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DHHS (NIOSH) Publication Number 2004−165
September 2004
SAFER • HEALTHIER • PEOPLE
TM
ii
Foreword
The purpose of this Alert is to increase awareness among health care workers and their em-
ployers about the health risks posed by working with hazardous drugs and to provide them
with measures for protecting their
health. Health care workers who prepare or administer
hazardous drugs or who work in areas where these drugs are used may be exposed to these
agents in the air or on work surfaces, contaminated clothing, medical equipment, patient
excreta, and other surfaces. Studies have associated workplace exposures to hazardous
drugs with health effects such as skin rashes and adverse reproductive outcomes (including
infertility, spontaneous abortions, and congenital malformations) and possibly leukemia and
other cancers. The health risk is influenced by the extent of the exposure and the potency
and toxicity of the hazardous drug. To provide workers with the greatest protection, employers
should (1) implement necessary administrative and engineering controls and (2) assure that
workers use sound procedures for handling hazardous drugs and proper protective equip
-
ment. The Alert contains a list of drugs that should be handled as hazardous drugs.
This Alert applies to all workers who handle hazardous drugs (for example, pharmacy and
nursing
personnel, physicians, operating room
personnel, environmental services workers,
workers in research laboratories, veterinary care workers, and shipping and receiving person
-
nel). Although not all workers in these categories handle hazardous drugs, the number of
exposed workers exceeds 5.5 million.
The Alert does not apply to workers in the drug manu-
facturing sector.
The production, distribution, and application of pharmaceutical medications are part of a
rapidly
growing field of patient
therapy. New areas of pharmaceutical development will bring
fundamental changes to methods for treating and preventing diseases. Both traditional med
-
ications and bioengineered drugs can be hazardous to health care workers who must handle
them. This NIOSH Alert will help make workers and employers more aware of these hazards
and provide the tools for preventing exposures.
John Howard, M.D.
Director
National Institute for Occupational
Safety and Health
Centers for Disease Control
and Prevention
iii
Contents
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Potential for Worker Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Conditions for Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Exposure Routes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Evidence for Worker Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Evidence for Health Effects in Workers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Mutagenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Developmental and Reproductive Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Current Standards and Recommendations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
OSHA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
EPA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Additional Guidelines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Case Reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Case 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Case 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Case 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Case 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Case 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Summary of Recommended Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Detailed Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Receiving and Storage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Drug Preparation and Administration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Initial steps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Preparing hazardous drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Administering hazardous drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Ventilated Cabinets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Use of cabinets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
vii
Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Air flow and exhaust . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Maintenance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Routine Cleaning, Decontaminating, Housekeeping, and Waste Disposal . . . . 16
Cleaning and decontaminating. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Housekeeping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Waste disposal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Spill Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Medical Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Additional Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Appendices
A. Drugs Considered Hazardous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
General Approach to Handling Hazardous Drugs. . . . . . . . . . . . . . . . . . . . . . 31
Defining Hazardous Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
ASHP Definition of Hazardous Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
NIOSH Revision of ASHP Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Determining Whether a Drug is Hazardous. . . . . . . . . . . . . . . . . . . . . . . 32
How to Generate Your Own List of Hazardous Drugs . . . . . . . . . . . . . . . . 33
Where to Find Information Related to Drug Toxicity . . . . . . . . . . . . . . . . . 34
Examples of Hazardous Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
B. Abbreviations and Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
C. NIOSH Hazardous Drug Safety Working Group . . . . . . . . . . . . . . . . . . . . . . . . 49
viii
Preventing Occupational Exposures to
Antineoplastic and Other Hazardous
Drugs in Health Care Settings
Warning!
Working with or near hazardous drugs in health care settings
may cause skin rashes, infertility, miscarriage, birth defects,
and possibly leukemia or other cancers.
The National Institute for Occupational
Safe
ty and Health (NIOSH) requests as-
sistance in preventing occupational ex-
posures to antineoplastic drugs (drugs
used
to treat cancer) and other hazard-
ous drugs in health care settings. Health
care
workers who work with or near haz-
ardous drugs may suffer from skin rash-
es, infertility, miscarriage, birth defects,
and p
ossibly leukemia or other cancers.
Workers may be exposed to hazardous
drugs in the air
or on work surfaces,
clothing, medical equipment, and pa-
tient urine or feces. The term hazardous
drugs, as it
is used in this Alert, includes
drugs that are known or suspected to
cause adverse health effects from ex-
posures in the workplace. They include
drugs used for cancer
chemotherapy,
antiviral drugs, hormones, some bio-
engineered drugs, and other miscella-
neous drugs. The health risk depends
on how much e
xposure a worker has to
these drugs and how toxic they are. Ex-
posure risks can be greatly reduced by
(1) making sure that engineering con-
trols such as a ventilated cabinet are
used
and (2) using
proper procedures
and protective equipment for handling
hazardous drugs.
This Alert warns health care workers
about the risks of
working with haz-
ardous drugs and recommends meth-
ods and equipment for protecting their
health.
The Alert addresses
workers in
health care settings, veterinary medi
-
cine, research laboratories, retail phar-
macies, and home health care agen-
cies; it does not address workers in the
drug
manufacturing sector.
Included in
the Alert are five case reports of work
-
ers who suffered adverse health effects
after being exposed
to antineoplastic
drugs.
NIOSH requests that employers, editors
of trade journals, safety
and health of-
ficials, and unions bring the recommen-
dations in this Alert to the attention of
all work
ers who are at risk.
1
BACKGROUND
Drugs have a successful history of use in
treating illnesses and injuries, and they
are responsible for many of our medical
advances over the past century. However,
virtually all drugs have side effects associ
-
ated with their use by patients. Thus, both
patients and workers
who handle them are
at risk of suffering these effects. In addi
-
tion, it is known that exposures to even very
small concentrations of
certain drugs may
be hazardous for workers who handle them
or work near them.
The term hazardous drugs was first
used by
the American Society of Hospital Pharma-
cists (ASHP) [ASHP 1990] and is currently
used
by the
Occupational Safety and Health
Administration (OSHA) [OSHA 1995, 1999].
Drugs are classified as hazardous if studies
in animals or humans indicate that expo
-
sures to them have a potential for causing
cancer, developmental
or reproductive tox-
icity, or harm to organs. Many hazardous
drugs
are used
to treat illnesses such as
cancer or HIV infection [Galassi et al. 1996;
McInnes and Schilsky 1996; Erlichman and
Moore 1996]. See Appendix A for examples
of hazardous drugs and a full discussion of
criteria used to define and classify them as
hazardous.
Although the potential therapeutic benefits
of hazardous drugs
outweigh the risks of side
effects for ill patients, exposed health care
workers risk these same side effects with no
therapeutic benefit. Occupational exposures
to hazardous drugs can lead to (1) acute
effects such as skin rashes [McDiarmid and
Egan 1988; Valanis et al. 1993a,b; Krstev
et al. 2003]; (2) chronic effects, including
adverse reproductive events [Selevan et al.
1985; Hemminki et al. 1985; Stücker et al.
1990; Valanis et al. 1997, 1999; Peelen et
al. 1999]; and
(3) possibly cancer [Skov et
al. 1992].
Guidelines have been established for han-
dling hazardous drugs, but adherence to
these
guidelines has
been reported to be
sporadic [Valanis et al. 1991, 1992; Ma
-
hon et al. 1994; Nieweg et al. 1994]. In
addition, measurable concentrations
of
some hazardous drugs have been docu
-
mented in the urine of health care workers
who prepared or
administered them—even
after safety precautions had been employed
[Ensslin et al. 1994, 1997; Sessink et al.
1992b, 1994a,b, 1997; Minoia et al. 1998;
Wick et al. 2003]. Environmental studies of
patient-care areas have documented mea
-
surable concentrations of drug contamina-
tion, even in facilities thought to be following
r
ec
ommended handling guidelines [Minoia
et al. 1998; Connor et al. 1999; Pethran et
al. 2003].
The numbers and types of work environments
containing antineoplastic drugs
are expand-
ing as these agents are used increasingly for
nonmalignant
rheumatologic and
immuno-
logic diseases [Baker et al. 1987; Moody et
al.
1987; Chabner
et al. 1996; Abel 2000]
and for chemotherapy in veterinary medi
-
cine [Rosenthal 1996; Takada 2003]. This
Alert summarizes the
health effects asso-
ciated with occupational exposure to these
agents
and provides
recommendations for
safe handling.
POTENTIAL FOR WORKER
EXPOSURE
Workers may be exposed to a drug through-
out its life cycle—from manufacture to
Hazardous Drugs in Health Care Settings 2
transport and distribution, to use in health
care or home care settings, to waste dis
-
posal. The number of workers who may be
exposed to hazardous
drugs exceeds 5.5
million [U.S. Census Bureau 1997; BLS
1998, 1999; NCHS 1996]. These workers
include shipping and receiving personnel,
pharmacists and pharmacy technicians,
nursing personnel, physicians, operating
room personnel, environmental services
personnel, and workers in veterinary prac
-
tices where hazardous drugs are used. This
Alert addresses workers
in health care set-
tings, veterinary medicine, research labora-
tories, retail pharmacies, and home health
care
agencies; it
does not address workers
in the drug manufacturing sector.
CONDITIONS FOR EXPOSURE
Both clinical and nonclinical workers may be
exposed to hazardous drugs when they cre
-
ate aerosols, generate dust, clean up spills,
or touch contaminated
surfaces during the
preparation, administration, or disposal of
hazardous drugs. The following list of activi
-
ties may result in exposures through inhala-
tion, skin contact, ingestion, or injection:
Reconstituting powdered or lyophilized
drugs and further diluting either the re-
constituted powder or concentrated liq-
uid forms of hazardous drugs [Fransman
et al. 2004]
Expelling air from syringes filled with haz-
ardous drugs
Administering hazardous drugs by intra-
muscular, subcutaneous, or intravenous
(IV) routes
Counting out individual, uncoated oral
doses and tablets from multidose bot-
tles
Unit-dosing uncoated tablets in a unit-
dose machine
Crushing tablets to make oral liquid
doses [Dorr and Alberts 1992; Shahsa-
varani et al. 1993; Harrison and Schultz
2000]
Compounding potent powders into cus-
tom-dosage capsules
Contacting measurable concentrations of
drugs present on drug vial exteriors, work
surfaces, floors, and final drug products
(bottles, bags, cassettes, and syringes)
[McDevitt et al. 1993; Sessink et al.
1992a,b, 1994b; Minoia et al. 1998;
Connor et al. 1999, 2002; Schmaus et
al. 2002]
Generating aerosols during the adminis-
tration of drugs, either by direct IV push
or by IV infusion
Priming the IV set with a drug-contain-
ing solution at the patient bedside (this
procedure should be
done in the phar-
macy)
Handling body fluids or body-fluid-con-
taminated clothing, dressings, linens,
and other materials
[Cass and Musgrave
1992; Kromhout et al. 2000]
Handling contaminated wastes gener-
ated at any step of the preparation or
administration process
Performing certain specialized proce-
dures (such as intraoperative intraperi-
toneal chemotherapy) in the operating
room [White et
al. 1996; Stuart et al.
2002]
Hazardous Drugs in Health Care Settings 3
Handling unused hazardous drugs or
hazardous-drug-contaminated waste
Decontaminating and cleaning drug
preparation or clinical areas
Transporting infectious, chemical, or
hazardous waste containers
Removing and disposing of personal pro-
tective equipment (PPE) after handling
hazardous drugs or waste
EXPOSURE ROUTES
Exposures to hazardous drugs may occur
through inhalation, skin contact, skin ab
-
sorption, ingestion, or injection. Inhalation
and skin contact/absorption
are the most
likely routes of exposure, but unintentional
ingestion from hand to mouth contact and
unintentional injection through a needle-
stick or sharps injury are also possible [Du
-
vall and Baumann 1980; Dorr 1983; Black
and Presson 1997; Schreiber et al. 2003].
A number of studies have attempted to
measure
airborne concentrations
of an-
tineoplastic drugs in health care settings
[Kleinberg
and Quinn
1981; Neal et al.
1983; McDiarmid et al. 1986; Pyy et al.
