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Mention of any company or product does not constitute endorsement by the National Insti-tute for Occupational Safety and Health (NIOSH). In addition, citations to Web sites externalto NIOSH do not constitute NIOSH endorsement of the sponsoring organizations or theirprograms or products. Furthermore, NIOSH is not responsible for the content of these Websites.

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DHHS (NIOSH) Publication Number 2004165

September 2004

SAFER HEALTHIER PEOPLE TM

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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 themwith measures for protecting their health. Health care workers who prepare or administerhazardous drugs or who work in areas where these drugs are used may be exposed to theseagents in the air or on work surfaces, contaminated clothing, medical equipment, patientexcreta, and other surfaces. Studies have associated workplace exposures to hazardousdrugs with health effects such as skin rashes and adverse reproductive outcomes (includinginfertility, spontaneous abortions, and congenital malformations) and possibly leukemia andother cancers. The health risk is inuenced by the extent of the exposure and the potencyand toxicity of the hazardous drug. To provide workers with the greatest protection, employers

should (1) implement necessary administrative and engineering controls and (2) assure thatworkers 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 andnursing 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 ofexposed 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 arapidly growing eld of patient therapy. New areas of pharmaceutical development will bringfundamental changes to methods for treating and preventing diseases. Both traditional med-ications and bioengineered drugs can be hazardous to health care workers who must handlethem. This NIOSH Alert will help make workers and employers more aware of these hazardsand provide the tools for preventing exposures.

John Howard, M.D.DirectorNational Institute for Occupational

Safety and HealthCenters for Disease Control

and Prevention

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Contents

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Potential 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

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Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Air ow and exhaust . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Maintenance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Routine Cleaning, Decontaminating, Housekeeping, and Waste Disposal . . . . 16 Cleaning andd econtaminating. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Housekeeping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Waste d isposal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 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 Dening Hazardous Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

ASHP Denition of Hazardous Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 NIOSH Revision of ASHP Denition . . . . . . . . . . . . . . . . . . . . . . . . . . . . 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

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Preventing Occupational Exposures to Antineoplastic and Other HazardousDrugs in Health Care Settings

Warning!

Working with or near hazardous drugs in health care settingsmay cause skin rashes, infertility, miscarriage, birth defects,

and possibly leukemia or other cancers.

The National Institute for OccupationalSafety and Health (NIOSH) requests as-sistance in preventing occupational ex-posures to antineoplastic drugs (drugsused to treat cancer) and other hazard-ous drugs in health care settings. Healthcare workers who work with or near haz-

ardous drugs may suffer from skin rash-es, infertility, miscarriage, birth defects,and possibly leukemia or other cancers.

Workers may be exposed to hazardousdrugs in the air or on work surfaces,clothing, medical equipment, and pa-tient urine or feces. The term hazardousdrugs , as it is used in this Alert, includesdrugs that are known or suspected tocause adverse health effects from ex-posures in the workplace. They includedrugs used for cancer chemotherapy,antiviral drugs, hormones, some bio-engineered drugs, and other miscella-neous drugs. The health risk dependson how much exposure a worker has tothese 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 areused and (2) using proper proceduresand protective equipment for handlinghazardous drugs.

This Alert warns health care workers

about the risks of working with haz-ardous drugs and recommends meth-ods and equipment for protecting theirhealth. The Alert addresses workers inhealth care settings, veterinary medi-cine, research laboratories, retail phar-macies, and home health care agen-cies; it does not address workers in thedrug manufacturing sector. Included inthe Alert are ve case reports of work-ers who suffered adverse health effectsafter being exposed to antineoplasticdrugs.

NIOSH requests that employers, editorsof trade journals, safety and health of-cials, and unions bring the recommen-dations in this Alert to the attention ofall work ers who are at risk.

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BACKGROUND

Drugs have a successful history of use intreating illnesses and injuries, and they

are responsible for many of our medicaladvances over the past century. However, virtually all drugs have side effects associ-ated with their use by patients. Thus, bothpatients and workers who handle them areat risk of suffering these effects. In addi-tion, it is known that exposures to even verysmall concentrations of certain drugs maybe hazardous for workers who handle themor work near them.

The termhazardous drugs was rst used bythe American Society of Hospital Pharma-cists (ASHP) [ASHP 1990] and is currentlyused by the Occupational Safety and HealthAdministration (OSHA) [OSHA 1995, 1999].Drugs are classied as hazardous if studiesin animals or humans indicate that expo-sures to them have a potential for causingcancer, developmental or reproductive tox-icity, or harm to organs. Many hazardous

drugs are used to treat illnesses such ascancer or HIV infection [Galassi et al. 1996;McInnes and Schilsky 1996; Erlichman andMoore 1996]. See Appendix A for examplesof hazardous drugs and a full discussion ofcriteria used to dene and classify them ashazardous.

Although the potential therapeutic benetsof hazardous drugs outweigh the risks of sideeffects for ill patients, exposed health careworkers risk these same side effects with notherapeutic benet. Occupational exposuresto hazardous drugs can lead to (1) acuteeffects such as skin rashes [McDiarmid andEgan 1988; Valanis et al. 1993a,b; Krstevet al. 2003]; (2) chronic effects, includingadverse reproductive events [Selevan et al.1985; Hemminki et al. 1985; Stcker et al.

