Procedures for Developing the 

NIOSH List of Hazardous Drugs 

in Healthcare Settings

Centers for Disease Control

and Prevention

National Institute for Occupational 

Safety and Health
Front cover photo image:

Photo by ©Yalax/iStock/Getty Images Plus
Procedures for Developing the NIOSH List 

of Hazardous Drugs in Healthcare Settings

Effective: April 2023

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health
This document is in the public domain and may be freely copied or reprinted.

Disclaimer

Mention of any company or product does not constitute endorsement by the National Institute

for Occupational Safety and Health (NIOSH), part of the Centers for Disease Control and

Prevention (CDC). In addition, citations of websites external to CDC/NIOSH do not constitute

CDC/NIOSH endorsement of the sponsoring organizations or their programs or products.

Furthermore, CDC/NIOSH is not responsible for the content of these websites.

Get More Information

Find NIOSH products and get answers to workplace safety and health questions:

1-800-CDC-INFO (1-800-232-4636) | TTY: 1-888-232-6348

cdc.gov/info | cdc.gov/niosh

NIOSH monthly newsletter: cdc.gov/niosh/eNews

Suggested Citation

NIOSH [2023]. Procedures for developing the NIOSH list of hazardous drugs in healthcare 

settings. By Whittaker C, Ovesen JL, MacKenzie BA, Hartley T, Berry KA, Piacentino J.

Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control

and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH)

Publication No. 2023-129, https://doi.org/10.26616/NIOSHPUB2023129.

DHHS (NIOSH) Publication No. 2023-129

DOI: https://doi.org/10.26616/NIOSHPUB2023129

April 2023

ii | Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings
Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings | iii

Foreword

In 2004, the National Institute for Occupational Safety and Health (NIOSH) published

Preventing Exposures to Antineoplastic and Other Hazardous Drugs in Healthcare Settings. This 

NIOSH Alert included a sample list of drugs that can be hazardous to healthcare workers with 

potential occupational exposure to those who handle, prepare, dispense, administer, or dispose 

of these drugs. The purpose of the Alert was to increase awareness among workers in healthcare 

settings and their employers about the health risks posed by working with hazardous drugs and 

to provide them with measures for protecting their health. NIOSH has periodically updated that 

list from 2010 through 2016 as the NIOSH List of Antineoplastic and Other Hazardous Drugs in 

Healthcare Settings (List). 

This document, Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare 

Settings, provides information about how the NIOSH List is developed and updated and how 

reevaluations can be requested. This information may be useful for healthcare facilities to examine 

new drugs and establish their own hazardous drug list. Find the latest information, including 

current publications, at NIOSH Hazardous Drug Exposures in Healthcare.
iv | Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings

Acknowledgements

For significant contributions to the development and review of this document, the authors 

acknowledge the following NIOSH contributors: 

 John Howard, MD 

 Frank J. Hearl, MS, PE (retired)

 Paul Middendorf, PhD (retired)

 Paul A. Schulte, PhD (retired)

 Rachel I. Weiss, JD

 Deborah Sammons, BS 

 Cheryl Lynn Hamilton, MEd 

For significant contributions to the initial development and implementation of the procedures 

outlined in this document, the authors acknowledge the following contributors:

 Thomas Connor, PhD

NIOSH (retired)

 D. Gayle DeBord, PhD

NIOSH (retired)

 Laurence Reed, PhD

NIOSH (retired)

 Michael Childress, DVM, MS, DACVIM

Purdue University, Department of Veterinary Clinical Sciences 

 Chun-Yip Hon, PhD, CPHI©, CIH, CRSP

Ryerson University, School of Occupational and Public Health

 Melissa McDiarmid, MD, MPH, DABT

University of Maryland, School of Medicine

 AnnMarie Walton, PhD, MPH, RN, OCN, CHES, FAAN

Duke University, School of Nursing
Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings | v

List of Acronyms

CBER Center for Biologics Evaluation and Research

CDER Center for Drug Evaluation and Research 

CERHR Center for the Evaluation of Risks to Human Reproduction

CFR Code of Federal Regulations

DHHS Department of Health and Human Services

EPA Environmental Protection Agency

FDA Food and Drug Administration

FOIA Freedom of Information Act

IARC International Agency for Research on Cancer

ME molecular entity 

MRHD maximum recommended human dose

MSHI manufacturer’s special handling information

NIOSH National Institute for Occupational Safety and Health

NTP National Toxicology Program 

OEL occupational exposure limit

OHAT Office of Health Assessment and Translation

USC United States Congress
This page intentionally left blank.
Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings | vii

Contents

Foreword . .

Acknowledgements . 

I. Authority .

II. Purposes .

A. Methodology for Adding Drugs to the List . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  

B. Requests to Add, Remove, or Move a Drug Between Tables of the List . . . . . . . . .  

C. Use of the List in Healthcare and Other Settings .

III. Background .

A. Exposure to Drugs in Healthcare Settings .

B. Health Effects From Exposure to Drugs in Healthcare Settings .

IV. NIOSH Definition of a Hazardous Drug .

V. Identifying, Screening, Evaluating, and Reviewing a Drug for 

Placement on the List .

