Federal Register / Vol. 76, No. 226 / Wednesday, November 23, 2011 / Proposed Rules 72355 

proposed AD would not have a 

substantial direct effect on the States, on 

the relationship between the national 

Government and the States, or on the 

distribution of power and 

responsibilities among the various 

levels of government. 

For the reasons discussed above, I 

certify this proposed regulation: 

(1) Is not a ‘‘significant regulatory 

action’’ under Executive Order 12866, 

(2) Is not a ‘‘significant rule’’ under 

the DOT Regulatory Policies and 

Procedures (44 FR 11034, February 26, 

1979), 

(3) Will not affect intrastate aviation 

in Alaska, and 

(4) Will not have a significant 

economic impact, positive or negative, 

on a substantial number of small entities 

under the criteria of the Regulatory 

Flexibility Act. 

List of Subjects in 14 CFR Part 39 

Air transportation, Aircraft, Aviation 

safety, Incorporation by reference, 

Safety. 

The Proposed Amendment 

Accordingly, under the authority 

delegated to me by the Administrator, 

the FAA proposes to amend 14 CFR part 

39 as follows: 

PART 39—AIRWORTHINESS 

DIRECTIVES 

1. The authority citation for part 39 

continues to read as follows: 

Authority: 49 U.S.C. 106(g), 40113, 44701. 

§ 39.13 [Amended] 

2. The FAA amends § 39.13 by adding 

the following new airworthiness 

directive (AD): 

Pratt & Whitney: Docket No. FAA–2011– 

1194; Directorate Identifier 2011–NE– 

36–AD. 

(a) Comments Due Date 

We must receive comments by January 23, 

2012. 

(b) Affected ADs 

None. 

(c) Applicability 

This AD applies to all Pratt & Whitney 

PW4050, PW4052, PW4056, PW4056(–3), 

PW4156, PW4060, PW4060(–3), PW4060A, 

PW4152, PW4152(–3), PW4156A, PW4158, 

PW4158(–3), PW4460, PW4460(–3), PW4462, 

and PW4462(–3) turbofan engines. 

(d) Unsafe Condition 

This AD was prompted by reports of five 

engine in-flight shutdowns and seven 

unplanned engine removals due to clogging 

of No. 4 bearing compartment oil pressure 

and scavenge tubes. We are issuing this AD 

to prevent an engine fire, a fractured fan 

drive shaft, and damage to the airplane. 

(e) Compliance 

Comply with this AD within the 

compliance times specified, unless already 

done. 

(f) Inspection and Cleaning of No. 4 Bearing 

Compartment for Coking 

(1) Within 1,000 cycles-in-service (CIS) 

after the effective date of this AD, initially 

inspect and clean the No. 4 bearing 

compartment in accordance with 

Accomplishment Instructions, paragraphs 

2.A. through 2.A.(4)(b)3 of Pratt & Whitney 

Alert Service Bulletin No. PW4ENG–A72– 

436, Revision 6, dated September 30, 1999. 

(2) Thereafter, within every additional 

1,000 CIS, perform the inspection and 

cleaning specified in paragraph (f)(1) of this 

AD. 

(g) Modification To Stop Buildup of Coking 

in the No. 4 Bearing Compartment 

(1) At the next engine visit to a 

maintenance facility that is capable of 

performing the following on-wing method or 

in-shop method of modification to the No. 4 

bearing compartment, but not to exceed 5 

years after the effective date of this AD, do 

the following: 

(i) Replace the No. 4 bearing packing 

transfer tube assembly; 

(ii) Replace the No. 4 bearing internal 

scavenge tube assembly; 

(iii) Remove the No. 4 bearing shield, and 

the No. 4 bearing shield option; and 

(iv) Install new No. 4 bearing shield 

options. 

(2) For doing the on-wing method of the 

modification, do the work in accordance with 

Accomplishment Instructions, Paragraphs 

2.A. through 2.A.(9)(a)3d of Pratt & Whitney 

Service Bulletin (SB) No. PW4ENG–72–472, 

Revision 5, dated April 14, 1998. 

(3) For doing the in-shop method of the 

modification, do the work in accordance with 

Paragraphs 2.B. through 2.B.(2)(f)2d of Pratt 

& Whitney SB No. PW4ENG–72–472, 

Revision 5, dated April 14, 1998. 

(h) Rerouting of the No. 4 Bearing Pressure 

and Scavenge Tubes 

(1) At the next shop visit at which the 

engine is sufficiently disassembled to 

perform the rerouting, but not to exceed 5 

years after the effective date of this AD, do 

the following: 

(i) Modify the turbine exhaust case to 

relocate the No. 4 bearing pressure and 

scavenge tube ports; 

(ii) Replace the internal No. 4 bearing 

pressure and scavenge tubes; 

(iii) Modify or replace the turbine case 

cooling brackets to support the new No. 4 

bearing pressure and scavenge tubes; 

(iv) Replace the turbine case manifolds as 

necessary; and 

(v) Install the new brackets and clamps to 

support the new routing configuration. 

(2) Do the work specified in paragraph (h) 

of this AD in accordance with 

Accomplishment Instructions paragraph 2 of 

Pratt & Whitney SB No. PW4ENG–79–76, 

Revision 4, dated February 14, 2002. 

(i) Terminating Action to the Repetitive 

Inspections and Cleaning 

Performing the modifications specified in 

both paragraphs (g) and (h), of this AD is 

terminating action to the repetitive 

inspections and cleanings specified in 

paragraph (f)(2) of this AD. 

(j) Alternative Methods of Compliance 

(AMOCs) 

The Manager, Engine Certification Office, 

may approve AMOCs for this AD. Use the 

procedures found in 14 CFR 39.19 to make 

your request. 

