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responsible for training NCUA http://www.regulations.gov Web site. I. Background Information employees in the obligations imposed DEA will accept attachments to On November 29, 1990, the President by the Privacy Act and this subpart. electronic comments in Microsoft Word, signed into law the Anabolic Steroids * * * * * WordPerfect, Adobe PDF, or Excel file Control Act of 1990 (Title XIX of Pub. [FR Doc. E8–8948 Filed 4–24–08; 8:45 am] formats. DEA will not accept any file L. 101–647), which became effective format other than those specifically BILLING CODE 7535–01–P February 27, 1991. This law established listed here. and regulated anabolic steroids as a Posting of Public Comments: Please class of drugs under schedule III of the DEPARTMENT OF JUSTICE note that all comments received are Controlled Substances Act (CSA). As a considered part of the public record and result, a new anabolic steroid is not Drug Enforcement Administration made available for public inspection scheduled according to the procedures online at http://www.regulations.gov set out in 21 U.S.C. 811, but can be 21 CFR Part 1300 and in the Drug Enforcement administratively classified as an Administration’s public docket. Such anabolic steroid through the rulemaking [Docket No. DEA–285P] information includes personal process by adding the steroid to the RIN 1117–AB17 identifying information (such as your regulatory definition of an anabolic name, address, etc.) voluntarily steroid in 21 CFR 1300.01(b)(4). Classification of Three Steroids as submitted by the commenter. On October 22, 2004, the President Schedule III Anabolic Steroids Under If you want to submit personal signed into law the Anabolic Steroid the Controlled Substances Act identifying information (such as your Control Act of 2004 (Pub. L. 108–358), which became effective on January 20, AGENCY: Drug Enforcement name, address, etc.) as part of your comment, but do not want it to be 2005. Section 2(a) of the Anabolic Administration (DEA), Department of Steroid Control Act of 2004 amended 21 Justice. posted online or made available in the public docket, you must include the U.S.C. 802(41)(A) by replacing the ACTION: Notice of proposed rulemaking. phrase ‘‘PERSONAL IDENTIFYING existing definition of ‘‘anabolic steroid.’’ The Anabolic Steroid Control Act of SUMMARY: This Notice of Proposed INFORMATION’’ in the first paragraph 2004 classifies a drug or hormonal Rulemaking (NPRM) proposes to of your comment. You must also place substance as an anabolic steroid if the classify the following three steroids as all the personal identifying information following four criteria are met: (A) The ‘‘anabolic steroids’’ under the you do not want posted online or made substance is chemically related to Controlled Substances Act (CSA): available in the public docket in the first testosterone; (B) the substance is boldione, desoxymethyltestosterone, paragraph of your comment and identify pharmacologically related to and 19-nor-4,9(10)-androstadienedione. what information you want redacted. testosterone; (C) the substance is not an The Drug Enforcement Administration If you want to submit confidential estrogen, progestin, or a corticosteroid; (DEA) believes that this action is business information as part of your and (D) the substance is not necessary in order to prevent the abuse comment, but do not want it to be dehydroepiandrosterone (DHEA). Any and trafficking of these steroids. If the posted online or made available in the substance that meets the criteria is regulations are amended, these steroids public docket, you must include the considered an anabolic steroid and must will be listed as schedule III controlled phrase ‘‘CONFIDENTIAL BUSINESS be listed as a schedule III controlled substances subject to the regulatory INFORMATION’’ in the first paragraph substance. DEA believes that boldione, control provisions of the CSA. of your comment. You must also desoxymethyltestosterone, and 19-nor- DATES: Written comments must be prominently identify confidential 4,9(10)-androstadienedione meet this postmarked, and electronic comments business information to be redacted definition of anabolic steroid and is must be sent on or before June 24, 2008. within the comment. If a comment has proposing that they be added to the list ADDRESSES: To ensure proper handling so much confidential business of anabolic steroids in 21 CFR of comments, please reference ‘‘Docket information that it cannot be effectively 1300.01(b)(4). No. DEA–285’’ on all written and redacted, all or part of that comment Anabolic steroids are a class of drugs electronic correspondence. Written may not be posted online or made with a basic steroid ring structure that comments via regular mail should be available in the public docket. produces anabolic and androgenic sent to the Deputy Administrator, Drug Personal identifying information and effects. The prototypical anabolic Enforcement Administration, confidential business information steroid is testosterone. Anabolic effects Washington, DC 20537, Attention: DEA identified and located as set forth above include promoting the growth of Federal Register Representative/ODL. will be redacted and the comment, in muscle. The androgenic effects consist Written comments sent via express mail redacted form, will be posted online and of promoting the development of male should be sent to DEA Headquarters, placed in the Drug Enforcement secondary sexual characteristics such as Attention: DEA Federal Register Administration’s public docket file. If facial hair, deepening of the voice, and Representative/ODL, 8701 Morrissette you wish to inspect the agency’s public thickening of the skin. Drive, Springfield, VA 22152. docket file in person, by appointment, In the United States, only a small Comments may be sent directly to DEA please see the FOR FURTHER INFORMATION number of anabolic steroids are electronically by sending an electronic CONTACT paragraph. approved for either human or veterinary message to use. Approved medical uses for anabolic FOR FURTHER INFORMATION CONTACT: [email protected]. steroids include treatment of androgen Christine A. Sannerud, PhD, Chief, Drug Comments may also be sent deficiency in hypogonadal males, and Chemical Evaluation Section, Office electronically through http:// adjunctive therapy to offset protein of Diversion Control, Drug Enforcement www.regulations.gov using the catabolism associated with prolonged Administration, Washington, DC 20537 electronic comment form provided on administration of corticosteroids, at (202) 307–7183. that site. An electronic copy of this treatment of delayed puberty in boys, document is also available at the SUPPLEMENTARY INFORMATION: treatment of metastatic breast cancer in