1990; Valanis et al. 1997, 1999; Peelen etal. 1999]; and (3) possibly cancer [Skov etal. 1992].

Guidelines have been established for han-

dling hazardous drugs, but adherence tothese guidelines has been reported to besporadic [Valanis et al. 1991, 1992; Ma-hon et al. 1994; Nieweg et al. 1994]. Inaddition, measurable concentrations ofsome hazardous drugs have been docu-mented in the urine of health care workerswho prepared or administered themevenafter 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 ofpatient-care areas have documented mea-surable concentrations of drug contamina-tion, even in facilities thought to be followingrecommended handling guidelines [Minoiaet al. 1998; Connor et al. 1999; Pethran etal. 2003].

The numbers and types of work environmentscontaining antineoplastic drugs are expand-ing as these agents are used increasingly fornonmalignant rheumatologic and immuno-logic diseases [Baker et al. 1987; Moody etal. 1987; Chabner et al. 1996; Abel 2000]and for chemotherapy in veterinary medi-cine [Rosenthal 1996; Takada 2003]. ThisAlert summarizes the health effects asso-ciated with occupational exposure to theseagents and provides recommendations forsafe handling.

POTENTIAL FOR WORKEREXPOSURE

Workers may be exposed to a drug through-out its life cyclefrom manufacture to

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transport and distribution, to use in healthcare or home care settings, to waste dis-posal. The number of workers who may beexposed to hazardous drugs exceeds 5.5million [U.S. Census Bureau 1997; BLS1998, 1999; NCHS 1996]. These workersinclude shipping and receiving personnel,pharmacists and pharmacy technicians,nursing personnel, physicians, operatingroom personnel, environmental servicespersonnel, and workers in veterinary prac-tices where hazardous drugs are used. ThisAlert addresses workers in health care set-tings, veterinary medicine, research labora-tories, retail pharmacies, and home healthcare agencies; it does not address workersin the drug manufacturing sector.

CONDITIONS FOR EXPOSURE

Both clinical and nonclinical workers may beexposed to hazardous drugs when they cre-ate aerosols, generate dust, clean up spills,or touch contaminated surfaces during thepreparation, administration, or disposal ofhazardous drugs. The following list of activi-ties may result in exposures through inhala-tion, skin contact, ingestion, or injection:

Reconstituting powdered or lyophilizeddrugs and further diluting either the re-constituted powder or concentrated liq-uid forms of hazardous drugs [Fransmanet al. 2004]

Expelling air from syringes lled with haz-ardous drugs

Administering hazardous drugs by intra-muscular, subcutaneous, or intravenous(IV) routes

Counting out individual, uncoated oraldoses 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 Schultz2000]

Compounding potent powders into cus-tom-dosage capsules

Contacting measurable concentrations ofdrugs present on drug vial exteriors, worksurfaces, oors, and nal 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 etal. 2002]

Generating aerosols during the adminis-tration of drugs, either by direct IV pushor by IV infusion

Priming the IV set with a drug-contain-ing solution at the patient bedside (thisprocedure should be done in the phar-macy)

Handling body uids or body-uid-con-taminated clothing, dressings, linens,and other materials [Cass and Musgrave1992; Kromhout et al. 2000]

Handling contaminated wastes gener-ated at any step of the preparation oradministration process

Performing certain specialized proce-dures (such as intraoperative intraperi-toneal chemotherapy) in the operatingroom [White et al. 1996; Stuart et al.2002]

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Handling unused hazardous drugs orhazardous-drug-contaminated waste

Decontaminating and cleaning drugpreparation or clinical areas

Transporting infectious, chemical, orhazardous waste containers

Removing and disposing of personal pro-tective equipment (PPE) after handlinghazardous drugs or waste

EXPOSURE ROUTES

Exposures to hazardous drugs may occurthrough inhalation, skin contact, skin ab-sorption, ingestion, or injection. Inhalationand skin contact/absorptionare the mostlikely routes of exposure, but unintentionalingestion from hand to mouth contact andunintentional injection through a needle-stick or sharps injury are also possible [Du-

vall and Baumann 1980; Dorr 1983; Blackand Presson 1997; Schreiber et al. 2003].

A number of studies have attempted tomeasure 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; Stuartet al. 2002; Kiffmeyer et al. 2002; Larson etal. 2003]. In most cases, the percentage of

air samples containing measurable airborneconcentrations of hazardous drugs was low,and the actual concentrations of the drugs,when present, were quite low. These resultsmay be attributed to the inefciency of sam-pling and analytical techniques used in thepast [Larson et al. 2003]. Both particulateand 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 ofareas where hazardous drugs are preparedand administered at health care facilities inthe United States and several other coun-tries [Sessink et al. 1992a; Sessink et al.1992b; McDevitt et al. 1993; Pethran etal. 1998; Minoia et al. 1998; Rubino et al.1999; Sessink and Bos 1999; Connor et al.1999; Micoli et al. 2001; Vandenbroucke etal. 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 concentrationsof one to ve hazardous drugs in variouslocations such as biological safety cabinet(BSC) surfaces, oors, counter tops, stor-age areas, tables and chairs in patient treat-ment areas, and locations adjacent to drug-handling areas. All of the studies reportedsome level of contamination with at least

one drug, and several reported contamina-tion with all the drugs for which assays wereperformed. Such widespread contaminationof work surfaces makes the potential forskin 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 areexperiencing serious health effects despitecurrent work practice guidelines. Protectionfrom hazardous drug exposures depends onsafety programs established by employers


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and followed by workers. Factors that affectworker 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

adverse effects from hazardous drugs increas-es with the amount and frequency of exposureand the lack of proper work practices.

