Hazardous drugs pose risks to healthcare workers through various routes of exposure. Proper handling of these drugs requires comprehensive safety plans developed by healthcare institutions with input from all relevant departments. These plans must include assessing the workplace, developing protocols, creating an institutional hazardous drug list, conducting environmental assessments, and implementing training programs for all employees who may be exposed. Thorough training and adherence to safety practices by both institutions and workers can help reduce occupational risks from hazardous drugs.

1. Alex Evans
P and T Article
Guidelines in the Safe Handling of Hazardous Substances
Alex Evans, PharmD Candidate
UNC Eshelman School of Pharmacy
Background​1
Hazardous drugs pose significant threats to healthcare workers, oftentimes on a daily basis, and
substantiate the need for proper education among all involved. Workers may be exposed through
transporting, distributing, unpacking, preparing, administering, and disposing of those drugs.
Effects on healthcare workers include fetal and reproductive toxicity as well as cancer.
Occupational cyclophosphamide exposure, for example, has been estimated to lead to as many as
50 additional cases of cancer each year for every million workers exposed. Moreover, controlled
surveys have revealed an increased frequency of complaints of minor ailments, such as chronic
coughing, headaches, and dizziness among healthcare workers who handle hazardous drugs at
work.
These risks can be reduced by educating workers as well as developing institutional protocols
that aim to identify hazardous drugs and limit occupational exposure to them. The aim of this
article is to provide an overview of ways in which both the institution as well as the worker can
strive to reduce occupational exposure to hazardous drugs. It is important to note that the
responsibility lies with both; it is up to the institution to develop sound practices, and it is up to
the workers to read and follow carefully the practices set forth by the institution.
Educational Resources​1­9
The American Society of Health­Systems Pharmacists (ASHP) publishes and updates guidelines
on handling hazardous drugs that are based on the primary literature as well as government
reports. This is a great place to begin to gather general information, get a good overview of
hazardous drugs in the workplace, and obtain many references. The guidelines are updated
occasionally, with the newest guidelines being current to 2004.
The Material Safety Data Sheet (MSDS) is another great resource specific to a particular drug. It
helps the institution assess the level of risk of exposure to the drug in question and gives
resources on potential routes of exposure, the acute and chronic health effects due to exposure,
proper first aid measures, fire and explosion data, appropriate personal protective equipment
(PPE) and handling procedures, and proper spill procedures. The MSDS may be obtained from
the manufacturer or distributor of the chemical.
The National Institute for Occupational Safety and Health (NIOSH), a division of the Centers for
Disease Control, also publish guidelines on preventing occupational exposure to hazardous drugs
in the healthcare setting. These guidelines, including a printable .pdf, are available for free
download online. In it, they describe the potential for exposure including routes of exposure,
evidence that workers get exposed, and recommendations on everything from handling and
packaging to proper selection of ventilation cabinets.
Other publications by NIOSH include guidelines on PPE in the workplace, medical surveillance
for healthcare workers exposed to hazardous drugs, and specific guidelines regarding the
handling of Micotil 300, an antibiotic used in veterinary medicine with health risks to humans.

2. The Occupational Safety and Health Administration (OSHA) publishes a technical manual, a
hazard communication standard, and an occupational exposure to hazardous chemicals in
laboratories standard. Other guidelines are published by the NIH, USP, and the Oncology
Nursing Society. The references for those guidelines may be found in NIOSH’s occupational
exposure reference.
What is a Hazardous Drug?​1,2,10,11
NIOSH classifies hazardous drugs on several criteria:
1. Carcinogenecity
2. Teratogenecity or developmental toxicity
3. Reproductive toxicity
4. Organ toxicity at low Doses
5. Genotoxicity
6. Structure and toxicity profiles of new drugs that mimic existing drugs determined
hazardous by the above criteria
ASHP’s classifications parallels those of NIOSH. It is up to the individual institution to make
judgment calls regarding whether a drug is hazardous.
The World Health Organization’s International Agency for Research on Cancer (IARC) provides
a complete list of agents they have reviewed for carcinogenicity. Their classification is based on
the following system: Class 1 (carcinogenic to humans), Class 2A (probably carcinogenic to
humans), Class 2B (possibly carcinogenic to humans), Class 3 (unclassifiable as to its
carcinogenicity to humans), and Class 4 (probably not carcinogenic to humans). It is not
exclusive to therapeutic agents, but is nonetheless a great resource to use when assessing
carcinogenecity.
The National Toxicology Program, part of the Department of Health and Human Services,
publishes the Report on Carcinogenecity (RoC), currently in its 12​th​
edition. The website is a bit
more difficult to navigate than the IARC, but would be useful to certain institutions.
Exposure Routes​1
Drugs may enter the body through inhalation, ingestion, contaminated food products,
hand­to­mouth, or dermal contact. The route of exposure that is most important is dependent on
the drug. For example, a report published in 1992 found no significant dermal absorption of
doxorubicin, vincristine, or vinblastine, implying a different route of exposure for those drugs.
Because the primary route is different for every drug and oftentimes is unknown, it is prudent to
protect workers against all possible routes of exposure.
The most important routes of exposure in the workplace (the way in which most drugs are
absorbed) are believed to be inhalation and dermal absorption. Standard sampling methods have
generally detected either none or very low levels of drugs in the aerosol and gaseous phase in the
pharmacy and clinic environment; however, there is some concern that many of the hazardous
drugs are volatile and thus wouldn’t be captured on a standard sampling filter. Thus the idea of
inhalational exposure is a topic of current debate and limited evidence.
As far as dermal absorption, numerous studies have confirmed the presence of hazardous drugs
on the surface of biological safety cabinets, tables, and counter tops. The ability for
contamination to spread to many surfaces in the work area further emphasizes the need for

