Journal of Oncology Pharmacy Practice http://opp.sagepub.

com/

Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: A pilot study
Chun-Yip Hon, Prescillia PS Chua, Quinn Danyluk and George Astrakianakis J Oncol Pharm Pract published online 8 August 2013 DOI: 10.1177/1078155213497070 The online version of this article can be found at: http://opp.sagepub.com/content/early/2013/08/08/1078155213497070

Published by:
http://www.sagepublications.com

Additional services and information for Journal of Oncology Pharmacy Practice can be found at: Email Alerts: http://opp.sagepub.com/cgi/alerts Subscriptions: http://opp.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav

>> OnlineFirst Version of Record - Aug 8, 2013 What is This?

Downloaded from opp.sagepub.com at Universiti Teknologi MARA (UiTM) on September 8, 2013

Original Article

Oncology Pharmacy Practice

J Oncol Pharm Practice 0(0) 17 ! The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1078155213497070 opp.sagepub.com

Journal of

Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: A pilot study
Chun-Yip Hon
School of Population and Public Health, University of British Columbia, Vancouver, Canada; School of Occupational and Public Health, Ryerson University, Toronto, Canada

Prescillia PS Chua
Workplace Health, Fraser Health, Burnaby, Canada; Prevention Division, WorkSafeBC, Canada

Quinn Danyluk
Workplace Health, Fraser Health, Burnaby, Canada

George Astrakianakis
School of Population and Public Health, University of British Columbia, Vancouver, Canada

Abstract Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide , Phenokil IITM, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatographytandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

Keywords Antineoplastic drugs, surface contamination, cleaning, healthcare, pilot study

Introduction
Occupational exposure of healthcare workers to antineoplastic drugs has been known since the 1970s.1 Documented health eects associated with exposure to these hazardous drugs include genetic changes, adverse reproductive eects and cancer.1 In order to minimize healthcare workers exposure, various agencies have

developed best-practice safe-handling guidelines. However, despite the implementation of these

Corresponding author: Chun-Yip Hon, School of Occupational and Public Health, Ryerson University, 350 Victoria Street, POD 247C, Toronto, Ontario M5B 2K3, Canada. Email: cyhon@ryerson.ca

Downloaded from opp.sagepub.com at Universiti Teknologi MARA (UiTM) on September 8, 2013

2 guidelines, quantiable amounts of antineoplastic drug contamination have been reported on various surfaces within hospital pharmacies.27 Residual drug on surfaces presents an opportunity for dermal contact which is believed to be the most likely route of exposure for healthcare workers.8,9 Cleaning of contaminated surfaces is one method to minimize antineoplastic drug exposure to healthcare workers, but specic cleaning recommendations are lacking. Since the publication of the Canadian Society of Hospital Pharmacists document entitled Hazardous Pharmaceuticals (including Cytotoxic Drugs): Guidelines for Handling and Disposal in 1997, new evidence regarding antineoplastic drug hazards and subsequent best practices have been published. Therefore, the current pertinence of this guideline, which is still referenced among oncology pharmacies in Canada, is questionable.10 The guidelines developed by the American Society of Health-System Pharmacists do not provide a detailed cleaning protocol; rather they state that decontamination of biological safety cabinets and isolators should be conducted per manufacturer recommendations.11 The 2004 best-practice document for the safe handling of hazardous drugs produced by the National Institute of Occupational Safety and Health (NIOSH) makes a general statement that drug-contaminated work surfaces are to be cleaned with an appropriate deactivation agent.1 More locally, neither the occupational health and safety regulations for British Columbia (BC) nor those for Ontario specify any cleaning procedures for antineoplastic drugs.12,13 Surprisingly, cleaning protocols are not even addressed in a best-practice safe drughandling document recently released by Cancer Care Ontario.14 The BC Cancer Agency, which provides a province-wide cancer treatment programme for BC residents, recommends that routine cleaning consist of applying water and a small amount of antiseptic, chlorhexidine, followed by 70% isopropyl alcohol (IPA) application for sterilization purposes.15 There is concern that the act of cleaning may actually spread the antineoplastic drugs rather than eliminating them resulting in a false sense of security for workers. An investigation conducted in a pharmaceutical plant found much higher amounts of antineoplastic drug detected following routine surface cleaning.16 In a study examining spills of antineoplastic waste, the authors found that the antineoplastic drug concentrations were dispersed to a much larger area than the original spill size.17 Members of our research team also found instances of higher contamination levels post-clean vs. pre-clean.18 Given the lack of consistent direction regarding cleaning protocols as well as uncertainty about eectiveness, local healthcare facilities in BC have adopted