Worker exposures have been assessed bystudies of biological markers of exposure.No single biological marker has been foundto be a good indicator of exposure to haz-ardous drugs or a good predictor of adversehealth effects [Baker and Connor 1996].Sessink and Bos [1999] noted that 11 of12 studies reported cyclophosphamide inthe urine of health care workers tested, in-dicating continued exposure despite safetyprecautions.

Harrison [2001] reported that six differ-ent drugs (cyclophosphamide, methotrex-ate, ifosfamide, epirubicin and cisplatin/carboplatin)were detected in the urine ofhealth 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 designedto protect workers. Examples include BSCs and isolatorsdesigned to prevent hazardous drugs inside the cabinetfrom escaping into the work environment. See the Glossaryin Appendix B for additional descriptions of engineeringcontrols.

of pharmacy and nursing personnel [Peth-ran et al. 2003; Wick et al. 2003]. Pethranand coworkers collected urine samples in14 German hospitals over a 3-year period.Cyclophosphamide, ifosfamide, doxorubi-cin, and epirubicin (but not daunorubicin oridarubicin) and platinum(from cisplatin orcarboplatin) were identied in urine samplesfrom many of the study participants. A U.S.investigation demonstrated that use of aclosed-system device for 6 months reducedboth the concentration of cyclophospha-mide or ifosfamide in the urine of exposedhealth care workers and the percentage ofsamples containing these drugs [Wick etal. 2003]. Hazardous drugs have also beendocumented in the urine of health careworkers who did not handle hazardous drugsbut were potentially exposed through fugi-tive aerosols or secondary contamination ofwork surfaces, clothing, or drug containers[Sessink et al. 1994b; Mader et al. 1996;Pethran et al. 2003].

EVIDENCE FOR HEALTH EFFECTSIN WORKERS

By the 1970s, the carcinogenicity of severalantineoplastic drugs in animals was wellestablished [Shimkin et al. 1966; Weis-berger 1975; Schmahl and Habs 1978].Likewise, a number of researchers during

this period linked the therapeutic use ofalkylating agents in humans to subsequentleukemias and other cancers [Harris 1975,1976; IARC 1979]. Many health care pro-fessionals began to question the safety ofoccupational exposure to these agents [Ngand Jaffe 1970; Donner 1978; Johansson1979].


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Mutagenicity

A number of studies indicate that antineo-plastic drugs may cause increased genotoxiceffects in pharmacists and nurses exposed inthe workplace [Falck et al. 1979; Andersonet al 1982; Nguyen et al. 1982; Rogers andEmmett 1987; Oestricher et al. 1990; Fuchset al. 1995; ndeger et al. 1999; Norppa etal. 1980; Nikula et al. 1984; McDiarmid etal. 1992; Sessink et al. 1994a; Burgaz et al.1988]. Several studies that have not linkedgenotoxic effects with worker exposures maybe explained by technical confounders and

a lack of accurate blood and urine samplingin exposed workers [Sorsa et al. 1985; Mc-Diarmid et al. 1992]. When all the data areconsidered, the weight of evidence associ-ates hazardous drug exposures at work withincreased genotoxicity [Sorsa and Anderson1996; Baker and Connor 1996; Bos andSessink 1997; Hewitt 1997; Sessink andBos 1999; Harrison and Schulz 2001].

Developmental and ReproductiveEffects

A recent review of 14 studies describedan association between exposure to anti-neoplastic drugs and adverse reproductiveeffects, and 9 studies showed some posi-tive association [Harrison 2001]. The majorreproductive effects found in these stud-ies were increased fetal loss [Selevan etal. 1985; Stcker et al. 1990], congenitalmalformations depending on the length ofexposure [Hemminki et al. 1985], low birthweight 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 careworkers exposures to antineoplastic drugs.A signicantly increased risk of leukemiahas been reported among oncology nursesidentied in the Danish cancer registry forthe period 19431987 [Skov et al. 1992].

The same group [Skov et al. 1990] foundan increased, but not signicant, risk of leu-kemia in physicians employed for at least6 months in a department where patientswere treated with antineoplastic drugs.

CURRENT STANDARDS ANDRECOMMENDATIONS

Currently, no NIOSH recommended exposurelimits (RELs), OSHA permissible exposurelimits (PELs), or American Conference ofGovernmental Industrial Hygienists (ACGIH)threshold limit values (TLVs) have beenestablished for hazardous drugs in general.

An OSHA PEL and an ACGIH TLV have beenestablished for soluble platinum salts [29CFR 1910.1000; ACGIH 2003]. However,these standards are based on sensitizationand not on the potential to cause cancer. APEL, 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; NIOSH2004; ACGIH 2003]. A workplace environ-mental exposure level (WEEL) has beenestablished for some antibiotics, includingchloramphenicol (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.


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on material safety data sheets (MSDSs) orfrom the manufacturer [Sargent and Kirk1988; 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 USC69016992] apply to the management ofhazardous wastes, which include nine anti-neoplastic drugs [40 CFR 260279].