A. Step 1: Identifying Potentially Hazardous Drugs .

B. Step 2: Screening Potentially Hazardous Drugs .

C. Step 3: Evaluating Potentially Hazardous Drugs .

D. Step 4: Peer Review of Potentially Hazardous Drugs . 

E. Step 5: Public Review of Potentially Hazardous Drugs . 

F. Step 6: Placement of Hazardous Drugs on the List and in Tables . 

VI. Request for a NIOSH Reevaluation . 

A. Request . 

B. Initial NIOSH Evaluation of a Request for a Reevaluation . 

C. NIOSH Review of Evidence Presented in the Request for a Reevaluation . 

D. Peer Review of the Initial Recommendation . 

E. Public Comment on the Initial Recommendation . 

F. Final Reevaluation Determination . 

Figure 1. Identifying, Screening, Evaluating, and Reviewing Drugs for 

Placement on the List . 
This page intentionally left blank.
Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings | 1

Procedures for Developing the NIOSH List

of Hazardous Drugs in Healthcare Settings

I. Authority

The Occupational Safety and Health Act of 1970.1

II. Purposes

A. Methodology for Adding Drugs to the List

This Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings

(Procedures) document describes the methodology the National Institute for Occupational Safety and Health (NIOSH) uses to determine whether a drug2

 meets the criteria

in the NIOSH definition of a hazardous drug.3 Drugs that meet the NIOSH definition of

a hazardous drug are placed on the NIOSH List of Hazardous Drugs in Healthcare Settings.

B. Requests to Add, Remove, or Move a Drug Between Tables of the List

The Procedures also sets forth procedures for a party to request that NIOSH (1) add a new

drug to the List, (2) reevaluate its decision to place, or not to place, a drug on the List and

thereby remove the drug from the List, or (3) reevaluate its decision to place a drug on a

particular table4

 of the List and thereby move the drug to another table of the List.

C. Use of the List in Healthcare and Other Settings

The List is designed to assist employers in identifying which drugs routinely handled

by employees are considered by NIOSH to be hazardous drugs. NIOSH recommends

using the List in conjunction with NIOSH risk management recommendations provided in Managing Hazardous Drug Exposures: Information for Healthcare Settings (Managing Exposures). The recommendations are designed to assist employers in establishing

hazardous drug management procedures specific to their workplace. The document is

available through the NIOSH Hazardous Drug Exposures in Healthcare website.

In addition to healthcare facilities, the List may also be applied in veterinary care settings,

drug research laboratories, retail pharmacies, and home healthcare agencies. Occupational

groups in these settings include pharmacy personnel, nursing personnel, physicians,

1

29 USC § 651 et seq. 2

For the purpose of the Procedures and the List, NIOSH adopts the U.S. Food and Drug Administration (FDA) definition of “drug” 

to include a substance recognized by an official pharmacopoeia or formulary; a substance intended for use in the diagnosis, cure, 

mitigation, treatment, or prevention of a disease; a substance (other than food) intended to affect the structure of any function of 

the body; a substance intended for use as a component of a medicine but not a device or a part or accessory of a device. Although 

biological products (“biologics”) are included in the FDA definition, they are not included in the drugs that NIOSH evaluates 

for potential inclusion on the List. See Section IV and Drugs@FDA Glossary of Terms at https://www.fda.gov/drugs/informationondrugs/ucm079436.htm#D. 3

For the NIOSH definition of a hazardous drug, see Section IV.

4

The List contains two tables. See Section V.C.7 (Step 3) for a description of the tables.
2 | Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings

physician assistants, operating room personnel, environmental services workers, research 

laboratorians, veterinary care workers, shipping and receiving personnel, and other 

potentially exposed personnel.5, 6 The List, and all subsequent updates, are advisory in 

nature and informational in content. 

III. Background 

A. Exposure to Drugs in Healthcare Settings

Workers in healthcare and related settings may be exposed to drugs while performing 

job tasks such as receipt, storage, preparation, compounding or similar manipulation, 

dispensing, transporting, administration, other patient care activities, and during spill 

cleanup, and/or disposal of drugs and patient waste. For the purposes of the Procedures,

these activities are collectively referred to as “handling.” Potential routes of exposure to 

hazardous drugs for workers in healthcare settings include inhalation (breathing), ingestion (consuming), dermal (skin) and mucosal membrane (eyes) absorption, and percutaneous (needle puncture).6

B. Health Effects From Exposure to Drugs in Healthcare Settings 

Although the exposures workers in healthcare settings may receive are typically lower 

than the therapeutic doses administered to patients undergoing medical treatment, “[any] 

clinically significant pharmacologic effect occurring as a result of occupational exposure is 

considered undesirable, even if it can be argued that the effect is therapeutically beneficial.”7

Exposure to various types of drugs used in patient care may increase the probability of 

an adverse health effect in a healthcare worker including (1) acute health effects, such 

as skin rashes, and mucous membrane irritation;8 (2) chronic health effects, including 

cancer;9 and (3) adverse reproductive events, such as infertility, spontaneous abortions, 

and congenital malformations.10

5

The Alert and List are not intended for use by workers or employers during pharmaceutical manufacturing because those worksites 

are not considered by NIOSH to be healthcare settings. 6

NIOSH [2004]. NIOSH Alert: preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings. By Burroughs GE, Connor TH, McDiarmid MA, Mead KR, Power LA, Reed LD, Coyle BJ, Hammond DR, Leone MM, 

Polovich M, Sharpnack DD. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control 

and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165, available 

at https://www.cdc.gov/niosh/docs/2004-165/. 7

Naumann BD, Sargent EV [1997]. Setting occupational exposure limits for pharmaceuticals. Occup Med 12(1):67–80. 8

Eisenberg S [2009]. Safe handling and administration of antineoplastic chemotherapy. J Infus Nurs 32(1):23–32; Massoomi F, Neff 

B, Pick A, Danekas P [2008]. Implementation of a safety program for handling hazardous drugs in a community hospital. Am 

J Health Syst Pharm 65:861–865; Krstev S, Perunicic B, Vidakovic A [2003]. Work practice and some adverse health effects in 

nurses handling antineoplastic drugs. Med Lav 94:432–439. 9

Connor TH, McDiarmid MA [2006]. Preventing occupational exposures to antineoplastic drugs in health care settings. CA 

Cancer J Clin 56:354–365; Lie JA, Kjaerheim K [2003]. Cancer risk among female nurses: a literature review. Eur J Cancer Prev 

12:517–526; Ratner PA, Spinelli JJ, Beking K, Lorenzi M, Chow Y, Teschke K, Le ND, Gallagher RP, Dimich-Ward H [2010]. 