Journal of Oncology Pharmacy Practice 0(0) their own specic procedures for decontaminating surfaces that may have antineoplastic drug residual. These cleaning procedures are quite varied from one another (based on personal communication with various pharmacy personnel at participating facilities). We undertook a pilot study to investigate several factors associated with cleaning protocols that may inuence the removal of antineoplastic drug residual from stainless steel test surfaces, the usual construction material of biological safety cabinets. The goal of the study was to identify the most eective combination of cleaning factors to minimize drug contamination on surfaces utilized for drug preparation.

Methodology
This study was conducted in a controlled laboratory environment at the School of Environmental Health within the University of British Columbia in Vancouver, Canada. Swatches of 16-gauge stainless steel (10 cm by 10 cm) were used as test surfaces, which matched the quality of steel used to manufacture the working surfaces of biological safety cabinets. The swatches were cleaned between trials by ultra-sonication for 30 min to eliminate cross-contamination. Known amounts of two commonly administered antineoplastic drugs in BC, methotrexate (MTX) and cyclophosphamide (CP), were placed on the swatches in order to evaluate the various cleaning parameters.

Cleaning variables examined

For each antineoplastic drug employed in the study, three cleaning variables were examined: (1) type of cleaning agent, (2) application method of cleaning agent and (3) use of IPA after cleaning agent application. The pilot study was organized into a series of trials based on each of the three variables of interest. Specic details of each variable are detailed below. Type of cleaning agent. Cleaning agents were selected based on their reported usage at local health authorities at the time of the study (BC Cancer Agency, Vancouver Coastal Health and Fraser Health). Four cleaning agents were investigated: CaviCide (a quaternary ammonium chloride-based cleaner) (Metrex, Orange, CA), Phenokil IITM (a phenolic-based cleaner) (M-Chem, Delta, BC), household bleach (sodium hypochlorite) and chlorhexidine (a chloro-phenoxy antiseptic) (Sigma Aldrich, Oakville, ON). Working concentrations of the cleaning agents were prepared and used as per health authority protocols at the time of the study: CaviCide (commercially available concentration i.e. not diluted), Phenokil IITM (0.02%), household bleach (5.25% sodium hypochlorite) and

Downloaded from opp.sagepub.com at Universiti Teknologi MARA (UiTM) on September 8, 2013

Hon et al. chlorhexidine (0.05%). For every test swatch, 0.5 mL of cleaning agent was applied (volume based on an extrapolation of observed volumes used by sta to clean the biological safety cabinets). Application method of cleaning agent. Cleaning agents were applied by either (a) pouring the agent directly onto the stainless steel surface or (b) pouring the agent onto a wipe that was subsequently used to wipe the stainless steel surface. These two scenarios are the most common methods of application in British Columbian acute care hospital pharmacies. Use of IPA after cleaning agent application. The eect of using 70% high-pressure liquid chromatography grade IPA (Fisher Scientic, Ottawa, ON) after the application of the cleaning agents was also investigated as this additional step is implemented at many local hospital pharmacies.

3 Residual drug contamination on the swatches was collected using a Kimwipe (Kimberly-Clark, Mississauga, ON) soaked in 1.0 mL of 0.1 M ammonium acetate (Sigma Aldrich, Oakville, ON) using a method described elsewhere.18 Collected wipe samples were stored at 20 C until analysis. Quantication of drug residual was determined using high-performance liquid chromatographytandem mass spectrometry based on a modied protocol by Sabatini et al.21 The analytical method employed had a 95% recovery rate, with detection limits of 0.014 ng/cm2 for CP and 0.0095 ng/cm2 for MTX. Each trial was performed in triplicate. In an eort to ensure consistency between trials and minimize the eect of inter-person variability, a lone research assistant was tasked with applying cleaning agents and collecting wipe samples from swatches. The percent of drug residual was calculated for each test swatch, and paired t-tests were performed to determine whether (a) there were dierences in mean drug residual between the two types of application methods and (b) the eect of using IPA after cleaning agent applied. ANOVAs were conducted to determine the dierence in percent residual for trial conditions of each cleaning agent. For those observations that were found to be less than the limit of detection, the percent residual was initially calculated (i.e. 0.0095/6.69 for MTX and 0.014/5.16 for CP) and then one-half of this value was used for statistical analysis purposes as is common for non-detects.22 The level of statistical signicance was set at p < 0.1 for paired t-tests and p < 0.05 for ANOVA. Statistical analyses were performed using Microsoft Excel (Microsoft, Seattle, WA).