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 CFR1910.1200]

Occupational exposure to hazardous che-micals in laboratories standard [29 CFR1910.1450]

OSHA Technical Manual ; Section VI,Chapter 2: Controlling Occupational Expo-sure to Hazardous Drugs [OSHA 1999].Main elements of these 1999 OSHAguidelines 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 astrict set of regulatory requirements [40CFR 260279]. The RCRA list of hazard-ous wastes was developed in 1976 andincludes only about 30 pharmaceuticals, 9of which are antineoplastic drugs. Recentevidence indicates that a number of drugformulations exhibit hazardous waste char-acteristics [Smith 2002]. OSHA [1999] andASHP [1990] recommend that hazardousdrug waste be disposed of in a manner simi-lar to that required for RCRA-listed hazard-ous waste. Hazardous drug waste includespartially lled vials, undispensed products,unused IVs, needles and syringes, gloves,gowns, underpads, contaminated materialsfrom spill cleanups, and containers such asIV bags or drug vials that contain more thantrace amounts of hazardous drugs and arenot 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: AGuide for Small Businesses [EPA 2001].

U.S. Environmental Protection Agency(EPA).RCRA Hazardous Waste Regula-tions [40 CFR Parts 260279].

Additional Guidelines

Additional guidelines that address hazard-ous drugs or the equipment in which theyare manipulated include the following:

Centers for Disease Control (CDC) andNational Institutes of Health (NIH).Pri-mary Containment for Biohazards [CDC/NIH 2000]. Provides guidance on theselection, installation, testing, and useof BSCs.


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NIH. Recommendations for the SafeHandling of Cytotoxic Drugs [NIH 2002].Includes recommendations for the safepreparation and administration of cyto-toxic drugs.

ASHP. ASHP Technical Assistance Bulle-tin on Handling Cytotoxic and HazardousDrugs [ASHP 1990]. An informed dis-cussion of the dangers and safe handlingprocedures for hazardous drugs.

Oncology Nursing Society.Chemotherapyand Biotherapy Guidelines and Recom-mendations for Practice [Brown et al.

2001]. Provides complete guidelines forthe administration of antineoplastic drugs,including safe handling guidelines.

Oncology Nursing Society. Safe Handlingof Hazardous Drugs [Polovich 2003].Includes proper handling guidelines forhazardous drugs.

United States Pharmacopeia. Chapter Pharmaceutical Compounding

Sterile Preparations [USP 2004]. Detailsthe procedures and requirements forcompounding sterile preparations andsets standards applicable to all settingsin which sterile preparations are com-pounded.

National Sanitation Foundation (NSF)and American National Standards Insti-tute (ANSI).NSF/ANSI 492002 Class II(Laminar Flow) Biosafety Cabinetry [NSF/ANSI 2002]. Addresses classication andcertication of Class II BSCs and providesa denition for Class III BSCs.

PDA.Technical Report No. 34: Designand Validation of Isolator Systems forthe Manufacturing and Testing of Health

Care Products [PDA 2001]. A supple-mental publication to the PDA Journalof Pharmaceutical Science and Technol-ogy. Provides denitions, design, and op-eration and testing guidance for types of

isolators used in the health care productmanufacturing industry. American Glovebox Society (AGS).

Guidelines for Gloveboxes ; 2nd edition[AGS 1998]. Provides guidance on thedesign, testing, use, and decommission-ing of glovebox containment systems.

CASE REPORTS

The following cases illustrate the range ofhealth effects reported after exposure toantineoplastic drugs:

Case 1

A female oncology nurse was exposed to asolution of carmustine when the completetubing system fell out of an infusion bottleof carmustine, and all of the solution poureddown her right arm and leg and onto theoor [McDiarmid and Egan 1988]. Althoughshe wore gloves, her right forearm was un-protected, and the solution penetrated herclothing and stockings. Feeling no sensationon the affected skin areas, she immediatelywashed her arm and leg with soap and waterbut did not change her clothing. A few hourslater, while at work, she began to experi-ence minor abdominal distress and profusebelching followed by intermittent episodes ofnonbloody diarrhea with cramping abdomi-nal pain. Profuse vomiting occurred, afterwhich she felt better. The nurse went to theemergency room, where her vital signs andphysical examination were normal. No spe-cic therapy was prescribed. She felt betterthe following day. Carmustine is known to


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cause gastric upset, and the investigatorsattributed her gastrointestinal distress tosystemic absorption of carmustine.

Case 2

A 39-year-old pharmacist suffered two epi-sodes of painless hematuria (blood in theurine) and was found to have cancer (agrade II papillary transitional cell carcinoma)[Levin et al. 1993]. Twelve years beforeher diagnosis, she had worked full timefor 20 months in a hospital IV preparationarea where she routinely prepared cyto-toxic agents, including cyclophosphamide,uorouracil, methotrexate, doxorubicin, andcisplatin. She used a horizontal laminar-owhood that directed the airow toward her.Because she was a nonsmoker and had noother known occupational or environmentalrisk factors, her cancer was attributed toher antineoplastic drug exposure at workthough a cause and effect relationship hasnot been established in the literature.