Cancer incidence and adverse pregnancy outcome in registered nurses potentially exposed to antineoplastic drugs. BMC Nurs 

9:15; Suspiro A, Prista J [2011]. Biomarkers of occupational exposure do [sic] anticancer agents: a mini-review. Toxicol Lett 

207:42–52. 10 Connor TH, Lawson CC, Polovich M, McDiarmid MA [2014]. Reproductive health risks associated with occupational exposures to 

antineoplastic drugs in health care settings: a review of the evidence. J Occup Environ Med 56:901–910; Lawson CC, Rocheleau 

CM, Whelan EA, Lividoti Hibert EN, Grajewski B, Spiegelman D, Rich-Edwards JW [2012]. Occupational exposures among nurses and risk of spontaneous abortion. Am J Obstet Gynecol 206:327.e1-8; NTP [2019]. NTP monograph on the systematic review 

of occupational exposure to cancer chemotherapy agents and adverse health outcomes. Monograph 5. Research Triangle Park, NC: 

National Toxicology Program; Selevan SG, Lindbohm ML, Hornung RW, Hemminki K [1985]. A study of occupational exposure 

to antineoplastic drugs and fetal loss in nurses. N Engl J Med 313(19):1173–1178.
Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings | 3

IV. NIOSH Definition of a Hazardous Drug

The NIOSH definition of a “hazardous” drug is a drug that is 

A. Approved for use in humans11 by the Food and Drug Administration’s (FDA) Center 

for Drug Evaluation and Research (CDER),12

B. Not otherwise regulated by the U.S. Nuclear Regulatory Commission,13 and

C. Either

1. Is accompanied by prescribing information in the “package insert”14 that includes a 

manufacturer’s special handling information (MSHI),15 or

2. Is determined to be a carcinogenic hazard, developmental hazard, reproductive 

hazard, genotoxic hazard, or other health hazard by exhibiting one or more of the 

following toxicity criteria in humans, animal models, or in vitro systems: 

 Carcinogenicity, 

 Developmental toxicity (including teratogenicity), 

 Reproductive toxicity, 

 Genotoxicity, 

 Organ toxicity at low doses,16 or a

 Structure and toxicity profile that mimics existing drugs determined hazardous by 

exhibiting any one of the previous five toxicity types.6

11Although only drugs approved by FDA for use in humans are included in the definition of hazardous drug, some of those drugs 

may be used in veterinary settings for treatment of animals and may be a hazard for veterinary care workers. 12Although biological products, such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, 

recombinant therapeutic proteins, are included in FDA definition of a drug, they are not included in the drugs that NIOSH 

evaluates for potential inclusion on the List because they are approved for use by FDA’s Center for Biologics Evaluation and 

Research (CBER), not by FDA’s CDER. This provision makes clear NIOSH’s long-standing practice of only considering drugs 

approved by FDA CDER. 1310 CFR Parts 19, 20, and 35. See https://www.nrc.gov/materials/miau/med-use.html. Drugs regulated by the Nuclear 

Regulatory Commission are not included on the List. 14See Drug Advertising: A Glossary of Terms at https://www.fda.gov/drugs/resourcesforyou/consumers/prescriptiondrugadvertising/ucm072025.htm. “Prescribing information is also called product information, product labeling, or the package insert (“the 

PI”). It is generally drafted by the drug company and approved by FDA. This information travels with a drug as it moves from 

the company to the pharmacist. It includes the details and directions healthcare providers need to prescribe the drug properly. 

It is also the basis for how the drug company can advertise its drug. The prescribing information includes such details about the 

drug as: its chemical description; how it works; how it interacts with other drugs, supplements, foods, and beverages; what condition(s) or disease(s) it treats; who should not use the drug; serious side effects, even if they occur rarely; commonly occurring side 

effects, even if they are not serious; effects on specific groups of patients, such as children, pregnant women, or older adults and 

how to use it in these populations.” 15MSHI includes language that informs those handling the drug of the need to follow heightened handling and disposal procedures. 

For example, language such as “follow special handling and disposal procedures” or “procedures for proper handling and disposal 

of anticancer drugs should be considered” is frequently used in package inserts. However, NIOSH does not consider language 

pertaining to packaging and temperature controls as MSHI. 16All drugs have toxic side effects, but some exhibit toxicity at low doses. The level of toxicity reflects a continuum from relatively 

nontoxic to production of toxic effects in patients at low doses (for example, a few milligrams or less). For example, a daily therapeutic dose of 10 milligrams per day (mg/day) or a dose of 1 milligram per kilogram (mg/kg) per day in laboratory animals that 

produces serious organ toxicity, developmental toxicity, or reproductive toxicity has been used by the pharmaceutical industry to 

develop occupational exposure limits (OELs) of less than 10 micrograms per cubic meter (μg/m3) after applying appropriate uncertainty factors. See Naumann BD, Sargent EV [1997]. Setting occupational exposure limits for pharmaceuticals. Occup Med 

12(1):67–80; Sargent EV, Kirk GD [1988]. Establishing airborne exposure control limits in the pharmaceutical industry airborne 

exposure control limits in the pharmaceutical industry. Am Ind Hyg Assoc J 49(6):309–313; Sargent EV, Naumann BD, Dolan 

DG, Faria EC, Schulman L [2002]. The importance of human data in the establishment of occupational exposure limits. Hum Ecol 

Risk Assess 8(4):805–822. OELs in this range are typically established for potent or toxic drugs in the pharmaceutical industry.
4 | Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings

However, if a drug also exhibits a molecular property17 that may limit the potential 

for adverse health effects from exposure to the drug in healthcare workers, it may be 

determined it is not a hazard.

