Federal Register / Vol. 88, No. 205 / Wednesday, October 25, 2023 / Proposed Rules 73293 

1Though DEA has used the term ‘‘final order’’ 

with respect to temporary scheduling orders in the 

past, this notice of intent adheres to the statutory 

language of 21 U.S.C. 811(h), which refers to a 

‘‘temporary scheduling order.’’ No substantive 

change is intended. 

the CO hazard presented by gas furnaces and 

boilers and the market for gas furnaces and 

boilers is forecast to grow. The rule 

establishes performance requirements to 

address the risk of CO poisoning associated 

with residential gas furnaces and boilers. The 

effective date provides a reasonable amount 

of time for manufacturers to comply with the 

rule and produce products that prevent the 

CO hazard. Given the deaths and injuries 

associated with CO leakage from gas furnaces 

and boilers, the Commission finds that the 

rule and its effective date are necessary to 

address the unreasonable risk of injury 

associated with gas furnaces and boilers. 

F. Public Interest 

The rule addresses an unreasonable risk of 

death and injuries presented from CO 

hazards associated with gas furnaces and 

boilers. Adherence to the requirements of the 

rule would reduce deaths and injuries from 

CO poisoning associated with gas furnaces 

and boilers; thus, the rule is in the public 

interest. 

G. Voluntary Standards 

If a voluntary standard addressing the risk 

of injury has been adopted and implemented, 

then the Commission must find that the 

voluntary standard is not likely to eliminate 

or adequately reduce the risk of injury or 

substantial compliance with the voluntary 

standard is unlikely. The Commission 

determines that the relevant U.S. voluntary 

standards (ANSI Z21.13–2022, ANSI Z21.47– 

2021, and ANSI Z21.86–2016) do not contain 

performance requirements to protect against 

the known failure modes or conditions 

identified that have been associated with the 

production and leakage of CO into living 

spaces of U.S. residences resulting in 

numerous deaths and injuries, and thus do 

not adequately address the hazard of CO 

exposure from residential gas furnaces and 

boilers. 

H. Reasonable Relationship of Benefits to 

Costs 

The Commission determines the benefits 

expected from the rule bear a reasonable 

relationship to its costs. The rule 

significantly reduces the CO hazard 

associated with residential gas furnaces and 

boilers, and thereby reduces the societal costs 

of the resulting injuries and deaths. When 

costs are compared to benefits, the estimated 

costs of the rule are greater than the 

estimated benefits. Staff calculates net 

benefits (benefits less costs) to be ¥$245.74 

million on annualized basis, discounted at 

three percent. The net benefits on per-unit 

basis are ¥$64.51, discounted at three 

percent. Alternatively, this can be described 

as the proposed rule being a net cost of 

¥64.51 per gas furnace or boiler, which 

represents approximately three percent of the 

average price of a gas furnace or boiler. 

Overall, the proposed rule has a benefit-cost 

ratio of 0.59; in other words, for every $1 in 

cost of the proposed rule, there is a return of 

$0.59 in benefits from mitigated deaths and 

injuries. However, the rule is estimated to 

address 90–100 percent of deaths caused by 

the CO hazard associated with gas furnaces 

and boilers, resulting in potential total 

societal annualized benefits from the rule of 

$356.52 million, discounted at three percent. 

Staff conducted a sensitivity analysis that 

showed if by 2035 manufacturers were able 

to develop compliant gas furnaces and 

boilers with CO sensors that did not need 

replacement, and if the analysis took into 

account that a child’s death is considered 

twice as costly as an adult death, the benefitcost ratio would increase to 0.78. 

I. Least-Burdensome Requirement That 

Would Adequately Reduce the Risk of Injury 

The Commission considered four 

alternatives to the proposed rule: (1) continue 

to work and advocate for change through the 

voluntary standards process; (2) rely on the 

use of residential CO alarms; (3) continue to 

conduct education and information 

campaigns; and (4) rely on recalls. Although 

these alternatives may be less burdensome 

alternatives to the rule, the Commission 

determines that none of the alternatives 

would adequately reduce the risk of deaths 

and injuries associated with gas furnaces and 

boilers that is addressed by the rule. 

Elina Lingappa, 

Paralegal Specialist, Consumer Product 

Safety Commission. 

[FR Doc. 2023–23302 Filed 10–24–23; 8:45 am] 

BILLING CODE 6355–01–P 

DEPARTMENT OF JUSTICE 

Drug Enforcement Administration 

21 CFR Part 1308 

[Docket No. DEA–1143] 

Schedules of Controlled Substances: 

Temporary Placement of N-Desethyl 

Isotonitazene and N-Piperidinyl 

Etonitazene in Schedule I 

AGENCY: Drug Enforcement 

Administration, Department of Justice. 

