Safe Handling of Hazardous Drugs

Hazardous drugs are drugs that pose a potential health risk to health care workers who may be exposed during preparation or administration. Such drugs require special handling because of their inherent toxicities. While most drugs are hazardous because they are cytotoxic, drugs from other categories are potentially harmful (such as the antiviral agent gancyclovir). Currently, the term "hazardous" is preferred over "chemotherapy" or "antineoplastic" because is it is more inclusive of drugs that present a risk (ASHP, 1990). Table 1 presents criteria for defining hazardous drugs.

A list of drugs that should be handled as hazardous can be found in Appendix A of the electronic document available from the Centers for Disease Prevention and Control (CDC) (NIOSH, 2004).

Historical Perspective

Nitrogen mustard, which was first used as a chemical weapon in World War I, caused bone marrow and lymph tissue regression in exposed service men. For this reason, the potent chemical was suggested as a treatment for lymphoid malignancies. This is often considered the beginning of the modern age of cancer chemotherapy (Brown et al., 2001).

Surgery and radiation therapy were the primary treatments for cancer in the 1950s. The National Chemotherapy Program, a federal program funded in 1955, supported the development of new chemotherapy agents. Due to advances in science, chemotherapy is now commonly administered for the treatment of cancer in patients with both solid tumors and hematologic malignancies. The United States Food and Drug Administration (FDA) approved 85 drugs used in the treatment of cancer between the years of 1949 and 1992, 85 drugs in the next eight years (1993-2000), and 34 drugs during the three-year period from 2001 to 2004 (FDA, 2004).

In the 1970s, several chemotherapy agents were linked to secondary leukemia and other cancers in treated patients. This information was accompanied by the notion that health risks might extend to persons occupationally exposed to the drugs (Donner, 1978; Ng, 1970). Lancet published the first convincing evidence in a letter to the editor by Falck, et al in 1979. In a small, but controlled study, mutagenic activity (as measured by the Ames test) was found in the urine of patients who received chemotherapy as well as nurses who administered chemotherapy. The Ames test measures genetic mutations in bacteria after exposure to compounds. Ninety percent of known carcinogens test positive on this test. The test is reliable during drug excretion in the urine, which is usually within 48 hours of exposure. It has neither high sensitivity nor specificity (Polovich, 2003). Several other studies followed that demonstrated risks from occupational exposure to chemotherapy.

The Occupational Safety and Health Administration (OSHA), whose mission is to protect the health and safety of workers, became interested in the occupational risk of handling chemotherapy agents in the early 1980s. During a visit to a northern California hospital, California OSHA became aware of the facility’s chemotherapy preparation practices. The subsequent investigation resulted in the facility being cited for failure to provide protection for the pharmacists (Power, 1983). The safe handling program that was implemented was described in the American Journal of Hospital Pharmacy (Stolar, Power, & Veile, 1983) and became the basis for the first American Society of Hospital Pharmacists (ASHP) Technical Assistance Bulletin on Handling Cytotoxic Drugs (ASHP, 1990).

After several years of published data suggesting harm from occupational exposure to chemotherapy drugs, OSHA published guidelines for the safe handling of those agents (1986). The guidelines described the equipment, garments, and work practices aimed at protecting pharmacists and nurses from exposure. While the guidelines are not considered as standards, enforceable by law, the guidelines are responsible for hospitals and other health care organizations’ implementation of safe handling precautions.

In the 1970s and 1980s it was common practice for nurses to perform drug preparation activities in medication rooms on nursing units (Stolar, 1988). The main route of exposure to hazardous drugs (Table 2) was thought to be inhalation of drug aerosols generated during preparation. To reduce this risk, OSHA guidelines state that cytotoxic drug preparation must be performed in a biological safety cabinet (BSC) in a designated area, usually a pharmacy. A BSC has vertical airflow that moves away from the worker, as opposed to horizontal airflow that moves away from the product toward the worker. Vertical airflow protects the worker, while horizontal airflow is designed to protect the sterile product from contamination. Air leaving a BSC is filtered through a HEPA (high efficiency particulate air) filter.

Nurses who administer chemotherapy can be exposed to aerosols or droplets of drugs generated during administration. Body fluids of patients receiving hazardous drugs are a potential source of exposure. Gloves and gowns are recommended to protect nurses against splash contamination during drug administration and handling patient wastes.