(k) Related Information 

(1) For more information about this AD, 

contact Stephen Sheely, Aerospace Engineer, 

Engine & Propeller Directorate, FAA, 12 New 

England Executive Park, Burlington, MA 

01803; phone: (781) 238–7750; fax: (781) 

238–7199; email: stephen.k.sheely@faa.gov. 

(2) For service information identified in 

this AD, contact Pratt & Whitney, 400 Main 

St., East Hartford, CT 06108; telephone: (860) 

565–8770; fax: (860) 565–4503. You may 

review copies of the referenced service 

information at the FAA, Engine & Propeller 

Directorate, 12 New England Executive Park, 

Burlington, MA. For information on the 

availability of this material at the FAA, call 

(781) 238–7125. 

Issued in Burlington, Massachusetts, on 

November 15, 2011. 

Peter A. White, 

Manager, Engine & Propeller Directorate, 

Aircraft Certification Service. 

[FR Doc. 2011–30138 Filed 11–22–11; 8:45 am] 

BILLING CODE 4910–13–P 

DEPARTMENT OF JUSTICE 

Drug Enforcement Administration 

21 CFR Part 1300 

[Docket No. DEA–341P] 

RIN 1117–AB31 

Classification of Two Steroids, 

Prostanozol and Methasterone, as 

Schedule III Anabolic Steroids Under 

the Controlled Substances Act 

AGENCY: Drug Enforcement 

Administration (DEA), Department of 

Justice. 

ACTION: Notice of proposed rulemaking. 

SUMMARY: This Notice of Proposed 

Rulemaking (NPRM) proposes to 

classify the following two steroids as 

‘‘anabolic steroids’’ under the 

Controlled Substances Act (CSA): 

prostanozol (17b-hydroxy-5aandrostano[3,2-c]pyrazole) and 

methasterone (2a,17a-dimethyl-5aandrostan-17b-ol-3-one). The Drug 

Enforcement Administration (DEA) 

believes that this action is necessary to 

prevent the abuse and trafficking of 

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72356 Federal Register / Vol. 76, No. 226 / Wednesday, November 23, 2011 / Proposed Rules 

these steroids. If the regulations are 

amended, these steroids will be listed as 

Schedule III controlled substances 

subject to the regulatory control 

provisions of the CSA. 

DATES: Electronic comments must be 

submitted and written comments must 

be postmarked on or before January 23, 

2012. Commenters should be aware that 

the electronic Federal Docket 

Management System will not accept 

comments after midnight Eastern Time 

on the last day of the comment period. 

ADDRESSES: To ensure proper handling 

of comments, please reference ‘‘Docket 

No. DEA–341’’ on all electronic and 

written correspondence. DEA 

encourages all comments be submitted 

electronically through http:// 

www.regulations.gov using the 

electronic comment form provided on 

that site. An electronic copy of this 

document and supplemental 

information to this proposed rule are 

also available at the http:// 

www.regulations.gov Web site for easy 

reference. Paper comments that 

duplicate the electronic submission are 

not necessary as all comments 

submitted to www.regulations.gov will 

be posted for public review and are part 

of the official docket record. Should 

you, however, wish to submit written 

comments via regular or express mail, 

they should be sent to the Drug 

Enforcement Administration, Attention: 

DEA Federal Register Representative/ 

OD, 8701 Morrissette Drive, Springfield, 

Virginia 22152. 

FOR FURTHER INFORMATION CONTACT: 

Rhea D. Moore, Office of Diversion 

Control, Drug Enforcement 

Administration, 8701 Morrissette Drive, 

Springfield, Virginia 22152; Telephone 

(202) 307–7165. 

SUPPLEMENTARY INFORMATION: 

Posting of Public Comments: Please 

note that all comments received are 

considered part of the public record and 

made available for public inspection 

online at http://www.regulations.gov 

and in the DEA’s public docket. Such 

information includes personal 

identifying information (such as your 

name, address, etc.) voluntarily 

submitted by the commenter. 

If you want to submit personal 

identifying information (such as your 

name, address, etc.) as part of your 

comment, but do not want it to be 

posted online or made available in the 

public docket, you must include the 

phrase ‘‘PERSONAL IDENTIFYING 

INFORMATION’’ in the first paragraph 

of your comment. You must also place 

all the personal identifying information 

you do not want posted online or made 

available in the public docket in the first 

paragraph of your comment and identify 

what information you want redacted. 

If you want to submit confidential 

business information as part of your 

comment, but do not want it to be 

posted online or made available in the 

public docket, you must include the 

phrase ‘‘CONFIDENTIAL BUSINESS 

INFORMATION’’ in the first paragraph 

of your comment. You must also 

prominently identify confidential 

business information to be redacted 

within the comment. If a comment has 

so much confidential business 

information that it cannot be effectively 

redacted, all or part of that comment 

may not be posted online or made 

available in the public docket. 

Personal identifying information and 

confidential business information 

identified and located as set forth above 

will be redacted, and the comment, in 

redacted form, will be posted online and 

placed in the DEA’s public docket file. 

Please note that the Freedom of 

Information Act applies to all comments 

received. If you wish to inspect the 

agency’s public docket file in person by 

appointment, please see the ‘‘For 

Further Information’’ paragraph. 

Background Information 

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 believes that 

prostanozol (17b-hydroxy-5aandrostano[3,2-c]pyrazole) and 

methasterone (2a,17a-dimethyl-5aandrostan-17b-ol-3-one) meet this 

definition of ‘‘anabolic steroid,’’ and is 

proposing that they be added to the list 

of anabolic steroids in 21 CFR 

1300.01(b)(4). 