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women, and treatment of anemia substance is chemically related to related to testosterone. The chemical associated with specific diseases (e.g., testosterone; (B) the substance is structure of 19-nor-4,9(10)- anemia of chronic renal failure, pharmacologically related to androstadienedione differs from Fanconi’s anemia, and acquired aplastic testosterone; (C) the substance is not an testosterone by the following three anemia). However, with the exception of estrogen, progestin, or a corticosteroid; chemical groups: A ketone group at the treatment of male hypogonadism, and (D) the substance is not DHEA. carbon 17, the absence of a methyl anabolic steroids are not the first-line group at carbon 19, and a double-bond A. Chemically Related to Testosterone treatment due to the availability of other between the ninth and tenth carbon. preferred treatment options. DEA is not To classify a substance as an anabolic The human body metabolizes the ketone aware of any legitimate medical use or steroid, a substance must be chemically group at carbon 17 into a hydroxyl New Drug Applications (NDA) for the related to testosterone. A Structure group that is present on testosterone. three substances that DEA is proposing Activity Relationship (SAR) evaluation Furthermore, the scientific literature to classify by this NPRM as anabolic for each of the substances compared the reports that both the absence of the steroids under the definition set forth chemical structure of the steroid to that methyl group at carbon 19 and the under 21 U.S.C. 802(41)(A). Moreover, of testosterone, as substances with a additional double bond in 19-nor- DEA has not been able to identify any structure similar to that of testosterone 4,9(10)-androstadienedione increase the chemical manufacturers currently using are predicted to possess comparable anabolic activity of the substance (Vida, these substances as intermediates in pharmacological and biological activity. 1969). their manufacturing process(es). Boldione is also known by the Adverse effects are associated with following chemical name: androsta-1,4- B. Pharmacologically Related to the use or abuse of anabolic steroids. diene-3,17-dione. DEA has determined Testosterone These effects depend on several factors that the chemical structure of boldione A substance must also be (e.g., age, sex, anabolic steroid used, the is chemically related to that of pharmacologically related to amount used, and the duration of use). testosterone. The chemical structure of testosterone (i.e., produce similar In early adolescents, the use of boldione differs from testosterone by biological effects) to be classified as a testosterone and other anabolic steroids only the following two chemical groups: schedule III anabolic steroid. The that have estrogenic effects can cause A ketone group at carbon 17 and a pharmacology of a steroid, as related to premature closure of the growth plates double bond between the first and testosterone, can be established by in long bones resulting in a permanently second carbon. The human body would performing one or more of the following stunted growth. In adolescent boys, be expected to metabolize the ketone androgenic and anabolic activity assays: anabolic steroid use can cause group at carbon 17 into a hydroxyl ventral prostate assay, seminal vesicle precocious sexual development. In both group that is present on testosterone. assay, levator ani assay, testicular girls and women, anabolic steroid use Furthermore, the scientific literature atrophy assay, gonadotropin induces permanent physical changes reports that the additional double bond suppression assay, and androgen such as deepening of the voice, at carbon 1 in boldione does not receptor binding and efficacy assays. increased facial and body hair growth, significantly decrease the anabolic These assays are described below. and the lengthening of the clitoris. In activity of the substance (Vida, 1969). Ventral Prostate Assay, Seminal men, anabolic steroid use can cause Boldione is an anabolic steroid Vesicle Assay, and Levator Ani Assay: shrinkage of the testicles, decreased precursor, being metabolized by the The classic scientific procedure for sperm count, and sterility. body into boldenone (Galletti and Gardi, examining the effects of a steroid as Gynecomastia (i.e., enlargement of the 1971), which is a schedule III anabolic compared to testosterone is to perform male breast tissue) can develop with the steroid (21 U.S.C. 801(41)(A)(vi)). the ventral prostate assay, seminal use of those anabolic steroids with Desoxymethyltestosterone (DMT) is vesicles assay, and levator ani assay. estrogenic actions. In both men and also known by the following names: Certain male accessory organs (i.e., the women, anabolic steroid use can 17a-methyl-5a-androst-2-en-17b-ol; and ventral prostate, seminal vesicles, and damage the liver and can cause high madol. DEA has determined that the levator ani muscle) specifically need cholesterol levels, which may increase chemical structure of testosterone to grow and remain the risk of strokes and heart attacks. desoxymethyltestosterone is chemically healthy. Upon the removal of the testes Furthermore, anabolic steroid use is related to testosterone. The chemical (i.e., castration), the primary purported to induce psychological structure of desoxymethyltestosterone endogenous source of testosterone is effects such as aggression, increased differs from testosterone by the eliminated causing the atrophy of the feelings of hostility, and psychological following four chemical features: The ventral prostate, seminal vesicles, and dependence and addiction. Upon abrupt lack of a ketone group at the third levator ani muscle (Eisenberg et al., termination of long-term anabolic carbon, a double bond between the 1949; Nelson et al., 1940; Scow, 1952; steroid use, a withdrawal syndrome may second and third carbon, the lack of a Wainman and Shipoundoff, 1941). appear including severe depression. double bond between the fourth and Numerous scientific studies have fifth carbon, and a methyl group at demonstrated the ability of exogenous II. Evaluation of Statutory Factors for carbon 17. Each of these four chemical testosterone administered to rats Classification as an Anabolic Steroid features is known through the scientific following castration to maintain the DEA is proposing by this NPRM to literature not to eliminate the anabolic normal weight and size of all three classify boldione, and androgenic activity of the substance testosterone sensitive organs (Biskind desoxymethyltestosterone, and 19-nor- (Brueggemeir et al., 2002; Vida, 1969). and Meyer, 1941; Dorfman and 4,9(10)-androstadienedione as anabolic 19-Nor-4,9(10)-androstadienedione is Dorfman, 1963; Kincl and Dorfman, steroids under the definition set forth also known by the following chemical 1964; Nelson et al., 1940; Scow, 1952; under 21 U.S.C. 802(41)(A). As noted names: 19-norandrosta 4,9(10)-diene- Wainman and Shipoundoff, 1941). previously, a drug or hormonal 3,17-dione; and estra-4,9(10)-diene-3,17- Thus, a steroid with testosterone-like substance is classified as an anabolic dione. DEA has determined that the activity will also prevent the atrophy of steroid by meeting the following four chemical structure of 19-nor-4,9(10)- these three testosterone-dependent definitional requirements: (A) The androstadienedione is chemically organs in castrated rats.