1988; McDevitt et al. 1993; Sessink et al.
1992a; Nygren and Lundgren 1997; Stuart
et al. 2002; Kiffmeyer et al. 2002; Larson et
al. 2003]. In most cases, the percentage of
air samples containing measurable airborne
concentrations of hazardous drugs was low,
and the actual concentrations of the drugs,
when present, were quite low. These results
may be attributed to the inefficiency of sam
-
pling and analytical techniques used in the
past [Larson et
al. 2003]. Both particulate
and gaseous phases of one antineoplastic
drug, cyclophosphamide, have been report-
ed in two studies [Kiffmeyer et al. 2002;
Larson et al. 2003].
Since the early 1990s, 14 studies have
examined environmental contamination
of
areas where hazardous drugs are prepared
and administered at health care facilities in
the United States and several other coun
-
tries [Sessink et al. 1992a; Sessink et al.
1992b; McDevitt et
al. 1993; Pethran et
al. 1998; Minoia et al. 1998; Rubino et al.
1999; Sessink and Bos 1999; Connor et al.
1999; Micoli et al. 2001; Vandenbroucke et
al. 2001; Connor et al. 2002; Kiffmeyer et
al. 2002; Schmaus et al. 2002; Wick et al.
2003]. Using wipe samples, most investi
-
gators measured detectable concentrations
of one to
five hazardous drugs in various
locations such as biological safety cabinet
(BSC) surfaces, floors, counter tops, stor
-
age areas, tables and chairs in patient treat-
ment areas, and locations adjacent to drug-
handling
areas. All
of the studies reported
some level of contamination with at least
one drug, and several reported contamina
-
tion with all the drugs for which assays were
performed.
Such widespread
contamination
of work surfaces makes the potential for
skin contact highly probable in both phar
-
macy and patient areas.
EVIDENCE FOR WORKER
EXPOSURE
Evidence indicates that workers are be-
ing exposed to hazardous drugs and are
experiencing serious health
effects despite
current work practice guidelines. Protection
from hazardous drug exposures depends on
safety programs established by employers
Hazardous Drugs in Health Care Settings 4
and followed by workers. Factors that affect
worker exposures include the following:
Drug handling circumstances (prepara-
tion, administration, or disposal)
Amount of drug prepared
Frequency and duration of drug handling
Potential for absorption
Use of ventilated cabinets*
PPE
Work practices
The likelihood that a worker will experience
adv
erse effects from hazardous drugs increas-
es with the amount and frequency of exposure
and
the lack of proper work practices.
Worker exposures have been assessed by
studies of biological
markers of exposure.
No single biological marker has been found
to be a good indicator of exposure to haz
-
ardous drugs or a good predictor of adverse
health effects [Baker
and Connor 1996].
Sessink and Bos [1999] noted that 11 of
12 studies reported cyclophosphamide in
the urine of health care workers tested, in
-
dicating continued exposure despite safety
precautions.
Harrison [2001] reported that six differ-
ent drugs (cyclophosphamide, methotrex-
ate, ifosfamide, epirubicin and cisplatin/
carboplatin)
were detected
in the urine of
health care workers by 13 of 20 inves-
tigations. Two recent studies have docu-
mented antineoplastic drugs in the urine
*
A ventilated cabinet is a type of engineering control designed
to protect workers. Examples include BSCs and isolators
designed to prevent hazardous drugs inside the cabinet
from escaping into the work environment. See the Glossary
in Appendix B for additional descriptions of engineering
controls.
of pharmacy and nursing personnel [Peth-
ran et al. 2003; Wick et al. 2003]. Pethran
and coworkers collected
urine samples in
14 German hospitals over a 3-year period.
Cyclophosphamide, ifosfamide, doxorubi
-
cin, and epirubicin (but not daunorubicin or
idarubicin) and platinum
(from cisplatin or
carboplatin) were identified in urine samples
from many of the study participants. A U.S.
investigation demonstrated that use of a
closed-system device for 6 months reduced
both the concentration of cyclophospha
-
mide or ifosfamide in the urine of exposed
health care workers
and the percentage of
samples containing these drugs [Wick et
al. 2003]. Hazardous drugs have also been
documented in the urine of health care
workers who did not handle hazardous drugs
but were potentially exposed through fugi
-
tive aerosols or secondary contamination of
work surfaces, clothing,
or drug containers
[Sessink et al. 1994b; Mader et al. 1996;
Pethran et al. 2003].
EVIDENCE FOR HEALTH EFFECTS
IN WORKERS
By the 1970s, the carcinogenicity of several
antineoplastic drugs in animals was well
established [Shimkin et al. 1966; Weis
-
berger 1975; Schmahl and Habs 1978].
Likewise, a number
of researchers during
this period linked the therapeutic use of
alkylating agents in humans to subsequent
leukemias and other cancers [Harris 1975,
1976; IARC 1979]. Many health care pro
-
fessionals began to question the safety of
occupational
exposure to
these agents [Ng
and Jaffe 1970; Donner 1978; Johansson
1979].
Hazardous Drugs in Health Care Settings 5
Mutagenicity
A number of studies indicate that antineo-
plastic drugs may cause increased genotoxic
eff
ects in pharmacists and nurses exposed in
the workplace [Falck et al. 1979; Anderson
et al 1982; Nguyen et al. 1982; Rogers and
Emmett 1987; Oestricher et al. 1990; Fuchs
et al. 1995; Ündeger et al. 1999; Norppa et
al. 1980; Nikula et al. 1984; McDiarmid et
al. 1992; Sessink et al. 1994a; Burgaz et al.
1988]. Several studies that have not linked
genotoxic effects with worker exposures may
be explained by technical confounders and
a lack of accurate blood and urine sampling
in exposed workers [Sorsa et al. 1985; Mc-
Diarmid et al. 1992]. When all the data are
considered, the weight of evidence associ
-
ates hazardous drug exposures at work with
inc
reased genotoxicity [Sorsa and Anderson
1996; Baker and Connor 1996; Bos and
Sessink 1997; Hewitt 1997; Sessink and
Bos 1999; Harrison and Schulz 2001].
Developmental and Reproductive
Effects
A recent review of 14 studies described
an association between exposure to anti-
neoplastic drugs and adverse reproductive
effects, and 9 studies showed some posi-
tive association [Harrison 2001]. The major
reproductive
effects found
in these stud-
ies were increased fetal loss [Selevan et
al. 1985; Stücker
et al. 1990], congenital
malformations depending on the length of
exposure [Hemminki et al. 1985], low birth
weight and congenital abnormalities [Peel
-
en et al. 1999], and infertility [Valanis et al.
1999].
Cancer
Several reports have addressed the rela-
tionship of cancer occurrence to health care
workers’ exposures to
antineoplastic drugs.
A significantly increased risk of leukemia
has been reported among oncology nurses
identified in the Danish cancer registry for
the period 1943−1987 [Skov et al. 1992].
The same group [Skov et al. 1990] found
an increased, but not significant, risk of leu
-
kemia in physicians employed for at least
6 months in a department where patients
were treated with antineoplastic drugs.
CURRENT STANDARDS AND
RECOMMENDATIONS
Currently, no NIOSH recommended exposure
limits (RELs), OSHA permissible exposure
limits (PELs), or American Conference of
Governmental Industrial Hygienists (ACGIH)
threshold limit values (TLVs
®
) have been
established for hazardous drugs in general.
An OSHA PEL and an ACGIH TLV have been
established for soluble platinum salts [29
CFR
†
1910.1000; ACGIH 2003]. However,
these standards are based on sensitization
and not on the potential to cause cancer. A
PEL, an REL, and a TLV have also been es
-
tablished for inorganic arsenic compounds,
which include the
antineoplastic drug ar-
senic trioxide [29 CFR 1910.1018; NIOSH
2004;
ACGIH
2003].
A workplace environ-
mental exposure level (WEEL) has been
established
for
some
antibiotics, including
chloramphenicol (AIHA 2002). Some phar
-
maceutical manufacturers develop risk-
based occupational exposure
limits (OELs)
to be used in their own manufacturing set
-
tings, and this information may be available
†
Code of Federal Regulations. See CFR in references.
Hazardous Drugs in Health Care Settings 6
on material safety data sheets (MSDSs) or
from the manufacturer [Sargent and Kirk
1988; Naumann and Sargent 1997; Sar
-
gent et al. 2002].
U.S. Environmental Protection Agency (EPA)
regulations under the
Resource Conserva-
tion and Recovery Act (RCRA) [42 USC
‡
6901−6992] apply to the management of
hazardous wastes, which include nine anti-
neoplastic drugs [40 CFR 260–279].
OSHA
OSHA originally published guidelines for anti-
neoplastic drugs in 1986 [OSHA 1986]. Cur-
rent OSHA standards and guidelines that ad-
dress hazardous drugs include the following:
Hazard communication standard [29 CFR
1910.1200]
Occupational exposure to hazardous che-
micals in laboratories standard [29 CFR
1910.1450]
OSHA Technical Manual; Section VI,
Chapter 2: Controlling Occupational Expo-
sure to Hazardous Drugs [OSHA 1999].
M
ai
n elements of these 1999 OSHA
guidelines include the following:
— Categorization of drugs as hazardous
— Hazardous drugs as occupational risks
— Work area
— Prevention of employee exposure
— Medical surveillance
— Hazard communication
— Training and information dissemina-
tion
— Recordkeeping
‡
United States Code. See USC in references.
EPA
EPA/RCRA regulations require that haz-
ardous waste be managed by following a
strict set of regulatory requirements [40
CFR 260–279]. The RCRA list of hazard-
ous wastes was developed in 1976 and
includes only about
30 pharmaceuticals, 9
of which are antineoplastic drugs. Recent
evidence indicates that a number of drug
formulations exhibit hazardous waste char-
acteristics [Smith 2002]. OSHA [1999] and
ASHP [1990] recommend
that hazardous
drug waste be disposed of in a manner simi-
lar to that required for RCRA-listed hazard-
ous waste. Hazardous drug waste includes
partially filled vials,
undispensed products,
unused IVs, needles and syringes, gloves,
gowns, underpads, contaminated materials
from spill cleanups, and containers such as
IV bags or drug vials that contain more than
trace amounts of hazardous drugs and are
not contaminated by blood or other poten-
tially infectious waste. Published EPA guide-
lines are as follows:
U.S. Environmental Protection Agency
(EPA). Managing Hazardous Waste: A
Guide for Small Businesses [EPA 2001].
U.S. Environmental Protection Agency
(EPA). RCRA Hazardous Waste Regula-
tions [40 CFR Parts 260–279].
Additional Guidelines
Additional guidelines that address hazard-
ous drugs or the equipment in which they
are manipulated include the following:
Centers for Disease Control (CDC) and
National Institutes of Health (NIH). Pri-
mary Containment for Biohazards [CDC/
NIH 2000]. Provides guidance on the
selection, installation, testing, and use
of BSCs.
Hazardous Drugs in Health Care Settings 7
NIH. Recommendations for the Safe
Handling of Cytotoxic Drugs [NIH 2002].
Includes recommendations for the safe
preparation and administration of cyto-
toxic drugs.
ASHP. ASHP Technical Assistance Bulle-
tin on Handling Cytotoxic and Hazardous
Drugs [ASHP 1990]. An
informed dis-
cussion of the dangers and safe handling
procedures for hazardous drugs.
Oncology Nursing Society. Chemotherapy
and Biotherapy Guidelines and Recom-
mendations for Practice [Br
own et al.
2001]. Provides complete guidelines for
the administration of antineoplastic drugs,
including safe handling guidelines.
Oncology Nursing Society. Safe Handling
of Hazardous Drugs [Polovich 2003].
Includes proper handling guidelines for
hazardous drugs.
United States Pharmacopeia. Chapter
<797> Pharmaceutical Compounding—
Sterile Preparations [USP 2004].
Details
the procedures and requirements for
compounding sterile preparations and
sets standards applicable to all settings
in which sterile preparations are com-
pounded.