Anabolic steroids are a class of drugs 

structurally related to the endogenous 

hormone testosterone that exert 

androgenic (masculinizing) as well as 

anabolic (body building) effects. These 

effects are mediated primarily through 

binding of the anabolic steroid to the 

androgen receptor in target tissues 

(Evans, 2004). Anabolic effects include 

promotion of protein synthesis in 

skeletal muscle and bone, while the 

androgenic effects are characterized by 

the development of male secondary 

sexual characteristics such as hair 

growth, deepening of the voice, 

glandular activity, thickening of the 

skin, and central nervous system effects, 

to name a few (Kicman, 2008). Anabolic 

efficacy is characterized by positive 

nitrogen balance and protein 

metabolism, resulting in increases in 

protein synthesis and lean body mass 

(Evans, 2004). These effects often come 

at a cost to the healthy individual who 

experiences clear physical and 

psychological complications (Trenton 

and Currier, 2005; Brower, 2002; Hall et 

al., 2005). 

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 (e.g., 

anemia of chronic renal failure, 

Fanconi’s anemia, and acquired aplastic 

anemia). However, with the exception of 

the treatment of male hypogonadism, 

anabolic steroids are not the first-line 

treatment due to the availability of other 

preferred treatment options. DEA is not 

aware of any legitimate medical use or 

New Drug Applications (NDA) for the 

two substances that DEA is proposing to 

classify by this NPRM as anabolic 

steroids under the definition set forth 

under 21 U.S.C. 802(41)(A). Moreover, 

DEA has not been able to identify any 

chemical manufacturers currently using 

these substances as intermediates in 

their manufacturing process(es). 

Adverse health effects are associated 

with abuse of anabolic steroids and 

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Federal Register / Vol. 76, No. 226 / Wednesday, November 23, 2011 / Proposed Rules 72357 

depend on several factors (e.g., age, sex, 

anabolic steroid used, the amount used, 

and the duration of use) (Hall and Hall, 

2005; Quaglio et al., 2009). These 

include cardiovascular, dermatological, 

behavioral, hepatic, and gender specific 

endocrine side effects. Anabolic steroids 

have direct and indirect impact on the 

developing adolescent brain and 

behavior (Sato et al., 2008). 

Furthermore, adolescent abuse of 

anabolic steroids may result in stunted 

growth due to premature closure of the 

growth plates in long bones. In 

adolescent boys, anabolic steroid abuse 

can cause precocious sexual 

development. In both girls and women, 

anabolic steroid abuse induces 

permanent physical changes such as 

deepening of the voice, increased facial 

and body hair growth, menstrual 

irregularities, and clitoral hypertrophy. 

In men, anabolic steroid abuse can 

cause testicular atrophy, decreased 

sperm count, and sterility. 

Gynecomastia (i.e., enlargement of the 

male breast tissue) can develop with the 

abuse of those anabolic steroids with 

estrogenic actions. In both men and 

women, anabolic steroid abuse can 

damage the liver and may result in high 

cholesterol levels, which may increase 

the risk of strokes and cardiovascular 

heart attacks. Furthermore, anabolic 

steroid abuse is purported to induce 

psychological effects such as aggression, 

increased feelings of hostility, and 

psychological dependence and 

addiction (Brower, 2002; Kanayama et 

al., 2008). Upon abrupt termination of 

long-term anabolic steroid abuse, a 

withdrawal syndrome may appear 

including severe depression. 

Additionally, polysubstance abuse is 

routinely associated with anabolic 

steroid abuse, where ancillary drugs, 

including recreational and prescription 

drugs, are abused in response to 

unwanted side effects (Hall et al., 2005; 

Parkinson et al., 2005; Skarberg et al., 

2009). 

A review of the scientific literature 

finds adverse health effects including 

liver toxicity with renal failure reported 

in conjunction with methasterone abuse 

(Shah et al., 2008; Jasiurkowski et al., 

2006; Singh et al., 2009; Nasr and 

Ahmad, 2008; and Krishnan et al., 

2009). In March 2006, the U.S. Food and 

Drug Administration (FDA) issued a 

Warning Letter in response to adverse 

health effects associated with the 

product Superdrol (methasterone). In 

July 2009, FDA issued a warning 

regarding bodybuilding products 

containing steroid or steroid-like 

substances. In this warning, a product 

containing the THP ether derivative of 

prostanozol was named in conjunction 

with other products presenting safety 

concerns. 

Evaluation of Statutory Factors for 

Classification as an Anabolic Steroid 

DEA is proposing by this NPRM to 

classify prostanozol (17b-hydroxy-5aandrostano[3,2-c]pyrazole) and 

methasterone (2a,17a-dimethyl-5aandrostan-17b-ol-3-one) 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 corticosteroid; 

and (D) the substance is not DHEA. 

(A) Chemically Related to Testosterone 

To classify a substance as an anabolic 

steroid, a substance must be chemically 

related to testosterone. A structure 

activity relationship (SAR) evaluation 

for each substance compared the 

chemical structure of the steroid to that 

of testosterone. Substances with a 

structure similar to that of testosterone 

are predicted to possess comparable 

pharmacological and biological activity. 

Prostanozol is also known by the 

following name: 17b-hydroxy-5aandrostano[3,2-c]pyrazole. DEA 

determined that the chemical structure 

of prostanozol is similar to testosterone, 

differing by only the attachment of a 

pyrazole ring at carbon 2 (C2) and 

carbon 3 (C3) positions of the 

androstane skeleton, replacing the C3- 

keto group and the lack of a double 

bond between carbon 4 (C4) and carbon 

5 (C5) positions. Similar modifications 

to testosterone’s chemical structure have 

been documented and, in general, they 

have been found to be well tolerated, 

displaying both anabolic and 

androgenic activity (Fragkaki et al., 

2009; Vida, 1969). Clinton and 

coworkers, in their synthesis of 

prostanozol, described the modification 

as a fusion of a pyrazole ring to the 

androstane steroidal nucleus at C2 and 

C3 (Clinton et al., 1961). Further 

analysis finds the chemical structure of 

prostanozol to be very similar to the 

anabolic steroid stanozolol. The two 

structures differ only about a 17amethyl group (alpha methyl group 

attached to carbon 17). 