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Testicular Atrophy Assay: [MyoD] and myosin heavy chain associated with castration. Boldione Administering testosterone to non- [MHC]). Another assay uses human administration also produced testicular castrated rats causes a decrease in serum breast cancer cells genetically altered to atrophy in intact rats. Another DEA levels of gonadotropins (i.e., luteinizing contain a specific reporter gene (e.g., sponsored study 2 at a laboratory at hormone [LH] and follicle stimulating luciferase gene) regulated by androgen Boston University examined the ability hormone [FSH]) from normal levels. receptor activation (Hartig et al., 2002; of boldione to bind to the androgen Gonadotropins are pituitary hormones Wilson et al., 2002). The expression of receptor and to cause the differentiation that affect the size and function of the a bioluminescent protein (e.g., of C3H10T1/2 stem cells into muscle testes. The suppression of these luciferase) signals both androgen cells (Bhasin, 2005). All of these effects gonadotropins by excess testosterone receptor binding and activation. caused by boldione in C3H10T1/2 stem results in a significant decrease in the cells were comparable to those of Results of the Androgenic and Anabolic size and weight of the testes (Boris et al., testosterone as established in Activity Assays 1970; McEuen et al., 1937; Moore and experiments using the same or similar Price, 1938). Accordingly, a steroid with In January 2006, DEA reviewed the methodology (Singh et al., 2003). testosterone-like activity will also published scientific literature for Collectively, the evidence indicates that significantly diminish the size and pharmacological data on the anabolic the pharmacology of boldione is similar weight of the testes. and androgenic activity of boldione, to testosterone. Gonadotropin Suppression Assay: desoxymethyltestosterone, and 19-nor- The castration of rats causes a 4,9(10)-androstadienedione using the Desoxymethyltestosterone substantial increase in the serum levels assays described above. As discussed Desoxymethyltestosterone was of gonadotropins (i.e., LH and FSH) further below, there was sufficient administered subcutaneously, orally, or above normal levels due to the removal information on the pharmacology of intramuscularly to castrated rats of the principal source of endogenous desoxymethyltestosterone in the (Dorfman and Kincl, 1963; Kincl and testosterone (Gay and Bogdanove, 1969; reviewed scientific literature to Dorfman, 1964; Nutting et al., 1966). By Swerdloff et al., 1972, 1973; Swerdloff determine that all three routes of administration, and Walsh, 1973). The administration of desoxymethyltestosterone is desoxymethyltestosterone prevented the testosterone to castrated animals pharmacologically related to atrophy of ventral prostate, seminal suppresses the increase in the serum testosterone (i.e., produces biological vesicle, and levator ani. levels of gonadotropins (Gay and effects similar to those of testosterone). Desoxymethyltestosterone also induced Bogdanove, 1969; Swerdloff et al., 1972; However, the published literature the expression of the bioluminescent Swerdloff and Walsh, 1973; Verjans et contained insufficient pharmacological protein luciferase in CAMA–1 breast al., 1974). The administration of data to determine whether boldione and cancer cells signaling androgen receptor anabolic steroids with testosterone-like 19-nor-4,9(10)-androstadienedione were binding and activation (Ayotte et al., activity will also prevent this increase pharmacologically related to 2006). Collectively, the evidence in serum levels of LH and FSH. testosterone. Consequently, as discussed indicates that the pharmacology of Androgen Receptor Binding and further below, DEA sponsored desoxymethyltestosterone is similar to Efficacy Assay: Androgen receptor pharmacological studies involving testosterone. binding and efficacy assays are also several different androgenic and 19-Nor-4,9(10)-Androstadienedione used to demonstrate that the activity of anabolic activity assays to generate the a steroid is similar to that of data necessary to make this DEA sponsored a study 3 by the testosterone. Testosterone produces its determination. Veteran’s Administration Puget Sound anabolic effects subsequent to binding Androgenic and anabolic activity Health Care System to determine the to and activating the androgen receptor. assay results indicate that boldione, anabolic and androgenic effects of 19- Different cell-based assays can compare desoxymethyltestosterone, and 19-nor- nor-4,9(10)-androstadienedione in intact candidate steroids to testosterone for 4,9(10)-androstadienedione have similar and castrated rats (Matsumoto and their ability to bind to and activate pharmacological activity as testosterone. Marck, 2006). The results of these studies were compared to the results of androgen receptors. Boldione There are several different types of a study by the same laboratory using a assays used to establish androgen DEA sponsored a study 1 by the similar protocol to characterize the receptor binding and efficacy. In one Veteran’s Administration Puget Sound androgenic and anabolic effects of assay, C3H10T1/2 stem cells express Health Care System to determine the testosterone (Marck et al., 2003). 19-nor- androgen receptors and are used to anabolic and androgenic effects of 4,9(10)-androstadienedione assess steroids for their ability to bind boldione in intact and castrated rats administered to castrated male rats by and activate the androgen receptor (Matsumoto and Marck, 2006). The silastic capsules implanted under the (Jasuja et al., 2005a,b; Singh et al., results of these studies were compared skin prevented the atrophy of the 2003). In these stem cells, the to the results of a study by the same ventral prostate, seminal vesicle, levator translocation of the androgen receptor to laboratory using a similar protocol to ani, and the rise in serum gonadotropins the nucleus of the cell in the presence characterize the androgenic and (LH and FSH) associated castration. of the ligand (e.g., testosterone or its anabolic effects of testosterone (Marck et Another DEA sponsored study at a active metabolite al., 2003). Boldione administered to laboratory at Boston University 4 dihydroxytestosterone) confirms that castrated male rats by silastic capsules the ligand bound to the androgen implanted under the skin prevented 2 The study by Boston University may be found receptor and activated the downstream atrophy of the ventral prostate, seminal at www.regulations.gov in the electronic docket vesicle, and levator ani, and the rise in associated with this rulemaking. signaling cascade. When activated, the 3 The study by the Veteran’s Administration C3H10T1/2 stem cells differentiate into serum gonadotropin (LH and FSH) Puget Sound Health Care System may be found at skeletal muscle cells as demonstrated by www.regulations.gov in the electronic docket the increase in the expression of muscle 1 The study by the Veteran’s Administration associated with this rulemaking. Puget Sound Health Care System may be found at 4 The study by Boston University may be found specific proteins (i.e., myogenic www.regulations.gov in the electronic docket at www.regulations.gov in the electronic docket determination transcription factor associated with this rulemaking. associated with this rulemaking.