V. Identifying, Screening, Evaluating, and Reviewing a Drug 

for Placement on the List18

NIOSH uses a sequential approach to determine whether a drug approved by FDA CDER 

meets the criteria in the NIOSH definition of a hazardous drug. 

A. Step 1: Identifying Potentially Hazardous Drugs 

1. NIOSH reviews the following FDA databases to identify drugs to be screened and evaluated for placement on the List:

a. Drugs@FDA: FDA Approved Drug Products by month.19 This FDA database lists 

new molecular entities (NME)20 with new drug applications21 and biologics 

license applications.22

b. Drug Safety-related Labeling Changes.

23 This FDA database identifies drugs with 

new safety labeling changes (new boxed warnings24 and/or warnings and precautions) or new pregnancy and lactation labeling information.25

2. NIOSH may also consider a request to add a drug to the List. Requests to add a drug 

must be submitted in writing to the NIOSH Director, include toxicity information 

from the package insert or any of the sources in Section V.C (Step 3) and explain how 

the drug meets the NIOSH definition of hazardous drug.26

a. If the request for an evaluation does not provide information that suggests a toxic 

effect that may meet one or more of the criteria in the NIOSH definition of a 

hazardous drug, then NIOSH will deny the request and notify the requester in 

writing explaining the decision. The drug is placed in Category 1. See Section V.E 

(Step 5).

b. If the provided toxicity information suggests a toxic effect that may meet one or 

more of the criteria in the NIOSH definition of a hazardous drug, then NIOSH 

17Properties of a drug molecule that may limit adverse effects in healthcare workers are typically chemical, physical, and structural 

properties that affect its absorption (ability to enter the cells of the body), e.g., chemical structure, molecular weight, or mass. 

See Clementi F, Fumagalli G [2015]. Molecular pharmacology. Hoboken, NJ: Wiley & Sons; Di L, Kerns EH [2016]. Drug-like 

properties: concepts, structure, design, and methods. Oxford, UK: Elsevier; Mattson P, Kihlberg J [2017]. How big is too big for 

cell permeability? J Med Chem 60(5):1662–1664, https://doi.org/10.1021/acs.jmedchem.7b00237. 18See Figure 1 for a diagram of the NIOSH procedures for identifying, screening, evaluating, and reviewing a drug for placement on 

the List. 19See https://www.accessdata.fda.gov/scripts/cder/daf/. 20See Drugs@FDA Glossary of Terms at https://www.fda.gov/Drugs/InformationOnDrugs/ucm079436.htm#N. (“An NME is an 

active ingredient that contains no active moiety that has been previously approved by the Agency in an application submitted under Section 505 of the Federal Food, Drug, and Cosmetic Act, or has been previously marketed as a drug in the United States.”) 2121 CFR Part 314.

2221 CFR Part 601.

23See https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/. 24See Drug Advertising: A Glossary of Terms at https://www.fda.gov/drugs/resourcesforyou/consumers/prescriptiondrugadvertising/ucm072025.htm. “Drugs that have special problems, particularly ones that may lead to death or serious injury, may have 

this warning information displayed within a box in the prescribing information. This is often referred to as a ‘boxed’ or ‘black 

box’ warning.” 2521 CFR § 201.57(c)(9)(i) and (ii) and 21 CFR § 201.80. Although rare, NIOSH notes any labeling changes that could affect the 

status of a drug that NIOSH has previously placed on the List. 26Requests can be sent to the following address: NIOSH, 395 E Street, S.W., Suite 9200, Washington, D.C. 20201.
Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings | 5

will evaluate the drug during the next evaluation cycle to determine if it will be 

proposed, or not be proposed, for addition to the List. Go to Section V.C (Step 3).

B. Step 2: Screening Potentially Hazardous Drugs 

1. NIOSH screens the identified drugs to determine whether 

a. The drug package insert specifies MSHI or

b. Information in the drug package insert27 suggests that a drug may exhibit at least one 

of the types of toxicity criteria found in the NIOSH definition of a hazardous drug.

2. Screening Outcomes

a. Manufacturer’s Special Handling Information (MSHI)

If the drug package insert contains MSHI, NIOSH will place the drug on the List. 

NIOSH will post notice of the addition on the most recent List website, accessible 

through the NIOSH Hazardous Drug Exposures in Healthcare website.28 Go to 

Section V.F (Step 6) for placement on the List.

b. Insufficient Toxicity Information in the Drug Package Insert to Meet the NIOSH 

Definition of Hazardous Drug29

If there is insufficient information in the drug package insert to suggest that the 

drug exhibits any one of the toxicity criteria in the NIOSH definition of hazardous 

drug, then NIOSH will not propose to add the drug to the List. Go to Section V.E 

(Step 5) for categorical determination.

c. Information in the Drug Package Insert Shows No Toxic Effect, or Shows a Toxic 

Effect that Does Not Meet the NIOSH Definition of a Hazardous Drug

If information in the drug package insert shows no toxic effect or shows a toxic 

effect that does not meet the hazard identification criteria in the NIOSH definition 

of hazardous drug, then NIOSH will not propose to add the drug to the List. Go 

to Section V.E (Step 5) for categorical determination.

d. Available Information in the Drug Package Insert Suggests a Toxic Effect

If available toxicity information in the drug package insert suggests a toxic effect that 

may meet one or more of the criteria in the NIOSH definition of a hazardous drug, 

then NIOSH will evaluate the drug to determine if it will be proposed, or not be proposed, for addition to the List. Go to Section V.C (Step 3) for further evaluation.