Methasterone is known by the 

following chemical names: 2a,17adimethyl-5a-androstan-17b-ol-3-one; 

2a,17a-dimethyl-17b-hydroxy-5aandrostan-3-one; 17a-methyldrostanolone; methasteron; 

methyldrostanolone; 2a,17adimethyldihydrotestosterone; and 

2a,17a-dimethyl-etiocholan-17b-ol-3- 

one. DEA has determined that the 

chemical structure of methasterone is 

chemically related to testosterone. The 

chemical structure of methasterone 

differs from testosterone by the 

following three chemical groups: an 

alpha methyl group at carbon 17 (C17), 

an alpha methyl group at C2, and the 

lack of a double bond between spanning 

C4 and C5. Removal of the C4–C5 

double bond (A-ring) and methylation at 

the C2 and C17 positions has been 

shown to increase anabolic activity 

(Zaffroni, 1960; Fragkaki et al., 2009). 

Furthermore, methyl group substitution 

at the C2 and C17 has been reported to 

impair aromatization, thus, prolonging 

the anabolic effect (Fragkaki et al., 

2009). 

(B) Pharmacologically Related to 

Testosterone 

A substance must also be 

pharmacologically related to 

testosterone (i.e., produce similar 

biological effects) to be classified as a 

Schedule III anabolic steroid. The 

pharmacology of a steroid, as related to 

testosterone, can be established by 

performing one or more of the following 

androgenic and anabolic activity assays: 

ventral prostate assay, seminal vesicle 

assay, levator ani assay, and androgen 

receptor binding and efficacy assays. 

These assays are described below. 

Ventral Prostate Assay, Seminal 

Vesicle Assay, and Levator Ani Assay: 

The classic scientific procedure for 

evaluating androgenic (masculinizing) 

and anabolic (muscularizing) effects of a 

steroid is the ventral prostate assay, 

seminal vesicle assay, and levator ani 

assay. This testing paradigm allows for 

the direct comparison to testosterone. 

Select male accessory tissues (i.e., the 

ventral prostate, seminal vesicles, and 

levator ani muscle) are testosterone 

sensitive, specifically requiring 

testosterone to grow and remain 

healthy. Upon the removal of the testes 

(i.e., castration), the primary 

endogenous source of testosterone is 

eliminated causing the atrophy of the 

ventral prostate, seminal vesicles, and 

levator ani muscle (Eisenberg et al., 

1949; Nelson et al., 1940; Scow, 1952; 

Wainman and Shipounoff, 1941). 

Numerous scientific studies have 

demonstrated the ability of exogenous 

testosterone or a pharmacologically 

similar steroid administered to rats 

following castration to maintain the 

normal weight and size of all three 

testosterone sensitive organs (Biskind 

and Meyer, 1941; Dorfman and 

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72358 Federal Register / Vol. 76, No. 226 / Wednesday, November 23, 2011 / Proposed Rules 

1 2009 BIOQUAL, Inc. study commissioned by the 

National Institutes of Health on behalf of DEA. 

Dorfman, 1963; Dorfman and Kincl, 

1963; Kincl and Dorfman, 1964; Nelson 

et al., 1940; Scow, 1952; Wainman and 

Shipounoff, 1941). Thus, a steroid with 

testosterone-like activity will also 

prevent the atrophy of these three 

testosterone-dependent organs in 

castrated rats. 

Castrated male rats are administered 

the steroid for a number of days, then 

the rats are euthanized and the 

previously described tissues are excised 

and weighed. Tissue weights from the 

three animal test groups are compared, 

castrated animals alone, castrated 

animals receiving the steroid, and 

healthy intact animals (control), to 

assess anabolic and androgenic activity. 

A reduction in tissue weights relative to 

the control group suggests a lack of 

androgenic and/or anabolic activity. An 

increase in tissue weights relative to the 

castrated rats receiving no steroid 

suggests an androgenic and/or anabolic 

effect. 

Androgen Receptor Binding and 

Efficacy Assay: Anabolic steroids bind 

with the androgen receptor to exert their 

biological effect. Affinity for the 

receptor is evaluated in the receptor 

binding assay, while the transactivation 

(functional) assay provides additional 

information as to both affinity and 

ability to activate the receptor. Receptor 

binding and transactivation studies are 

valuable tools in evaluating 

pharmacological activity and drawing 

comparisons to other substances. A 

steroid displaying affinity for the 

androgen receptor and properties of 

being an agonist in transactivation 

studies is determined to be 

pharmacologically similar to 

testosterone. 

Studies used to evaluate anabolic 

steroids are the androgen receptor 

binding assay and the androgen receptor 

transactivation assay. Both are wellestablished and provide significant 

utility in evaluating steroids for affinity 

to their biological target and the 

modulation of activity. The androgen 

receptor binding assay provides specific 

detail as to the affinity of a steroid for 

the androgen receptor (biological target 

of anabolic steroids). To assess further 

whether the steroid is capable of 

activating the androgen receptor, the 

androgen receptor transactivation assay 

evaluates the binding of a steroid to the 

androgen receptor and subsequent 

interaction with DNA. In this study, 

transcription of a reporter gene provides 

information as to a steroid’s ability to 

modulate a biological event. This 

activity measurement provides 

information as to the potency of a 

steroid to bind to a receptor and either 

initiate or inhibit the transcription of 

the reporter gene. The androgen 

receptor binding assay and androgen 

receptor transactivation assay are highly 

valuable tools in assessing the potential 

activity of a steroid and comparing the 

activity to testosterone. 

Results of the Androgenic and Anabolic 

Activity Assays 

DEA reviewed the published 

scientific literature, and 

pharmacological studies were 

undertaken to collect additional 

information on prostanozol and 

methasterone in several different 

androgenic and anabolic activity assays. 