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examined the ability of 19-nor-4,9(10)- scheduling of these substances. As an import declaration filed with DEA androstadienedione to bind to the discussed further below, all (21 CFR 1312.18). Importation of these androgen receptor and to cause the requirements pertaining to controlled substances would be illegal unless the differentiation of C3H10T1/2 stem cells substances in schedule III would pertain person importing these substances is into muscle cells (Bhasin, 2005). All of to these three substances. registered with DEA as an importer or these effects caused by 19-nor-4,9(10)- researcher and files the required androstadienedione in C3H10T1/2 stem IV. Impact of Proposed Rule declaration for each shipment. An cells were comparable to those of Effect of Classifying These Substances individual who purchases any of these testosterone as established in as Anabolic Steroids substances directly from foreign experiments using the same or similar If this rulemaking is finalized as companies and has them shipped to the methodology (Singh et al., 2003). proposed, DEA will classify boldione, U.S. will be considered to be importing Collectively, the evidence indicates that desoxymethyltestosterone, and 19-nor- even if the steroids are intended for personal use. Illegal importation of the pharmacology of 19-nor-4,9(10)- 4,9(10)-androstadienedione as schedule androstadienedione is similar to these substances would be a violation of III anabolic steroids. If classified as testosterone. the CSA that may result in schedule III anabolic steroids, any imprisonment and fines (21 U.S.C. 960). C. Not Estrogens, Progestins, and person who manufactures, distributes, Corticosteroids dispenses, imports, or exports boldione, Requirements for Handling Substances DEA has determined that boldione, desoxymethyltestosterone, or 19-nor- Defined as Anabolic Steroids desoxymethyltestosterone, and 19-nor- 4,9(10)-androstadienedione, or who Upon consideration of public 4,9(10)-androstadienedione are engages in research or conducts comments from this NPRM, DEA may unrelated to estrogens, progestins, and instructional activities with respect to issue a final rule classifying boldione, corticosteroids. DEA evaluated the SAR these three substances would be desoxymethyltestosterone, and 19-nor- for each of the substances. The chemical required to obtain a schedule III 4,9(10)-androstadienedione as anabolic structure of each substance was registration in accordance with the CSA steroids. If classified as anabolic compared to that of estrogens, and its implementing regulations. steroids, boldione, progestins, and corticosteroids because Manufacturers and importers of these desoxymethyltestosterone, and 19-nor- the chemical structure can be related to three substances would be required to 4,9(10)-androstadienedione would its pharmacological and biological register with DEA and would be become subject to CSA regulatory activity. DEA found that the three permitted to distribute these substances controls and administrative, civil, and substances lacked the necessary only to other DEA registrants. Only criminal sanctions applicable to the chemical structures to impart significant persons registered as dispensers would manufacture, distribution, dispensing, estrogenic activity (e.g., aromatic A ring) be allowed to dispense these three importation, and exportation of a (Duax et al., 1988; Jordan et al., 1985; substances to end users. The CSA schedule III controlled substance, Williams and Stancel, 1996), defines a practitioner as ‘‘a physician, including the following: progestational activity (e.g., 17b-alkyl dentist, veterinarian, scientific Registration. Any person who group) (Williams and Stancel, 1996), or investigator, pharmacy, hospital, or manufactures, distributes, dispenses, corticosteroidal activity (e.g., 17b-ketone other person licensed, registered, or imports, exports, or engages in research group or 11b-hydroxyl group) (Miller et otherwise permitted, by the United or conducts instructional activities with al., 2002). States or the jurisdiction in which he a substance defined as an anabolic practices or does research, to distribute, steroid, or who desires to engage in such D. Not Dehydroepiandrosterone dispense, conduct research with respect activities, would be required to be Dehydroepiandrosterone, also known to, administer, or use in teaching or registered to conduct such activities as DHEA, is exempt from control as an chemical analysis, a controlled with schedule III controlled substances anabolic steroid by definition (21 U.S.C. substance in the course of professional in accordance with 21 CFR part 1301. 802(41)(A)). Boldione, practice or research’’ (21 U.S.C. Security. Substances defined as desoxymethyltestosterone, and 19-nor- 802(21)). At present, there are no anabolic steroids would be subject to 4,9(10)-androstadienedione are not approved medical uses for these three schedule III–V security requirements dehydroepiandrosterone and are substances. Until a manufacturer and would be required to be therefore not exempted from control on applies to the Food and Drug manufactured, distributed, and stored in this basis. Administration and gains approval for accordance with 21 CFR 1301.71, products containing these substances, 1301.72(b), (c), and (d), 1301.73, III. Conclusion no person may dispense them in 1301.74, 1301.75(b) and (c), 1301.76 and Therefore, based on the above, DEA response to a prescription. 