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NORA Symposium 2008: Public Market for Ideas and Partnerships

Poster #024

Hazardous Drug Exposures to Health Care Workers

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Abstract

Healthcare workers may be exposed to antineoplastic drugs during compounding and patient administration. Several adverse health effects are associated with exposure to these drugs. Surfaces where antineoplastic drugs are handled are known to be contaminated with antineoplastic drugs. Some drugs have been shown to be present in the urine of pharmacists and nurses and several biomarkers of genotoxicity have shown significant elevations in exposed workers. The present study characterized workplace contamination and worker exposure by employing several approaches, including: documenting handling of antineoplastic drugs by pharmacy and nursing personnel using a detailed work diary; measuring surface contamination and area and breathing zone concentrations in air samples; measuring the levels of specific drugs in the urine of the workers; and evaluating two biomarkers of genotoxicity. Modifiers of exposure, such as use of engineering and administrative controls and personal protective equipment, number of reported contacts (handling events) with the drugs, and training of workers were evaluated in order to further characterize exposure scenarios. Initial results indicate general contamination of the nursing areas with the drugs was typically higher than that in the pharmacy areas.

Background

Drugs have a successful history in treating illnesses and injuries, and they are responsible for many medical advances over the past century. However, virtually all drugs have side effects associated with their use by patients. Thus, both patients and workers who handle them are at risk of suffering these effects. In addition, it is known that exposures to even very small concentrations of certain drugs may be hazardous for workers who handle them or work near them. Although the potential therapeutic benefits of antineoplastic drugs outweigh the risks of side effects for ill patients, exposed healthcare workers risk these same side effects with no therapeutic benefit. Occupational exposures to hazardous drugs can lead to: (1) acute effects such as skin rashes (2) chronic effects, including adverse reproductive events and (3) possibly cancer. Workers may be exposed to an antineoplastic drug throughout its life cycle-from manufacture to transport and distribution, to use in healthcare or home care settings, to waste disposal. The number of workers who may be exposed to hazardous drugs exceeds 8 million. These workers include shipping and receiving personnel, pharmacists and pharmacy technicians, nursing personnel, physicians, operating room personnel, environmental services personnel, and workers in veterinary practices where hazardous drugs are used. Several studies over the past 20 years have demonstrated that workplaces are contaminated with antineoplastic drugs and that the drugs are present in the urine of workers. Most of these studies have taken place outside the U.S. and are usually limited to only one or two endpoints, such as environmental contamination, urinary levels of the drugs, genotoxic damage or other endpoints. A comprehensive evaluation of these parameters along with work history, exposure history and other modifying factors has rarely been carried out.

Approach

In order to assess exposure of healthcare workers to antineoplastic drugs, NIOSH employed a comprehensive approach in this study. The study design was a cohort study stratified by exposure with approximately equal numbers of workers (nurses, nursing aides, pharmacists and pharmacy technicians) who were exposed to antineoplastic drugs and nursing and pharmacy personnel who were not exposed to these drugs (non-oncology nursing personnel, administrators, poison control pharmacists and others). Several parameters were included to determine overall exposure scenarios. These included: measuring several commonly used drugs in surface wipe samples; measuring drugs in breathing zone and area air samples; measuring drugs in the urine of healthcare workers; determining frequencies in two markers of genotoxicity (micronucleus and comet assays); collecting extensive work history data; and documenting worker exposure history for the six weeks prior to collecting environmental and biological samples. In addition, modifiers of exposure were also determined for the workers. These included: diet and medication history, radiation and environmental tobacco smoke exposure, exercise, work practices, training, and use of PPE. The study was conducted at three facilities where cancer patients are routinely treated with a variety of antineoplastic drugs. For the exposed group, blood and urine samples were collected at the end of the 6 weeks of recorded drug exposures. The total number of handling events involving antineoplastic drugs was determined for each individual in the exposed group.

Results

Results from the six-week drug handling diary indicate that the pharmacy personnel had more handling events than nursing personnel and that Site 3 handled more antineoplastic drugs than the other two sites (Table 1). The drugs with the most handling events (in descending order) were paclitaxel, doxorubicin, 5-fluorouracil and cyclophosphamide. The activities recorded include: mode of administration, drug preparation or verification, I.V. line priming, personal protective equipment use and others.