Findings from these studies indicate 

that in addition to being structurally 

similar to testosterone, prostanozol and 

methasterone have similar 

pharmacological activity as testosterone. 

Prostanozol 

The chemical synthesis and anabolic 

and androgenic effects of prostanozol 

(17b-hydroxy-5a-androstano[3,2- 

c]pyrazole) were published in 1961 

(Clinton et al., 1961). Clinton and 

coworkers evaluated the anabolic 

activity by means of nitrogen balance 

and androgenic activity based on weight 

changes of the ventral prostrate of 

prostanozol upon subcutaneous 

administration to rats with the reference 

standard testosterone propionate. The 

potency ratio of anabolic activity to 

androgenic activity for prostanozol was 

reported to be eight (Clinton et al., 

1961). In another study, prostanozol was 

reported to have approximately the 

same relative binding affinity for human 

sex steroid binding protein as 

testosterone (Cunningham et al., 1981). 

To build on these findings, a 

pharmacological study 1 was conducted 

to evaluate the anabolic and androgenic 

effects of prostanozol in castrated male 

rats. Results were compared to 

testosterone by a similar protocol. 

Administration of prostanozol to 

castrated male rats by subcutaneous 

injection prevented the atrophy (loss in 

weight) of the ventral prostate, seminal 

vesicles, and levator ani muscle.1 These 

testosterone sensitive tissues 

experienced increases in weight 

comparable to testosterone in castrated 

male rats. Results from this study 

support that prostanozol possesses both 

androgenic and anabolic activity. 

Additional studies were conducted to 

further assess prostanozol’s anabolic 

effect. In a competitive binding assay, 

prostanozol was found to possess 

affinity for the androgen receptor 

comparable to testosterone.1 In the 

androgen receptor transactivation assay, 

prostanozol displayed increased activity 

relative to testosterone.1 Effects elicited 

by prostanozol in this transactivation 

assay were consistent and comparable to 

those of testosterone. Taken together, 

data from in vitro and in vivo assays 

indicate the pharmacology of 

prostanozol to be similar to testosterone. 

Methasterone 

The synthesis of methasterone 

(2a,17a-dimethyl-5a-androstan-17b-ol3-one) was reported in 1956 and the 

anabolic activity in 1959 (Ringold and 

Rosenkranz, 1956; Ringold et al., 1959). 

Methasterone was described as a potent 

anabolic agent exhibiting weak 

androgenic activity in the castrated male 

rat (Ringold et al., 1959). Zaffaroni and 

coworkers reported methasterone 

possessed one-fifth the androgenic 

activity and four times the anabolic 

activity of the anabolic steroid 

methyltestosterone, when administered 

orally to the experimental animal 

(Zaffaroni et al., 1960). 

Additional pharmacological studies 

were undertaken to further evaluate the 

androgenic and anabolic effects of 

methasterone. 1 Methasterone was 

administered subcutaneously and orally 

to castrated male rats. By both routes of 

administration, methasterone prevented 

the atrophy (loss in weight) of ventral 

prostate, seminal vesicles, and levator 

ani muscle. Tissue weight increases for 

the castrated methasterone-treated 

animals were comparable to the 

castrated rats treated with testosterone 

and methyltestosterone. These results 

were consistent with earlier findings 

that methasterone is anabolic and 

androgenic (Zaffaroni, 1960; Ringold et 

al., 1959). Functional assays were also 

undertaken to further evaluate 

methasterone.1 Methasterone displayed 

affinity for the androgen receptor 

comparable to testosterone in a 

competitive binding assay.1 In the 

androgen receptor transactivation assay, 

methasterone displayed increased 

activity relative to testosterone.1 Effects 

elicited by methasterone in the 

androgen transactivation assay were 

consistent and comparable to those of 

testosterone. Collectively, in vivo and in 

vitro results indicate that the 

pharmacology of methasterone is similar 

to testosterone. 

(C) Not Estrogens, Progestins, and 

Corticosteroids 

DEA has determined that prostanozol 

and methasterone are unrelated to 

estrogens, progestins, and 

corticosteroids. DEA evaluated the SAR 

for each of the substances. The chemical 

structure of each substance was 

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Federal Register / Vol. 76, No. 226 / Wednesday, November 23, 2011 / Proposed Rules 72359 

compared to that of estrogens, 

progestins, and corticosteroids, since 

chemical structure can be related to its 

pharmacological and biological activity. 

DEA found that these two substances 

lack the necessary chemical structures 

to impart significant estrogenic activity 

(e.g., aromatic A ring) (Duax et al., 1988; 

Jordan et al., 1985; Williams and 

Stancel, 1996), progestational activity 

(e.g., 17b-alkyl group) (Williams and 

Stancel, 1996), or corticosteroidal 

activity (e.g., 17b-ketone group or 11bhydroxyl group) (Miller et al., 2002). 

Furthermore, methasterone was 

reported to display anti-estrogenic 

activity in mouse assay to assess 

estrogen stimulated uterine growth 

(Dorfman et al., 1961). To assess the 

estrogenic, progestational, and 

corticosteroid activity of prostanozol 

and methasterone, these substances 

were evaluated in receptor binding and 

functional transactivation assays. 

Prostanozol and methasterone showed 

low binding affinity for the estrogen, 

progesterone, and glucocorticoid 

receptors. Furthermore, these steroids 

displayed low to no transactivation 

mediated by the estrogen receptors, 

progesterone receptors, or 

glucocorticoid receptors. Therefore, 

based on these data, prostanozol and 

methasterone are not estrogens, 

progestins, or corticosteroids and these 

anabolic steroids are not exempt from 

control on this basis. 

(D) Not Dehydroepiandrosterone 

Dehydroepiandrosterone, also known 

as DHEA, is exempt from control as an 

anabolic steroid by definition (21 U.S.C. 