1301.77. concludes that boldione, Manufacture, import, export, Labeling and Packaging. All labels desoxymethyltestosterone, and 19-nor- distribution, or sale of boldione, and labeling for commercial containers 4,9(10)-androstadienedione meet the desoxymethyltestosterone, and 19-nor- of substances defined as anabolic CSA definition of ‘‘anabolic steroid’’ 4,9(10)-androstadienedione, except by steroids would be required to comply because each substance is: (A) DEA registrants, would become a with requirements of 21 CFR 302.03– Chemically related to testosterone; (B) violation of the CSA that may result in 1302.07. pharmacologically related to imprisonment and fines (21 U.S.C. 841 Inventory. Every registrant required to testosterone; (C) not an estrogen, and 960). Possession of these three keep records and who possesses any progestin, or a corticosteroid; and (D) steroids, unless legally obtained, would quantity of any substance defined as an not DHEA (21 U.S.C. 802(41)). All also become subject to criminal anabolic steroid is required to keep an anabolic steroids are classified as penalties (21 U.S.C. 844). inventory of all stocks of the substances schedule III controlled substances (21 In addition, under the CSA, these on hand pursuant to 21 CFR 1304.03, U.S.C. 812). Once a substance is three substances could be imported only 1304.04 and 1304.11. Every registrant determined to be an anabolic steroid, for medical, scientific, or other who desires registration in schedule III DEA has no discretion regarding the legitimate uses (21 U.S.C. 952(b)) under for any substance defined as an anabolic

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steroid shall conduct an inventory of all desoxymethyltestosterone; and nine As discussed above, the effect of this stocks of the substances on hand at the dietary supplements purport to contain rule would be to remove products time of registration. 19-nor-4,9(10)-androstadienedione. All containing these substances from the Records. All registrants would be 22 dietary supplements are marketed over-the-counter marketplace. DEA has required to keep records pursuant to 21 and sold on the Internet. no basis for estimating the size of the CFR 1304.03, 1304.04, 1304.05, 1304.21, The manufacturers and distributors of market for these products. DEA notes, 1304.22, 1304.23 and 1304.26. the 22 identified dietary supplements however, that virtually all of the Prescriptions. All prescriptions for purported to contain boldione, substances are imported. According to these schedule III substances or for desoxymethyltestosterone, or 19-nor- U.S. International Trade Commission products containing these schedule III 4,9(10)-androstadienedione also sell a data, the import value of all anabolic substances would be required to be variety of other dietary supplements. steroids in 2006 was $6 million. These issued pursuant to 21 CFR 1306.03– DEA has identified a substantial number three substances would be a subset of 1306.06 and §§ 1306.21–1306.27. All of Internet distributors that sell these those imports. The value of anabolic prescriptions for these schedule III dietary supplements. However, these steroid imports for the first six months compounds or for products containing distributors also sell a variety of other of 2007 declined by 35 percent although these schedule III substances, if nutritional products. Without the quantity imported increased. The authorized for refilling, would be information on the percentage of total market for these products limited to five refills within six months revenues derived from these dietary containing these substances, therefore, of the date of issuance of the supplements, however, DEA is not able is probably quite small. Moreover, DEA prescription. to determine the economic impact of the believes that the importation of these Importation and Exportation. All removal of these dietary supplements three substances is for illegitimate importation and exportation of any alone on the business of the firms. DEA purposes. substance defined as an anabolic steroid has not been able to identify any The benefit of controlling these would be required to be in compliance chemical manufacturers that are substances is to remove from the with 21 CFR part 1312. currently using these substances as marketplace substances that have Criminal Liability. Any activity with intermediates in their manufacturing dangerous side effects and no legitimate any substance defined as an anabolic process(es). DEA seeks comment on medical use in treatment in the United steroid not authorized by, or in violation whether this regulation, if promulgated States. As discussed in detail above, of, the Controlled Substances Act or the as a Final Rule, will have a significant these substances can produce serious Controlled Substances Import and economic impact on a substantial health effects in adolescents and adults. Export Act is unlawful. number of small entities. If medical uses for these substances are As of August 2007, DEA identified 20 developed and approved, the drugs Disposal of Anabolic Steroids chemical manufacturers and distributors would be available as schedule III If this regulation is finalized as that sell at least one of the three controlled substances