National Sanitation Foundation (NSF)
and American National Standards Insti-
tute (ANSI). NSF
/ANSI 49–2002 Class II
(Laminar Flow) Biosafety Cabinetry [NSF/
ANSI 2002]. Addresses classification and
certification of Class II BSCs and provides
a definition for Class III BSCs.
PDA. Technical Report No. 34: Design
and Validation of Isolator Systems for
the Manufacturing and Testing of Health
Care Products [PDA 2001]. A
supple-
mental publication to the PDA Journal
of Pharmaceutical Science
and Technol-
ogy. Provides definitions, design, and op-
eration and testing guidance for types of
isolators
used in
the health care product
manufacturing industry.
American Glovebox Society (AGS).
Guidelines for Gloveboxes; 2nd edition
[AGS 1998]. Provides guidance on the
design, testing, use, and decommission
-
ing of glovebox containment systems.
CASE REPORTS
The following cases illustrate the range of
health effects reported after exposure to
antineoplastic drugs:
Case 1
A female oncology nurse was exposed to a
solution of carmustine when the complete
tubing system fell out of an infusion bottle
of carmustine, and all of the solution poured
down her right arm and leg and onto the
floor [McDiarmid and Egan 1988]. Although
she wore gloves, her right forearm was un
-
protected, and the solution penetrated her
clothing and stockings.
Feeling no sensation
on the affected skin areas, she immediately
washed her arm and leg with soap and water
but did not change her clothing. A few hours
later, while at work, she began to experi
-
ence minor abdominal distress and profuse
belching
followed by
intermittent episodes of
nonbloody diarrhea with cramping abdomi
-
nal pain. Profuse vomiting occurred, after
which she felt
better. The nurse went to the
emergency room, where her vital signs and
physical examination were normal. No spe
-
cific therapy was prescribed. She felt better
the following day
. Carmustine is known to
Hazardous Drugs in Health Care Settings 8
cause gastric upset, and the investigators
attributed her gastrointestinal distress to
systemic absorption of carmustine.
Case 2
A 39-year-old pharmacist suffered two epi-
sodes of painless hematuria (blood in the
urine) and was
found to have cancer (a
grade II papillary transitional cell carcinoma)
[Levin et al. 1993]. Twelve years before
her diagnosis, she had worked full time
for 20 months in a hospital IV preparation
area where she routinely prepared cyto
-
toxic agents, including cyclophosphamide,
fluorouracil, methotrexate, doxorubicin,
and
cisplatin. She used a horizontal laminar-flow
hood that directed the airflow toward her.
Because she was a nonsmoker and had no
other known occupational or environmental
risk factors, her cancer was attributed to
her antineoplastic drug exposure at work—
though a cause and effect relationship has
not been established in the literature.
Case 3
A 41-year-old nurse who had worked on an
oncology ward for 13 years suffered from
nasal discharge, difficult breathing, and at
-
tacks of coughing 1 to 2 hours after begin-
ning work [Walusiak et al. 2002]. During the
third year of
her employment on the ward,
she developed difficult breathing while away
from work. Her total IgE was low, and spe
-
cific IgE antibodies to common agents and
skin prick tests
to common allergens (in-
cluding latex) were all negative. The patient
was
subjected to
a number of single-blind
bronchial challenge tests with antineoplastic
drugs, and she was monitored by spirometry
and peak expiratory flow measurements. On
the basis of clinical findings, the investiga
-
tors concluded that the evidence was con-
sistent with a diagnosis of allergic asthma.
Case 4
A malfunctioning BSC resulted in possible
exposure of nursing personnel to a number
of antineoplastic drugs that were prepared
in the BSC [Kevekordes et al. 1998]. Blood
samples from the nurses were analyzed
for genotoxic biomarkers 2 and 9 months
after replacement of the faulty BSC. At
2 months, both sister chromatid exchanges
(SCEs) and micronuclei were significantly
elevated compared with those of a matched
control group. At 9 months, the micronu
-
clei concentrations were similar to those of
t
he
2-month controls. SCEs were not deter-
mined at 9 months. The investigators con-
cluded that the elevation in biomarkers had
r
es
ulted from the malfunctioning of the BSC,
which resulted in worker exposure to the an
-
tineoplastic drugs. They also concluded that
the
subsequent replacement with a new BSC
contributed to the reduced effect seen with
the micronucleus test at 9 months.
Case 5
A 41-year-old patient-care assistant work-
ing on an oncology floor developed an
itc
hy rash approximately 30 minutes after
emptying a commode of urine into a toilet
[Kusnetz and Condon 2003]. She denied
any direct contact with the urine, wore a
protective gown and nitrile gloves, and fol
-
lowed hospital policy for the disposal of
m
at
erials contaminated with antineoplastic
drugs. The rash subsided after 1 to 2 days.
Three weeks later, she had a similar reac
-
tion approximately 1 hour after performing
t
he
same procedure for another patient.
Upon investigation, it was found that both
hospital patients had recently been treated
with vincristine and doxorubicin. The patient-
care assistant had no other signs or symp
-
toms and reported no changes in lifestyle
Hazardous Drugs in Health Care Settings 9
and no history of allergies or recent infec-
tions. After treatment with diphenhydramine
(intramuscular) and oral
corticosteroids, her
symptoms disappeared. Although the cause
could not be definitely confirmed, both vin-
cristine and doxorubicin have been
RECOMMENDATIONS
associ-
ated with allergic reactions when given to
patients. The aerosolization
of the drug pres-
ent in the urine may have provided enough
exposure for symptoms to develop.
CONCLUSIONS
Recent evidence summarized in this Alert
documents that worker exposure to hazard
-
ous drugs is a persistent problem. Although
most air-sampling
studies have not demon-
strated significant airborne concentrations
of these drugs,
the sampling methods used
in the past have come into question [Larson
et al. 2003] and may not be a good indi-
cator of contamination in the workplace. In
all studies involving
examination of surface
wipe samples, researchers have determined
that surface contamination of the workplace
is common and widespread. Also, a number
of recent studies have documented the ex-
cretion of several indicator drugs in the urine
of health care
workers. Results from studies
indicate that worker exposure to hazardous
drugs in health care facilities may result in
adverse health effects.
Appropriately designed studies have begun
and
are continuing to characterize the ex-
tent and nature of health hazards associated
wit
h these ongoing exposures. NIOSH is cur-
rently conducting studies to further identify
pot
ential sources of exposure and methods
to reduce or eliminate worker exposure to
these drugs. To minimize these potentially
acute (short-term) and chronic (long-term)
effects of exposure
to hazardous drugs at
work, NIOSH recommends that at a mini
-
mum, employers and health care workers
follow the recommendations
presented in
this Alert.
Summary of Recommended
Procedures
1. Assess the hazards in the workplace.
Evaluate the workplace to identify and
assess hazards before anyone begins
work with hazardous drugs. As part of
this evaluation, assess the following:
— Total working environment
— Equipment (i.e., ventilated cabinets,
closed-system
drug transfer
devices,
glovebags, needleless systems, and
PPE)
— Physical layout of work areas
— Types of drugs being handled
— Volume, frequency, and form of drugs
h
an
dled (tablets, coated versus un-
coated, powder versus liquid)
— Equipment maintenance
— Decontamination and cleaning
— Waste handling
— Potential exposures during work, in-
cluding hazardous drugs, bloodborne
pathogens,
and chemicals
used to
deactivate hazardous drugs or clean
drug-contaminated surfaces
— Routine operations
Hazardous Drugs in Health Care Settings 10
— Spill response
— Waste segregation, containment, and
dis
posal
Regularly review the current inventory
of hazardous drugs, equipment, and
practices, seeking input from affect-
ed workers. Have
the safety
and health
staff or an internal committee perform
this review.
Conduct regular training reviews with
all potentially exposed workers in work-
places where hazardous drugs are used.
Seek ongoing input
from workers who
handle hazardous drugs and from other
potentially exposed workers regarding the
quality and effectiveness of the preven
-
tion program. Use this input from workers
to provide the
safest possible equipment
and conditions for minimizing exposures.
This approach is the only prudent public
health approach, since safe concentra
-
tions for occupational exposure to haz-
ardous drugs have not been conclusively
determined.
2. Handle drugs safely.
Implement a program for safely han-
dling hazardous drugs at work and
review this program
annually on the
basis of the workplace evaluation.
Establish work policies and procedures
specific to the handling of hazardous
drugs. These policies and procedures
should address and define the following:
— Presence of hazardous drugs
— Labeling
— Storage
— Personnel issues (such as exposure
of pregnant workers)
— Spill control
— Detailed procedures for preparing,
administering,
and disposing
of haz-
ardous drugs
Establish procedures and provide
training for handling hazardous drugs
safely, cleaning up spills, and us
-
ing all equipment and PPE properly.
Inform workers about
the location and
proper use of spill kits. Make these kits
available near all potential sources of
exposure. Make sure that training con
-
forms to the requirements of the OSHA
hazard communication standard
[29
CFR 1910.1200] and other relevant
OSHA requirements such as the PPE
standard [29 CFR 1910.132]. In addi
-
tion, establish procedures for cleaning
and decontaminating work
areas and
for proper waste handling and disposal
of all contaminated materials, including
patient waste.
Establish work practices related to
both drug manipulation techniques
and to general hygiene practices—
such as not permitting eating or drink
-
ing in areas where drugs are handled
(
th
e pharmacy or clinic).
3. Use and maintain equipment
properly.
Develop workplace procedures for
using and maintaining all equipment
that functions to reduce exposure—
such as ventilated cabinets, closed-
system drug-transfer devices, needle-
less systems, and PPE.
Detailed Recommendations
Receiving and Storage
Begin exposure control when hazardous
drugs enter the facility. The most sig-
nificant exposure risk during distribution
Hazardous Drugs in Health Care Settings 11
and transport is from spills resulting from
damaged containers.
Prepare workers for the possibility that
spills might occur while they are han-
dling containers (even when packaging
is
intact during
routine activities), and
provide them with appropriate PPE.
Make sure that medical products have
labeling on the outsides of containers
that will be understood by all workers
who will be separating hazardous from
nonhazardous drugs.
Wear chemotherapy gloves [ASTM in
press], protective clothing, and eye
protection when opening containers
to unpack hazardous drugs. Such PPE
protects workers and helps prevent con
-
tamination from spreading if damaged
containers are found.
Wear chemotherapy gloves to prevent
contamination when transporting the vial
or syringe to the work area.
Store hazardous drugs separately from
other drugs, as recommended by ASHP
[1990] and other chemical safety stan
-
dards.
Store and transport hazardous drugs in
closed containers that minimize the risk
of breakage.
Make sure the storage area has sufficient
general exhaust ventilation to dilute and
remove any airborne contaminants.
Depending on the physical nature and
quantity of the stored drugs, consider in-
stalling a dedicated emergency exhaust
fan
that is
large enough to quickly purge
airborne contaminants from the storage
room in the event of a spill and prevent
contamination in adjacent areas.
Drug Preparation and Administration
Initial steps
As part of the hazard assessment de-
scribed earlier, evaluate and review the
entire drug preparation
and administra-
tion process to identify points at which
drugs
might be
released into the work
environment. Always consider the possi
-
bility of contamination on the outside of
containers [Ros et
al. 1997; Hepp and
Gentschew 1998; Delporte et al. 1999;
Nygren et al. 2002; Favier et al. 2003;
Mason et al. 2003].
Limit access to areas where drugs are
prepared to protect persons not involved
in drug preparation.
Coordinate tasks associated with prepar-
ing and administering hazardous drugs
for most effective
control of worker expo-
sures.
Preparing hazardous drugs
Use a ventilated cabinet designed to
reduce worker exposures while preparing
hazardous drugs (see following section
entitled Ventilated Cabinets).
Train all staff who use ventilated cabinets
to employ work practices established for
their particular equipment. The safe use
of any control depends on proper work.
Practice proper technique and use of
equipment.
Include initial and periodic assessments
of technique in the safety program [Har-
rison et al. 1996], and verify technique
during drug administration.
Wear protective gloves and gowns if you
are involved in preparation activities
such as opening drug packaging, han
-
dling vials or finished products, labeling
Hazardous Drugs in Health Care Settings 12
hazardous drug containers, or disposing
of waste.