ACTION: Proposed amendment; notice of 

intent. 

SUMMARY: The Administrator of the Drug 

Enforcement Administration is issuing 

this notice of intent to publish a 

temporary order to schedule two 

synthetic benzimidazole-opioid 

substances, including their isomers, 

esters, ethers, salts, and salts of isomers, 

esters, and ethers whenever the 

existence of such isomers, esters, ethers, 

and salts is possible, in schedule I of the 

Controlled Substances Act. When it is 

issued, the temporary scheduling order 

will impose the regulatory controls and 

administrative, civil, and criminal 

sanctions applicable to schedule I 

controlled substances on persons who 

handle (manufacture, distribute, reverse 

distribute, import, export, engage in 

research, conduct instructional 

activities or chemical analysis, or 

possess) or propose to handle these two 

specified substances. 

DATES: October 25, 2023. 

FOR FURTHER INFORMATION CONTACT: 

Terrence L. Boos, Drug and Chemical 

Evaluation Section, Diversion Control 

Division, Drug Enforcement 

Administration; Mailing Address: 8701 

Morrissette Drive, Springfield, Virginia 

22152; Telephone: (571) 362–3249. 

SUPPLEMENTARY INFORMATION: The notice 

of intent contained in this document is 

issued pursuant to the temporary 

scheduling provisions of 21 U.S.C. 

811(h). The Drug Enforcement 

Administration (DEA) intends to issue a 

temporary scheduling order 1 (in the 

form of a temporary amendment) to add 

the following two substances, including 

their isomers, esters, ethers, salts, and 

salts of isomers, esters, and ethers 

whenever the existence of such isomers, 

esters, ethers, and salts is possible, to 

schedule I under the Controlled 

Substances Act (CSA): 

• N-ethyl-2-(2-(4-isopropoxybenzyl)-5- 

nitro-1H-benzimidazol-1-yl)ethan-1- 

amine (commonly known as N-desethyl 

isotonitazene), and 

• 2-(4-ethoxybenzyl)-5-nitro-1-(2- 

(piperidin-1-yl)ethyl)-1H-benzimidazole 

(commonly known as either Npiperidinyl etonitazene or 

etonitazepipne). 

The temporary scheduling order will 

be published in the Federal Register on 

or after November 24, 2023. 

Legal Authority 

The CSA provides the Attorney 

General (as delegated to the 

Administrator of DEA (Administrator) 

pursuant to 28 CFR 0.100) with the 

authority to temporarily place a 

substance in schedule I of the CSA for 

two years without regard to the 

requirements of 21 U.S.C. 811(b), if he 

finds that such action is necessary to 

avoid an imminent hazard to the public 

safety. 21 U.S.C. 811(h)(1). In addition, 

if proceedings to control a substance are 

initiated under 21 U.S.C. 811(a)(1) while 

the substance is temporarily controlled 

under section 811(h), the Attorney 

General may extend the temporary 

scheduling for up to one year. 21 U.S.C. 

811(h)(2). 

Where the necessary findings are 

made, a substance may be temporarily 

scheduled if it is not listed in any other 

schedule under 21 U.S.C. 812, or if there 

is no exemption or approval in effect for 

the substance under section 505 of the 

Federal Food, Drug, and Cosmetic Act, 


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2The Secretary of HHS has delegated to the 

Assistant Secretary for Health of HHS the authority 

to make domestic drug scheduling 

recommendations. 58 FR 35460, July 1, 1993. 

3Butonitazene, etodesnitazene, flunitazene, 

metodesnitazene, metonitazene, N-pyrrolidino 

etonitazene, and protonitazene 

21 U.S.C. 355. 21 U.S.C. 811(h)(1); 21 

CFR part 1308. 

Background 

The CSA requires the Administrator 

to notify the Secretary of the 

Department of Health and Human 

Services (HHS) of an intent to place a 

substance in schedule I of the CSA 

temporarily (i.e., to issue a temporary 

scheduling order). 21 U.S.C. 811(h)(4). 

The Administrator transmitted the 

required notice to the Assistant 

Secretary for Health of HHS (Assistant 

Secretary),2 by letter dated April 3, 

2023, regarding N-desethyl 

isotonitazene and N-piperidinyl 

etonitazene. The Assistant Secretary 

responded to this notice by letter dated 

May 11, 2023, and advised that based on 

a review by the Food and Drug 

Administration (FDA), there are 

currently no investigational new drug 

applications (INDs) or approved new 

drug applications (NDAs) for N-desethyl 

isotonitazene and N-piperidinyl 

etonitazene. The Assistant Secretary 

also stated that HHS had no objection to 

the temporary placement of these 

substances in schedule I. N-Desethyl 

isotonitazene and N-piperidinyl 

etonitazene currently are not listed in 

any schedule under the CSA, and no 

exemptions or approvals under 21 

U.S.C. 355 are in effect for these 

substances. 