802(41)(A)). Prostanozol and 

methasterone are not 

dehydroepiandrosterone and therefore, 

are not exempt from control on this 

basis. 

Conclusion 

Therefore, based on the above, DEA 

concludes that prostanozol and 

methasterone 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)). 

All anabolic steroids are classified as 

Schedule III controlled substances (21 

U.S.C. 812). Once a substance is 

determined to be an anabolic steroid, 

DEA has no discretion regarding the 

scheduling of these substances. As 

discussed further below, all 

requirements pertaining to controlled 

substances in Schedule III would 

pertain to these substances. 

Impact of Proposed Rule and Effect of 

Classifying These Substances as 

Anabolic Steroids 

If this rulemaking is finalized as 

proposed, DEA will classify prostanozol 

(17b-hydroxy-5a-androstano[3,2- 

c]pyrazole) and methasterone (2a,17adimethyl-5a-androstan-17b-ol-3-one) as 

Schedule III anabolic steroids. If 

classified as Schedule III anabolic 

steroids, any person who manufactures, 

distributes, dispenses, imports, or 

exports prostanozol or methasterone or 

who engages in research or conducts 

instructional activities with respect to 

these two substances would be required 

to obtain a Schedule III registration in 

accordance with the CSA and its 

implementing regulations. 

Manufacturers and importers of these 

two substances would be required to 

register with DEA and would be 

permitted to distribute these substances 

only to other DEA registrants. Only 

persons registered as dispensers would 

be allowed to dispense these substances 

to end users. The CSA defines a 

practitioner as ‘‘a physician, dentist, 

veterinarian, scientific investigator, 

pharmacy, hospital, or other person 

licensed, registered, or otherwise 

permitted, by the United States or the 

jurisdiction in which he practices or 

does research, to distribute, dispense, 

conduct research with respect to, 

administer, or use in teaching or 

chemical analysis, a controlled 

substance in the course of professional 

practice or research.’’ 21 U.S.C. 802(21). 

At present, there are no approved 

medical uses for these two substances. 

Until a manufacturer applies to the FDA 

and gains approval for products 

containing these substances, no person 

may dispense them in response to a 

prescription. 

Manufacture, import, export, 

distribution, or sale of prostanozol (17bhydroxy-5a-androstano[3,2-c]pyrazole) 

and methasterone (2a,17a-dimethyl-5aandrostan-17b-ol-3-one) except by DEA 

registrants, would become a violation of 

the CSA that may result in 

imprisonment and fines (see, e.g., 21 

U.S.C. 841, 960). Possession of these 

two steroids, unless legally obtained, 

would also become subject to criminal 

penalties (21 U.S.C. 844). 

In addition, under the CSA, these two 

substances could be imported only for 

medical, scientific, or other legitimate 

uses (21 U.S.C. 952(b)) under an import 

declaration filed with DEA (21 CFR 

1312.18). Importation of these 

substances would be illegal unless the 

person importing these substances is 

registered with DEA as an importer or 

researcher and files the required 

declaration for each shipment. An 

individual who purchases either of 

these substances directly from foreign 

companies and has them shipped to the 

United States will be considered to be 

importing even if the steroids are 

intended for personal use. Illegal 

importation of these substances would 

be a violation of the CSA that may result 

in imprisonment and fines (21 U.S.C. 

960). 

Requirements for Handling Substances 

Defined as Anabolic Steroids 

Upon consideration of public 

comments from this NPRM, DEA may 

issue a final rule classifying prostanozol 

(17b-hydroxy-5a-androstano[3,2- 

c]pyrazole) and methasterone (2a,17adimethyl-5a-androstan-17b-ol-3-one) as 

anabolic steroids. If classified as 

anabolic steroids, prostanozol and 

methasterone would become 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: 

Registration. Any person who 

manufactures, distributes, dispenses, 

imports, exports, or engages in research 

or conducts instructional activities with 

a substance defined as an anabolic 

steroid, or who desires to engage in such 

activities, would be required to be 

registered to conduct such activities 

with Schedule III controlled substances 

in accordance with 21 CFR Part 1301. 

Security. Substances defined as 

anabolic steroids would be subject to 

Schedule III–V security requirements 

and would be required to be 

manufactured, distributed, and stored in 

accordance with 21 CFR 1301.71, 

1301.72(b), (c), and (d), 1301.73, 

1301.74, 1301.75(b) and (c), 1301.76 and 

1301.77. 

Labeling and Packaging. All labels 

and labeling for commercial containers 

of substances defined as anabolic 

steroids would be required to comply 

with requirements of 21 CFR 1302.03– 

1302.07. 

Inventory. Every registrant required to 

keep records and who possesses any 

quantity of any substance defined as an 

anabolic steroid would be required to 

keep an inventory of all stocks of the 

substances on hand pursuant to 21 

U.S.C. 827 and 21 CFR 1304.03, 1304.04 

and 1304.11. Every registrant who 

desires registration in Schedule III for 

any substance defined as an anabolic 

steroid would be required to conduct an 

inventory of all stocks of the substances 

on hand at the time of registration. 

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72360 Federal Register / Vol. 76, No. 226 / Wednesday, November 23, 2011 / Proposed Rules 

Records. All registrants would be 

required to keep records, as generally 

provided in 21 U.S.C. 827(a) and 

specifically pursuant to 21 CFR 1304.03, 

1304.04, 1304.05, 1304.21, 1304.22, 

1304.23 and 1304.26. 

Prescriptions. All prescriptions for 

these Schedule III substances or for 

products containing these Schedule III 

substances would be required to be 

issued pursuant to 21 U.S.C. 829(b) and 

21 CFR 1306.03–1306.06 and 1306.21– 

1306.27. All prescriptions for these 

Schedule III compounds or for products 

containing these Schedule III 

substances, if authorized for refilling, 

would be limited to five refills within 

six months of the date of issuance of the 

prescription. Controlled substance 

dispensing via the Internet would have 

to comply with 21 U.S.C. 829(e). 