Number of handling events by study site
	Site 1		Site 2		Site 3
Drug	Pharmacy	Nursing	Pharmacy	Nursing	Pharmacy	Nursing	Total
Cyclophosphamide	78	26	120	21	339	52	636
Ifosfamide	9	3	51	3	77	37	180
5-Fluorouracil	33	21	71	0	479	68	672
Paclitaxel	199	114	246	1	841	79	1480
Doxorubicin	119	61	135	14	394	69	792
Cytarabine	62	38	93	41	58	12	304
All others	658	496	1450	94	2384	653	5735
Total	1158	759	2166	174	4572	970	9799

For the three study sites, 158 wipe samples were collected from a number of surfaces, including: biological safety cabinets, floors, counter tops, carts, trays and storage areas in pharmacy areas; furniture, equipment and floors in patient rooms; counters, floors, carts and storage areas in nursing areas. The wipe samples were analyzed for 6 antineoplastic drugs (Table 2). Sample analysis was performed using LC/MS/MS and limits of detection (LOD) for the wipe samples ranged from 0.07 to 0.22 ng/cm².

Proportion of wipe samples >LOD by study site
	Site 1		Site 2		Site 3
	Pharmacy	Nursing	Pharmacy	Nursing	Pharmacy	Nursing	Percent
Cyclophosphamide	13/28	2/22	21/23	1/13	12/33	9/26	40.0
Ifosfamide	5/28	0/22	10/23	1/13	10/33	8/26	23.5
5-Fluorouracil	7/28	1/22	4/23	0/13	12/33	13/26	25.5
Paclitaxel	0/28	0/22	9/23	0/13	12/33	3/26	16.6
Doxorubicin	0/28	0/22	0/23	0/13	0/33	1/26	0.7
Cytarabine	2/28	0/22	3/23	0/13	0/33	0/26	2.1

Biological samples were collected at the end of the 6-week diary period from 68 pharmacists and nurses who handled antineoplastic drugs and 53 non-exposed individuals who served as controls. All urine voids were collected from the study subjects for the four hours before the end of the work shift and for the four hours after the end of the work shift. The samples were pooled for each four hour period, resulting in two pooled samples for each participant. In addition to the pooled samples, individual samples are being analyzed for 15% of the participants. Blood samples were collected and slides prepared for the micronucleus and comet assays.

Conclusions

The presence of several of the drugs was observed in wipe samples collected in a number of locations at all three sites. Pharmacy areas were typically more contaminated than patient treatment areas. Results from the urine analysis, micronucleus and comet assays will be compared to area contamination, drug handling histories, work logs, and other variables.

Future Directions

Information resulting from this study will be used to provide future recommendations for the safe handling of antineoplastic and other hazardous drugs in healthcare settings.

References

1. Connor TH Anderson RW, Sessink PJM et al. Surface contamination with antineoplastic agents in six cancer treatment centers in the United Sates and Canada. Am J Health-Syst Pharm. 1999; 56:1427-1432.
2. Connor TH, Sessink PJM, Harrison BR et al. Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: Results of three studies. Am J Health-Syst Pharm. 2005: 62:475-48.
3. Connor TH and McDiarmid MA. Preventing occupational exposures to antineoplastic drugs in health care settings. CA: A Cancer J for Clinicians. 2006; 56:354-365.
4. Fransman W, Vermeulen R, Kromhout H. Dermal exposure to cyclophosphamide in hospitals during preparation, nursing and cleaning activities. Int Arch Occup Health. 2005; 78:403-412.
5. McDevitt JJ, Lees PSJ, McDiarmid MA. Exposure of hospital pharmacists and nurses to antineoplastic agents. J Occup Med. 1993; 35:57-60.
6. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings DHHS (NIOSH) Pub No. 2004-165, September 2004.
7. Sessink PJM, Van der Kerkhof MCA, Anzion RBM et al. Environmental contamination and assessment of exposure to antineoplastic agents by determination of cyclophosphamide in urine of exposed pharmacy technicians: is skin absorption an important exposure route? Arch Environ Health. 1994; 49(3):165-169.
8. Spivey S, Connor TH. Determining sources of workplace contamination with antineoplastic drugs and comparing conventional IV drug preparation with a closed system. Hosp Pharm. 2003; 38:135-139.
9. Turci R, Sottani C, Spagnoli G et al. Biological and environmental monitoring of hospital personnel exposed to antineoplastic agents: a review of analytical methods. J Chromatog B. 2003; 789:169-209.

Disclaimer

The findings and conclusions in this poster are those of the author(s) and do not necessarily represent the views of the National Institute for Occupational Safety and Health. Citations to Web sites external to NIOSH do not constitute NIOSH endorsement of the sponsoring organizations or their programs or products. Furthermore, NIOSH is not responsible for the content of these Web sites.