To find that temporarily placing a 

substance in schedule I of the CSA is 

necessary to avoid an imminent hazard 

to the public safety, the Administrator 

must consider three of the eight factors 

set forth in 21 U.S.C. 811(c): the 

substance’s history and current pattern 

of abuse; the scope, duration, and 

significance of abuse; and what, if any, 

risk there is to the public health. 21 

U.S.C. 811(h)(3). This consideration 

includes any information indicating 

actual abuse, diversion from legitimate 

channels, and clandestine importation, 

manufacture, or distribution of these 

substances. 21 U.S.C. 811(h)(3). 

Substances meeting the statutory 

requirements for temporary scheduling 

may only be placed in schedule I. 21 

U.S.C. 811(h)(1). Substances in schedule 

I have high potential for abuse, no 

currently accepted medical use in 

treatment in the United States, and a 

lack of accepted safety for use under 

medical supervision. 21 U.S.C. 

812(b)(1). 

Two Benzimidazole-Opioids: NDesethyl Isotonitazene and NPiperidinyl Etonitazene 

The continued encounter of novel 

psychoactive substances (NPS) on the 

recreational drug market poses a threat 

to public safety. Following the classwide scheduling of fentanyl-related 

substances, there has been an increase 

in the emergence of synthetic opioids 

that are not structurally related to 

fentanyl. Beginning in 2019, a new class 

of synthetic opioids known as 

benzimidazole-opioids, commonly 

referred to as ‘‘nitazenes,’’ emerged on 

the recreational drug market. This class 

of substances was first synthesized in 

the 1950s by CIBA Aktiengesellschaft in 

Switzerland, and it has a similar 

pharmacological profile to fentanyl, 

morphine, and other mu-opioid receptor 

agonists. Between August 2020 and 

April 2022, DEA temporarily controlled 

eight benzimidazole-opioids because 

they posed a threat to public safety. 87 

FR 21556 (Apr. 12, 2022); 85 FR 51342 

(Aug. 20, 2020). Recently, additional 

benzimidazole-opioids have been 

identified within the rapidly expanding 

class of ‘‘nitazene’’ compounds on the 

recreational drug market. N-Desethyl 

isotonitazene and N-piperidinyl 

etonitazene are some of the recently 

encountered ‘‘nitazene’’ synthetic 

opioids identified on the illicit drug 

market. 

The continued trafficking and 

identification of benzimidazole-opioids 

in toxicology cases pose a significant 

threat to public health and safety. 

Adverse health effects associated with 

the misuse and abuse of synthetic 

opioids have led to devastating 

consequences including death. 

Preclinical pharmacology data 

demonstrate that N-desethyl 

isotonitazene and N-piperidinyl 

etonitazene have pharmacological 

profiles similar to those of the potent 

benzimidazole-opioids etonitazene and 

isotonitazene, schedule I opioid 

substances. N-Desethyl isotonitazene, an 

active metabolite of isotonitazene, has 

been positively identified in 

postmortem cases that involved 

isotonitazene. N-Piperidinyl etonitazene 

has been positively identified in at least 

three toxicology cases. As the United 

States continues to experience a high 

number of opioid-involved overdoses 

and mortalities, the introduction of new 

designer opioids further exacerbates the 

current opioid epidemic. 

Available data and information for Ndesethyl isotonitazene and Npiperidinyl etonitazene, summarized 

below, indicate that these substances 

have high potentials for abuse, no 

currently accepted medical uses in 

treatment in the United States, and a 

lack of accepted safety for use under 

medical supervision. DEA’s three-factor 

analysis is available in its entirety under 

‘‘Supporting and Related Material’’ of 

the public docket for this action at 

www.regulations.gov under Docket 

Number DEA–1143. 

Factor 4. History and Current Pattern of 

Abuse 

In the late 1950s, pharmaceutical 

research laboratories of the Swiss 

chemical company CIBA 

Aktiengesellschaft synthesized a group 

of structurally unique benzimidazole 

derivatives with analgesic properties; 

however, the research effort did not 

produce any medically approved 

analgesic products. These 

benzimidazole derivatives include 

schedule I substances, such as synthetic 

opioids clonitazene, etonitazene, and 

isotonitazene. 

Since 2019, there has been an 

emergence of nitazene compounds on 

the illicit drug market, which have been 

positively identified in numerous cases 

of fatal overdose events. In August 2020, 

isotonitazene was placed in schedule I 

of the CSA (85 FR 51342). Subsequently, 

seven additional benzimidazoleopioids 3 have been placed in schedule 

I of the CSA (87 FR 21556). 