Data indicated that health care workers who used safe handling precautions were not exposed (Anderson et al., 1982). Organizations acquired BSCs, gowns, gloves, and goggles, and implemented the recommendations in pharmacies and nursing units. Health care workers felt assured that following the guidelines would protect them from the hazards of exposure.

Environmental Contamination With Hazardous Drugs

Following the implementation of the OSHA guidelines, there was a decrease in the number of publications related to occupational exposure to hazardous drugs. This seemed to be a reflection of the decreased concern. In 1992, Sessink and others published new data related to hazardous drug exposure. This was the first of 14 studies (NIOSH, 2004) that found hazardous drug residue on work surfaces in pharmacies and drug administration areas. The first U.S. study of its type was published in 1993 (McDevitt, Lees, & McDiarmid). This study looked for cyclophosphamide in surface wipe samples in an oncology pharmacy and an outpatient oncology clinic of a university hospital. A total of 76 wipe samples were collected from the inside of the biological safety cabinet, floor, and countertop in the pharmacy, and from countertops, sink, and a video display terminal in the clinic. Eighteen percent of samples from the pharmacy and 14% of samples from the clinic had detectable amounts of cyclophosphamide. A larger U.S. study, conducted at six cancer centers in the United States and Canada, reported hazardous drug contamination in 75% of pharmacy samples and 65% of samples from drug administration areas (Connor, Anderson, Sessink, Broadfield, & Power, 1999). Results suggest that current work practices do not prevent the release of hazardous drugs, resulting in drug residue on surfaces. Drug residue on surfaces can result in exposure for health care workers through the dermal route.

While drug exposure does not always result in absorption, internal dose (which reflects drug uptake, metabolism, and excretion) can be measured (Labuhn, Valanis, Schoeny, Loveday, & Vollmer, 1998). Due to advances in science, highly sensitive tests that were not available in the 1980s are now able to measure the presence of hazardous drugs in the urine of health care workers. One review reported that cyclophosphamide was present in the urine of health care workers in 11 of 12 studies, despite the use of precautions (Sessink & Bos, 1999).

Potential For Exposure

The surface contamination studies demonstrated that engineering controls and work practices do not prevent the release of hazardous drugs. Drug handling activities such as reconstitution, transfer between containers, spiking and unspiking IV containers, priming IV tubing, and connecting or disconnecting syringes from injection ports may result in leakage and surface contamination.

The OSHA guidelines suggest that drugs may leak during the manipulations required to reconstitute powders and the transfer of drug from one container to another. Since contamination has been found on the outside of biological safety cabinets and on floors around them, it is clear that such engineering controls do not always contain the hazard. Incorrect operator technique can interfere with airflow and allow the escape of drug aerosols. Accidental drug spills obviously contribute to surface contamination. A drug spilled inside a BSC can be transferred to the outside of drug containers.

One study measured floor contamination with fluorouracil and ifosfamide after the renovation and cleaning of a pharmacy. Surprisingly, there was persistent contamination after two months of construction when the pharmacy area was not operational (Connor, Anderson, Sessink, & Spivey, 2002). In another setting, a clean, but used BSC was installed in a newly constructed drug preparation room. The authors reported contamination of the cabinet itself and its direct surroundings after its installation (Vandenbroucke & Robays, 2001). Both reports raise the question of the efficacy of current methods for cleaning and decontamination of areas where hazardous drugs are prepared.

IV equipment has been designed with patient safety in mind, and not health care worker protection. In drug administration areas, spiking IV containers with IV tubing, and unspiking to remove tubing results in leakage (Vandenbroucke & Robays, 2001). One study demonstrated leakage from needle-less connectors on IV equipment (Kromhout, et al., 2000). Another study used a fluorescent scanning device to detect doxorubicin (Adriamycin®) contamination spots on health care workers’ gloves, clothing, and hands after glove removal (Labuhn et al., 1998). The spots were not visible without the scanning devices, and the workers were not aware of the contamination. These studies indicate that leakage from conventional IV equipment is a potential source of exposure for nurses.