3. proper institutional standards and training for employees.
Assessing the Workplace and Developing a Comprehensive Safety Plan​1
Before hazardous drugs are ordered the workplace needs to be assessed to determine if it can
properly handle their presence. Employees need to be trained, and policies need to be in place
with the proper committees responsible for updating those policies. The culmination of this
results in the comprehensive safety plan for the hospital.
The safety plan must be developed with input from all involved, including those involved in
transport, preparation, administration, and disposal. The departments involved might include
pharmacy, medical staff, nursing, housekeeping, transportation, maintenance, safety, and clinical
laboratories.
Developing an institutional list of hazardous drugs1
One of the most important steps in the comprehensive safety program involves the creation of a
list of hazardous drugs that are used at the institution. Steps must be taken to identify those drugs
as soon as they arrive and throughout the life of the drug at the institution, ending with proper
disposal. It is also important that this list be updated on a regular basis. New drugs added to
formulary or ordered at the institution should be evaluated using the MSDS provided and other
applicable resources for all potential toxicities, as described above.​
Institutions must make the MSDS available for all hazardous agents used. Part of the safety
program should include a process for updating the database of MSDS’s as new drugs and
chemicals are introduced into the workplace.
Environmental assessment1
All hazardous drugs, areas where hazardous drugs are going to be handled, and packaging
associated with hazardous drugs should be labeled so that it is obvious to all workers of the
contents. It is important to make sure that labels are universally understood so that language
barriers don’t endanger safety. If workers aren’t aware of the risks they can’t protect themselves
from them, so proper labeling is one of the most crucial aspects of the entire program.
Areas where hazardous drugs are prepared or administered should be separated from other areas
of the hospital and clearly labeled for staff. For some institutions, this might mean expanding or
renovating existing areas to accommodate the new requirements. Additional biological safety
cabinets will be needed as well, which requires more space and some thought as to airflow and
design of the hospital.
Shelving and carts where hazardous drugs are stored or transported should have a sufficient
barrier on them to prevent vials from falling off and breaking. Moreover, hazardous drugs should
be stored in a different area than non­hazardous drugs, so additional shelving will be necessary
when the decision is made to use hazardous drugs.
Training Programs1
Training programs should include everyone with potential for exposure to hazardous drugs, not
just the medical staff. Maintenance workers, housekeepers, and volunteers are just some of the
staff with the potential for exposure. It is potentially even more crucial that non­medical staff be
included because they are less likely than medical staff to be able to recognize hazardous drugs,
fully understand the implications of exposure, and know the appropriate steps to take to reduce

4. exposure.
It is the opinion of the author that a good practice would be to train all employees of the hospital
to some degree. Graded training programs could be developed that included basic training for
everyone as well as training for specific tasks such as preparation, administration, clean­up, and
disposal. Basic training might include topics such as recognizing labeling, routes of exposure,
appropriate PPE, and hospital resources in case of accidental exposure or a spill that needs
clean­up.
Appropriate PPE1,3,12,13
Gloves: Gloves are essential whenever working with hazardous drugs. As stated above, a major
route of exposure is through dermal contact. Workers should be wearing double gloves that are
powder­free. The powder on gloves tends to concentrate the contamination, making it easier to
become exposed or to expose other workers through surface contamination.
The American Society for Testing and Materials (ASTM) has testing standards for determining if
glove materials can withstand penetration with chemotherapy agents. Materials that are sufficient
include latex, nitrile, and neoprene/polyurethane. Any gloves being used for chemotherapy
should meet these testing standards and be designated separately in the hospitals as
chemotherapy gloves.
Other practices to reduce exposure include changing gloves every 30 minutes, if contaminated
with a spill, or become compromised with a tear or break in the barrier. Workers should inspect
gloves before use, wash hands before and after use, and dispose of all PPE in designated bins
after use. 70% isopropyl alcohol may be used to sanitize gloves as it has been shown not to
degrade the barrier provided by the gloves.
Gowns: Gowns should be worn anytime during preparation, administration, spill control, and
waste management. They should be of a non­ or low­permeable, lint­free fabric and disposable.
Because washable gowns absorb fluids, they are inappropriate for hazardous drug PPE. In
addition, only gowns with a polyethylene or vinyl coating will provide adequate protection
against spills with hazardous drugs. Early evidence suggests that gowns might offer protection
for two to three hours, but further research is still needed.
Eye and face protection: When there is a possibility of a splash or spill face protection should be
worn. It is best to wear face shields rather than goggles because they offer protection of the entire
face rather than just the eyes.
Shoe and hair covers: In sterile compounding shoe and hair covers decrease the chance of
contamination in the sterile room. However, when compounding with hazardous substances,
used shoe and hair covers should be considered contaminated and need to be removed prior to
leaving the room. Moreover, since they are contaminated, they should be removed with gloved
hands only.
Respirators: Respirators are required anytime there might be a splash or spill outside of the
biological safety cabinet. Workers using respirators must be trained and fit­tested for the
respirator as required by the OSHA Respiratory Protection Standard. Surgical masks do not
provide appropriate protection and only a NIOSH­approved respirator should be used. The
NIOSH N95 respirator provides protection against airborne particles but offers no protection
against gases and vapors.