Recently, two additional 

benzimidazole-opioids have emerged on 

the illicit drug market. Law enforcement 

officers have encountered N-desethyl 

isotonitazene and N-piperidinyl 

etonitazene in several solid forms (e.g., 

powder and tablets). These substances 

are not approved pharmaceutical 

products and are not approved for 

medical use anywhere in the world. The 

Assistant Secretary in a letter to DEA 

dated May 11, 2023, stated that there are 

no FDA-approved NDAs or INDs for Ndesethyl isotonitazene and Npiperidinyl etonitazene in the United 

States; hence, there are no legitimate 

channels for these substances as 

marketed drug products. 

The appearance of benzimidazoleopioids on the illicit drug market is 

similar to other designer opioid drugs 

that are trafficked for their psychoactive 

effects. These substances are likely to be 

abused in the same manner as schedule 

I opioids, such as etonitazene, 

isotonitazene, and heroin. 

In 2022, N-desethyl isotonitazene was 

identified in counterfeit tablets in the 

United States and United Kingdom. 

Recent reporting by Center for Forensic 


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4CFSRE NPS Discovery Public Alert 2023. Case 

Example—N-desethyl isotonitazene. January 2023. 

5A partnership between the American College of 

Medical Toxicology (ACMT) and the Center for 

Forensic Science Research and Education (CFSRE) 

was established to comprehensively assess the role 

and prevalence of synthetic opioids and other drugs 

among suspected overdose events in the United 

States. CFSRE NPS Monograph. N-Piperidinyl 

etonitazene. November 22, 2021. 

6Email communication with EMCDDA dated 

January 23, 2023. 

7While law enforcement data are not direct 

evidence of abuse, it can lead to an inference that 

a drug has been diverted and abused. See 76 FR 

77330, 77332 (Dec. 12, 2011). 

8NFLIS-Drug represents an important resource in 

monitoring illicit drug trafficking, including the 

diversion of legally manufactured pharmaceuticals 

into illegal markets. NFLIS-Drug is a comprehensive 

information system that includes data from forensic 

laboratories that handle the nation’s drug analysis 

cases. NFLIS-Drug participation rate, defined as the 

percentage of the national drug caseload 

represented by laboratories that have joined NFLISDrug, is currently 98.5 percent. NFLIS-Drug 

includes drug chemistry results from completed 

analyses only. While NFLIS-Drug data is not direct 

evidence of abuse, it can lead to an inference that 

a drug has been diverted and abused. See 76 FR 

77330, 77332. NFLIS-Drug data was queried on 

January 19, 2023. 

9CFSRE NPS Discovery Public Alert January 

2023. Accessed January 25, 2023. 

10NSDUH, formerly known as the National 

Household Survey on Drug Abuse (NHSDA), is 

conducted annually by the Department of Health 

and Human Services’ Substance Abuse and Mental 

Health Services Administration (SAMHSA). It is the 

primary source of estimates of the prevalence and 

incidence of nonmedical use of pharmaceutical 

drugs, illicit drugs, alcohol, and tobacco use in the 

United States. The survey is based on a nationally 

representative sample of the civilian, noninstitutionalized population 12 years of age and 

older. The survey excludes homeless people who 

do not use shelters, active military personnel, and 

residents of institutional group quarters such as 

jails and hospitals. The NSDUH provides yearly 

national and state level estimates of drug abuse, and 

includes prevalence estimates by lifetime (i.e., ever 

used), past year, and past month abuse or 

dependence. The 2021 NSDUH annual report is 

available at Key Substance Use and Mental Health 

Indicators in the United States: Results from the 

2021 National Survey on Drug Use and Health 

(samhsa.gov) (last accessed January 24, 2023). 

Science Research and Education 

(CFSRE) indicates that in the United 

States, N-desethyl isotonitazene was 

identified in counterfeit oxycodone 

round blue tablets in Florida.4 Further, 

in December 2022, N-desethyl 

isotonitazene was identified in samples 

called ‘‘dope’’ in the Philadelphia drug 

supply. N-Desethyl isotonitazene was 

also co-identified in ‘‘dope’’ samples 

containing xylazine, fentanyl, parafluorofentanyl, and designer 

benzodiazepines (e.g., flubromazepam 

and bromazolam). 