One closed-system device is available in the United States. PhaSeal® consists of several components with a double-membrane system that traps drug aerosols, prevents leakage when withdrawing drug from a vial, allows leak-free drug transfers, and provides for a "dry-spike" of an IV bag (PhaSeal, 2004). Several studies have demonstrated the effectiveness of the closed-system device in reducing surface contamination. (Connor et al., 2002); Vandenbroucke & Robays, 2001; Wick, Slawson, Jorgenson & Tyler, 2003). The system is not in common use, however, largely due to cost.

As a result of all of these findings, there is new attention focused on the risks of health care workers who handle hazardous drugs. The data suggest that:

• Biological safety cabinets (BSCs) provide imperfect protection against hazardous drug exposure. Other types of ventilated cabinets may provide containment, but are not currently available in pharmacies (NIOSH, 2004.)
• Routine handling activities can result in contamination of the worker and work environment.
• There is frequent and persistent contamination of the environment where hazardous drugs are handled.
• Dermal absorption of hazardous drugs as a result of contact with contaminated surfaces is another potential route of exposure.
• Failure to use personal protective equipment can result in inadvertent contamination of clothing.
• Workers who are not directly involved in activities related to hazardous drug handling are at risk for exposure.
• Drug exposure can result in drug absorption that can be measured.

Magnitude of Exposure to Occupational Hazardous Drugs

While most hazardous drugs are used in the treatment of persons with cancer, they are also used for non-oncology indications, such as rheumatoid arthritis, lupus, nephritis, and multiple sclerosis. For example, methotrexate is used as a medical treatment for tubal ectopic pregnancy. The increasing use of such drugs outside the oncology arena increases the number of health care workers who may be potentially exposed.

It is estimated that as many as 5.5 million health care workers have the opportunity for exposure to hazardous drugs in the workplace (U. S. Department of Commerce, 1999). Most patients are in a health care setting such as a hospital, clinic, or physician’s office when receiving hazardous drugs, but some patients are treated in the home. By far, health care workers at greatest risk for exposure are pharmacists who prepare hazardous drugs, and nurses who may both mix and administer the drugs. However, all other individuals involved in both direct and indirect care of persons who receive such drugs should be considered potentially exposed.

Risks of Exposure

The potential adverse health risks from occupational exposure to hazardous drugs are based on the inherent toxicities of the drugs. The same health effects that occur in patients who receive therapeutic doses of the drugs are possible if employees are exposed. Hazardous drugs are genotoxic, carcinogenic, teratogenic or cause developmental toxicity. Many result in adverse reproductive outcomes and cause organ toxicity at low doses.

Health care workers who have been exposed to hazardous drugs have reported acute symptoms such as skin irritation, sore throat, cough, dizziness, headache, allergic reaction, diarrhea, nausea, and vomiting (Harrison, 2001). Liver damage was reported in three consecutive head nurses on a particular oncology unit who worked with chemotherapy for several years (Sotaniemi, Sutinen, Arranto, Sutinen, Sotaniemi, 1983).

Harrison (2001) reviewed fourteen studies that looked at adverse reproductive outcomes of health care workers exposed to hazardous drugs. Nine of the studies showed adverse outcomes related to exposure. The outcomes included fetal loss, congenital malformations, and infertility.

Selevan, Lindbohm, Hornung, and Hemminki (1985) reported an odds ratio of 2.3 for fetal loss among nurses exposed during the first trimester of pregnancy. An odds ratio of 1.7 for spontaneous abortion was found in another study of nurses exposed to antineoplastic drugs (Stucker et al., 1990). Hemminki reported an odds ratio of 4.7 for fetal malformations in nurses who were exposed to hazardous drugs greater than once per week in the first trimester of pregnancy (Hemminki, Kyyronen, & Lindbohm, 1985).

In a matched case-control study of nurses and pharmacists, a small but significant relationship was found between women who handled antineoplastic agents and infertility. A similar odds ratio was found for men, but was not statistically significant because of the small number of men in the study (Valanis, Volmer, Labuhn & Glass, 1997).

Based on urinary excretion of cyclophosphamide in pharmacists and nurses, Bos and Sessink (1997) calculated the systemic uptake of the drug. Based on the level of exposure of 3.6-18 m g per day, they proposed an increase in the risk of cancer of 1.4 to 10 additional cases per million workers per year. An exposure of 16-80 m g per day, which has been calculated based on urinary excretion of cyclophosphamide in exposed nurses, may represent an increase in cancer risk estimated at 7-50 excess cases per million (Connor et al., 1999).