5. Biological Safety Cabinets (BSCs)1
BSCs should be used when preparing hazardous drugs. There are several types of BSCs, but any
that are used for hazardous drugs should have a negative­airflow design that moves air away
from the worker. It is best to consult the manufacturer of the BSC on the various designs so they
can help the institution get the right BSCs for their needs. Proper training of the BSC is crucial to
its success, and thus training should be part of the safety program.
Decontamination1,14
Deactivation of a hazardous drug is the best method for cleaning a spill. Currently there is no
chemical that will deactivate all hazardous drugs, but information about controlling spills may be
found in the MSDS. Isopropyl alcohol is not recommended because it will not deactivate most
drugs and instead might spread the contamination. A solution of sodium hypochlorite (bleach) is
recommended for many drugs and is a reasonable first choice if no information about clean­up is
readily available.
Medical Surveillance Programs4
NIOSH recommends that institutions develop surveillance programs to monitor employees’
exposure to hazardous drugs. This includes baseline and periodic follow­up physicals that might
include lab tests such as a CBC and UA, questions regarding reproductive and general health,
and follow­up for workers with a significant exposure. In addition, compliance regarding the use
of PPE should be evaluated periodically so that the appropriate changes may be made to
maximize compliance. If available, the environment may be assessed for surface contamination.
Conclusions​1,4
An estimated 5.5 million workers are potentially exposed to hazardous drugs in the workplace.
Considering the potential for serious acute and chronic health adverse effects, it is imperative
that the proper precautions are taken when the decision is made to use hazardous drugs in the
institution. The precautions are multifactorial, and include proper education and training,
planning of the worksite, identification, exposure protection, decontamination, and medical
surveillance. The responsibility lies with both the institution and the individual to make the
workplace safer for everyone involved.
References:
1. ASHP Council on Professional Affairs. ASHP Guidelines on Handling Hazardous Drugs.
Am J Health­Syst Pharm. ​2006; 63:1172­93.
2. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous
drugs in health care settings. National Institute for Occupational Safety and Health.
Accessed online at ​http://www.cdc.gov/niosh/docs/2004­165 ​on December 12, 2009.
3. Personal protective equipment for health care workers who work with hazardous drugs.
National Institute for Occupational Safety and Health. Accessed online at
http://www.cdc.gov/niosh/docs/wp­solutions/2009­106​ on December 12, 2009.
4. Medical surveillance for health care workers exposed to hazardous drugs. National
Institute for Occupational Safety and Health. Accessed online at
http://www.cdc.gov/niosh/docs/wp­solutions/2007­117​ on December 13, 2009.

6. 5. Preventing worker deaths and injuries when handling Micotil 300​©​
. National Institute for
Occupational Safety and Health. Accessed online at
http://www.cdc.gov/niosh/docs/wp­solutions/2007­124​ on December 13, 2009.
6. Controlling occupational exposure to hazardous drugs. Occupational Safety and Health
Administration. Accessed online at
http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html​ on December 13, 2009.
7. Hazard communication standard [29 CFR 1910.1200]. Occupational Safety and Health
Administration. Accessed online at
http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=100
99​ on December 13, 2009.
8. Occupational exposure to hazardous chemicals in laboratories standard [29 CFR
1910.1450]. Occuaptional Safety and Health Administration. Accessed online at
http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=101
06​ on December 13, 2009.
9. Material Safety Data Sheet – Estriol. Science Lab.com. Accessed online at
www.sciencelab.com/x​MSDS​­​Estriol​­9925870​ on December 26, 2009.
10. IARC monographs on the evaluation of carcinogenic risks to humans. World Health
Organization. Accessed online at ​http://monographs.iarc.fr/ENG/Classification/index.php
on December 26, 2009.
11. The National Toxicology Program. Accessed at ​http://ntp.niehs.nih.gov/​ on December 26,
2009.
12. Nixon S, Schulmeister L. Safe handling of hazardous drugs: are you protected? Clin J Onc
Nurs 2009; 13(4):433­9.
13. Respiratory Control Standards. Occupational Safety and Health Administration. Accessed
online at ​http://www.osha.gov/SLTC/respiratoryprotection/standards.html​ on December
26, 2009.
14. Allen LV. Compounding with hazardous drugs. Secundum Artem 2008;15(2). Accessed at
http://www.paddocklabs.com/publications.html​ on December 26, 2009.