Importation and Exportation. All 

importation and exportation of any 

substance defined as an anabolic steroid 

would be required to be in compliance 

with 21 U.S.C. 952(b) and 953(e) and 21 

CFR Part 1312. 

Criminal Liability. Any activity with 

any substance defined as an anabolic 

steroid not authorized by, or in violation 

of, the Controlled Substances Act or the 

Controlled Substances Import and 

Export Act would be unlawful. 

Disposal of Anabolic Steroids 

If this regulation is finalized as 

proposed, persons who possess 

substances that become 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. The DEA 

Diversion field office will provide the 

person with instructions regarding the 

disposal. A list of local DEA Diversion 

field offices may be found at http:// 

www.deadiversion.usdoj.gov. 

Regulatory Analyses 

Regulatory Flexibility Act 

The Administrator hereby certifies 

that this rulemaking has been drafted in 

accordance with the Regulatory 

Flexibility Act (5 U.S.C. 601–612). DEA 

is not able to determine whether this 

regulation, if promulgated as a Final 

Rule, will not have a significant 

economic impact on a substantial 

number of small entities. DEA has not 

identified any company based in the 

United States that manufactures or 

distributes these substances. Thus, DEA 

does not believe this proposed rule 

would have a significant economic 

impact on a substantial number of small 

entities. Because DEA is unable to 

determine whether this regulation as 

proposed would have a significant 

economic impact on a substantial 

number of small entities, DEA seeks 

comment on whether this regulation, if 

promulgated as a Final Rule, will have 

a significant economic impact on a 

substantial number of small entities. 

As of March 2010, DEA had identified 

approximately 75 dietary supplements 

that were currently or had been 

promoted for building muscle and 

increasing strength that purported to 

contain prostanozol or methasterone. 

Thirteen dietary supplements were 

purported to contain prostanozol and 62 

dietary supplements were purported to 

contain methasterone. These dietary 

supplements are marketed and sold over 

the Internet. 

The manufacturers and distributors of 

dietary supplements purported to 

contain prostanozol and methasterone 

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. Without 

information on the percentage of 

revenues derived from these dietary 

supplements, DEA is not able to 

determine the economic impact of the 

removal of these dietary supplements 

alone on the business of the firms. 

These steroids have been the focus of 

warning letters issued by the FDA. 

However, products continue to be 

marketed despite these warnings. DEA 

has not been able to identify any 

chemical manufacturers that are 

currently using these substances as 

intermediates in their manufacturing 

process(es). 

As of March 2010, DEA had identified 

13 chemical manufacturers and 

distributors that sell at least one of the 

two steroids addressed in this NPRM. 

Most of these companies are located in 

China and sell a variety of other 

anabolic 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. DEA has not identified any 

company based in the United States that 

manufactures or distributes these 

substances. DEA notes, upon placement 

into Schedule III, these substances may 

be used for analytical purposes. 

Executive Orders 12866 and 13563 

This rulemaking has been drafted in 

accordance with the principles of 

Executive Order 12866, 1(b), as 

reaffirmed by Executive Order 13563. 

This rule is not a significant regulatory 

action but has been reviewed by the 

Office of Management and Budget. As 

discussed above, the effect of this rule 

would be to remove products containing 

these substances from the over-thecounter 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 

in 2009 was $5.9 million. These two 

substances would be a subset of those 

imports. The total market for products 

containing these substances, therefore, 

is probably quite small. Moreover, DEA 

believes that the importation of these 

two substances is for illegitimate 

purposes. 

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 

would 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 would bar the importation, 

exportation, and sale of these two 

substances except for legitimate 

research or industrial uses. 

Executive Order 12988 

This regulation meets the applicable 

standards set forth in Sections 3(a) and 

3(b)(2) of Executive Order 12988 Civil 

Justice Reform. 

Executive Order 13132 

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. 

Executive Order 13175 

This proposed rule will not have 

Tribal implications and will not impose 

substantial direct compliance costs on 

Indian Tribal governments. 

Paperwork Reduction Act 

This rule proposes to regulate two 

anabolic steroids, which are neither 

approved for medical use in humans nor 

approved for administration to cattle or 

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Federal Register / Vol. 76, No. 226 / Wednesday, November 23, 2011 / Proposed Rules 72361 

other non-humans. Under this proposal, 

only chemical manufacturers who may 

use these substances as chemical 

intermediates for the synthesis of other 

steroids would be required to register 

with DEA under the CSA. However, 

DEA has not been able to identify any 

chemical manufacturers that are 

currently using these substances as 

intermediates in their manufacturing 

process(es). Although this proposal is 

unlikely to impose a new collection of 

information requirement under the 

Paperwork Reduction Act of 1995, 44 

U.S.C. 3501–3521, DEA is nevertheless 

seeking input from the chemical 

industry on any manufacturing 

process(es) that may be affected. 

Unfunded Mandates Reform Act of 1995 

This rule will not result in the 

expenditure by state, local, and Tribal 

governments, in the aggregate, or by the 

private sector, of $136,000,000 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, 2 U.S.C. 

1532. 

List of Subjects in 21 CFR Part 1300 

Chemicals, Drug traffic control. 

For the reasons set out above, 21 CFR 

part 1300 is proposed to be amended as 

follows: 

PART 1300—DEFINITIONS 

1. The authority citation for part 1300 

continues to read as follows: 

Authority: 21 U.S.C. 802, 821, 829, 871(b), 

951, 958(f). 

2. Section 1300.01 is proposed to be 

amended by: 

A. Redesignating paragraphs 

(b)(4)(xxxii) through (b)(4)(lxiii) as 

(b)(4)(xxxiii) through (b)(4)(lxiv), 

B. Adding a new paragraph 

(b)(4)(xxxii), 

C. Further redesignating newly 

designated paragraphs (b)(4)(lviii) 

through (b)(4)(lxiv) as (b)(4)(lix) through 

(b)(4)(lxv), and 

D. Adding new paragraph (b)(4)(lviii). 

The additions read as follows: 

§ 1300.01 Definitions relating to controlled 

substances. 