Practice Challenges

From the mid-1980s until the information about surface contamination became available, there was little interest or concern among health care workers. Information about health effects from low levels of occupational exposure is sparse in recent literature. The fact that many reports of adverse effects were published before the implementation of safe handling precautions, has contributed to the lack of concern among nurses regarding hazardous drug handling.

Table 3 describes the personal protective equipment essential for hazardous drug handling. Many researchers have reported poor compliance of health care worker’s with these PPE recommendations. (Mahon et al., 1994; Nieweg et al., 1994; Rogers & Emmett, 1987). A recent study by Martin and Larsen (2003) reported the chemotherapy-handling practices of nurses working in outpatient settings. While the study demonstrated that 94% of participants incorporated glove use into their practice, only about half used chemotherapy-designated gloves. Gown use has increased in frequency when compared to data from the 1970s, but many nurses reported wearing cloth laboratory coats, which do not provide protection against chemical penetration.

Information about safe handling of hazardous drugs is not always available in drug resource books commonly used by nurses. While there is a thorough discussion of the topic in oncology-related publications, the typical drug "handbook" focuses on patient safety and does not even recommend that nurses wear gloves. Such precautions are listed in Micromedex®, but only when one accesses that information.

Pharmaceutical package inserts are a common source of information to nurses, and are readily available online or in the Physicians Desk Reference (PDR). Currently there is a standard clause in the package insert of cytotoxic drugs that states:

"Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate." [Emphasis added by author] (Cell Therapeutics, 2000).

Clearly, there is evidence to the contrary. The NIOSH Hazardous Drug Safe Handling Working Group proposed more than three years ago that appropriate language be substituted, but the FDA has not adopted the recommendation. The group was informed that the process of replacing the language in every applicable package insert would be monumental.

Components of a Safe Handling Program

The development of a safe handling program requires multidisciplinary planning in the hospital setting with input from administration, medicine, nursing, pharmacy, risk management, safety, and environmental services staff. Such interdisciplinary groups should review national guidelines regularly and develop policies and procedures based on the guidelines. In health care organizations such as physician offices or clinics, limited resources may affect the scope of the program.

The National Institute for Occupational Safety and Health (NIOSH, 2004) recently released an Alert Preventing Occupational Exposures To Antineoplastic And Other Hazardous Drugs In Healthcare Settings, which is the most recent set of recommendations for safe handling. (In addition to the pdf of this document, the text is available at www.cdc.gov/niosh/docs/2004-165/). The purpose of the Alert is to inform health care workers of the continuing risk of exposure and to outline the responsibility of employers and health care workers related to safe handling. The employer responsibilities include:

• Developing policies and procedures for the safe storage, transport, administration, and disposal of hazardous agents.
• Identifying those hazardous drugs used in the facility and determining methods for updating the list.
• Making guidance documents such as Material Safety Data Sheets (MSDS) available to health care workers who handle hazardous drugs.
• Requiring that all employees who handle hazardous drugs wear personal protective equipment (PPE) designated for the purpose (Table 3).
• Requiring a BSC for the preparation of hazardous drugs.
• Prohibiting eating, drinking, etc. in areas where hazardous drugs are handled.
• Providing mandatory training for all employees based on their hazardous drug handling tasks.
• Developing a hazardous-drug spill management policy and procedure.
• Setting forth a plan for medical surveillance of personnel handling hazardous drugs.
• Addressing in a policy workers’ hazardous drug handling during pregnancy. The Oncology Nursing Society recommends that employers provide alternate duty to employees who request other assignments due to pregnancy, the desire to conceive, or breast-feeding (Brown et al., 2001).
• Monitoring compliance with safe-handling policies and procedures.

The health care worker responsibilities include:

• Participating in training before handling hazardous drugs and updating knowledge based on new information.
• Referring to guidance documents as necessary for information regarding hazardous drugs.
• Utilizing BSCs in drug preparation.
• Consistently using recommended gloves, gowns, and face and respiratory protection.
• Washing hands after drug handling activities and removal of PPE.
• Disposing of materials contaminated with hazardous drugs separately from other waste in designated containers.
• Cleaning up hazardous drug spills immediately according to recommended procedures.
• Following institutional procedures for reporting and following up on accidental exposure to hazardous drugs.