in response to a proposed, persons who possess substances addressed in this NPRM. prescription issued by a medical substances that become classified as Most of the companies are located in professional for a legitimate medical anabolic steroids and who wish to China and sell a variety of steroids. DEA purpose. Until that time, however, this dispose of them rather than becoming notes that, as the vast majority of action would bar the importation, registered to handle them should entities handling these substances are exportation, and sale of these three contact their local DEA Diversion field Internet based, it is virtually impossible substances except for legitimate office for assistance in disposing of to accurately quantify the number of research or industrial uses. these substances legally. DEA Diversion persons handling these substances at Executive Order 12988 field office will provide the person with any given time. Further, DEA has no instructions regarding the disposal. A information regarding the percentage of This regulation meets the applicable list of local DEA Diversion field offices revenue these substances constitute for standards set forth in Sections 3(a) and may be found at http:// each handler. 3(b)(2) of Executive Order 12988 Civil www.deadiversion.usdoj.gov. DEA has identified one company Justice Reform. based in the U.S. that is a DEA registrant Regulatory Certifications that manufactures and distributes at Executive Order 13132 Regulatory Flexibility Act least one of these substances as This rulemaking does not preempt or reference products for testing modify any provision of state law; nor The Deputy Administrator hereby laboratories. DEA notes, upon does it impose enforcement certifies that this rulemaking has been placement into schedule III, these responsibilities on any state; nor does it drafted in accordance with the substances may be used for analytical diminish the power of any state to Regulatory Flexibility Act (5 U.S.C. purposes. This company is registered enforce its own laws. Accordingly, this 601–612). DEA is not able to determine with DEA and is already in compliance rulemaking does not have federalism whether this regulation will, if with the CSA and DEA implementing implications warranting the application promulgated as a Final Rule, not have regulations regarding the handling of of Executive Order 13132. a significant economic impact on a schedule III substances. substantial number of small entities. As Paperwork Reduction Act of August 2007, DEA identified 22 Executive Order 12866 This rule proposes to regulate three dietary supplements promoted for The Deputy Administrator hereby anabolic steroids, which are neither building muscle and increasing strength certifies that this rulemaking has been approved for medical use in humans nor that are purported to contain boldione, drafted in accordance with Executive approved for administration to cattle or desoxymethyltestosterone, or 19-nor- Order 12866 section 1(b). It has been other non-humans. Under this proposal, 4,9(10)-androstadienedione. Four determined that this rule is a significant only chemical manufacturers who may dietary supplements purport to contain regulatory action. Therefore, this action use these substances as chemical boldione; nine dietary supplements has been reviewed by the Office of intermediates for the synthesis of other purport to contain Management and Budget. steroids would be required to register

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with DEA under the CSA. However, F. Adding new paragraph (b)(4)(xlvii) Gay, V.L. and Bogdanove, E.M. (1969). DEA has not been able to identify any to read as follows: Plasma and pituitary LH and FSH in the chemical manufacturers that are castrated rat following short-term steroid § 1300.01 Definitions relating to controlled treatment. Endocrinology, 84: 1132–1142. currently using these substances as substances. Hartig, P.C., Bobseine, K.L., Britt, B.H., intermediates in their manufacturing * * * * * Cardon, M.C., Lambright, C.R., Wilson, process(es). Therefore, DEA is V.S., and Gray, L.E. (2002). Development of specifically seeking input from the (b) * * * (4) * * * two androgen receptor assays using chemical industry on any adenoviral transduction of MMTV-Luc (xiii) boldione (androsta-1,4-diene-3,17- reporter and/or hAR for endocrine manufacturing process(es) that maybe dione) impacted by this rulemaking. Thus, screening. Toxicological Sciences, 66: 82– DEA does not expect this proposal to * * * * * 90. (xvii) desoxymethyltestosterone (17a- Jasuja, R., Catlin, D.H., Miller, A., Chang, Y.