An evaluation of nitrile gloves as an alternative
to natural rubber latex for handling
chemotherapeutic agents
Elizabeth R 1
Gross
Don F Groce
2
Introduction. In 1986 and 1995, the Occupational
Safety and Health Administration issued guidelines for
the handling of chemotherapeutic agents. Natural
rubber latex gloves are recommended for all levels of
handling these drugs; these gloves provide both pro-
tection to the health care worker and a high degree of
manual dexterity in performing tasks requiring fine
motor skills. However, many health care workers
experience allergic reactions to natural rubber latex,
with symptoms ranging from minor skin irritation to
systemic anaphylaxis; the latter is a serious life-threat-
ening condition. Therefore, it is extremely important
that alternative glove materials be found that offer
protection against biological and chemical agents and
also afford health care workers ease of use and fit.
Methods. In this study, we tested a thin-gauge
(0.0045-inch gauge) disposable nitrile glove; this
glove, which offers fine motor skill ability to its users,
has been tested against a wide range of chemicals but
has not yet been tested specifically against chemo-
therapeutic agents. Using American Society for Test-
ing and Materials method F739-92, these gloves were
Since the late 1970s, it has been recognized that chemo-
therapeutic agents arenonspecific in their ability to kill
cells; therefore, these agents affect healthy cells as well.
For a cancer patient who might otherwise die from his
From the 1Dana-Farber Cancer Institute, Boston, Massachusetts
02115; and 2Best Manufacturing Company, Menlo, Georgia 30731.
Address correspondence and reprint requests to Elizabeth R.
Gross, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA
02115.
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tested for permeation resistance at three concentra-
tions, simulating exposures to Pharmacy, Nursing,
and Housekeeping staff. Eleven commonly used che-
motherapeutic drugs were investigated. Conductivity
was used to determine whether drug was present in
the test solutions.
Result. Drug was not detected in any of the
samples collected. When carmustine was tested, the
effluent had a distinct alcohol odor, but no conduc-
tivity was noted.
Conclusions. These disposable nitrile
appear to be acceptable for preparing the chemother-
gloves
apy agents tested. Hospitals must be open to finding
replacements to natural rubber latex products and
must alert their staff members about the potential for
latex sensitivity in both patients and other staff mem-
bers. Manufacturers of non-latex gloves should be
encouraged to conduct chemotherapy permeability
studies on their products.
Key Words: Nitrile; glove; permeability:
chemotherapy drugs; latex sensitivity.
or her disease, the risk is outweighed by the
toxicity
treatment benefit. However, for the pharmacist prepar-
ing the drug, the nurse administering it, or the house-
keeping personnel disposing of the waste material, there
is no benefit to any level of exposure to these agents.
The main routes of exposure to health care workers
are through the inhalation of any aerosolized drug or
through skin absorption. Pharmacists and some nursing
staff handle the concentrated solutions provided by the
drug manufacturer while preparing the dilution for
165-
166
intravenous administration.Nursing staff and the house-
keeping personnel potentially exposed to this lower
are
concentration of the chemotherapeutic agent during
administration as well as to any drug or metabolites
excreted in the body fluids of the patient. Oncology
pharmacists, technicians, nurses, or other health care
workers such as housekeeping staff may potentially be
exposed to a wide variety of chemotherapeutic agents.
In 1986 and again in 1995, the Occupational Safety
and Health Administration (OSHA) has issued guidelines
for the safe handling of chemotherapeutic agents; these
guidelines recognize the possibility of these various
exposure scenarios to hospital personnel. The guide-
lines rely on:
~ vertical-flow, high-efficiency particulate air-fil-
tered class IIB biosafety cabinets for the prepara-
tion of the drug, which are intended to minimize
the release of any aerosols produced;
~ good work practices, again to minimize aerosol
generation; and
~
personal protective equipment, including gowns
and surgical latex gloves.