In 2021, N-piperidinyl etonitazene 

emerged on the illicit synthetic drug 

market, as evidenced by its 

identification in toxicological analysis 

of biological samples.5 In addition, there 

have been encounters of N-piperidinyl 

etonitazene in Europe. As reported in 

January 2022 by the European 

Monitoring Center for Drugs and Drug 

Addiction (EMCDDA), the European 

Union Early Warning System Network 

identified N-piperidinyl etonitazene in 

Germany in October 2021. As of January 

23, 2023, a total of four European 

countries have reported identifications 

of N-piperidinyl etonitazene in powder 

form to the EMCDDA.6

Factor 5. Scope, Duration and 

Significance of Abuse 

N-Desethyl isotonitazene and Npiperidinyl etonitazene, similar to 

etonitazene and isotonitazene (schedule 

I substances), have been described as 

potent synthetic opioids, and evidence 

suggests they are abused for their 

opioidergic effects. The abuse of these 

benzimidazole-opioids, similar to other 

synthetic opioids, has resulted in 

serious adverse health effects. Between 

October 2019 and January 2020, Ndesethyl isotonitazene was positively 

identified in 13 postmortem samples 

and 64 driving-under-the-influence-ofdrugs (DUID) cases involving 

isotonitazene in the United States. 

Although, N-desethyl isotonitazene has 

only been identified as a metabolite of 

isotonitazene in toxicology cases, the 

pharmacological profile of this 

substance demonstrates it is a highly 

potent synthetic opioid similar to 

etonitazene, isotonitazene, and fentanyl. 

As such, the identification of this 

substance as a parent drug in the 

recreational drug market is worrisome. 

Data from law enforcement suggest 

that N-desethyl isotonitazene and Npiperidinyl etonitazene are being 

abused in the United States as 

recreational drugs.7 Since 2022, there 

have been three encounters reported to 

DEA’s National Forensic Laboratory 

Information System (NFLIS)-Drug 8

(Federal, State, and local laboratories) 

database pertaining to the trafficking, 

distribution, and abuse of N-desethyl 

isotonitazene. These three encounters of 

N-desethyl isotonitazene were reported 

to NFLIS-Drug from two states: Florida 

(2) and Kansas (1). 

Based on information collected from 

NFLIS-Drug, N-desethyl isotonitazene 

was identified in tablet form or as 

residue. Reporting from CFSRE show 

that N-desethyl isotonitazene was 

identified in a counterfeit oxycodone 

tablet in Florida,9 suggestive that it 

might be presented as a substitute for 

heroin or fentanyl and likely abused in 

the same manner as either of those 

substances. 

The lack of identification of Npiperidinyl etonitazene in NFLIS-Drug 

may be due to the rapid appearance of 

these benzimidazole-opioids and under 

reporting as forensic laboratories try to 

secure reference standards for this 

substance. However, N-piperidinyl 

etonitazene has been positively 

identified in toxicology cases in the 

United States and encountered by law 

enforcement in Europe. 

The population likely to abuse these 

benzimidazole-opioids appears to be the 

same as those abusing prescription 

opioid analgesics, fentanyl, and other 

synthetic drugs. This is evidenced by 

the types of other drugs co-identified in 

biological samples and law enforcement 

encounters. Because abusers of Ndesethyl isotonitazene and Npiperidinyl etonitazene are likely to 

obtain these substances through 

unregulated sources, the identity, 

purity, and quantity of these substances 

are uncertain and inconsistent, thus 

posing significant adverse health risks 

to the end user. The misuse and abuse 

of opioids have been demonstrated and 

are well-characterized. According to the 

most recent data from the National 

Survey on Drug Use and Health 

(NSDUH),10 as of 2021, an estimated 9.2 

million people aged 12 years or older 

misused opioids in the past year, 

including 8.7 million prescription pain 

reliever misusers and 1.1 million heroin 

users. In 2021, an estimated 5.6 million 

people had an opioid use disorder in the 

past year, which included 5.0 million 

people with a prescription pain reliever 

use disorder and 1.0 million people 

with heroin use disorder. This 

population abusing opioids is likely to 

be at risk of abusing N-desethyl 

isotonitazene and N-piperidinyl 

etonitazene. Individuals who initiate 

(i.e., use a drug for the first time) use of 

these benzimidazole-opioids are likely 

to be at risk of developing substance use 

disorder, overdose, and/or death, 

similar to that of other opioid analgesics 

(e.g., fentanyl, morphine, etc.). Law 

enforcement and toxicology reports 

demonstrate that N-desethyl 

isotonitazene and N-piperidinyl 

etonitazene are being illicitly 

distributed and abused. 