Wear PPE (including double gloves and
protective gowns) while reconstituting
and admixing drugs:
— Make sure that gloves are labeled
as chemotherapy gloves and make
sure
such information is available on
the box [ASTM in press] or from the
manufacturer.
— Consider latex-sensitive workers
[NIOSH 1997] and
remember that a
number of glove materials are suit-
able for protecting workers from an-
tineoplastic drugs [Connor 1999;
Singleton and Connor
1999; Klein et
al. 2003].
— Consider using chemotherapy gloves
for hazardous drugs
that are not che-
motherapy drugs or for which no in-
formation is available.
— Use double gloving for all activities in-
volving hazardous drugs. Make sure
that
the outer
glove extends over
the cuff of the gown [Connor 1999;
Brown et al. 2001].
— Inspect gloves for physical defects
before use.
— Wash hands with soap and water be-
fore donning protective gloves and
immediately after removal.
— Change gloves every 30 minutes or
w
he
n torn, punctured, or contami-
nated. Discard them immediately in a
yel
low chemotherapy waste container
[ASHP 1990; Brown et al. 2001].
— Use disposable gowns made of
polyethylene-coated polypropylene
(which is
nonlinting and nonabsor
-
bent). These gowns offer better pro-
tection than polypropylene gowns
a
ga
inst many of the antineoplastic
drugs [Connor 1993; Harrison and
Kloos 1999]. Make sure gowns have
closed fronts, long sleeves, and elas
-
tic or knit closed cuffs.
— Dispose of protective gowns after
each use.
— Use disposable sleeve covers to pro-
tect the wrist area and remove the
covers after the task is complete.
When drug preparation is complete, seal
the final product in a plastic bag or other
sealable container for transport before
taking it out of the ventilated cabinet.
Seal and wipe all waste containers inside
the ventilated cabinet before removing
them from the cabinet.
Remove all outer gloves and sleeve cov-
ers and bag them for disposal while you
are inside the ventilated cabinet.
Wash hands with soap and water imme-
diately after removing gloves.
Consider using devices such as closed-
system transfer devices, glovebags, and
needleless systems when transferring
hazardous drugs from primary packaging
(such as vials) to dosing equipment (such
as infusion bags, bottles, or pumps).
Closed systems limit the potential for gen
-
erating aerosols and exposing workers to
s
ha
rps. Evidence documents a decrease in
Hazardous Drugs in Health Care Settings 13
drug contaminants inside a Class II BSC
when a closed-system transfer device
is used [Sessink et al. 1999; Vandenb
-
roucke and Robays 2001; Connor et al.
2002; Nygren et
al. 2002; Spivey and
Connor 2003; Wick et al. 2003].
— Remember that a closed-system
transfer device is
not an acceptable
substitute for a ventilated cabinet
and should be used only within a
ventilated cabinet.
— Use appropriate PPE and work prac-
tices even when you are using a
closed system.
Have pharmacy personnel prime the IV
tubing and syringes inside the ventilated
cabinet, or prime them in-line with non-
drug solutions—never in the patient’s
room.
Administering hazardous drugs
Administer drugs safely by using protec-
tive medical devices (such as needleless
and closed systems)
and techniques
(such as priming of IV tubing by phar
-
macy personnel inside a ventilated
cabinet or priming
in-line with nondrug
solutions).
Wear PPE (including double gloves,
goggles, and protective gowns) for all ac-
tivities associated with drug administra-
tion—opening the outer bag, assembling
the
delivery system,
delivering the drug
to the patient, and disposing of all equip
-
ment used to administer drugs.
Attach drug administration sets to the IV
bag, and prime them before adding the
drug to the bag.
Never remove tubing from an IV bag con-
taining a hazardous drug.
Do not disconnect tubing at other points
in the system until the tubing has been
thoroughly flushed.
Remove the IV bag and tubing intact
when possible.
Place disposable items directly in a yel-
low chemotherapy waste container and
close the lid.
Remove outer gloves and gowns, and
bag them for disposal in the yellow che-
motherapy waste container at the site of
drug administration.
Double-bag the chemotherapy waste
before removing the inner gloves.
Consider double bagging all contami-
nated equipment.
Wash hands with soap and water before
leaving the drug administration site.
Ventilated Cabinets
Use of cabinets
Mix, prepare, and otherwise manipu-
late, count, crush, compound powders,
or pour liquid
hazardous drugs inside a
ventilated cabinet designed to prevent
hazardous drugs from being released
into the work environment.
Do not use supplemental engineering
or process controls (such as needleless
systems, glove bags, and closed-system
drug transfer devices) as a substitution
for ventilated cabinets, even though
such controls may reduce the potential
for exposure when preparing and admin
-
istering hazardous drugs.
Selection
Consult the following document for per-
formance test methods and selection
Hazardous Drugs in Health Care Settings 14
criteria for BSCs: Primary Containment
for Biohazards: Selection, Installation
and Use of Biological Safety Cabinets,
2nd edition [CDC/NIH 2000].
Select a ventilated cabinet depending on
the need for aseptic processing. Aseptic
technique is important for protecting
hazardous drugs from possible contami
-
nation. However, it is also important to
consider worker protection
and to as-
sure that worker safety and health is
not
sacrificed. Therefore, when asepsis
is required or recommended, use ven-
tilated cabinets designed for both haz-
ardous drug containment and aseptic
processing.
Aseptic requirements
are
generally regulated by individual State
boards of pharmacy [Thompson 2003;
USP 2004].
When asepsis is not required, a Class I
BSC or an isolator intended for contain-
ment applications (a “containment isola-
tor”) may be sufficient.
When aseptic technique is required, use
one of the following ventilated cabinets:
— Class II BSC (Type B2 is preferred,
but Types
A2 and B1 are allowed
under certain conditions)
— Class III BSC
— Isolators intended for asepsis and
con
tainment (aseptic containment iso-
lators) [NSF/ANSI 2002; PDA 2001]
Air flow and exhaust
Regardless of type, equip each ventilated
cabinet with a continuous monitoring de-
vice to confirm adequate air flow before
each use.
Use a high-efficiency particulate air filter
(HEPA filter) for the exhaust from these
controls, and where feasible, exhaust
100% of the filtered air to the outside.
Install the outside exhaust so that the
exhausted air is not pulled back into the
building by the heating, ventilating, and
air conditioning (HVAC) systems or by the
windows, doors, or other points of entry.
Place fans downstream of the HEPA filter
so that contaminated ducts are main-
tained under negative pressure.
Do not use a ventilated cabinet that recir-
culates air inside the cabinet or exhausts
air back into
the room environment un-
less the hazardous drug(s) in use will not
volatilize
(evaporate) while
they are be-
ing handled or after they are captured by
the
HEPA
filter. Information about vola-
tilization should be supplied by the drug
manufacturer
(possibly in
the MSDS) or
by air-sampling data.
Seek additional information about place-
ment of the cabinet, exhaust system, and
sta
ck design from NSF/ANSI 49–2002
[NSF/ANSI 2002]. Incorporate their rec
-
ommendations regardless of the type of
ven
tilated cabinet selected.
Maintenance
Identify a safety and health representa-
tive familiar with potential drug expo-
sures and their hazards. Ask that person
to
review in
advance all maintenance ac-
tivities performed on ventilated cabinets
and
exhaust systems
associated with
hazardous drug procedures.
Develop a written safety plan for all rou-
tine maintenance activities performed on
equipment that could
be contaminated
with hazardous drugs.
Hazardous Drugs in Health Care Settings 15
Properly install and maintain and rou-
tinely clean any Class II BSC.
— Field-certify its performance (1) after
installation,
relocation, maintenance
repairs
to internal components, and
HEPA filter replacement, and (2) ev
-
ery 6 months thereafter [NSF/ANSI
2002; OSHA 1999].
— Prominently display a current field-
certification
label on
the ventilated
cabinet [NSF/ANSI 2002].
Treat other types of ventilated cabinets
similarly with regard to care and fre-
quency-of-performance verification
t
es
ts.
Select the appropriate performance and
test methods for isolators, depending on
the type (containment-only or aseptic
containment), the operating pressure
(positive or negative and designed mag
-
nitude), and the toxicity of the hazardous
drug:
— At a minimum, provide isolators with
a leak test
and a containment in-
tegrity test such as those described
in Guidelines
for Gloveboxes [AGS
1998].
—
Perform a HEPA filter leak test (de-
scribed in NSF/ANSI [2002]) for iso-
lators that rely on HEPA filtration for
containment.
— Perform additional tests as required
by
local and/or
national jurisdictions
to verify aseptic conditions.
Make sure that workers performing main-
tenance are
— familiar with applicable safety plans,
— warned about hazards, and
— trained in appropriate work tech-
niques and PPE needed to minimize
exposure.
Remove all hazardous drugs and chemi-
cals, and decontaminate the ventilated
cabinet before beginning
maintenance
activities.
Warn occupants in the affected areas
immediately before the maintenance ac-
tivity begins, and place warning signs on
all equipment that may be affected.
Strictly follow all applicable lockout/tagout
procedures [29 CFR 1910.147].
Decontaminate and bag equipment parts
removed for replacement or repair before
they are taken outside the facility.
Seal used filtration media in plastic im-
mediately upon removal, and tag it for
disposal as chemotherapy
waste; or dis-
pose of it as otherwise directed by the
environmental safety and
health office or
applicable regulation.
Routine Cleaning, Decontaminating,
Housekeeping, and Waste Disposal
Cleaning and decontaminating
Perform cleaning and decontamination
work in areas that are sufficiently venti-
lated to prevent buildup of hazardous air-
borne drug concentrations. Develop pro-
tocols prohibiting the use of unventilated
areas
such as
storage closets for drug
storage or any tasks involving hazardous
drugs.
Clean work surfaces with an appropri-
ate deactivation agent (if available) and
cleaning agent before
and after each ac-
tivity and at the end of the work shift.
Hazardous Drugs in Health Care Settings 16
Establish periodic cleaning routines for
all work surfaces and equipment that
may become contaminated, including
administration carts and trays.
At a minimum, wear safety glasses with
side shields and protective gloves for
cleaning and decontaminating work.
Wear face shields if splashing is possible.
Wear protective double gloves for decon-
taminating and cleaning work.
— Select them by referring to the MSDS,
glove selection guidelines, or informa-
tion from the glove manufacturer.
— Make sure the gloves are chemically
resistant to the decomtamination or
cleaning agent used.
Housekeeping
Wear two pairs of protective gloves and a
disposable gown if you must handle lin-
ens, feces, or urine from patients who
have received hazardous drugs within
the last 48 hours—or in some cases,
within the last 7 days [Cass and Mus-
grave 1992].
Dispose of the gown after each use or
whenever it becomes contaminated.
Wear face shields if splashing is possible.
Remove the outer gloves and the gown
by turning them inside out and plac-
ing them into the yellow chemotherapy
waste container. Repeat the procedure
for the inner gloves.
Wash hands with soap and water after
removing the gloves.
Waste disposal
Be aware of the various types of waste
generated by preparing and administer-
ing hazardous drugs: partially filled vials,
undispensed products, unused IVs, nee-
dles and syringes, gloves, gowns, under-
pads, and contaminated materials from
spill cleanups.
Place trace wastes (those that contain
less than 3% by weight of the original
quantity of hazardous drugs)—such
as needles, empty vials and syringes,
gloves, gowns, and tubing—in yellow
chemotherapy waste containers. As-
suring that drug-contaminated waste is
properly contained will protect workers
from respiratory exposure to volatile or
micro-aerosolized drugs [Connor et al.
2000; Kiffmeyer et al. 2002; Larson et
al. 2003].
— Place soft trace items (those that are
contaminated with trace amounts of
hazardous drugs) in yellow chemo-
therapy bags for disposal by incin-
eration at a regulated medical waste
facility.
— Place empty vials and sharps such
as needles and syringes in chemo-
therapy waste containers designed
to protect workers from injuries and
dispose of them by incineration at a
regulated medical waste facility.