Case 3

A 41-year-old nurse who had worked on anoncology ward for 13 years suffered fromnasal discharge, difcult breathing, and at-tacks of coughing 1 to 2 hours after begin-ning work [Walusiak et al. 2002]. During thethird year of her employment on the ward,she developed difcult breathing while awayfrom work. Her total IgE was low, and spe-cic IgE antibodies to common agents andskin prick tests to common allergens (in-cluding latex) were all negative. The patientwas subjected to a number of single-blindbronchial challenge tests with antineoplasticdrugs, and she was monitored by spirometryand peak expiratory ow measurements. Onthe basis of clinical ndings, the investiga-tors concluded that the evidence was con-sistent with a diagnosis of allergic asthma.

Case 4

A malfunctioning BSC resulted in possibleexposure of nursing personnel to a numberof antineoplastic drugs that were prepared

in the BSC [Kevekordes et al. 1998]. Bloodsamples from the nurses were analyzedfor genotoxic biomarkers 2 and 9 monthsafter replacement of the faulty BSC. At2 months, both sister chromatid exchanges(SCEs) and micronuclei were signicantlyelevated compared with those of a matchedcontrol group. At 9 months, the micronu-clei concentrations were similar to those ofthe 2-month controls. SCEs were not deter-mined at 9 months. The investigators con-cluded that the elevation in biomarkers hadresulted from the malfunctioning of the BSC,which resulted in worker exposure to the an-tineoplastic drugs. They also concluded thatthe subsequent replacement with a new BSCcontributed to the reduced effect seen withthe micronucleus test at 9 months.

Case 5

A 41-year-old patient-care assistant work-ing on an oncology oor developed anitchy rash approximately 30 minutes afteremptying a commode of urine into a toilet[Kusnetz and Condon 2003]. She deniedany direct contact with the urine, wore aprotective gown and nitrile gloves, and fol-lowed hospital policy for the disposal ofmaterials contaminated with antineoplasticdrugs. The rash subsided after 1 to 2 days.

Three weeks later, she had a similar reac-tion approximately 1 hour after performingthe same procedure for another patient.Upon investigation, it was found that bothhospital patients had recently been treatedwith vincristine and doxorubicin. The patient-care assistant had no other signs or symp-toms and reported no changes in lifestyle


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and no history of allergies or recent infec-tions. After treatment with diphenhydramine(intramuscular) and oral corticosteroids, hersymptoms disappeared. Although the causecould not be denitely conrmed, both vin-

cristine and doxorubicin have been

RECOMMENDATIONS

associ-ated with allergic reactions when given topatients. The aerosolization of the drug pres-ent in the urine may have provided enoughexposure for symptoms to develop.

CONCLUSIONS

Recent evidence summarized in this Alertdocuments that worker exposure to hazard-ous drugs is a persistent problem. Althoughmost air-sampling studies have not demon-strated signicant airborne concentrationsof these drugs, the sampling methods usedin the past have come into question [Larsonet al. 2003] and may not be a good indi-cator of contamination in the workplace. Inall studies involving examination of surface

wipe samples, researchers have determinedthat surface contamination of the workplaceis common and widespread. Also, a numberof recent studies have documented the ex-cretion of several indicator drugs in the urineof health care workers. Results from studiesindicate that worker exposure to hazardousdrugs in health care facilities may result inadverse health effects.

Appropriately designed studies have begunand are continuing to characterize the ex-tent and nature of health hazards associatedwith these ongoing exposures. NIOSH is cur-rently conducting studies to further identifypotential sources of exposure and methodsto reduce or eliminate worker exposure tothese drugs. To minimize these potentially

acute (short-term) and chronic (long-term)effects of exposure to hazardous drugs atwork, NIOSH recommends that at a mini-mum, employers and health care workersfollow the recommendations presented inthis Alert.

Summary of RecommendedProcedures

1. Assess the hazards in the workplace. Evaluate the workplace to identify and

assess hazards before anyone beginswork with hazardous drugs. As part ofthis evaluation, assess the following:

Total working environment

Equipment (i.e., ventilated cabinets,closed-systemdrug transferdevices,glovebags, needleless systems, andPPE)

Physical layout of work areas

Types of drugs being handled

Volume, frequency, and form of drugshandled (tablets, coated versus un-coated, powder versus liquid)

Equipment maintenance

Decontamination and cleaning

Waste handling Potential exposures during work, in-

cluding hazardous drugs, bloodbornepathogens, and chemicals used todeactivate hazardous drugs or cleandrug-contaminated surfaces

Routine operations


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Spill response

Waste segregation, containment, anddisposal

Regularly review the current inventory

of hazardous drugs, equipment, and practices, seeking input from affect-ed workers. Have the safety and healthstaff or an internal committee performthis review.

Conduct regular training reviews withall potentially exposed workers in work-

places where hazardous drugs are used.Seek ongoing input from workers whohandle hazardous drugs and from otherpotentially exposed workers regarding thequality and effectiveness of the preven-tion program. Use this input from workersto provide the safest possible equipmentand conditions for minimizing exposures.

This approach is the only prudent publichealth approach, since safe concentra-tions for occupational exposure to haz-ardous drugs have not been conclusivelydetermined.

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 proceduresspecic to the handling of hazardousdrugs. These policies and proceduresshould address and dene 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 providetraining for handling hazardous drugs

safely, cleaning up spills, and us-ing all equipment and PPE properly.Inform workers about the location andproper use of spill kits. Make these kitsavailable near all potential sources ofexposure. Make sure that training con-forms to the requirements of the OSHAhazard communication standard [29CFR 1910.1200] and other relevantOSHA requirements such as the PPEstandard [29 CFR 1910.132]. In addi-tion, establish procedures for cleaningand decontaminating work areas andfor proper waste handling and disposalof all contaminated materials, includingpatient waste.