C. Step 3: Evaluating Potentially Hazardous Drugs 

27Although the entire drug package insert is examined, certain specific sections may indicate that the drug exhibits at least one of 

the types of hazard information (toxicity) criteria found in the NIOSH definition of hazardous drug: package inserts for drugs 

approved prior to FDA’s drug labeling regulations may not include those specific numbered sections although the same type of 

content is included. See 21 CFR §§ 201.56(b)(1) and 201.80. Section 1: Box warning, if available [21 CFR § 201.57(c)(1)]; 

Section 5: Warnings and Precautions (any organ toxicity, carcinogenicity, or embryo-fetal toxicity) [21 CFR § 201.57(c)(6)]; 

Section 6: Adverse Reactions (any post-marketing experience reported by the manufacturer)[21 CFR § 201.57(c)(7); Section 8: 

Use in Special Populations (pregnancy information, any human animal development toxicity) [21 CFR § 201.57(c)(9)]; Section 

13: Non-clinical toxicology (animal data on carcinogenesis, mutagenesis and impairment of fertility)[21 CFR § 201.57(c)(14)]; 

Section 15: References, if available [21 CFR § 201.57(c)(16)]; and Section 16: Storage and Handling, if available (special handling or disposal information for workers) [21 CFR § 201.57(c)(17)]. 28See https://www.cdc.gov/niosh/topics/hazdrug/default.html. 29“Insufficient” in this context indicates that in some cases, in its review of all available information, FDA did not find a concern for 

toxicity of a particular type and such tests were not required or that the available toxicity data are insufficient to meet the NIOSH 

criteria for a hazardous drug.
6 | Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings

1. Sources of Toxicity Information for Evaluating Screened Drugs When Available Information Suggests Toxic Effect (Section V.B.2.d, Step 2).

NIOSH may consult the following sources of information to evaluate each screened 

drug for potential toxic effect:

a. Information in the drug package insert. 

b. FDA information pertaining to new drug safety labeling changes.30

c. Molecular properties of the drug from available sources, such as safety data sheets 

(SDSs).

d. When available, relevant information about carcinogenicity from

i. the National Toxicology Program (NTP) within the U.S. Department of Health 

and Human Services,31 and

ii. the World Health Organization’s International Agency for Research on Cancer 

(IARC).32

e. When available, relevant information about reproductive toxicity, teratogenicity, 

or developmental toxicity from the NTP Center for the Evaluation of Risks to 

Human Reproduction (CERHR),33 and from its successor, the Office of Health 

Assessment and Translation (OHAT),34

f. When available, published, peer-reviewed scientific literature about the hazard 

potential of a particular drug, including any animal or human studies cited in the 

package insert, and

g. When available, hazard identification information from SDSs provided by the 

manufacturer.

2. Two-Part Approach to Evaluate Screened Drugs for Potential Hazards35

a. Toxicity Criteria

NIOSH evaluates information from humans36 and animals37 using the toxicity 

criteria in Section V.C.3 (Step 3) for determining whether a drug exhibits one of 

the toxicities set out in the NIOSH definition of a hazardous drug.

i. For genotoxicity, relevant information from in vitro systems is also included in 

the evaluation.38

ii. Although human data are generally preferable to animal or in vitro data for in30See https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/. 31NTP [2021]. 15th report on carcinogens. Research Triangle Park, NC: U.S. Department of Health and Human Services. See

https://ntp.niehs.nih.gov/pubhealth/roc/index-1.html#toc1. 32IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Lyon, France. See http://monographs.iarc.fr/ENG/Classification/index.php. 33For available NTP Monographs, see http://ntp.niehs.nih.gov/pubhealth/hat/noms/index.html. 34See https://ntp.niehs.nih.gov/go/ohathandbook. 35Only screened drugs that might exhibit at least one of the toxicity criteria in the NIOSH definition of hazardous drug undergo a 

full evaluation. 36In evaluating human studies, the following questions are reviewed: (1) Has a plausible association been established between exposure to the drug and an adverse health effect? (2) Is there a temporal relation consistent with cause and effect? (3) What is the 

strength of the association? (4) Is there evidence of an exposure—adverse health effect association? 37In evaluating animal studies, the following questions are reviewed: (1) Are there multiple independent studies with consistent 

results? (2) Is there site concordance across species and/or structural analogs? (3) Are there multiple observations by sex, species, 

and sites? (4) Is there a progression in severity and/or type of lesions with increased exposure or dose? (5) Are the routes of exposure relevant to the human experience? 38Environmental Protection Agency (EPA) [1986]. Guidelines for mutagenicity risk assessment. 

See https://www.epa.gov/risk/guidelines-mutagenicity-risk-assessment.
Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings | 7

dicating potential adverse health effects, NIOSH carefully considers all relevant 

data in its evaluation of screened drugs. 

b. Molecular Properties

NIOSH evaluates whether the molecular properties of a drug may limit the potential for adverse health effects in healthcare workers exposed to the hazardous drug. 

3. Toxicity Criteria 

a. Carcinogenicity 

i. Drug Package Insert

A finding of carcinogenicity in the prescribing information of the drug package 

insert generally supports a NIOSH finding of carcinogenicity.

ii. Safety Data Sheet (SDS)

A report of carcinogenicity in an SDS generally supports a NIOSH finding of 

carcinogenicity.

iii. Authoritative Sources

A finding of carcinogenicity from any one of the following sources generally 

supports a NIOSH finding of carcinogenicity. 

(a) NTP Report on Carcinogens (“known to be human carcinogen” or “reasonably anticipated to be a human carcinogen”)39 or

(b) IARC (“Group 1 carcinogenic or Group 2A probably carcinogenic” or 

“Group 2B possibly carcinogenic”).40

iv. Human Studies

A finding of human carcinogenicity in published peer-reviewed scientific literature generally supports a finding of carcinogenicity.

v. Animal Studies

(a) NIOSH will assess animal studies found in any of the sources described in 

Section V.C.1 (Step 3) and consider the evidence of carcinogenicity, including whether tumors are reported in more than one animal species and sex. 