Do not place hazardous drug-contami-
nated sharps in red sharps containers
that are used for infectious wastes,
since these are often autoclaved or
microwaved [ASHP 1990; OSHA 1999;
Smith 2002].
Dispose of P-listed arsenic trioxide and
its containers and any bulk amounts
of U-listed drugs [40 CFR 261.33] in
Hazardous Drugs in Health Care Settings 17
hazardous waste containers at a RCRA-
permitted incinerator. Nine hazardous
drugs in Appendix A are listed as hazard-
ous waste
§
by EPA.
Consider disposing of other bulk hazard-
ous drugs (that is, expired or unused vi-
als, ampoules, syringes, bags, and bot-
tles of hazardous drugs or solutions of
any other items
with more than trace
contamination) in a manner similar to
that required for RCRA-defined hazard-
ous wastes as recommended by ASHP
[1990] and OSHA [1999].
Spill Control
Manage hazardous drug spills according
to the established, written policies and
procedures for each workplace.
Be aware that the size of the spill might
determine who is authorized to conduct
the cleanup and decontamination and
how the cleanup is managed.
Assure that the written policies and pro-
cedures address the protective equip-
ment required for various spill sizes, the
possible spreading of
material, restricted
access to hazardous drug spills, and
signs to be posted.
Assure that cleanup of a large spill is
handled by workers who are trained in
handling hazardous materials [29 CFR
1910.120].
Locate spill kits and other cleanup mate-
rials in the immediate area where expo-
sures may occur.
§
Arsenic trioxide is a P-listed hazardous waste. Chlorambucil,
cyclophosphamide, daunorubicin HCI, diethylstilbestrol,
melphalan, mitomycin, streptozocin, and uracil mustard
are U-listed hazardous wastes. See 40 CFR 261.33.
As required by OSHA, follow a complete
respiratory protection program, including
fit-testing, if you wear respirators such
as those contained in some spill kits
[29 CFR 1910.134]. Use NIOSH-certi
-
fied respirators [42 CFR 84]. Surgical
masks do not
provide adequate pro-
tection.
Dispose of all spill cleanup materials in a
hazardous chemical waste container, in
accordance with EPA/RCRA regulations
regarding hazardous waste—not in a
chemotherapy waste or biohazard con
-
tainer.
Medical Surveillance
In addition to preventing exposure to haz-
ardous drugs and carefully monitoring the
env
ironment, make medical surveillance
an important part of any safe handling
program for hazardous drugs.
If you handle hazardous drugs, partici-
pate in medical surveillance programs
provided at your workplace.
If you handle hazardous drugs but have
no medical surveillance program at work,
see your private health care provider for
routine medical care. Be sure to inform
him or her about your occupation and
possible exposures to hazardous drugs.
Refer to the OSHA Technical Manual:
Controlling Occupational Exposure to
Hazardous Drugs, Section VI Chapter 2
[OSHA 1999]. This document currently
recommends that workers handling haz
-
ardous drugs be monitored in a medical
surveillance program that
includes the
taking of a medical and exposure history,
physical examination, and some labora
-
tory tests.
Hazardous Drugs in Health Care Settings 18
Refer to the guidelines of professional
organizations such as the ASHP [1990]
and the Oncology Nursing Society [Brown
et al. 2001], which recommend medi-
cal surveillance as the recognized stan-
dard of occupational health practice for
hazardous
drug handlers.
The American
College of Occupational and Environ-
mental Medicine (ACOEM) also recom-
mends surveillance for these workers in
their Reproductive
Hazard Management
Guidelines
[ACOEM 1996].
Use a worker’s past exposure his
ACKNOWLEDGMENTS
tory as
a surrogate measure of potential expo
-
sure intensity.
If you are an occupational health profes-
sional who is examining a drug-exposed
worker, ask
questions that focus on the
worker’s symptoms relating to the organ
systems that are known targets for the
hazardous drugs.
— For example, after an acute expo-
sure such as a splash or other drug
contact with skin
or mucous mem-
branes, focus the physical examina-
tion on the exposed areas and the
clinical signs of
rash or irritation to
those areas.
— Include a complete blood count with
dif
ferential and a reticulocyte count in
the baseline and periodic laboratory
tests. These may be helpful as an
indicator of bone marrow reserve.
Monitor the urine of workers who handle
hazardous drugs with a urine dipstick or
a microscopic examination of the urine
for blood [Brown et al. 2001]. Sev-
eral antineoplastic agents are known to
cause
bladder damage
and blood in the
urine of treated patients.
Conduct environmental sampling and/or
biological monitoring when exposure is
suspected or symptoms have been noted.
ADDITIONAL INFORMATION
Additional information about exposure to
hazardous drugs is available at 1–800–35–
NIOSH (1–800–356–4674), fax: 1–513–
533–8573, E-mail: [email protected], or
Web site: www.cdc.gov/NIOSH.
Additional information about hazardous drug
safety is available at www.osha.gov.
This Alert was written by G. Edward Burroughs,
Ph.D., C.I.H.
1
; Thomas H. Connor, Ph.D.
1
;
Melissa A. McDiarmid, M.D., M.P.H.
4
; Kenneth
R. Mead, M.S., P.E.
1
; Luci A. Power, M.S.,
R.Ph.
6
; and Laurence D. Reed, M.S.
1
Major contributors to this Alert were Barbara
J. Coyle, B.S.N., R.N. C.O.H.N.-S.
2
; Duane R.
Hammond, B.S.M.E.
1
; Melissa M. Leone, R.N.,
B.S.N.
3
; Marty Polovich, M.N., R.N., A.O.C.N.
5
;
and Douglas D. Sharpnack, D.V.M.
1
Contributions to this Alert were also made
by members of the NIOSH Hazardous Drug
Safe Handling Working Group. A complete
listing of the agencies and organizations who
contributed to this Alert is listed in Appendix
C. Anne C. Hamilton, Vanessa Becks, Susan
Afanuh, Jane W
eber, Andre Allen, Anne Vo-
taw, and Teresa Lewis provided editorial and
production services.
1
NIOSH;
2
State of Wisconsin;
3
Apria Healthcare;
4
University
of Maryland;
5
Oncology Nursing Society;
6
University of
California Medical Center
Hazardous Drugs in Health Care Settings 19
Support for the development of this Alert
was provided by the National Occupation-
al Research Agenda (NORA) Control Tech-
nology and Personal Protective Equipment
T
eam and the NORA
Reproductive Health
Research Team.
Please direct comments, questions, or re-
quests for additional information to the fol-
lowing:
Director, Division of Applied Research
and Technology
National Institute for Occupational
Safety and Health
4676 Columbia Parkway
Cincinnati, OH 45226–1998
Telephone: 1–513–533–8462 or
1–800–35–NIOSH
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Hazardous Drugs in Health Care Settings 30
APPENDIX A
DRUGS CONSIDERED HAZARDOUS
General Approach to Handling
Hazardous Drugs
In this Alert, NIOSH presents a standard
precautions or universal precautions ap
-
proach to handling hazardous drugs safely:
that is, NIOSH recommends
that all hazard-
ous drugs be handled as outlined in this
Alert. Therefore, no attempt
has been made
to perform drug risk assessments or pro
-
pose exposure limits. The area of new drug
development is rapidly evolving
as unique
approaches are being taken to treat cancer
and other serious diseases.
Defining Hazardous Drugs
Hazardous drugs include those used for
cancer chemotherapy, antiviral drugs, hor
-
mones, some bioengineered drugs, and
other miscellaneous drugs. The
definition of
hazardous drugs used in this Alert is based
on an ASHP definition that was originally
developed in 1990 [ASHP 1990]. Thus the
definition may not accurately reflect the
toxicity criteria associated with the newer
generation of pharmaceuticals entering the
health care setting. For example, bioen
-
gineered drugs target specific sites in the
body; and although they
may or may not be
toxic to the patient, some may not pose a
risk to health care workers.
NIOSH and other organizations are still
gathering data on the
potential toxicity and
health effects related to highly potent drugs
and bioengineered drugs. Therefore, when
working with any hazardous drug, health
care workers should follow a standard pre
-
cautions approach along with any recom-
mendations included in the manufacturer’s
MSDSs.
ASHP Definition of Hazardous
Drugs
The ASHP defines hazardous drugs in their
1990 revision of Technical Assistance Bul-
letin on Handling Hazardous Drugs [
ASH
P
1990]. The bulletin gives criteria for identify-
ing potentially hazardous drugs that should
b
e ha
ndled in accordance with an established
safety program [McDiarmid et al. 1991; Ar
-
rington and McDiarmid 1993]. The criteria
are p
rioritized to reflect the hierarchy of
potential toxicity described below. Since the
hazardous drugs covered by this Alert were
designed as therapeutic agents for humans,
human toxicity profiles should be considered
superior to any data from animal models
or in vitro systems. Additional guidance for
defining hazardous drugs is available in the
following citations: carcinogenicity [61 Fed.
Reg. 17960–18011 (1996b); IARC 2004],
teratogenicity [56 Fed. Reg. 63798–63826
(1991)], developmental toxicity [56 Fed.
Reg. 63798–63826 (1991)], and reproduc
-
tive toxicity [61 Fed. Reg. 56274–56322
Hazardous Drugs in Health Care Settings 31
(1996a)]. Physical characteristics of the
agents (such as liquid versus solid, or wa-
ter versus lipid solubility) also need to be
considered in
determining the potential for
occupational exposure.
NIOSH Revision of ASHP
Definition
The 1990 ASHP definition of hazardous
drugs
**
was revised by the NIOSH Working
Group on Hazardous Drugs for this Alert.
Drugs considered hazardous include those
that exhibit one or more of the following six
characteristics in humans or animals:
1. Carcinogenicity
2. Teratogenicity or other developmental
toxicity
††
3. Reproductive toxicity
††
4. Organ toxicity at low doses
††
**
ASHP [1990] definition of hazardous drugs:
1. Genotoxicity (i.e., mutagenicity and clastogenicity in
short-term test systems)
2. Carcinogenicity in animal models, in the patient popula-
tion, or both, as reported by the International Agency for
Re
search on Cancer (IARC)
3. Teratogenicity or fertility impairment in animal studies
or in treated patients
4. Evidence of serious organ or other toxicity at low doses
in animal models or treated patients.
††
All 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 mg/
day or a dose of 1 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 µg/m
3
after
applying appropriate uncertainty factors [Sargent and
Kirk 1988; Naumann and Sargent 1997; Sargent et
al. 2002]. OELs in this range are typically established
for potent or toxic drugs in the pharmaceutical industry.
Under all circumstances, an evaluation of all available
data should be conducted to protect health care
workers.
5. Genotoxicity
‡
‡
6. Structure and toxicity profiles of new
drugs that mimic existing drugs de-
termined hazardous by the above
criteria.
Determining Whether a Drug is
Hazardous
Many hazardous drugs used to treat cancer
bind to or damage DNA (for example, alkylat-
ing agents). Other antineoplastic drugs, some
an
tivirals, antibiotics, and bioengineered drugs
interfere with cell growth or proliferation, or
with DNA synthesis. In some cases, the
nonselective actions of these drugs disrupt
the growth and function of both healthy and
diseased cells, resulting in toxic side effects
for treated patients. These nonselective
actions can also cause adverse effects in
health care workers who are inadvertently
exposed to hazardous drugs.
Early concerns about occupational expo-
sure to antineoplastic drugs first appeared
in
the 1970s. Although the antineoplastic
drugs remain the principal focus of this
Alert, other drugs may also be considered
hazardous because they are potent (small
quantities produce a physiological effect) or
cause irreversible effects. As the use and
number of these potent drugs increase, so
do opportunities for hazardous exposures
among health care workers. For example,
antineoplastic drugs such as cyclophospha
-
mide have immunosuppressant effects that
pr
oved beneficial for treating nonmalignant
‡‡
In evaluating mutagenicity for potentially hazardous drugs,
responses from multiple test systems are needed before
precautions can be required for handling such agents.
The EPA evaluations include the type of cells affected
and in vitro versus in vivo testing [51 Fed. Reg. 34006–
34012 (1986)].