Establish work practices related to both drug manipulation techniquesand to general hygiene practices

such as not permitting eating or drink-ing in areas where drugs are handled(the pharmacy or clinic).

3. Use and maintain equipmentproperly.

Develop workplace procedures forusing and maintaining all equipmentthat functions to reduce exposure

such as ventilated cabinets, closedsystem drug-transfer devices, needle-less systems, and PPE.

Detailed Recommendations

Receiving and Storage

Begin exposure control when hazardousdrugs enter the facility. The most sig-nicant exposure risk during distribution


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and transport is from spills resulting fromdamaged containers.

Prepare workers for the possibility thatspills might occur while they are han-dling containers (even when packagingis intact during routine activities), andprovide them with appropriate PPE.

Make sure that medical products havelabeling on the outsides of containersthat will be understood by all workerswho will be separating hazardous fromnonhazardous drugs.

Wear chemotherapy gloves [ASTM inpress], protective clothing, and eyeprotection when opening containersto unpack hazardous drugs. Such PPEprotects workers and helps prevent con-tamination from spreading if damagedcontainers are found.

Wear chemotherapy gloves to preventcontamination when transporting the vialor syringe to the work area.

Store hazardous drugs separately fromother drugs, as recommended by ASHP[1990] and other chemical safety stan-dards.

Store and transport hazardous drugs inclosed containers that minimize the riskof breakage.

Make sure the storage area has sufcientgeneral exhaust ventilation to dilute andremove any airborne contaminants.

Depending on the physical nature andquantity of the stored drugs, consider in-stalling a dedicated emergency exhaustfan that is large enough to quickly purgeairborne contaminants from the storageroom in the event of a spill and preventcontamination 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 whichdrugs might be released into the workenvironment. Always consider the possi-bility of contamination on the outside ofcontainers [Ros et al. 1997; Hepp andGentschew 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 involvedin drug preparation. Coordinate tasks associated with prepar-

ing and administering hazardous drugsfor most effective control of worker expo-sures.

Preparing hazardous drugs

Use a ventilated cabinet designed toreduce worker exposures while preparinghazardous drugs (see following sectionentitledVentilated Cabinets ).

Train all staff who use ventilated cabinetsto employ work practices established fortheir particular equipment. The safe useof any control depends on proper work.

Practice proper technique and use ofequipment.

Include initial and periodic assessmentsof technique in the safety program [Har-rison et al. 1996], and verify techniqueduring drug administration.

Wear protective gloves and gowns if youare involved in preparation activitiessuch as opening drug packaging, han-dling vials or nished products, labeling


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hazardous drug containers, or disposingof waste.

Wear PPE (including double gloves andprotective gowns) while reconstituting

and admixing drugs: Make sure that gloves are labeled

as chemotherapy gloves and makesure such information is available onthe box [ASTM in press] or from themanufacturer.

Consider latex-sensitive workers[NIOSH 1997] andremember that anumber of glove materials are suit-able for protecting workers from an-tineoplastic drugs [Connor 1999;Singleton and Connor 1999; Klein etal. 2003].

Consider using chemotherapy glovesfor hazardous drugs that are not che-motherapy drugs or for which no in-formation is available.

Use double gloving for all activities involving hazardous drugs. Make surethat the outer glove extends overthe cuff of the gown [Connor 1999;Brown et al. 2001].

Inspect gloves for physical defectsbefore use.

Wash hands with soap and water be-

fore donning protective gloves andimmediately after removal.

Change gloves every 30 minutes orwhen torn, punctured, or contami-nated. Discard them immediately in a

yellow chemotherapy waste container[ASHP 1990; Brown et al. 2001].

Use disposable gowns made ofpolyethylene-coated polypropylene(which is nonlinting and nonabsor -bent). These gowns offer better pro-tection than polypropylene gownsagainst many of the antineoplasticdrugs [Connor 1993; Harrison andKloos 1999]. Make sure gowns haveclosed fronts, long sleeves, and elas-tic or knit closed cuffs.

Dispose of protective gowns aftereach use.

Use disposable sleeve covers to pro-

tect the wrist area and remove thecovers after the task is complete.

When drug preparation is complete, sealthe nal product in a plastic bag or othersealable container for transport beforetaking it out of the ventilated cabinet.

Seal and wipe all waste containers insidethe ventilated cabinet before removing

them from the cabinet. Remove all outer gloves and sleeve cov-

ers and bag them for disposal while youare 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, andneedleless systems when transferringhazardous drugs from primary packaging(such as vials) to dosing equipment (suchas infusion bags, bottles, or pumps).Closed systems limit the potential for gen-erating aerosols and exposing workers tosharps. Evidence documents a decrease in


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criteria for BSCs:Primary Containmentfor Biohazards: Selection, Installationand Use of Biological Safety Cabinets ,2nd edition [CDC/NIH 2000].

Select a ventilated cabinet depending onthe need for aseptic processing. Aseptictechnique is important for protectinghazardous drugs from possible contami-nation. However, it is also important toconsider worker protection and to as-sure that worker safety and health isnot sacriced. Therefore, when asepsisis required or recommended, use ven-tilated cabinets designed forboth haz-ardous drug containment and asepticprocessing. Aseptic requirements aregenerally regulated by individual Stateboards of pharmacy [Thompson 2003;USP 2004].