(b) Tumors in multiple organs, tumors that are not rodent-specific, and high 

incidence of a single tumor type in one species or sex are positive findings 

that generally support a NIOSH finding of carcinogenicity. 

(c) Adverse effects that occur near, at, or below the maximum recommended 

human dose (MRHD) generally support a NIOSH finding of carcinogenicity. 

b. Developmental Toxicity

39See https://ntp.niehs.nih.gov/pubhealth/roc/index-1.html. 40See https://monographs.iarc.fr/list-of-classifications-volumes/.
8 | Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings

i. Drug Package Insert 

A finding of developmental toxicity in humans in the drug package insert generally supports a NIOSH finding of developmental toxicity.

ii. SDS or Peer-Reviewed Scientific Literature 

A finding of developmental toxicity in an SDS or published, peer-reviewed scientific literature generally supports a NIOSH finding of developmental toxicity.

iii. NTP 

A conclusion of “serious concern for adverse effects” or “concern for adverse 

effects” or “some concern for adverse effects” by the NTP that human development might be adversely affected by exposure generally supports a NIOSH 

finding of developmental toxicity.

iv. Animal Studies

(a) Studies found in any of the sources described in Section V.C.1 (Step 3) 

report developmental toxicity generally support a positive finding for developmental toxicity. 41

(b) Adverse effects that occur near, at, or below MRHD generally support a 

NIOSH finding of developmental toxicity. 

c. Reproductive Toxicity

i. Drug Package Insert

A positive finding of reproductive toxicity in humans generally supports a 

NIOSH finding of reproductive toxicity.

ii. SDS or Peer-Reviewed Scientific Literature 

A finding of reproductive toxicity in an SDS or in published, reviewed scientific 

literature generally supports a NIOSH finding of reproductive toxicity.

iii. NTP 

A conclusion by the NTP of “serious concern for adverse effects,” or “concern 

for adverse effects,” or “some concern for adverse effects” on human reproduction generally supports a NIOSH finding of reproductive toxicity.

iv. Animal Studies

(a) Studies found in any of the sources described in Section V.C.1 (Step 3) that 

report reproductive toxicity generally support a NIOSH finding of reproductive toxicity. 

(b) Adverse effects that occur near, at, or below the MRHD generally support a 

NIOSH finding of reproductive toxicity. 

d. Organ Toxicity at Low Doses

41However, effects on the fetus only in the presence of maternal toxicity do not generally support a NIOSH finding of teratogenicity 

or other developmental toxicity. Some substances cause developmental effects only at a dose level that is maternally toxic (Kera 

KS [1985]. Maternal toxicity: a possible etiological factor in embryo-fetal deaths and fetal malformations of rodent-rabbit species. 

Teratology 31(1):129–153). This supports the conclusion that developmental effects are secondary to maternal toxicity, thereby 

decreasing the significance of fetal toxicity in the presence of signs of maternal toxicity. See Chahoud I, Ligensa A, Dietzel L, Faqi 

AS [1999]. Correlation between maternal toxicity and embryo/fetal effects. Reprod Toxicol 13:375–381.
Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings | 9

i. Human Studies

Studies found in any of the sources described in Section V.C.1 (Step 3) that report 

organ toxicity at a daily therapeutic dose less than or equal to 10 milligrams per 

day (mg/day) generally support a NIOSH finding of organ toxicity at low doses.42

ii. Animal Studies

Studies found in any of the sources described in Section V.C.1 (Step 3) that 

report serious organ toxicity in animal models at doses less than 1 milligram 

per kilogram per day (mg/kg/day) generally support a NIOSH finding of organ 

toxicity at low doses.

e. Genotoxicity

i. Human Studies

Human genotoxicity studies are not commonly available for evaluation. If available, 

NIOSH gives preference to human genotoxicity studies over animal and in vitro 

studies. However, NIOSH considers all relevant information in its evaluation.

ii. Animal Studies

(a) Studies found in any of the sources described in Section V.C.1 (Step 3) 

that report genotoxicity in laboratory animals generally support a NIOSH 

finding of genotoxicity. 

(b) Generally, in vivo animal testing is given greater weight than in vitro testing.

iii. In Vitro Systems

(a) Positive genotoxicity results in two or more in vitro test systems reported in 

any of the sources described in Section V.C.1 (Step 3) generally support a 

NIOSH finding of genotoxicity.

(b) Consistent findings of genotoxicity among human, animal and/or in vitro 

systems generally support a NIOSH finding of genotoxicity.

f. Structure and Toxicity Profile that Mimics Existing Drugs Determined Hazardous

A finding that a drug is an isomer or close chemical analog of a drug that meets the 

definition of a hazardous drug generally supports including it on the List. This criterion is typically used when toxicity information specific to the drug under evaluation 

is insufficient to evaluate whether it meets the definition of a hazardous drug.

4. Molecular Properties 

a. Factors Considered in Assessing Molecular Properties

The molecular properties of a drug may limit the potential mechanism of toxicity or 

limit the relevant routes of exposure of a drug.43 An assessment that the molecular 

properties of a drug may limit the potential for adverse health effects in healthcare 

workers supports a NIOSH finding that the drug does not meet the criteria in the 

NIOSH definition of a hazardous drug. 

42See supra note 16. 43For example, very large drug molecules may be therapeutically active and potentially toxic when injected, but may be too large to 

be absorbed appreciably through inhalation, ingestion, dermal, or percutaneous (needle puncture) routes of exposure.
10 | Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings

b. Factors Not Considered in Assessing Molecular Properties

NIOSH does not consider dosage form as a molecular property of a drug because the 

same active pharmaceutical product can be offered in several different dosage forms, 

new dosage forms can be offered later, and some dosage forms can be discontinued. 