Hazardous Drugs in Health Care Settings 32
diseases such as rheumatoid arthritis
and multiple sclerosis [Baker et al. 1987;
Moody et al. 1987; Chabner et al. 1996;
Abel 2000].
This appendix presents criteria and sources
of information
for determining whether a
drug is hazardous. When a drug has been
judged to be hazardous, the various precau
-
tions outlined in this Alert should be applied
when handling
that drug. Also included is a
list of drugs that should be handled as haz-
ardous. This list is based on a compilation of
lists
from
four health care facilities and one
drug manufacturers’ organization.
In addition to using the list of hazardous drugs
presented here,
each organization should
create its own list of drugs considered to
be hazardous. This appendix presents guid
-
ance for making such a facility-specific list
(see section
entitled How to Generate your
own List of Hazardous Drugs). Once this list
is made, newly purchased drugs should be
evaluated against the organization’s hazard
-
ous drug criteria and added to the list if they
are deemed hazardous.
Some organizations may have inadequate
resources for
determining their own list of
hazardous drugs. If so, the sample list of
hazardous drugs in this appendix (current
only to the printing date of this document)
will help employers and workers to deter
-
mine when precautions are needed. Howev-
er, reliance on such a published list is a con-
cern because it quickly becomes outdated
as new
drugs continually enter the market
or listed drugs are removed when additional
information becomes available. To fill this
knowledge gap, NIOSH will update an inter
-
net list annually, adding new drugs consid-
ered to be hazardous and removing those
that require reclassification. This hazardous
dr
ug list will be posted on the NIOSH Web
site at www.cdc.gov/niosh.
How to Generate Your Own List of
Hazardous Drugs
The OSHA hazard communication standard
[29 CFR 1910.1200] requires employers to
develop a hazard communication program
appropriate for their unique workplace. An
essential part of the program is the identifi
-
cation of all hazardous drugs a worker may
encounter in
the facility. Compliance with
the OSHA hazard communication standard
entails (1) evaluating whether these drugs
meet one or more of the criteria for defining
hazardous drugs and (2) posting a list of the
hazardous drugs to ensure worker safety.
Institutions may wish to compare their lists
to the sample listing in this document or on
the NIOSH Web site.
It is not likely that every health care pro-
vider or facility will use all drugs that have
received
U.S.
Food and Drug Administra-
tion (FDA) approval, and the OSHA hazard
communication standard
does not mandate
evaluation of every marketed drug. Instead,
compliance requires practice-specific as
-
sessments for drugs used at any one time
by a
facility. However, hazardous drug evalu-
ation is a continual process. Local hazard
communication programs
should provide
for assessment of new drugs as they en-
ter the marketplace, and when appropriate,
reassessment
of
their presence on haz-
ardous drug lists as toxicological data be-
come available to support recategorization.
T
oxicological
data are often incomplete or
unavailable for investigational drugs. How
-
ever, if the mechanism of action suggests
that there
may be a concern, it is prudent
Hazardous Drugs in Health Care Settings 33
to handle them as hazardous drugs until
adequate information becomes available to
exclude them.
Some drugs defined as hazardous may not
po
se a significant risk of direct occupational
exposure because of their dosage formula-
tion (for example, coated tablets or cap-
su
les—solid, intact medications that are ad-
ministered to patients without modifying the
fo
rmulation). However, they may pose a risk
if solid drug formulations are altered, such as
by crushing tablets or making solutions from
them outside a ventilated cabinet.
Where to Find Information
Related to Drug Toxicity
Practice-specific lists of hazardous drugs
(usually developed by pharmacy or nursing
departments) should be comprehensive, in-
cluding all hazardous medications routinely
used or
very likely to be used by a local prac-
tice. Some of the resources that employers
can use
to evaluate the hazard potential of
a drug include, but are not limited to, the
following:
MSDSs
Product labeling approved by the U.S.
FDA (package inserts)
Special health warnings from drug man-
ufacturers, FDA, and other professional
groups and organizations
Reports and case studies published in
medical and other health care profession
journals
Evidence-based recommendations from
other facilities that meet the criteria de-
fining hazardous drugs
Examples of Hazardous Drugs
The following list contains a sampling of ma-
jor hazardous drugs. The list was compiled
from information
provided by (1) four insti-
tutions that have generated lists of hazard-
ous drugs for their respective facilities, (2)
the
American
Hospital Formulary Service
Drug Information (AHFS DI) monographs
[ASHP/AHFS DI 2003], and (3) several other
sources. The OSHA hazard communication
standard requires hazardous drugs to be
handled using special precautions. The man
-
date applies not only to health care profes-
sionals who provide direct patient care but
a
l
so to others who support patient care by
participating in product acquisition, storage,
transportation, housekeeping, and waste dis
-
posal. Institutions may want to adopt this list
o
r
compare theirs with the list on the NIOSH
Web site.
Caution: Drugs purchased and used by a
fa
cility may have entered the marketplace
after the list below was assembled. There
-
fore, this list may not be all-inclusive.
If you use a drug that is not included in the
l
i
st of examples, check the available litera-
ture to see whether the unlisted drug should
b
e
treated as hazardous. Check the MSDS
or the proper handling section of the pack
-
age insert; or check with other institutions
th
at might be using the same drug. If any
of the documents mention carcinogenicity,
genotoxicity, teratogenicity, or reproductive or
developmental toxicity, use the precautions
stipulated in this Alert. If a drug meets one or
more of the criteria for hazardous drugs listed
in this Alert, handle it as hazardous.
The listing below is a sample of what will be
available on the NIOSH Web site [www.cdc.gov/
niosh], and this list will be updated annually.
Hazardous Drugs in Health Care Settings 34
Sample list of drugs that should be handled as hazardous*
AHFS Pharmacologic-Therapeutic
Drug Source Classification
Aldesleukin 4,5 10:00 Antineoplastic agents
Alemtuzumab 1,3,4,5 10:00 Antineoplastic agents
Alitretinoin 3,4,5 84:36 Miscellaneous skin and
mucous membrane agents (Retinoid)
Altretamine 1,2,3,4,5 Not in AHFS (Antineoplastic agent)
Amsacrine 3,5 Not in AHFS (Antineoplastic agent)
Anastrozole 1,5 10:00 Antineoplastic agents
Arsenic trioxide 1,2,3,4,5 10:00 Antineoplastic agents
Asparaginase 1,2,3,4,5 10:00 Antineoplastic agents
Azacitidine 3,5 Not in AHFS (antineoplastic agent)
Azathioprine 2,3,5 92:00 Unclassified therapeutic
agents (immunosuppressant)
Bacillus Calmette-Guerin 1,2,4 80:12 Vaccines
Bexarotene 2,3,4,5 10:00 Antineoplastic agents
Bicalutamide 1,5 10:00 Antineoplastic agents
Bleomycin 1,2,3,4,5 10:00 Antineoplastic agents
Busulfan 1,2,3,4,5 10:00 Antineoplastic agents
Capecitabine 1,2,3,4,5 10:00 Antineoplastic agents
Carboplatin 1,2,3,4,5 10:00 Antineoplastic agents
Carmustine 1,2,3,4,5 10:00 Antineoplastic agents
Cetrorelix acetate 5 92:00 Unclassified therapeutic
agents (GnRH antagonist)
Chlorambucil 1,2,3,4,5 10:00 Antineoplastic agents
Chloramphenicol 1,5 8:12 Antibiotics
Choriogonadotropin alfa 5 68:18 Gonadotropins
Cidofovir 3,5 8:18 Antivirals
Cisplatin 1,2,3,4,5 10:00 Antineoplastic agents
Cladribine 1,2,3,4,5 10:00 Antineoplastic agents
Colchicine 5 92:00 Unclassified therapeutic
agents (mitotic inhibitor)
(See footnotes at end of table)
Hazardous Drugs in Health Care Settings 35
Sample list of drugs that should be handled as hazardous* (Continued)
AHFS Pharmacologic-Therapeutic
Drug Source Classification
Cyclophosphamide 1,2,3,4,5 10:00 Antineoplastic agents
Cytarabine 1,2,3,4,5 10:00 Antineoplastic agents
Cyclosporin 1 92:00 Immunosuppressive agents
Dacarbazine 1,2,3,4,5 10:00 Antineoplastic agents
Dactinomycin 1,2,3,4,5 10:00 Antineoplastic agents
Daunorubicin HCl 1,2,3,4,5 10:00 Antineoplastic agents
Denileukin 3,4,5 10:00 Antineoplastic agents
Dienestrol 5 68:16.04 Estrogens
Diethylstilbestrol 5 Not in AHFS (nonsteroidal synthetic
estrogen)
Dinoprostone 5 76:00 Oxytocics
Docetaxel 1,2,3,4,5 10:00 Antineoplastic agents
Doxorubicin 1,2,3,4,5 10:00 Antineoplastic agents
Dutasteride 5 92:00 Unclassified therapeutic
agents (5-alpha reductase inhibitor)
Epirubicin 1,2,3,4,5 10:00 Antineoplastic agents
Ergonovine/methylergonovine 5 76:00 Oxytocics
Estradiol 1,5 68:16.04 Estrogens
Estramustine phosphate 1,2,3,4,5 10:00 Antineoplastic agents
sodium
Estrogen-progestin combina- 5 68:12 Contraceptives
tions
Estrogens, conjugated 5 68:16.04 Estrogens
Estrogens, esterified 5 68:16.04 Estrogens
Estrone 5 68:16.04 Estrogens
Estropipate 5 68:16.04 Estrogens
Etoposide 1,2,3,4,5 10:00 Antineoplastic agents
Exemestane 1,5 10:00 Antineoplastic agents
Finasteride 1,3,5 92:00 Unclassified therapeutic
Agents (5-alpha reductase inhibitor)
Floxuridine 1,2,3,4,5 10:00 Antineoplastic agents
(See footnotes at end of table)
Hazardous Drugs in Health Care Settings 36
Sample list of drugs that should be handled as hazardous* (Continued)
AHFS Pharmacologic-Therapeutic
Drug Source Classification
Fludarabine 1,2,3,4,5 10:00 Antineoplastic agents
Fluorouracil 1,2,3,4,5 10:00 Antineoplastic agents
Fluoxymesterone 5 68:08 Androgens
Flutamide 1,2,5 10:00 Antineoplastic agents
Fulvestrant 5 10:00 Antineoplastic agents
Ganciclovir 1,2,3,4,5 8:18 Antiviral
Ganirelix acetate 5 92:00 Unclassified therapeutic
agents (GnRH antagonist)
Gemcitabine 1,2,3,4,5 10:00 Antineoplastic agents
Gemtuzumab ozogamicin 1,3,4,5 10:00 Antineoplastic agents
Gonadotropin, chorionic 5 68:18 Gonadotropins
Goserelin 1,2,5 10:00 Antineoplastic agents
Hydroxyurea 1,2,3,4,5 10:00 Antineoplastic agents
Ibritumomab tiuxetan 3 10:00 Antineoplastic agents
Idarubicin 1,2,3,4,5 Not in AHFS (antineoplastic agent)
Ifosfamide 1,2,3,4,5 10:00 Antineoplastic agents
Imatinib mesylate 1,3,4,5 10:00 Antineoplastic agents
Interferon alfa-2a 1,2,4,5 10:00 Antineoplastic agents
Interferon alfa-2b 1,2,4,5 10:00 Antineoplastic agents
Interferon alfa-n1 1,5 10:00 Antineoplastic agents
Interferon alfa-n3 1,5 10:00 Antineoplastic agents
Irinotecan HCl 1,2,3,4,5 10:00 Antineoplastic agents
Leflunomide 3,5 92:00 Unclassified therapeutic agents
(antineoplastic agent)
Letrozole 1,5 10:00 Antineoplastic agents
Leuprolide acetate 1,2,5 10:00 Antineoplastic agents
Lomustine 1,2,3,4,5 10:00 Antineoplastic agents
Mechlorethamine 1,2,3,4,5 10:00 Antineoplastic agents
Megestrol 1,5 10:00 Antineoplastic agents
Melphalan 1,2,3,4,5 10:00 Antineoplastic agents
(See footnotes at end of table)