Factor 6. What, if Any, Risk There Is to 

the Public Health 

The increase in opioid overdose 

deaths in the United States has been 

exacerbated recently by the availability 

of potent synthetic opioids on the illicit 

drug market. Data obtained from preclinical studies demonstrate that Ndesethyl isotonitazene and Npiperidinyl etonitazene exhibit 

pharmacological profiles similar to that 

of etonitazene, isotonitazene, and other 

mu-opioid receptor agonists. These two 


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11 12 Month-ending August 2022 Provisional 

Number of Drug Overdose Deaths. Reported 

provisional data as of January 4, 2023. https://

www.cdc.gov/nchs/nvss/vsrr/drug-overdosedata.htm. Accessed January 24, 2023. 

12 DAWN. Preliminary Findings from DrugRelated Emergency Department Visits, 2021. 

Preliminary Findings from Drug-Related Emergency 

Department Visits, 2021 (samhsa.gov). Accessed 

January 25, 2023. 

13NPS Discovery Program at the Center for 

Forensic Science Research and Education: 

Monograph. N-Piperidinyl etonitazene Toxicology 

Analytical Report. November 22, 2021. 

benzimidazole-opioids bind to and act 

as an agonist at the m-opioid receptors. 

It is well established that substances 

that act as mu-opioid receptor agonists 

have a high potential for addiction and 

can induce dose-dependent respiratory 

depression. 

Consistent with any mu-opioid 

receptor agonist, the potential health 

and safety risks for users of N-desethyl 

isotonitazene and N-piperidinyl 

etonitazene are high. N-Desethyl 

isotonitazene and N-piperidinyl 

etonitazene have been positively 

identified in toxicology cases. The 

public health risks attendant to the 

abuse of mu-opioid receptor agonists are 

well established. These risks include 

large numbers of drug treatment 

admissions, emergency department 

visits, and fatal overdoses. According to 

the Centers for Disease Control and 

Prevention (CDC), opioids, mainly 

synthetic opioids other than methadone, 

are predominantly responsible for drug 

overdose deaths in recent years. 

According to CDC provisional data, 

synthetic opioid-related overdose deaths 

in the United States increased from 

57,834 in 2020 to 71,238 in 2021.11

Overdose deaths involving opioids 

increased from an estimated 70,029 in 

2020, to 80,816 in 2021. In 2021, 

according to Drug Abuse Warning 

Network (DAWN), preliminary findings 

indicate 1.03 million drug-related 

emergency department visits involved 

opioids (fentanyl, heroin, and other 

opioid pain medications taken alone or 

in combination with other opioids and/ 

or other drugs).12

N-Piperidinyl etonitazene was 

detected in suspected opioid overdose 

cases in three patients from New Jersey 

over a period of three days in July 2021. 

Of those patients, two reported the use 

of cocaine; one reported the use of 

heroin and alprazolam. Similarly, 

according to a 2021 CFSRE report, Npiperidinyl etonitazene was coidentified with fentanyl in two cases 

and para-fluorofentanyl in one other 

case.13

Between October 2019 and January 

2020, N-desethyl isotonitazene, an 

active metabolite of isotonitazene was 

identified in numerous toxicology cases 

involving isotonitazene. In DUID cases, 

N-desethyl isotonitazene was present in 

64 samples containing isotonitazene and 

was found with isotonitazene in 13 

postmortem samples. Although, Ndesethyl isotonitazene was only 

identified as a metabolite of 

isotonitazene in these cases, the 

pharmacological profile of this 

substance demonstrate that it is a highly 

potent synthetic opioid similar to 

etonitazene, isotonitazene, and fentanyl. 

As such, the identification of this 

substance as a parent drug in the 

recreational drug market is worrisome. 

Finding of Necessity of Schedule I 

Placement To Avoid Imminent Hazard 

to Public Safety 

In accordance with 21 U.S.C. 

811(h)(3), based on the available data 

and information summarized above, the 

uncontrolled manufacture, distribution, 

reverse distribution, importation, 

exportation, conduct of research and 

chemical analysis, possession, and 

abuse of N-desethyl isotonitazene and 

N-piperidinyl etonitazene pose 

imminent hazards to public safety. DEA 

is not aware of any currently accepted 

medical uses for these substances in the 

United States. A substance meeting the 

statutory requirements for temporary 

scheduling, found in 21 U.S.C. 

811(h)(1), may only be placed in 

schedule I. Substances in schedule I 

must have a high potential for abuse, no 

currently accepted medical use in 

treatment in the United States, and a 

lack of accepted safety for use under 

medical supervision. Available data and 

information for N-desethyl isotonitazene 

and N-piperidinyl etonitazene indicate 

that these substances meet the three 

statutory criteria. As required by 21 

U.S.C. 811(h)(4), the Administrator 

transmitted to the Assistant Secretary, 

via letter dated April 3, 2023, notice of 

her intent to place N-desethyl 

isotonitazene and N-piperidinyl 

etonitazene in schedule I on a 

temporary basis. HHS had no objection 

to the temporary placement of these 

substances in schedule I. 