5. Integrated Toxicity and Molecular Properties Hazard Assessment 

NIOSH considers the toxicity and molecular properties (“integrated assessment”) of a 

hazardous drug when making a determination if the drug meets the NIOSH definition of a hazardous drug. 

6. Evaluation Outcomes

a. Not Proposed for Placement on the List

Evaluated drugs are not proposed for placement on the List when the integrated 

assessment does not support a NIOSH determination that the drug meets the 

NIOSH definition of a hazardous drug. 

b. Proposed for Placement on the List

Evaluated drugs are proposed for placement on the List when the integrated assessment supports a NIOSH determination that the drug meets the NIOSH definition of a hazardous drug. 

7. Tabular Arrangement of Hazardous Drugs on the List44

a. Table 1 contains drugs that have MSHI in the package insert and/or meet the 

NIOSH definition of a hazardous drug and one or more of these criteria: 

i. Are classified by the NTP as “known to be a human carcinogen,” and 

ii. Are classified by the IARC as Group 1 “carcinogenic to humans” or Group 2A 

“probably carcinogenic to humans.” 

b. Table 2 contains drugs that meet the NIOSH definition of a hazardous drug and

i. Do not have MSHI,

ii. Are not classified by the NTP as “known to be a human carcinogen,” and 

iii. Are not classified by the IARC as Group 1 “carcinogenic to humans” or Group 

2A “probably carcinogenic to humans.”

D. Step 4: Peer Review of Potentially Hazardous Drugs

Consistent with the Office of Management and Budget’s Information Quality Guidelines,45 NIOSH conducts peer review examining NIOSH’s approach to identifying, 

screening, evaluating, and placing a drug on, moving a drug within, or removing a drug 

from the List. Particular emphasis in the peer review is placed on the integrated hazard 

assessment and the applicability of the decision criteria. After peer review, NIOSH 

reexamines the decision criteria with respect to the peer review comments and reevaluates drug placement on the List.

44In addition to the two tables, each update of the List includes description of changes made to the List. 45Office of Management and Budget [2004]. Final information quality bulletin for peer review. Available at https://www.govinfo.

gov/content/pkg/FR-2005-01-14/pdf/05-769.pdf.
Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings | 11

E. Step 5: Public Review of Potentially Hazardous Drugs 

NIOSH publishes a Federal Register notice seeking public comment on the following 

four categorical determinations of the evaluated drugs and, for drugs proposed for placement on the List, their tabular location on the List:

Category 1—Insufficient Toxicity Information Available to Meet NIOSH Definition of 

Hazardous Drug

Screened drugs with insufficient information to determine whether the drug exhibits any 

one of the toxicity criteria found in the NIOSH definition of hazardous drug are not eligible 

for evaluation and are not proposed for placement on the List (Section V.B.2.b, Step 2).

Category 2—Available Information Shows a Toxic Effect that Does Not Meet the 

NIOSH Definition of a Hazardous Drug

Screened drugs with available toxicity information showing a toxic effect that does not 

meet the NIOSH definition of hazardous drug are not proposed for placement on the 

List (Section V.B.2.c, Step 2).

Category 3—Available Toxicity Information Does Not Support a Determination that 

the Drug Meets the NIOSH Definition of a Hazardous Drug

Evaluated drugs are not proposed for placement on the List when toxicity and molecular 

properties assessment does not support a NIOSH determination that the drug meets the 

NIOSH definition of a hazardous drug (Section V.C.6.a, Step 3).

Category 4—Available Toxicity and Molecular Properties Assessment Supports a Determination that the Drug Meets the NIOSH Definition of a Hazardous Drug 

Evaluated drugs are proposed for placement on the List when toxicity and molecular 

properties assessment supports a determination that the drug meets the NIOSH definition of a hazardous drug (Section V.C.6.b, Step 3).

F. Step 6: Placement of Hazardous Drugs on the List and in Tables

1. After consideration of peer review and public comments, the NIOSH Director will 

make a final determination on whether to place an evaluated drug on the List and 

determine the tabular location of the drug on the List.

2. NIOSH will publish the updated List, available through the NIOSH Hazardous 

Drug Exposures in Healthcare website,28 and announce the availability of the updated 

List in a Federal Register notice. 

VI. Request for a NIOSH Reevaluation

A. Request

A request by a party asking NIOSH to reevaluate its determination to place, or not to place, 

a drug on the List, or a decision to place a drug on a particular table of the List, must

1. Be submitted in writing as a letter to the NIOSH Director,46 including a letter summarizing the request,47 and 

46Requests can be submitted to the following address: NIOSH, 395 E Street, S.W., Suite 9200, Washington, D.C. 20201.

47The requestor should prepare a letter keeping in mind that NIOSH will publish the letter for public view. See Section VI.B.3. NIOSH 

will maintain the confidentiality of any proprietary and/or trade secret information provided to NIOSH to the full extent it is 

permitted to do so under the Federal Trade Secret Act, 18 USC § 1905, and the Freedom of Information Act, 5 USC § 552 (FOIA). 

NIOSH will maintain personally identifiable information in accordance with the Privacy Act of 1974, 5 USC § 552a.
12 | Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings

2. Present new scientific information that is relevant to the issue of whether the drug 

does or does not meet the NIOSH definition of a hazardous drug or a

decision to place a drug on a particular table of the List.

Note: If the request for a reevaluation does not contain new scientific information, 

the request will not be considered a valid request for a NIOSH reevaluation.