Implications for Nursing and Health Care Organizations

There are several implications for nursing and health care organizations related to implementing a safe handling program for hazardous drugs. A discussion of regulatory requirements, organizational challenges, and personnel compliance with recommendations follows.

The OSHA guidelines for safe handling of cytotoxic agents are not standards. This has led some individuals to consider the guidelines as "optional." They can be enforced under the general duty clause, in the Code of Federal Regulations (CFR) which requires that employers provide a safe or healthful employment and places of employment (CFR, 2003a), should OSHA be called in investigate a complaint.

Other applicable standards include the Hazard Communication Standard (CFR, 2003b) that requires employees to be informed of the risks of all hazardous materials in their workplace. Access to Employee Exposure and Medical Records (CFR, 2003c) assures that employees who work with toxic substances have the right to examine and copy workplace monitoring records as well as their employee medical records.

The regulations related to appropriate disposal of hazardous drug waste are complicated. The Resource Conservation and Recovery Act (RCRA) gives the Environmental Protection Agency (EPA) the responsibility of regulating hazardous wastes (RCRA, 1976). A hazardous drug, however, does not necessarily become hazardous waste. For regulatory purposes, certain materials are defined as hazardous waste when they are discarded, if they possess certain characteristics (acute toxicity, reactivity, ignitability, or corrosivity), or if they are listed as a particular type of waste. (EPA, 2003). For example, the hazardous drugs chlorambucil and melphalan have strict disposal requirements. They appear on the "U-List" of commercial chemicals, named for their hazardous waste identification numbers that begin with the letter "U." While only eight cytotoxic drugs appear on the EPA list, it has not been updated in thirty years.

Many drugs with similar toxicities should be disposed of in the same manner, but this is not a legal requirement in every state. Cost of disposal is a concern, since licensed waste handlers must dispose of regulated waste. The NIOSH Alert contains a further discussion of hazardous waste handling (NIOSH, 2004, p. 17-18.)

A comprehensive safe handling program should include a policy for reporting and following up on employees’ accidental exposure to hazardous drugs (Table 4). The procedures should:

• Outline the chain of command and time requirements for reporting accidental exposure.
• Indicate the type of incident report required and the specific information that should be included in the report.
• Describe circumstances when the employee should report to the Emergency Department and/or Employee Health professional.
• Determine diagnostic testing required to assess the potential health effects from the accidental exposure and provide them at no cost to the employee. Illness or injury that occurs from accidental hazardous drug exposure should be covered under Workers Compensation.
• Provide for confidentiality of the employee’s medical records.

The health and safety of workers who handle hazardous drugs should be a high priority. There are challenges to implementing a comprehensive program for the protection of workers. Some barriers are related to administrative issues, such as cost or staffing, while others are related to personnel’s knowledge, attitudes, and compliance. A brief discussion of some of the barriers follows.

• Cost of implementing precautions. Chemotherapy gowns and gloves cost more than those used for other purposes. A closed system for drug preparation and administration is available, but contributes to the cost of every dose. BSCs should be externally vented (NIOSH, 2004); however, many organizations would have to incur significant expense to comply with this recommendation. While the issue of cost cannot be ignored, it must be weighed against the potential cost of a single negative health effect in a nurse or pharmacist.
• Lack of sufficiently prepared staff. Inexperienced staff may be responsible for handling hazardous drugs in units or areas that do not normally care for patient populations who are treated with them. Specific training requirements are necessary to adequately prepare staff to take on these responsibilities, based on their role (ASHP, 1990; Brown et al., 2001, Polovich, 2003).
• Staffing difficulties when employees request alternative duty. Staff may elect to refrain from handling hazardous drugs when actively trying to conceive, being pregnant, or breast feeding (Brown et al., 2001). Supervisors and managers are faced with providing appropriate staffing while also complying with staff requests. When chemotherapy administration is an exclusive service, such as in oncology infusion areas, providing fully cross-trained staff can be problematic.
• Discomfort associated with wearing chemical protective gowns. Two studies noted that gowns providing the best protection are hot and uncomfortable because of lack of air flow through coated materials (Harrison & Kloos, 1999; Laidlaw, Connor, Theiss, Anderson, & Matney, 1985). This discomfort can lead to decreased compliance.
• Concern for patients’ reactions to protective garments. Some authors have suggested that patients may be frightened or anxious when nurses dress in protective garb while administering hazardous drugs (Rogers & Emmett, 1987; Society of Hospital Pharmacists of Australia, 1981).
• Lack of concern for potential health effects associated with occupational exposure. Some nurses may not believe that they are at risk for problems related to hazardous drug exposure because they have not experienced any themselves or know others who have experienced problems. The ability to connect occupational history and health history is limited in our mobile society, because nurses rarely begin and end their career in the same organization.
• Non-adherence to recommended precautions. There is no research addressing why nurses fail to comply with current recommendations for handling hazardous drugs. Future research might determine whether non-adherence is related to lack of knowledge about the risks, lack of knowledge about recommended precautions, or lack of perceived effectiveness of the precautions.