* * * * * 

(b) * * * 

(4) * * * 

(xxxii) Methasterone (2a,17adimethyl-5a-androstan-17b-ol-3-one) 

* * * * * 

(lviii) Prostanozol (17b-hydroxy-5aandrostano[3,2-c]pyrazole) 

* * * * * 

Dated: November 8, 2011. 

Michele M. Leonhart, 

Administrator. 

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[FR Doc. 2011–30081 Filed 11–22–11; 8:45 am] 

BILLING CODE 4410–09–P 

DEPARTMENT OF THE TREASURY 

Internal Revenue Service 

26 CFR Part 1 

[REG–149625–10] 

RIN 1545–BK03 

Application of the Segregation Rules 

to Small Shareholders 

AGENCY: Internal Revenue Service (IRS), 

Treasury. 

ACTION: Notice of proposed rulemaking. 

SUMMARY: This document contains 

proposed regulations under section 382 

of the Internal Revenue Code (Code). 

These proposed regulations provide 

guidance regarding the application of 

the segregation rules to public groups 

under section 382 of the Code. These 

regulations affect corporations. 

DATES: Written or electronic comments 

and requests for a public hearing must 

be received by February 21, 2012. 

ADDRESSES: Send submissions to: 

CC:PA:LPD:PR (REG–149625–10), room 

5203, Internal Revenue Service, P.O. 

Box 7604, Ben Franklin Station, 

Washington, DC 20044. Submissions 

may be hand delivered Monday through 

Friday between the hours of 8 a.m. and 

4 p.m. to CC:PA:LPD:PR (REG–149625– 

10), Courier’s Desk, Internal Revenue 

Service, 1111 Constitution Avenue NW., 

Washington, DC, or sent electronically 

via the Federal eRulemaking Portal at 

http://www.regulations.gov/ (IRS REG– 

149625–10). 

FOR FURTHER INFORMATION CONTACT: 

Concerning the proposed regulations, 

Stephen R. Cleary, (202) 622–7750; 

concerning submission of comments or 

to request a public hearing, 

Oluwafunmilayo (Funmi) P. Taylor, 

(202) 622–7180 (not toll-free numbers). 

SUPPLEMENTARY INFORMATION: 

Background 

1. Segregation and Aggregation— 

Statute, Legislative History, and Current 

Regulations 

Section 382 imposes a limitation on a 

corporation’s use of net operating loss 

carryovers following a change in 

ownership. The legislative history 

explains that a limitation is necessary 

following a change in ownership 

because new shareholders otherwise 

would have an opportunity to 

contribute income-producing assets (or 

divert income opportunities) to the 

corporation, thus inappropriately 

accelerating the use of net operating loss 

carryovers. The section 382 limitation is 

intended to prevent a corporation from 

obtaining greater loss utilization than it 

could have achieved absent a change in 

ownership. S. Rep. No. 99–313 at 232 

(1986). 

A loss corporation has an ownership 

change if the percentage of stock of a 

loss corporation that is owned by one or 

more 5-percent shareholders has 

increased by more than 50 percentage 

points over the lowest percentage of 

stock of the loss corporation owned by 

such shareholders at any time during 

the testing period (generally, a threeyear period). For purposes of section 

382, the attribution rules of section 

318(a)(2) apply, without limitation, to 

treat individuals as the owners of loss 

corporation stock. Pursuant to section 

382(g)(4)(A), individual shareholders 

who own less than five percent of a loss 

corporation are aggregated and treated 

as a single 5-percent shareholder (a 

public group). 

The regulations extend the public 

group concept to situations in which a 

loss corporation is owned by one or 

more entities, as defined in § 1.382–3(a) 

(generally, partnerships, corporations, 

estates, and trusts). If an entity directly 

or indirectly owns five percent or more 

of the loss corporation, that entity has 

its own public group if its owners who 

are not 5-percent shareholders own, in 

the aggregate, five percent or more of the 

loss corporation. (Such an entity is 

referred to as a 5-Percent Entity in this 

preamble.) 

The segregation rules, which are 

generally contained in § 1.382–2T(j), 

and the exceptions thereto, which are 

generally contained in § 1.382–3(j), 

apply to certain transactions affecting 

ownership by the loss corporation’s 

direct public group and by the public 

groups of a 5-Percent Entity. The 

application of the segregation rules 

results in the creation of a new public 

group in addition to the one (or more) 

that existed previously. That new group 

is treated as a new 5-percent 

shareholder that increases its ownership 

interest in the loss corporation. 

Section 382(g)(4)(B) mandates 

application of the segregation rules to 

transactions constituting equity 

structure shifts of the loss corporation. 

Generally, equity structure shifts are 

acquisitive asset reorganizations and 

recapitalizations under section 368. 

Section 382(g)(3)(B) provides regulatory 

authority to treat public offerings and 

similar transactions as equity structure 

shifts. Pursuant to that authority, the 

current segregation rules, subject to the 

cash issuance and small issuance 

exceptions (described in this preamble), 

treat issuances of stock under section 

1032, redemptions, and redemption-like 

transactions as segregation events. The 

segregation rules also apply to transfers 

of loss corporation stock by an 

individual 5-percent shareholder to 

public shareholders and a 5-Percent 

Entity’s transfer of loss corporation 

stock to public shareholders. 

The small issuance and cash issuance 

exceptions exempt certain amounts of 

stock issuances from the segregation 

rules. Generally, the small issuance 

exception exempts the total amount of 

stock issued during a taxable year to the 

extent it does not exceed 10 percent of 

the total value of the corporation’s 

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