B. Initial NIOSH Evaluation of a Request for a Reevaluation

After receipt of a request for a reevaluation, NIOSH will

1. Determine if the request meets the requirements in Section VI.A,

2. Notify the requestor by letter of the decision whether the request meets the 

requirements of Section VI.A, and

3. Following initial examination of a reevaluation request, publish the letter requesting 

the reevaluation review, and NIOSH’s response to the request, accessible through the 

NIOSH Hazardous Drug Exposures in Healthcare website.28

C. NIOSH Review of Evidence Presented in the Request for a Reevaluation 

If NIOSH determines that the request meets the requirements in Section VI.A, 

NIOSH will

1. Review all of the information NIOSH used to make its determination to place the 

requested drug on the List, or not to place the drug on the List, or place the drug on a 

particular table of the List, including the original identification, screening and evaluation reviews conducted by NIOSH, and all peer reviewer and public comments. 

2. Review the request for a reevaluation and search for any additional hazard identification (toxicity) and hazard characterization information about the drug that is relevant 

to the criteria set out in the NIOSH definition of a hazardous drug.

3. Develop an initial recommendation and summary of evidence about whether to 

maintain or change the status of the drug subject to the reevaluation request.

D. Peer Review of the Initial Recommendation

NIOSH will conduct peer review consistent with the Office of Management and Budget’s Information Quality Guidelines48 of its reevaluation recommendation on whether 

to maintain or change the status of the drug subject to the review request.

E. Public Comment on the Initial Recommendation

NIOSH will solicit public comments on the initial recommendation to maintain or 

change the status of the drug subject to the reevaluation request in a Federal Register

notice with a public comment period of 30 days.

48See supra note 45.
Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings | 13

F. Final Reevaluation Determination

1. After consideration of peer review and public comments, NIOSH will make a final 

reevaluation determination and inform the requestor by letter of the final reevaluation 

determination.

2. NIOSH will publish the final reevaluation determination in a Federal Register notice, 

and on the NIOSH Hazardous Drug Exposures in Healthcare website.28 If appropriate, 

NIOSH will make a change to the status of the drug subject to the reevaluation (e.g., 

remove, add, or move) in the next update of the List. 
14 | Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings

Figure 1. Identifying, Screening, Evaluating, and Reviewing Drugs for Placement on the List

Step 1

Identifying 

Drugs

NIOSH reviews FDA databases (Drugs@FDA and Drug Safety-related Labeling Changes) and receives requests from the public to identify drugs for screening.

Drugs submitted for screening

 New molecular entities with new drug applications and biologics license applications

 New safety labeling changes or new pregnancy and lactation labeling information

 Requests from the public

Step 2

Screening 

Drugs

NIOSH screens identified drugs to determine whether the drug package insert specifies Manufacturer’s Special Handling Information (MSHI) or information in 

the drug package insert suggests that a drug may exhibit at least one of the types of toxicity criteria found in the NIOSH definition of hazardous drug.

Manufacturer’s 

Special Handling 

Information

Information suggests a toxic effect(s) that may meet the NIOSH definition of 

hazardous drug.

 Insufficient toxicity information 

available to meet NIOSH definition of 

hazardous drug. 

 Available information shows no toxic 

effect or a toxic effect that does not 

meet the NIOSH definition of a 

hazardous drug. Step 3

Evaluating 

Drugs 

NIOSH evaluates information from humans and animals using the toxicity criteria in 

Section V.C.3 for determining whether a drug exhibits one of the toxicities set out in 

the NIOSH definition of hazardous drug; and NIOSH evaluates whether the molecular 

properties of a drug may limit the potential for adverse health effects in healthcare 

workers exposed to the hazardous drug.

Integrated Hazard Assessment

Supports a NIOSH determination that 

the drug meets the NIOSH definition of 

a hazardous drug.

Integrated Hazard Assessment

Does not support a NIOSH 

determination that the drug meets the 

NIOSH definition of a hazardous drug.

Step 4

Peer 

Review

NIOSH conducts peer review examining NIOSH’s approach to identifying, screening, 

evaluating, and placing a drug on, moving a drug within, or removing a drug from 

the List, with an emphasis on the integrated hazard assessment and the applicability 

of the decision criteria. After peer review, NIOSH again reviews decision criteria with 

consideration from the peer review and reevaluates drug placement on the List.

Integrated Hazard Assessment

Supports a NIOSH determination that 

the drug meets the NIOSH definition of 

a hazardous drug.

Integrated Hazard Assessment

Does not support a NIOSH 

determination that the drug meets the 

NIOSH definition of a hazardous drug.

Step 5

Public 

Comment

NIOSH publishes a Federal Register notice seeking public comment on the screened and evaluated drugs, and for drugs proposed for 

placement on the List, their tabular location on the List.

Category 4

 Integrated hazard assessment 

supports a NIOSH determination 

that the drug meets the NIOSH 

definition of a hazardous drug.

Category 3

 Integrated hazard assessment does 

not support a NIOSH determination that the drug meets the 

NIOSH definition of a hazardous 

drug.

Categories 1 and 2

 Insufficient toxicity information 

available to meet NIOSH definition of 

hazardous drug. 

 Available information shows a toxic 

effect that does not meet the NIOSH 

definition of a hazardous drug.

Step 6

Placement on 

the List

After consideration of peer review and public comments, the NIOSH Director determines whether to place an evaluated drug on the List,

and if so, in which table.

Drugs placed on the List

 Manufacturer’s Special Handling Information (MSHI)

 Integrated hazard assessment supports a determination that the drug meets the NIOSH 

definition of a hazardous drug. 

Drugs not placed on the List

 Insufficient toxicity information available to meet the NIOSH definition of 

a hazardous drug. 

 Available information shows a toxic effect that does not meet the NIOSH 

definition of a hazardous drug.

 Integrated hazard assessment does not support a NIOSH determination that 

the drug meets the NIOSH definition of a hazardous drug. 
This page intentionally left blank.
Promoting productive workplaces through 

safety and health research

DHHS (NIOSH) Publication No. 2023-129

DOI: https://doi.org/10.26616/NIOSHPUB2023129