Until 1986, polyvinyl
chloride gloves were widely
used by hospital staff involved with chemotherapy
agents; however, this material was specifically ruled out
by OSHA as being more permeable than the latex to
many cytotoxic drugs. Natural rubber latex gloves were
recommended because they provide both protection to
the health care worker using them and a high degree of
manual dexterity in performing tasks requiring fine
motor skills. In one study, compliance with OSHA
guidelines was good: 92% of staff who prepare these
agents and 82% of those administering the drugs wore
2
the gloves.2
However, as noted in a medical alert issued by the
Food and Drug Administration on March 29, 19913 as
well as one issued by the National Institute for Occupa-
tional Safety and Health in 1997,4 some patients and w-6
to 7% of surgical personnel are apparently extremely
sensitive to latex products. The reactions to the natural
latex rubber have ranged from a mild contact dermatitis
to a more life-threatening systemic anaphylaxis. Several
patients have died as a result of anaphylactoid reactions
during barium enema procedures. Health care workers
with previous evidence of allergy or sensitivity have also
undergone such reactions both at work and during
medical procedures. In a 1992 study of 1495 operating
room nurses that was conducted by Zaza et al at the
Centers for Disease Control and Prevention, 21% re-
ported latex reactions, with 86% reporting itching, 54%
reporting rash, 51 % reporting dermatitis, 11 % reporting
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hives, 11% reporting facial swelling, and 4% reporting
wheezing; 2% reported being hospitalized as a result of
their exposure5
Natural rubber or polyisoprene comes from the sap
of the rubber tree Hevea brasiliensis. It is isolated from
the latex sap, purified, and chemically treated to in-
crease its elasticity, strength, and durability. Accelerators
may be added to facilitate the cross-linking process. In
addition, once molded, many gloves are further treated
with cornstarch powder, lubricants, or deodorants.
Many of these agents can act as nonprotein allergens
that, once the glove is wetted, as with sweating, can be
solubilized and readily absorbed through the skin.
The issue of glove sensitivity is complex, since there
are three separate allergic responses that may occur as a
result of wearing gloves. The first reaction is a nonaller-
genic chemical irritation that is characterized by dry,
crusty skin and by a cessation of symptoms when the
latex product is removed. This response may occur as a
reaction to residual chemicals left on the glove after
manufacturing, such as accelerators, preservatives, or
vulcanizing agents.
The second reaction is an allergic contact dermatitis
that is a T-cell-mediated response; this reaction often
occurs 6 to 48 hours after contact. The skin is dry,
crusty, and thickened with hard bumps and sores. With
repeated exposures, the dermatitis may extend beyond
the contact area. Again, it is believed that this reaction is
precipitated by unreacted or residual chemicals from the
manufacturing process or by other nonprotein allergens;
some of these allergens include accelerators such as
mercaptobenzothiazole, tetramethylthiuram, and dithio-
carbamates as well as antioxidants such as p-phenylene-
diamine.
The third and most severe reaction appears to affect
primarily atopic or allergic individuals and is in response
to some of the water-soluble proteins found in latex.
Because these proteins are readily solubilized, they can
be transferred to the powder in some gloves. The
reaction may be raised pink hives which can extend
beyond the point of contact, or there can be serious
systemic involvement, including respiratory distress, diz-
ziness, nausea, abdominal pain, and itching of the eyes.
As reported in the Food and Drug Administration alert,
sensitized patients may go into anaphylactic shock;
depending upon the severity of the reaction and the
speed with which the person is treated, death may
result.
Therefore, it is crucial that hospitals be aware of
these possible latex-sensitivities in both their staff and
patient populations. It is also extremely important that
alternative glove materials be found that offer equivalent
protection to natural rubber from both biological and
chemical agents and also afford health care workers ease

Table 1. Results
*LDL =
Lowest detectable limit.
tBDT Breakthrough detection time.
=
.twhen testing carmustine, the conductivity reading indicated that none of the drug being tested had permeated the test material, because the conductivity did not
change. However, a strong odor of ethanol was detected in the collection water at the end of the test.
ND, none detected.
of use and fit. Other studies of glove permeability to
chemotherapeutic agents have been conducted, but
none have used a nitrile-based glove product . 6-10
In 1993, we evaluated a thin-gauge (0.0045-inch
gauge) disposable nitrile glove (N-DEX, Best Manufactur-
ing Company, Menlo, Ga). This glove offers fine motor
skill ability to its users, has been tested against a wide
range of chemicals and biologicals, has been shown to
be puncture-resistant, but has not yet been tested against
chemotherapeutic agents.
MATERIALS AND METHODS
On consultation with the Pharmacy Department of the
Dana-Farber Cancer Institute, 11 drugs that were repre-
sentative of the five major classes of chemotherapy
currently in use were chosen. These included cisplatin,
carmustine, ifosfamide, dacarbazine, fluorouracil, meth-
otrexate, doxorubicin, mitomycin, vincristine, etopo-
side, and mitoxantrone. These drugs represent a variety
of agent classes (alkylators, antimetabolites, antibiotics,
and mitotic inhibitors), a variety of dissimilar chemical
structures, and are used to treat a variety of cancers.