Conclusion 

This Notice of Intent provides the 30- 

day notice pursuant to 21 U.S.C. 

811(h)(1) of DEA’s intent to issue a 

temporary scheduling order. In 

accordance with 21 U.S.C. 811(h)(1) and 

(3), the Administrator considered 

available data and information, herein 

set forth the grounds for her 

determination that it is necessary to 

temporarily schedule N-desethyl 

isotonitazene and N-piperidinyl 

etonitazene in schedule I of the CSA, 

and finds that placement of these 

substances in schedule I is necessary to 

avoid an imminent hazard to the public 

safety. 

The temporary placement of Ndesethyl isotonitazene and Npiperidinyl etonitazene in schedule I of 

the CSA will take effect pursuant to a 

temporary scheduling order, which will 

not be issued before November 24, 2023. 

Because the Administrator hereby finds 

this temporary scheduling order 

necessary to avoid an imminent hazard 

to the public safety, it will take effect on 

the date the order is published in the 

Federal Register and remain in effect for 

two years, with a possible extension of 

one year, pending completion of the 

regular (permanent) scheduling process. 

21 U.S.C. 811(h)(1) and (2). The 

Administrator intends to issue a 

temporary scheduling order as soon as 

possible after the expiration of 30 days 

from the date of publication of this 

document. Upon the temporary order’s 

publication, N-desethyl isotonitazene 

and N-piperidinyl etonitazene will then 

be subject to the CSA’s schedule I 

regulatory controls and to 

administrative, civil, and criminal 

sanctions applicable to their 

manufacture, distribution, reverse 

distribution, importation, exportation, 

research, conduct of instructional 

activities and chemical analysis, and 

possession. 

The CSA sets forth specific criteria for 

scheduling drugs or other substances. 

Regular scheduling actions in 

accordance with 21 U.S.C. 811(a) are 

subject to formal rulemaking procedures 

‘‘on the record after opportunity for a 

hearing’’ conducted pursuant to the 

provisions of 5 U.S.C. 556 and 557. 21 

U.S.C. 811. The regular scheduling 

process of formal rulemaking affords 

interested parties appropriate process 

and the government any additional 

relevant information needed to make a 

determination. Final decisions that 

conclude the regular scheduling process 

of formal rulemaking are subject to 

judicial review. 21 U.S.C. 877. 

Temporary scheduling orders are not 

subject to judicial review. 21 U.S.C. 

811(h)(6). 

Regulatory Analyses 

The CSA provides for expedited 

temporary scheduling actions where 

necessary to avoid an imminent hazard 

to the public safety. Under 21 U.S.C. 

811(h)(1), the Administrator, as 

delegated by the Attorney General, may, 

by order, temporarily place substances 

in schedule I. Such orders may not be 

issued before the expiration of 30 days 

from: (1) The publication of a notice in 

the Federal Register of the intent to 


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Federal Register / Vol. 88, No. 205 / Wednesday, October 25, 2023 / Proposed Rules 73297 

issue such order and the grounds upon 

which such order is to be issued, and (2) 

the date that notice of the proposed 

temporary scheduling order is 

transmitted to the Assistant Secretary, 

as delegated by the Secretary of HHS. 21 

U.S.C. 811(h)(1). 

Inasmuch as section 811(h) directs 

that temporary scheduling actions be 

issued by order and sets forth the 

procedures by which such orders are to 

be issued, including the requirement to 

publish in the Federal Register a Notice 

of Intent, the notice-and-comment 

requirements of section 553 of the 

Administrative Procedure Act (APA), 5 

U.S.C. 553, do not apply to this Notice 

of Intent. The APA expressly 

differentiates between orders and rules, 

as it defines an ‘‘order’’ to mean a ‘‘final 

disposition, whether affirmative, 

negative, injunctive, or declaratory in 

form, of an agency in a matter other 

than rule making.’’ 5 U.S.C. 551(6) 

(emphasis added). This contrasts with 

permanent scheduling actions, which 

are subject to formal rulemaking 

procedures done ‘‘on the record after 

opportunity for a hearing,’’ and final 

decisions that conclude the scheduling 

process and are subject to judicial 

review. 21 U.S.C. 811(a) and 877. The 

specific language chosen by Congress 

indicates its intent that DEA issue 

orders instead of proceeding by 

rulemaking when temporarily 

scheduling substances. Given that 

Congress specifically requires the 

Administrator (as delegated by the 

Attorney General) to follow rulemaking 

procedures for other kinds of scheduling 

actions, see 21 U.S.C. 811(a), it is 

noteworthy that, in section 811(h)(1), 

Congress authorized the issuance of 

temporary scheduling actions by order 

rather than by rule. 