When asepsis is not required, a Class IBSC or an isolator intended for contain-ment applications (a containment isola-tor) may be sufcient.

When aseptic techniqueis required, use

one of the following ventilated cabinets: Class II BSC (Type B2 is preferred,

but Types A2 and B1 are allowedunder certain conditions)

Class III BSC

Isolators intended for asepsis andcontainment (aseptic containment iso-lators) [NSF/ANSI 2002; PDA 2001]

Air ow and exhaust

Regardless of type, equip each ventilatedcabinet with a continuous monitoring de-

vice to conrm adequate air ow beforeeach use.

Use a high-efciency particulate air lter(HEPA lter) for the exhaust from these

controls, and where feasible, exhaust100% of the ltered air to the outside.

Install the outside exhaust so that theexhausted air is not pulled back into the

building by the heating, ventilating, andair conditioning (HVAC) systems or by thewindows, doors, or other points of entry.

Place fans downstream of the HEPA lterso that contaminated ducts are main-tained under negative pressure.

Do not use a ventilated cabinet that recir-culates air inside the cabinet or exhaustsair 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 bythe HEPA lter. Information about vola-tilization should be supplied by the drugmanufacturer (possibly in the MSDS) orby air-sampling data.

Seek additional information about place-ment of the cabinet, exhaust system, and

stack design from NSF/ANSI 492002[NSF/ANSI 2002]. Incorporate their rec-ommendations regardless of the type of

ventilated cabinet selected.

Maintenance

Identify a safety and health representa-tive familiar with potential drug expo-sures and their hazards. Ask that personto review in advance all maintenance ac-tivities performed on ventilated cabinetsand exhaust systems associated withhazardous drug procedures.

Develop a written safety plan for all rou-tine maintenance activities performed onequipment that could be contaminatedwith hazardous drugs.


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Properly install and maintain and rou-tinely clean any Class II BSC.

Field-certify its performance (1) afterinstallation,relocation, maintenancerepairs to internal components, andHEPA lter replacement, and (2) ev-ery 6 months thereafter [NSF/ANSI2002; OSHA 1999].

Prominently display a current eld-certication label on the ventilatedcabinet [NSF/ANSI 2002].

Treat other types of ventilated cabinetssimilarly with regard to care and fre-quency-of-performance verificationtests.

Select the appropriate performance andtest methods for isolators, depending onthe type (containment-only or asepticcontainment), the operating pressure(positive or negative and designed mag-nitude), and the toxicity of the hazardousdrug:

At a minimum, provide isolators witha leak test and a containment in-tegrity test such as those describedin Guidelines for Gloveboxes [AGS1998].

Perform a HEPA lter leak test (de-scribed in NSF/ANSI [2002]) for iso-lators that rely on HEPA ltration forcontainment.

Perform additional tests as requiredby local and/or national jurisdictionsto 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 minimizeexposure.

Remove all hazardous drugs and chemi-cals, and decontaminate the ventilatedcabinet before beginning maintenanceactivities.

Warn occupants in the affected areasimmediately before the maintenance ac-tivity begins, and place warning signs onall equipment that may be affected.

Strictly follow all applicable lockout/tagoutprocedures [29 CFR 1910.147].

Decontaminate and bag equipment partsremoved for replacement or repair beforethey are taken outside the facility.

Seal used ltration media in plastic im-mediately upon removal, and tag it fordisposal as chemotherapywaste; or dis-pose of it as otherwise directed by theenvironmental safety andhealth ofce orapplicable regulation.

Routine Cleaning, Decontaminating,Housekeeping, and Waste Disposal

Cleaning and decontaminating

Perform cleaning and decontaminationwork in areas that are sufciently 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 drugstorage or any tasks involving hazardousdrugs.

Clean work surfaces with an appropri-ate deactivation agent (if available) andcleaning agent before and after each ac-tivity and at the end of the work shift.


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Establish periodic cleaning routines forall work surfaces and equipment thatmay become contaminated, includingadministration carts and trays.

At a minimum, wear safety glasses withside shields and protective gloves forcleaning 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 orcleaning agent used.

Housekeeping

Wear two pairs of protective gloves and adisposable gown if you must handle lin-

ens, feces, or urine from patients whohave received hazardous drugs withinthe last 48 hoursor in some cases,within the last 7 days [Cass and Mus-grave 1992].

Dispose of the gown after each use orwhenever it becomes contaminated.

Wear face shields if splashing is possible.

Remove the outer gloves and the gownby turning them inside out and plac-ing them into the yellow chemotherapywaste container. Repeat the procedurefor the inner gloves.

Wash hands with soap and water afterremoving the gloves.

Waste d isposal

Be aware of the various types of wastegenerated by preparing and administer-ing hazardous drugs: partially lled vials,undispensed products, unused IVs, nee-dles and syringes, gloves, gowns, under-pads, and contaminated materials fromspill cleanups.

Place trace wastes (those that containless than 3% by weight of the originalquantity of hazardous drugs)suchas needles, empty vials and syringes,gloves, gowns, and tubingin yellowchemotherapy waste containers. As-suring that drug-contaminated waste isproperly contained will protect workersfrom respiratory exposure to volatile ormicro-aerosolized drugs [Connor et al.2000; Kiffmeyer et al. 2002; Larson etal. 2003].

