This rule will not result in the expenditure by state, local, and tribal governments, in the aggregate or by the private sector, of $120,000,000 or more (adjusted for inflation) in any one year and will not significantly or uniquely affect small governments. Therefore, no actions were deemed necessary under the provisions of the Unfunded Mandates Reform Act of 1995.
This rule is not a major rule as defined by Section 804 of the Small Business Regulatory Enforcement Fairness Act of 1996 (Congressional Review Act). This rule will not result in an annual effect on the economy of $100,000,000 or more; a major increase in cost or prices; or significant adverse effects on competition, employment, investment, productivity, innovation, or on the ability of United States-based companies to compete with foreign-based companies in domestic and export markets.
Chemicals, Drug traffic control.
21 U.S.C. 802, 821, 829, 871(b), 951, 958(f).
(b) * * *
(4) * * *
(xiii) boldione (androsta-1,4-diene-3,17-dione)
(xvii) desoxymethyltestosterone (17α-methyl-5α-androst-2-en-17β-ol) (a.k.a., madol)
(xlvii) 19-nor-4,9(10)-androstadienedione (estra-4,9(10)-diene-3,17-dione)