Hazardous Drugs in Health Care Settings 37
Sample list of drugs that should be handled as hazardous* (Continued)
AHFS Pharmacologic-Therapeutic
Drug Source Classification
Menotropins 5 68:18 Gonadotropins
Mercaptopurine 1,2,3,4,5 10:00 Antineoplastic agents
Methotrexate 1,2,3,4,5 10:00 Antineoplastic agents
Methyltestosterone 5 68:08 Androgens
Mifepristone 5 76:00 Oxytocics
Mitomycin 1,2,3,4,5 10:00 Antineoplastic agents
Mitotane 1,4,5 10:00 Antineoplastic agents
Mitoxantrone HCl 1,2,3,4,5 10:00 Antineoplastic agents
Mycophenolate mofetil 1,3,5 92:00 Immunosuppressive agents
Nafarelin 5 68:18 Gonadotropins
Nilutamide 1,5 10:00 Antineoplastic agents
Oxaliplatin 1,3,4,5 10:00 Antineoplastic agents
Oxytocin 5 76:00 Oxytocics
Paclitaxel 1,2,3,4,5 10:00 Antineoplastic agents
Pegaspargase 1,2,3,4,5 10:00 Antineoplastic agents
Pentamidine isethionate 1,2,3,5 8:40 Miscellaneous anti-infectives
Pentostatin 1,2,3,4,5 10:00 Antineoplastic agents
Perphosphamide 3,5 Not in AHFS (antineoplastic agent)
Pipobroman 3,5 Not in AHFS (antineoplastic agent)
Piritrexim isethionate 3,5 Not in AHFS (antineoplastic agent)
Plicamycin 1,2,3,5 Not in AHFS (antineoplastic agent)
Podoflilox 5 84:36 Miscellaneous skin and mucous
membrane agents (mitotic inhibitor)
Podophyllum resin 5 84:36 Miscellaneous skin and mucous
membrane agents (mitotic inhibitor)
Prednimustine 3,5 Not in AHFS (antineoplastic agent)
Procarbazine 1,2,3,4,5 10:00 Antineoplastic agents
Progesterone 5 68:32 Progestins
Progestins 5 68:12 Contraceptives
(See footnotes at end of table)
Hazardous Drugs in Health Care Settings 38
Sample list of drugs that should be handled as hazardous* (Continued)
AHFS Pharmacologic-Therapeutic
Drug Source Classification
Raloxifene 5 68:16.12 Estrogen agonists-antago-
nists
Raltitrexed 5 Not in AHFS (antineoplastic agent)
Ribavirin 1,2,5 8:18 Antiviral
Streptozocin 1,2,3,4,5 10:00 Antineoplastic agents
Tacrolimus 1,5 92:00 Unclassified therapeutic
agents (immunosuppressant)
Tamoxifen 1,2,5 10:00 Antineoplastic agents
Temozolomide 3,4,5 10:00 Antineoplastic agents
Teniposide 1,2,3,4,5 10:00 Antineoplastic agents
Testolactone 5 10:00 Antineoplastic agents
Testosterone 5 68:08 Androgens
Thalidomide 1,3,5 92:00 Unclassified therapeutic
agents (immunomodulator)
Thioguanine 1,2,3,4,5 10:00 Antineoplastic agents
Thiotepa 1,2,3,4,5 10:00 Antineoplastic agents
Topotecan 1,2,3,4,5 10:00 Antineoplastic agents
Toremifene citrate 1,5 10:00 Antineoplastic agents
Tositumomab 3,5 Not in AHFS (antineoplastic agent)
Tretinoin 1,2,3,5 84:16 Cell stimulants and
proliferants (retinoid)
Trifluridine 1,2,5 52:04.06 antivirals
Trimetrexate glucuronate 5 8:40 Miscellaneous anti-infectives
(folate antagonist)
Triptorelin 5 10:00 Antineoplastic agents
Uracil mustard 3,5 Not in AHFS (antineoplastic agent)
Valganciclovir 1,3,5 8:18 Antiviral
Valrubicin 1,2,3,5 10:00 Antineoplastic agents
Vidarabine 1,2,5 52:04.06 Antivirals
Vinblastine sulfate 1,2,3,4,5 10:00 Antineoplastic agents
(See footnotes at end of table)
Hazardous Drugs in Health Care Settings 39
Sample list of drugs that should be handled as hazardous* (Continued)
AHFS Pharmacologic-Therapeutic
Drug Source Classification
Vincristine sulfate 1,2,3,4,5 10:00 Antineoplastic agents
Vindesine 1,5 Not in AHFS (antineoplastic agent)
Vinorelbine tartrate 1,2,3,4,5 10:00 Antineoplastic agents
Zidovudine 1,2,5 8:18:08 Antiretroviral agents
*These lists of hazardous drugs were used with the permission of the institutions that provided them and were adapted for
use by NIOSH. The sample lists are intended to guide health care providers in diverse practice settings and should not
be construed as complete representations of all of the hazardous drugs used at the referenced institutions. Some drugs
defined as hazardous may not pose a significant risk of direct occupational exposure because of their dosage formulation
(for example, intact medications such as coated tablets or capsules that are administered to patients without modifying
the formulation). However, they may pose a risk if solid drug formulations are altered outside a ventilated cabinet (for
example, if tablets are crushed or dissolved, or if capsules are pierced or opened).
1
The NIH Clinical Center, Bethesda, MD (Revised 8/2002).
The NIH Health Clinical Center Hazardous Drug (HD) List is part of the NIH Clinical Center’s hazard communication
program. It was developed in compliance with the OSHA hazard communication standard [29 CFR 1910.1200] as it
applies to hazardous drugs used in the workplace. The list is continually revised and represents the diversity of medical
practice at the NIH Clinical Center; however, its content does not reflect an exhaustive review of all FDA-approved
medications that may be considered hazardous, and it is not intended for use outside the NIH.
2
The Johns Hopkins Hospital, Baltimore, MD (Revised 9/2002).
3
The Northside Hospital, Atlanta, GA (Revised 8/2002).
4
The University of Michigan Hospitals and Health Centers, Ann Arbor, MI (Revised 2/2003).
5
This sample listing of hazardous drugs was compiled by the Pharmaceutical Research and Manufacturers of America
(PhRMA) using information from the AHFS DI monographs published by ASHP in selected AHFS Pharmacologic-
Therapeutic Classification categories [ASHP/AHFS DI 2003] and applying the definition for hazardous drugs. The list also
includes drugs from other sources that satisfy the definition for hazardous drugs [PDR 2004; Sweetman 2002; Shepard
2001; Schardein 2000; REPROTOX 2003]. Newly approved drugs that have structures or toxicological profiles that mimic
the drugs on this list should also be included. This list was revised in June 2004.
Hazardous Drugs in Health Care Settings 40
IV
APPENDIX B
ABBREVIATIONS AND GLOSSARY
Abbreviations
ACGIH American Conference of Governmental Industrial Hygienists
ACOEM American College of Occupational and Environmental Medicine
AHFS American Hospital Formulary Service
AHFS DI American Hospital Formulary Service Drug Information
AGS American Glovebox Society
ANSI American National Standards Institute
ASHP American Society of Health-System Pharmacists (before 1995,
American Society of Hospital Pharmacists)
BSC Biological safety cabinet
CDC Centers for Disease Control and Prevention
FDA U.S. Food and Drug Administration
ft foot (feet)
HEPA high-efficiency particulate air
HIV human immunodeficiency virus
HVAC heating, ventilating, and air conditioning
IARC International Agency for Research on Cancer
intravenous
kg kilogram(s)
LPN licensed practical nurse
m
3
cubic meter(s)
mg milligram(s)
min minute (s)
MSDS material safety data sheet
NIH National Institutes of Health
Hazardous Drugs in Health Care Settings 41
NIOSH National Institute for Occupational Safety and Health
NSF National Sanitation Foundation
OEL(s) occupational exposure limit(s)
ONS Oncology Nursing Society
OSHA Occupational Safety and Health Administration
PDA PDA (formerly, the Parenteral Drug Association)
PEL(s) permissible exposure limit(s)
PPE personal protective equipment
RCRA Resource Conservation and Recovery Act
REL(s) recommended exposure limit(s)
RN registered nurse
SCE(s) sister chromatid exchange(s)
TLVs
®
threshold limit values of the ACGIH
µg microgram
WEEL workplace environmental exposure limit
Glossary
Antineoplastic drug: A chemotherapeu-
tic agent that controls or kills cancer cells.
Drugs used in
the treatment of cancer are
cytotoxic but are generally more damaging
to dividing cells than to resting cells.
Aseptic: Free of living pathogenic organ-
isms or infected materials.
Barrier system: An
open system
that can
exchange unfiltered air and contaminants
with the surrounding environment.
Barrier isolator: This term has
various in-
terpretations, especially as they pertain to
hazard containment and
aseptic process-
ing. For this reason, it has been omitted
from this Alert.
Biohazard: An infectious agent
or hazard-
ous biological material that presents a risk
to the health
of humans or the environment.
Biohazards include tissue, blood or body flu
-
ids, and materials such as needles or other
equipment contaminated with
these infec-
tious agents or hazardous biological materi-
als.
Biomarker: A
biological, biochemical
or
structural change that serves as an indica-
tor of potential damage to cellular compo-
nents, whole cells, tissues, or organs.
BSC (biological safety cabinet): A
BSC
may
be one of several types, as described
here [CDC/NIH 1999; NSF/ANSI 2002]:
Class I BSC: A BS
C that protects per-
sonnel and the work environment but
doe
s not protect the product. It is a
Hazardous Drugs in Health Care Settings 42
negative-pressure, ventilated cabinet usu-
ally operated with an open front and a
mi
nimum face velocity at the work open-
ing of at least 75 ft/min. A Class I BSC is
si
milar in design to chemical fume hood
except all of the air from the cabinet is
exhausted through a HEPA filter (either
into the laboratory or to the outside).
Class II BSC: A ventilated
BSC that
protects personnel, product, and the
work environment. A Class II BSC has
an open front with inward airflow for per-
sonnel protection, downward HEPA-fil-
tered laminar airflow for product protec-
tion, and HEPA-filtered exhausted air for
environmental protection.
Type A1 (formerly, Type A): T
h
ese
Class II BSCs maintain a minimum in-
flow velocity of 75 ft/min, have HEPA-
fil
tered downflow air that is a portion
of the mixed downflow and inflow air
from a common plenum, may exhaust
HEPA-filtered air back into the labora-
tory or to the environment through an
e
x
haust canopy, and may have posi-
tive-pressure contaminated ducts and
pl
enums that are not surrounded by
negative-pressure plenums. They are
not suitable for use with volatile toxic
chemicals and volatile radionucleo-
tides.
Type A2 (formerly, Type B3): These
Class
II
BSCs maintain a minimum
inflow velocity of 100 ft/min, have
HEPA-filtered downflow air that is a
portion of the mixed downflow and
inflow air from a common exhaust
plenum, may exhaust HEPA-filtered
air back into the laboratory or to the
environment through an exhaust
canopy, and have all contaminated
ducts and plenums under negative-
pressure or
surrounded by negative-
pressure ducts and plenums. If these
cabinets are used for minute quanti-
ties of volatile toxic chemicals and
trace amounts
of radionucleotides,
they must be exhausted through
properly functioning exhaust cano-
pies.
Type B1: These Class II BSCs main-
t
ain a minimum inflow velocity of 100
ft
/min, have HEPA-filtered downflow
air composed largely of uncontami-
nated, recirculated inflow air, exhaust
mo
st of the contaminated downflow
air through a dedicated duct exhaust-
ed to the atmosphere after passing
it
through a HEPA filter, and have all
contaminated ducts and plenums un-
der negative pressure or surrounded
by
negative-pressure ducts and ple-
nums. If these cabinets are used
fo
r work involving minute quantities
of volatile toxic chemicals and trace
amounts of radionucleotides, the
work must be done in the directly ex-
hausted portion of the cabinet.