The resistance of the nitrile material to permeation
was tested according to American Society for Testing
and Materials (ASTM) test method F739-85.11 The ASTM
method is designed to simulate total, constant immer-
sion contact for an 8-hour period. The test side of the
cell was loaded with collection medium; the medium
used was one in which the test drug was freely soluble.
Since most of the chemotherapeutic drugs tested are
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167
salts, the collection medium used was deionized water;
the analytical method chosen to detect the drug in the
collection medium was conductivity. Each drug at each
concentration was tested in triplicate for reproducibility
as required in the 1991 version of this method. The
conductivity of the collection medium was measured
every 15 minutes for 8 hours.
As outlined in the ASTM method, samples of the
nitrile gloves that had been taken from the palm of the
glove were loaded into 2-inch glass permeation cells.
The challenge side of the test cell was loaded with the
particular concentration of the drug being tested. Serial
dilutions of the drug were performed to simulate differ-
ent exposures to which health care workers might be
exposed. These included the concentrated dose (Table
1, #1) as supplied by the drug manufacturer, a more
dilute solution (Table 1, #2) representing therapeutic
doses administered to inpatients, and an even more
dilute concentration (Table 1, #3) representing that in
excreted body fluids.
Breakthrough was considered to occur when a
change in conductivity was observed. For closed loops
such as this system, the cumulative concentration was
measured for the entire 8-hour period; the permeation
rate was calculated from that concentration. For quanti-
tation, standards of the drugs were prepared in the
collection medium. Serial dilutions of these &dquo;knowns&dquo;
provided conductivity data for quantitation. Permeation
rates are expressed in micrograms of chemical per
square centimeter of glove material per minute. Break-
through detection time is the time in minutes from the
initial exposure of a chemical to the outer surface of the
168
glove to the time that the chemical can first be detected
on the interior of the glove.
RESULTS
As shown in the Table, none of the 11 agents was
detected at any of the concentrations tested. Although
there was no change in conductivity with carmustine,
which there should have been if the drug had been
detected, there was a strong smell of ethanol in the
collection water. Ethanol would not increase the con-
ductivity, but the carmustine would. This fmding needs
to be studied further to be certain that none of the drug
permeated. It is possible that some drugs that must be
dissolved in ethanol would permeate with the ethanol.
DISCUSSION/CONCLUSIONS
The ASTM F739-85 simulates a worst-case exposure
scenario of total immersion for 8 hours of constant
contact; this level of exposure is unlikely to occur in
&dquo;real&dquo; life. However, if some of the drug were to get on
the surface of the glove, constant contact might occur,
and permeation might be possible.
All of the testing cited in this paper was performed
in 1993. The concentrations used for testing are reflec-
tive of those recommended by the drug manufacturer in
1993 and the therapeutic dose administered at that time.
Since then, some therapeutic doses may have changed;
however, this should not affect the relevance of this
study, since the intent of the testing was to challenge the
glove material to a wide range of concentrations, includ-
ing a maximum stock solution concentration. It is also
important to note that the formulation of the glove has
not changed over the years. While the palm area of the
glove was challenged in all of the testing performed, it
should be stressed that the nitrile glove tested has
uniform thickness over its entire surface. The nitrile
polymer used is stronger and more chemical resistant
than latex, so the manufacturer has not found it neces-
sary to make the gloves thicker in the fingertips, where
contact with chemotherapy is more likely to occur.
We have indicated to our staff that the nitrile gloves
are a safe alternative to the natural rubber latex ones for
handling all concentrations of chemotherapy; in fact, we
use powder-free nitrile gloves in our outpatient pharma-
cies. However, we do advise our staff that accelerators,
powder, and other chemicals used in the glove-manufac-
turing process can elicit a contact dermatitis. For exam-
ple, mercaptobenzothiazole is used in the processing of
this nitrile glove. While reaction to this reagent is a less
dramatic allergic response than the response to the
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natural rubber proteins, some sensitive individuals may
still respond to this material.
Hospitals must be open to fmding replacements to
natural rubber latex products and must alert their staff
members about the potential for latex sensitivity in both
patients and other staff members. They must also en-
courage manufacturers of non-latex gloves to conduct
chemotherapy permeability studies on their products.
ACKNOWLEDGMENTS
This study was presented at the American Industrial
Hygiene Conference and Exposition in May, 1993. We
thank Marvin Diamond, RPh, Sylvia Bartel, RPh, and
Karen Byers, MS, for their assistance in this work.
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