Place soft trace items (those that arecontaminated with trace amounts ofhazardous drugs) in yellow chemo-therapy bags for disposal by incin-

eration at a regulated medical wastefacility.

Place empty vials and sharps suchas needles and syringes in chemo-therapy waste containers designedto protect workers from injuries anddispose of them by incineration at aregulated medical waste facility.

Do not place hazardous drug-contami-nated sharps in red sharps containersthat are used for infectious wastes,since these are often autoclaved ormicrowaved [ASHP 1990; OSHA 1999;Smith 2002].

Dispose of P-listed arsenic trioxide andits containers and any bulk amountsof U-listed drugs [40 CFR 261.33] in


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hazardous waste containers at a RCRA-permitted incinerator. Nine hazardousdrugs 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 ofany other items with more than tracecontamination) in a manner similar tothat required for RCRA-dened hazard-ous wastes as recommended by ASHP[1990] and OSHA [1999].

Spill Control

Manage hazardous drug spills accordingto the established, written policies andprocedures for each workplace.

Be aware that the size of the spill mightdetermine who is authorized to conductthe cleanup and decontamination andhow the cleanup is managed.

Assure that the written policies and pro-cedures address the protective equip-ment required for various spill sizes, thepossible spreading of material, restrictedaccess to hazardous drug spills, andsigns to be posted.

Assure that cleanup of a large spill ishandled by workers who are trained inhandling hazardous materials [29 CFR1910.120].

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 mustardare U-listed hazardous wastes. See 40 CFR 261.33.

As required by OSHA, follow a completerespiratory protection program, includingt-testing, if you wear respirators suchas those contained in some spill kits[29 CFR 1910.134]. Use NIOSH-certi-ed respirators [42 CFR 84]. Surgical

masks do not provide adequate pro-tection.

Dispose of all spill cleanup materials in ahazardous chemical waste container, inaccordance with EPA/RCRA regulationsregarding hazardous waste not in achemotherapy waste or biohazard con-tainer.

Medical Surveillance

In addition to preventing exposure to haz-ardous drugs and carefully monitoring theenvironment, make medical surveillancean important part of any safe handlingprogram 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 forroutine medical care. Be sure to informhim or her about your occupation andpossible exposures to hazardous drugs.

Refer to the OSHA Technical Manual:Controlling Occupational Exposure to

Hazardous Drugs , Section VI Chapter 2[OSHA 1999]. This document currentlyrecommends that workers handling haz-ardous drugs be monitored in a medicalsurveillance program that includes thetaking of a medical and exposure history,physical examination, and some labora-tory tests.


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Refer to the guidelines of professionalorganizations such as the ASHP [1990]and the Oncology Nursing Society [Brownet al. 2001], which recommend medi-cal surveillance as the recognized stan-dard of occupational health practice forhazardous drug handlers. The AmericanCollege of Occupational and Environ-mental Medicine (ACOEM) also recom-mends surveillance for these workers intheir Reproductive Hazard ManagementGuidelines [ACOEM 1996].

Use a workers past exposure his

ACKNOWLEDGMENTS

tory asa surrogate measure of potential expo-

sure intensity. If you are an occupational health profes-

sional who is examining a drug-exposedworker, ask questions that focus on theworkers symptoms relating to the organsystems that are known targets for thehazardous drugs.

For example, after an acute expo-sure such as a splash or other drugcontact with skin or mucous mem-branes, focus the physical examina-tion on the exposed areas and theclinical signs of rash or irritation tothose areas.

Include a complete blood count withdif ferential and a reticulocyte count inthe baseline and periodic laboratorytests. These may be helpful as anindicator of bone marrow reserve.

Monitor the urine of workers who handlehazardous drugs with a urine dipstick ora microscopic examination of the urinefor blood [Brown et al. 2001]. Sev-eral antineoplastic agents are known tocause bladder damage and blood in theurine of treated patients.

Conduct environmental sampling and/orbiological monitoring when exposure issuspected or symptoms have been noted.

ADDITIONAL INFORMATION

Additional information about exposure tohazardous drugs is available at 180035NIOSH (18003564674), fax: 15135338573, E-mail: [email protected], orWeb site:www.cdc.gov/NIOSH.

Additional information about hazardous drugsafety is available atwww.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; KennethR. 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 BarbaraJ. 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 madeby members of the NIOSH Hazardous DrugSafe Handling Working Group. A completelisting of the agencies and organizations whocontributed to this Alert is listed in AppendixC. Anne C. Hamilton, Vanessa Becks, SusanAfanuh, Jane Weber, Andre Allen, Anne Vo-taw, and Teresa Lewis provided editorial andproduction services.

1NIOSH;2State of Wisconsin;3Apria Healthcare;4Universityof Maryland;5Oncology Nursing Society;6University ofCalifornia Medical Center

mailto:[email protected]://www.cdc.gov/NIOSHhttp:///reader/full/www.osha.govmailto:[email protected]://www.cdc.gov/NIOSHhttp:///reader/full/www.osha.gov

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Support for the development of this Alertwas provided by the National Occupation-al Research Agenda (NORA) Control Tech-nology and Personal Protective Equipment

T eam and the NORA Reproductive HealthResearch 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 452261998 Telephone: 15135338462 or

180035NIOSH

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