- impose any additional paperwork methyl-5a-androst-2-en-17-ol) (a.k.a., C., Herbst, K.L., Starcevic, B., Artaza, J.N., burden on the regulated industry. madol) Singh, R., Datta, G., Sarkissian, A., Unfunded Mandates Reform Act of 1995 Chandsawangbhuwana, C., Baker, M., and * * * * * Bhasin, S. (2005a). Tetrahydrogestrinone is This rule will not result in the (xlvii) 19-nor-4,9(10)- an androgenic steroid that stimulates expenditure by state, local, and tribal androstadienedione (estra-4,9(10)- androgen receptor-mediated, myogenic governments, in the aggregate or by the diene-3,17-dione) differentiation in C3H10T1/2 multipotent private sector, of $120,000,000 or more * * * * * mesenchymal cells and promotes muscle accretion in orchidectomized male rats. (adjusted for inflation) in any one year Dated: April 11, 2008. Endocrinology, 146 (10): 4472–4478. and will not significantly or uniquely Michele M. Leonhart, Jasuja, R., Ramaraj, P., Mac, R.P., Singh, A.B., affect small governments. Therefore, no Deputy Administrator. Storer, T.W., Artaza, J., Miller, A., Singh, actions were deemed necessary under R., Taylor, W.E., Lee, M.L., Davidson, T., the provisions of the Unfunded List of References Sinha-Hikim, I., Gonzalez-Cadavid, N.F., and Bhasin, S. (2005b). (s-4-Androstene- Mandates Reform Act of 1995. Ayotte, C., Goudreault, D., Gauthier, J., 3,17-dione binds androgen receptor, Ayotte, P., Larochelle, C., and Poirier, D. promotes myogenesis in vitro, and Congressional Review Act (2006). Characterization of chemical and increases serum testosterone levels, fat-free hormonal properties of new steroid related This rule is not a major rule as mass, and muscle strength in hypogonadal to doping of athletes. Presented at the defined by Section 804 of the Small men. Journal of Clinical Endocrinology and Cologne Workshop on Dope Analysis, June Business Regulatory Enforcement Metabolism, 90(2): 855–863. 2006. Jordan, V.C., Mittal, S., Gosden, B., Koch, R., Fairness Act of 1996 (Congressional Bhasin, S. (2005). [Pharmacological analysis and Lieberman, M.E. (1985). Structure- Review Act). This rule will not result in of boldione and 19-nor-4,9(10)- an annual effect on the economy of androstadienedione for androgenic activity activity relationships of estrogen. $100,000,000 or more; a major increase using C3H10T1/2 stem cells]. Unpublished Environmental Health Perspectives, 61: 91–110. in cost or prices; or significant adverse report. Biskind, G.R. and Meyer, M.A. (1941). The Kincl, F.A. and Dorfman, R.I. (1964). effects on competition, employment, Anabolic-androgenic potency of various investment, productivity, innovation, or comparative androgenic potency of testosterone, methyltestosterone and steroids in a castrated rat assay. Steroids, on the ability of United States-based testosterone propionate administered in 3: 109–122. companies to compete with foreign- pellet form. Endocrinology, 28(2): 217–221. Marck, B.T., Wolden-Hanson, T., Tolliver, based companies in domestic and Boris, A., Stevenson, R.H., and Trmal, T. J.M., Matsumoto, A.M. (2003). Use of export markets. (1970). Comparative androgenic, DEXA to assess the anabolic actions of myotrophic and antigonadotrophic androgens on relative lean body mass and List of Subjects in 21 CFR Part 1300 properties of some anabolic steroids. bone mineral density in orchidectomized prepubertal rats. Unpublished manuscript, Chemicals, Drug traffic control. Steroids, 15(1):61–71. Brueggemeier, R.W., Miller, D.D., and Dalton, Veteran’s Affairs Puget Sound Health Care For the reasons set out above, 21 CFR J.T. (2002). Estrogen, Progestins and System, Seattle, WA. part 1300 is proposed to be amended as Androgens. In D.A. Williams and T.L. Matsumoto, A.M. and Marck, B.T. (2006). follows: Lemke (Eds.) Foye’s Principle of Medicinal DEA Agreement No. DEA–04–P0007 Final Chemistry (5th ed.). Philadelphia, Report [Analysis of the androgenic and PART 1300—DEFINITIONS Lippincott Williams and Wilkins. anabolic activities of 1,4-androstadien- Dorfman, R.I. and Dorfman, A.S. (1963). The 3,17-dione and 19-nor-4,9(10)- 1. The authority citation for part 1300 assay of subcutaneously injected androgens androstadienedione in male Sprague continues to read as follows: in the castrated rat. ACTA Endocrinologica, Dawley rats]. Unpublished report. McEuen, C.S., Selye, H., and Collip, J.B. Authority: 21 U.S.C. 802, 871(b), 951, 42: 245–253. Dorfman, R.I. and Kincl, F.A. (1963). Relative (1937). Effects of testosterone on somatic 958(f). potency of various steroids in an anabolic- growth. Proceedings of the Society for 2. Section 1300.01 is amended in androgenic assay using the castrated rat. Experimental Biology and Medicine, 36: paragraph (b)(4) by: Endocrinology, 72: 259–266. 390–394. Miller, D.D., Brueggemeier, R.W., and Dalton, A. Redesignating paragraphs Duax, W.L., Griffin, J.F., Weeks, C.M., and Wawrzak, Z. (1988). The mechanism of J.T. (2002). Adrenocorticoids. In D.A. (b)(4)(xiii) through (b)(4)(lx) as action of steroid antagonists: Insight from Williams and T.L. Lemke (Eds.) Foye’s (b)(4)(xiv) through (b)(4)(lxi), crystallographic studies. Journal of Steroid Principle of Medicinal Chemistry (5th ed.). B. Adding a new paragraph Biochemistry and Molecular Biology, 31: Philadelphia, Lippincott Williams and (b)(4)(xiii), 481–492. Wilkins. C. Redesignating new paragraphs Eisenberg E, Gordan GS and Elliott HW Moore, C.R. and Price, D. (1938). Some (b)(4)(xvii) through (b)(4)(lxi) as (1949). Testosterone and tissue respiration effects of testosterone and testosterone- (b)(4)(xviii) through (b)(4)(lxii), of the castrate male rat with possible test propionate in the rat. The Anatominal for myotrophic activity. Endocrinology, Record, 71(1):59–78. D. Adding new paragraph (b)(4)(xvii), 45(2): 113–119. Nelson, D., Greene, R.R. and Wells, J.A. E. Redesignating new paragraphs Galletti, F. and Gardi, R. (1971). Metabolism (1940). Variations in the effectiveness of (b)(4)(xlvii) through (b)(4)(lxii) as of 1-dehydroandrostanes in man. Steroids, percutaneously applied androgens in the (b)(4)(xlviii) through (b)(4)(lxiii), and 18(1): 39–50. rat. Endocrinology, 26: 651–655.