Even assuming that this Notice of 

Intent is subject to section 553 of the 

APA, the Administrator finds that there 

is good cause to forgo its notice-andcomment requirements, as any further 

delays in the process for issuing 

temporary scheduling orders would be 

impracticable and contrary to the public 

interest given the manifest urgency to 

avoid an imminent hazard to the public 

safety. 

Although DEA believes this notice of 

intent to issue a temporary scheduling 

order is not subject to the notice-andcomment requirements of section 553 of 

the APA, DEA notes that in accordance 

with 21 U.S.C. 811(h)(4), the 

Administrator took into consideration 

comments submitted by the Assistant 

Secretary in response to the notices that 

DEA transmitted to the Assistant 

Secretary pursuant to such subsection. 

Further, DEA believes that this 

temporary scheduling action is not a 

‘‘rule’’ as defined by 5 U.S.C. 601(2), 

and, accordingly, is not subject to the 

requirements of the Regulatory 

Flexibility Act. The requirements for the 

preparation of an initial regulatory 

flexibility analysis in 5 U.S.C. 603(a) are 

not applicable where, as here, DEA is 

not required by section 553 of the APA 

or any other law to publish a general 

notice of proposed rulemaking. As 

discussed above, DEA is issuing this 

notice of intent pursuant to DEA’s 

authority to issue a temporary 

scheduling order. 21 U.S.C. 811(h)(1). 

Therefore, in this instance, since DEA 

believes this temporary scheduling 

action is not a ‘‘rule,’’ it is not subject 

to the requirements of the Regulatory 

Flexibility Act when issuing this 

temporary action. 

In accordance with the principles of 

Executive Orders (E.O.) 12866 and 

13563, this action is not a significant 

regulatory action. E.O. 12866 directs 

agencies to assess all costs and benefits 

of available regulatory alternatives and, 

if regulation is necessary, to select 

regulatory approaches that maximize 

net benefits (including potential 

economic, environmental, public health, 

and safety effects; distributive impacts; 

and equity). E.O. 13563 is supplemental 

to and reaffirms the principles, 

structures, and definitions governing 

regulatory review as established in E.O. 

12866. E.O. 12866, sec. 3(f), as amended 

by E.O. 14094, sec. 1(b), provides the 

definition of a ‘‘significant regulatory 

action,’’ requiring review by the Office 

of Management and Budget. Because 

this is not a rulemaking action, this is 

not a significant regulatory action as 

defined in Section 3(f) of E.O. 12866. 

This action will not have substantial 

direct effects 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. Therefore, in 

accordance with E.O. 13132, it is 

determined that this action does not 

have sufficient federalism implications 

to warrant the preparation of a 

Federalism Assessment. 

List of Subjects in 21 CFR Part 1308 

Administrative practice and 

procedure, Drug traffic control, 

Reporting and recordkeeping 

requirements. 

For the reasons set out above, DEA 

proposes to amend 21 CFR part 1308 as 

follows: 

PART 1308—SCHEDULES OF 

CONTROLLED SUBSTANCES 

■ 1. The authority citation for part 1308 

continues to read as follows: 

Authority: 21 U.S.C. 811, 812, 871(b), 

956(b), unless otherwise noted. 

■ 2. In § 1308.11, add paragraphs (h)(62) 

and (63) to read as follows: 

§ 1308.11 Schedule I 

* * * * * 

(h) * * * 

*******

(62) N-ethyl-2-(2-(4-isopropoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)ethan-1-amine, its isomers, esters, ethers, salts, and 

salts of isomers, esters and ethers (Other name: N-desethyl isotonitazene) ........................................................................... 9760 

(63) 2-(4-ethoxybenzyl)-5-nitro-1-(2-(piperidin-1-yl)ethyl)-1H-benzimidazole, its isomers, esters, ethers, salts, and salts of isomers, esters and ethers (Other names: N-piperidinyl etonitazene; etonitazepipne) ................................................................. 9761 

Signing Authority 

This document of the Drug 

Enforcement Administration was signed 

on October 16, 2023, by Administrator 

Anne Milgram. That document with the 

original signature and date is 

maintained by DEA. For administrative 

purposes only, and in compliance with 

requirements of the Office of the Federal 

Register, the undersigned DEA Federal 

Register Liaison Officer has been 

authorized to sign and submit the 

document in electronic format for 

publication, as an official document of 

DEA. This administrative process in no 

way alters the legal effect of this 

document upon publication in the 

Federal Register. 

Heather Achbach, 

Federal Register Liaison Officer, Drug 

Enforcement Administration. 

[FR Doc. 2023–23379 Filed 10–24–23; 8:45 am] 

BILLING CODE 4410–09–P 


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