Overcoming the barriers to implementing a comprehensive safe handling program requires the support of administration, pharmacy, and nursing. Administrators must demonstrate commitment to providing a safe environment. Following education and training, clinical staff must role model consistent use of safe handling precautions and monitor compliance to precautions.

Summary

Hazardous drug handling is potentially risky work. Many nurses have the potential to be exposed to hazardous drugs in the workplace. OSHA, ASHP, ONS, and NIOSH all provide guidelines for the safe handling of hazardous drugs. While not providing complete protection, it is believed that adherence to current recommendations will reduce health care workers’ exposure. By reducing exposure, the negative health effects should be reduced. It is time for nurses to take their own occupational safety as seriously as the safety of the patients under their care.

Hyperlink Section

Agency for Healthcare Research and Quality. (2004). National guideline clearinghouse, safe handling of hazardous drugs. Retrieved August 2, 2004 from: www.guideline.gov/summary/summary.aspx?view_id=1&doc_id=4152.

American Society of Hospital Pharmacists. (1990). ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. American Journal of Hospital Pharmacy, 47, 1033-49. Retrieved August 2, 2004 from:
www.ashp.org/bestpractices/.

Centers for Disease Prevention and Control. (2000). Primary containment for biohazards: selection, installation and use of biological safety cabinets. [Figures]. Retrieved August 2, 2004 from: www.cdc.gov/od/ohs/biosfty/bsc/bsc.htm.

Environmental Protection Agency. (2003). Introduction to hazardous waste identification. Solid Waste and Emergency Response. Retrieved July 17, 2004 from: www.epa.gov/epaoswer/hotline/training/hwid.pdf.

International Agency for Research on Cancer. (2004). Overall evaluations of carcinogenicity to humans. Lyon, France: Author. Retrieved August 2, 2004 from: www.iarc.fr/.

Murhammer, J., Ross, M., & Bebout, K. (2004). Material safety data sheets. University of Iowa Healthcare, Virtual Hospital. Retrieved August 2, 2004 from: www.vh.org/adult/provider/pharmacyservices/RXUpdate/2004/01rxu.html.

PhaSeal. (2004). Product information. Retrieved May 4, 2004 from: www.phaseal.com/siteUS/movies.asp?main=filmsmain&right=filmsright.

Oncology Nursing Society. (2004). Safe handling of hazardous drugs online course. Retrieved August 2, 2004 from: http://onsopcontent.ons.org/Meetings/safehandling/home.html.

Author

Martha (Marty) Polovich, MN, RN, AOCN
Email: marty.polovich@southernregional.org

Martha Polovich is an Oncology Clinical Nurse Specialist at Southern Regional Health System in the South suburban Atlanta area. She has been caring for persons with cancer and administering chemotherapy since 1980. Ms. Polovich has been a trainer and instructor trainer for the Oncology Nursing Society’s Cancer Chemotherapy Course since 1998. She is co-editor of the ONS publication Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (2001) and editor of Safe Handling of Hazardous Drugs (2003).

Ms. Polovich represents the Oncology Nursing Society on the National Institute for Occupational Safety and Health (NIOSH) Hazardous Drug Safe Handling Working Group. She participated in the preparation of the NIOSH Alert "Reducing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings" which was published online in March 2004 and is available at: www.cdc.gov/niosh/docs/2004-HazDrugAlert/pdfs/2004-HazDrugAlert.pdf.