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Nutting, E.F., Klimstra, P.D., and Counsell, DEPARTMENT OF THE TREASURY PART 1—[CORRECTED] R.E. (1966). Anabolic-androgenic activity of A-ring modified androstane derivatives. Internal Revenue Service § 1.411(a)(13)–1 [Corrected] Part I: A comparison of parenteral activity. 4. On page 73691, column 1, ACTA Endocrinologica, 53: 627–634. 26 CFR Part 1 § 1.411(a)(13)–1(d)(3)(ii), line 18, the Scow, R.O. (1952). Effect of testosterone on language ‘‘larger annual benefit at muscle and other tissues and on carcass [REG–104946–07] normal’’ is corrected to read ‘‘smaller composition in hypophysectomized, annual benefit at normal’’. thyroidectomized, and gonadectomized 5. On page 73691, column 2, RIN 1545–BG36 male rats. Endocrinology, 51: 42–51. § 1.411(a)(13)–1(d)(3)(iii)(B), line 9, the Singh, R., Artaza, J.N., Taylor, W.E., Hybrid Retirement Plans; Correction language ‘‘reasonably expected to result Gonzalez-Cadavid, N.F., and Bhasin, S. in a larger’’ is corrected to read (2003). Androgens stimulate myogenic AGENCY: Internal Revenue Service (IRS), ‘‘reasonably expected to result in a differentiation and inhibit adipogenesis in Treasury. smaller’’. C3H 10T1/2 pluripotent cells through an ACTION: Correction to notice of proposed § 1.411(b)(5)–1 [Corrected] androgen receptor-mediated pathway. rulemaking. Endocrinology, 144(11): 5081–5088. 6. On page 73693, column 3, Swerdloff, R.S., Grover, P.K., Jacobs, H.S., SUMMARY: This document contains § 1.411(b)(5)–1(c)(3)(ii)(A), line 17, the and Bain, J. (1973). Search for a substance corrections to a notice of proposed language ‘‘participant under the lump which selectively inhibits FSH—Effects of rulemaking (REG–104946–07) that was sum-based’’ is corrected to read steroids and prostaglandins on serum FSH published in the Federal Register on ‘‘participant under the lump sum-based and LH levels. Steroids, 21(5): 703–722. Friday, December 28, 2007 (72 FR benefit’’. Swerdloff, R.S. and Walsh, P.C. (1973). 73680) providing guidance relating to 7. On page 73695, column 1, Testosterone and oestradiol suppression of sections 411(a)(13) and 411(b)(5) of the § 1.411(b)(5)–1(c)(5) Example 1. (ii), line LH and FSH in adult male rats: Duration Internal Revenue Code concerning 17, the language ‘‘permitted to elect of castration, duration of treatment and certain hybrid defined benefit plans. (with spousal consent)’’ is corrected to combined treatment. ACTA read ‘‘permitted to elect (with spousal Endocrinologica, 73: 11–21. FOR FURTHER INFORMATION CONTACT: Lauson C. Green or Linda S. F. Marshall consent if applicable)’’. Swerdloff, R.S., Walsh, P.C., and Odell, W.D. 8. On page 73695, column 2, (1972). Control of LH and FSH secretion in at (202) 622–6090 (not a toll-free number). § 1.411(b)(5)–1(c)(5) Example 2. (iii), the male: Evidence that aromatization of line 5, the language ‘‘consent) payment androgens to estradiol is not required for SUPPLEMENTARY INFORMATION: in the same generalized’’ is corrected to inhibition of gonadotropin secretion. Background read ‘‘consent if applicable) payment in Steroids, 20(1): 13–22. the same generalized’’. Verjans, H.L., Eik-Nes, K.B., Aafjes, J.H., Vels, The correction notice that is the 9. On page 73695, column 3, F.J.M., and van der Molen, H.J. (1974). subject of this document is under § 1.411(b)(5)–1(c)(5) Example 2. (v), line Effects of testosterone propionate, 5alpha- section 411 of the Internal Revenue 12, the language ‘‘of 5.5 percent. dihydrotestosterone propionate and Code. Thereafter, Participant’s A’s’’ is oestradiol benzoate on serum levels of LH and FSH in the castrated adult male rat. Need for Correction corrected to read ‘‘of 5.5 percent. Thereafter, Participant A’s’’. ACTA Endocrinologica, 77: 643–654. As published, the notice of proposed Vida, J.A. (1969). Androgens and Anabolic rulemaking (REG–104946–07) contains LaNita Van Dyke, Agents: Chemistry and Pharmacology. New errors that may prove to be misleading Chief, Publications and Regulations Branch, York: Academic Press. and are in need of clarification. Legal Processing Division, Associate Chief Wainman, P. and Shipounoff, G.C. (1941). Counsel (Procedure and Administration). Correction of Publication The effects of castration and testosterone [FR Doc. E8–9026 Filed 4–24–08; 8:45 am] propionate on the striated perineal Accordingly, the publication of the BILLING CODE 4830–01–P musculature in the rat. Endocrinology, notice of proposed rulemaking (REG– 29(6): 975–978. 104946–07), which was the subject of Williams, C.L. and Stancel, G.M (1996). FR Doc. E7–25025, is corrected as DEPARTMENT OF THE TREASURY Estrogens and Progestins. In J.G. Hardman, follows: L.E. Limbird, P.B. Molinoff, R.W. Ruddon, 1. On page 73683, column 3, in the Internal Revenue Service A. Goodman Gilman (Eds.) Goodman and preamble, first paragraph of the column, Gilman’s The Pharmacological Basis of line 15, the language ‘‘reasonably 26 CFR Part 20 Therapeutics (9th ed.). New York: expected to result in a larger’’ is [REG–112196–07] McGraw-Hill, 1411–1440. corrected to read ‘‘reasonably expected Wilson, V.S., Bobseine, K., Lambright, C.R., to result in a smaller’’. RIN 1545–BH64 and Gray, L.E. (2002). A novel cell line, 2. On page 73685, column 1, third MDA-kb2, that stably expresses an Gross Estate; Election to Value on paragraph of the column, line 8, the Alternate Valuation Date androgen- and glucocorticoid-responsive language ‘‘ ‘capital’ rule of section reporter for the detection of hormone 411(b)(5)(b)(i)(II)’’ is corrected to read AGENCY: receptor agonists and antagonists. Internal Revenue Service (IRS), ‘‘ ‘capital’ rule of section Toxicological Sciences, 66: 69–81. Treasury. 411(b)(5)(B)(i)(II)’’. ACTION: Notice of proposed rulemaking. [FR Doc. E8–8842 Filed 4–24–08; 8:45 am] 3. On page 73689, column 2, line 3 BILLING CODE 4410–09–P from the bottom of the fifth paragraph SUMMARY: This document contains of the column, the language ‘‘section proposed regulations that provide 411(d)(6) is available for the’’ is guidance relating to the availability of corrected to read ‘‘section 411(d)(6) the election to use the alternate relief is available for the’’. valuation method under section 2032 of

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