Type B2 (total exhaust): T
h
ese Class
II BSCs maintain a minimum inflow ve-
locity of 100 ft/min, have HEPA-filtered
do
wnflow air drawn from the laboratory
or the outside, exhaust all inflow and
downflow air to the atmosphere after
filtration through a HEPA filter with-
out recirculation inside the cabinet or
re
turn to the laboratory, and have all
contaminated ducts and plenums un-
der negative pressure or surrounded by
di
rectly exhausted negative-pressure
ducts and plenums. These cabinets
may be used with volatile toxic chemi-
cals and radionucleotides.
Hazardous Drugs in Health Care Settings 43
Class III BSC: A BSC with a totally en-
closed, ventilated cabinet of gas-tight
co
nstruction in which operations are con-
ducted through attached rubber gloves
a
n
d observed through a nonopening view
window. This BSC is maintained under
negative pressure of at least 0.50 inch
of water gauge, and air is drawn into the
cabinet through HEPA filters. The exhaust
air is treated by double HEPA filtration or
single HEPA filtration/incineration. Pas
-
sage of materials in and out of the cabi-
net is generally performed through a dunk
t
a
nk (accessible through the cabinet floor)
or a double-door pass-through box (such
as an autoclave) that can be decontami
-
nated between uses. For a more detailed
de
scription, refer to CDC/NIH [2000],
Primary Containment for Biohazards: Se-
lection, Installation and Use of Biological
Sa
fety Cabinets, 2nd edition. [www.cdc.
gov/od/ohs/biosfty/bsc/bsc.htm].
Chemotherapy drug: A chemical agent
used to treat diseases. The term usually
refers to a drug used to treat cancer.
Chemotherapy glove: A medical
glove that
has been approved by the FDA for use when
handling antineoplastic drugs.
Chemotherapy waste: Di
scarded items such
as gowns, gloves, masks, IV tubing, empty
bags, empty drug vials, needles and syringes,
and other items generated while preparing
and administering antineoplastic agents.
Closed system: A device
that does not ex-
change unfiltered air or contaminants with
the adjacent environment.
Closed system drug-transfer device: A d
rug
transfer device that mechanically prohibits the
transfer of environmental contaminants into
the system and the escape of hazardous
drug or
vapor concentrations outside the
system.
Cytotoxic: A pharmacologic
compound that
is detrimental or destructive to cells within
the body.
Deactivation: Tr
eating a chemical agent (such
as a hazardous drug) with another chemical,
heat, ultraviolet light, or other agent to create
a less hazardous agent.
Decontamination: Inactivation, neutraliza
-
tion, or removal of toxic agents, usually by
chemical means.
Engineering controls: De
vices designed
to eliminate or reduce worker exposures to
chemical, biological, radiological, ergonomic,
or physical hazards. Examples include labo
-
ratory fume hoods, glove bags, retracting sy-
ringe needles, sound-dampening materials
t
o
reduce noise levels, safety interlocks, and
radiation shielding.
Genotoxic: Capable of
damaging the DNA
and leading to mutations.
Glove box: A controlled
environment work
enclosure providing a primary barrier from
the work area. Operations are performed
through sealed gloved openings to protect
the worker, the ambient environment, and/
or the product.
Glove bag: A glove
box made from a flex-
ible plastic film. Operations are performed
through sealed
gloved openings to protect
the worker, the work environment, and/or
the product.
Hazardous drug: An
y drug identified by at
least one of the following six criteria: carci-
nogenicity, teratogenicity or developmental
Hazardous Drugs in Health Care Settings 44
toxicity, reproductive toxicity in humans, or-
gan toxicity at low doses in humans or ani-
mals, genotoxicity, or new drugs that mimic
existing hazardous drugs in structure or tox-
icity.
Hazardous waste: Any
waste
that is a
RCRA-listed hazardous waste [40 CFR
261.30–33] or that meets a RCRA charac
-
teristic of ignitability, corrosivity, reactivity, or
toxicity as defined in 40 CFR 261.21–24.
Health care settings: All hospitals,
medi-
cal clinics, outpatient facilities, physicians’
offices, retail
pharmacies, and similar facili-
ties dedicated to the care of patients.
Health care worker: All
workers
who are
involved in the care of patients. These in-
clude pharmacists, pharmacy technicians,
nurses
(registered
nurses [RNs], licensed
practical nurses [LPNs], nurses aids, etc.),
physicians, home health care workers and
environmental services workers (house
-
keeping, laundry, and waste disposal).
HEPA filter: High-efficiency
particulate
air
filter rated 99.97% efficient in capturing
0.3-micron-diameter particles.
Horizontal laminar flow hood (horizontal
laminar flow
clean bench): A device that
protects the work product and the work area
by supplying HEPA-filtered air to the rear of
the cabinet and producing a horizontal flow
across the work area and out toward the
worker.
Isolator: A device
that is sealed or is sup-
plied with air through a microbially retentive
filtration system
(HEPA minimum) and may
be reproducibly decontaminated. When
closed, an isolator uses only decontami
-
nated interfaces (when necessary) or rapid
transfer ports (RTPs) for materials transfer.
When open,
it allows for the ingress and/or
egress of materials through defined open
-
ings that have been designed and validated
to preclude
the transfer of contaminants or
unfiltered air to adjacent environments. An
isolator can be used for aseptic processing,
for containment of potent compounds, or
for simultaneous asepsis and containment.
Some isolator designs allow operations
within the isolator to be conducted through
attached rubber gloves without compromis
-
ing asepsis and/or containment.
Aseptic isolator: A ventilated
isolator
designed to exclude external contamina-
tion from entering the critical zone inside
the isolator
.
Aseptic
containment isolator: A ven-
tilated
isolator designed to meet the
requirements of
both an aseptic isolator
and a containment isolator.
Containment isolator: A ventilated
iso-
lator designed to prevent the toxic ma-
terials processed inside it from escaping
to the surrounding environment.
Lab coat: A
disposable
or reusable open-
front coat, usually made of cloth or other
permeable material.
MSDS: Material safety data sheet. These
s
heets contain summaries provided by the
manufacturer to describe the chemical prop
-
erties and hazards of specific chemicals and
wa
ys in which workers can protect them-
selves from exposure to these chemicals.
Mutagenic: C
a
pable of increasing the spon-
taneous mutation rate by causing changes in
th
e DNA.
Hazardous Drugs in Health Care Settings 45
OEL: Occupational exposure limit. An indus-
try or other nongovernment exposure limit
usually based
on scientific calculations of
airborne concentrations of a substance that
are considered to be acceptable for healthy
workers.
PDA: An international trade association
serving
pharmaceutical science and tech-
nology. Formerly known as the Parenteral
Drug Association.
PEL: OSHA
permissible
exposure limit: The
time-weighted average concentration of a
substance to which nearly all workers may
be exposed for up to 8 hours per day, 40
hours per week for 30 years without adverse
effects. A PEL may also include a skin des
-
ignation.
PPE: Personal protective equipment. Items
such
as gloves, gowns, respirators, goggles,
face shields, and others that protect indi-
vidual workers from hazardous physical or
chemical exposures.
REL: NIOSH
recommended
exposure limit:
An occupational exposure limit recommend-
ed by NIOSH as being protective of worker
health and
safety over a working lifetime.
The REL is frequently expressed as a time-
weighted average exposure to a substance
for up to a 10-hour workday during a 40
-
hour work week.
Respirator: A type
of PPE that prevents
harmful materials from entering the respi-
ratory system, usually by filtering hazardous
agents from
workplace air. A surgical mask
does not offer respiratory protection.
Risk assessment: Characterization of
po-
tentially adverse health effects from human
exposure to
environmental or occupational
hazards. Risk assessment can be divided
into five major steps: hazard identification,
dose-response assessment,
exposure as-
sessment, risk characterization, and risk
communication.
Sister chromatid exchange: T
h
e exchange
of segments of DNA between sister chroma-
tids.
Standard precautions (formerly univer-
sal precautions): The
practice
in health
care of treating all patients as if they were
infected with HIV or other similar diseases
by using barriers to avoid known means of
transmitting infectious agents [CDC 1987,
1988]. These barriers can include nonporous
gloves, goggles, and face shields. Careful
handling and disposal of sharps or the use
of needleless systems are also important.
TLVs
®
: Threshold limit values. These values
are exposure limits established by the AC-
GIH. They refer to airborne concentrations
of chemical
substances and represent con-
ditions under which it is believed that nearly
all workers
may be repeatedly exposed, day
after day, over a working lifetime, without
adverse health effects.
Ventilated cabinet: A type
of engineering
control designed for purposes of worker pro-
tection (as used in this document). These
devices are
designed to minimize worker ex-
posures by controlling emissions of airborne
contaminants through the following:
The full or partial enclosure of a potential
contaminant source
The use of airflow capture velocities to
capture and remove airborne contami-
nants near their point of generation
The use of air pressure relationships that
define the direction of airflow into the
cabinet
Hazardous Drugs in Health Care Settings 46
Examples of ventilated cabinets include
BSCs, containment isolators, and laboratory
fume hoods.
WEEL (workplace environmental expo-
sure level): Occupational exposure
limits
developed by the American Industrial Hy-
giene Association as a chemical concen-
tration to which nearly all workers may be
repeatedly
exposed for a working lifetime
without adverse health effects.
Hazardous Drugs in Health Care Settings 47
APPENDIX C
NIOSH HAZARDOUS DRUG SAFETY WORKING GROUP
The following members of the NIOSH Haz-
ardous Drug Safety Working Group provided
leadership, information, and
recommenda-
tions for this document:
Tito Aldape, Microflex Corporation
Roger W
. Anderson, Dr.P
.H., University of
Texas M.D. Anderson Cancer Center
Britton Berek, Joint Commission on
Accreditation of Healthcare Organizations
Stephen Brightwell, NIOSH
G. Edward Burroughs, Ph.D., C.I.H., NIOSH
Thomas H. Connor, Ph.D., NIOSH
Ba
rbara D. Coyle, B.S.N., R.N. C.O.H.N.-S.,
State of Wisconsin
Gayle DeBord, Ph.D., NIOSH
Robert DeChristoforo, M.S., National
Institutes of Health
Phillup C. Dugger
, U.S. Oncology, Inc.
Barbara A
. Grajewski, Ph.D., NIOSH
Dori Greene, U.S. Oncology, Inc.
Duane R. Hammond, B.S.M.E., NIOSH
Bruce R. Harrison, M.S., R.Ph., B.C.O.P.,
Department of Veterans Affairs
Hye-Joo Kim, U.S. Food and Drug
Administration
L.D. King, International Academy of
Compounding Pharmacists
Nancy Kramer
, R.N., B.S.N., Coram
Healthcare
R. David Lauper, Pharm.D., SuperGen, Inc.
Melissa M. Leone, R.N., B.S.N., Apria
Healthcare
Chiu S. Lin, Ph.D., U.S. F
ood and Drug
Administration
Barbara A. MacKenzie, NIOSH
Charlene Maloney
, NIOSH
Melissa A. McDiarmid, M.D., M.P.H.,
University of Maryland
Kenneth M. Mead, M.S., P.E., NIOSH
Martha T
. O’Lone, U.S. Food and Drug
Administration
Jerry Phillips, U.S. Food and Drug
Administration
Marty Polovich, M.N., R.N., A
.O.C.N.,
Oncology Nursing Society
Luci Power, M.S., R.Ph., University of
California Medical Center
Angela C. Presson, M.D., M.P.H., OSHA
Hank Rahe, Containment Technologies
Group, Inc
Laurence D. Reed, M.S., NIOSH
Anita L. Schill, Ph.D., M.P.H., NIOSH
Teresa Schnorr
, Ph.D., NIOSH
Douglas Sharpnack, D.V.M., NIOSH
Hazardous Drugs in Health Care Settings 49
Charlotte A. Smith, M.S., R.Ph.,
PharmEcology Associates, LLC
Sandi Yurichuk, American Federation of
State, County and Municipal Employees
American Nurses Association
American Society of Health-System
Pharmacists
Oncology Nursing Society
Pharmaceutical Research and
Manufacturers of America
Service Employees International Union
U.S. Environmental Protection Agency
Baxa Corporation
Nuaire, Inc
The Baker Company
, Inc.
Hazardous Drugs in Health Care Settings 50