Test trials
Each trial involved one cleaning agent with one possible combination of the remaining variables (application type and use of IPA) to remove antineoplastic drugs from the stainless steel swatches. The stainless steel swatches were initially spiked with known concentrations of one of the two antineoplastic drugs of interest in this study either 6.69 ng/cm2 of MTX or 5.16 0.025 ng/cm2 of CP (a range of CP concentrations was used for testing other variables not discussed in the current manuscript). These concentrations are reective of drug contamination levels found in biological safety cabinets reported in the literature.19,20 Each swatch then had a cleaning agent applied either directly onto the surface and then wiped or indirectly by initially soaking a wipe with the cleaning agent. If the cleaning agent was applied directly to the swatch, it was allowed to remain on the surface for 10 s before being wiped to allow for contact time. If the cleaning agent was placed onto a wipe, the swatch was cleaned with the wipe for 10 s. Regardless of the application method of the cleaning agent, a new WypAll X60 cleaning wipe (Kimberly-Clark, Mississauga, ON) was used for cleaning each surface. The swatches then sat for 15 s following cleaning agent application to allow for drying before being tested for residual contamination. For those trials examining the eect of IPA after cleaning agent usage, the swatch was wiped with a WypAll X60 cleaning wipe that had been soaked with 1.0 mL of 70% high-pressure liquid chromatography grade IPA. As with the cleaning agent application, the swatches sat for 15 s to allow for drying of IPA before collection of the surface wipe.

Results
The amount of antineoplastic drug contamination removed from all test swatches ranged from 89% to 100% (Table 1). For all test trials, measureable amounts of antineoplastic drugs were found on 70 of the 96 (73%) stainless steel swatches (not shown). The use of bleach resulted in the lowest residual amount of MTX compared to other cleaning agents. On the contrary, chlorhexidine had the highest residual amount of MTX compared to the other cleaning agents. For CP, there were no dierences in drug residual levels when the cleaning agent was applied onto wipe; however, there was a statistically signicant dierence when the cleaning agent was applied directly onto the stainless steel surface. In almost all instances, when IPA was used after the cleaning agent had already been applied, the amount of drug residual was further decreased. The greatest magnitude in reduction in drug residual following use of

Downloaded from opp.sagepub.com at Universiti Teknologi MARA (UiTM) on September 8, 2013

4
1.11 (1.001.18) 0.71 (0.610.77) 1.42 (1.121.93) 0.81 (10.4412.39) p < 0.05

Journal of Oncology Pharmacy Practice 0(0) IPA was associated with chlorhexidine being applied initially onto the wipe used to clean MTX. Of note, when the cleaning agent was applied onto the wipe and then IPA was subsequently used, the residual amount of CP was less than the limit of detection for all cleaning agents tested (Table 1). A comparison of the amount of drug residual based on the method of application for each cleaning agent (Table 2) indicates that, for MTX, there was no statistical dierence in residual levels regardless of cleaning agent. For CP, only one cleaning agent, Phenokil, resulted in residual levels that had a statistically signicant dierence (higher drug residual levels when cleaning agent was applied directly onto surface). Overall, when IPA was used after the cleaning agent, nine of the 16 sets of trials had a statistically signicant reduction in drug residual levels. Stratifying this further, seven of eight sets of trials involving CP and two of the eight sets of trials with MTX as the spiked drug resulted in a statistically signicant reduction in drug residual following IPA use. Of note, when the cleaning agent was applied directly onto the surface and then IPA was subsequently used, there was a statistically signicant reduction in the residual amount of CP for all four cleaning agents tested.

with IPA afterwards

CP

Mean% (range) Mean% (range) Mean% (range) Mean% (range)

Table 1. Mean and range of percent methotrexate and cyclophosphamide residual by cleaning agent and cleaning parameter.

Cleaning agent applied onto surface

without IPA afterwards

0.14 (0.140.14) 0.14 (0.140.14) 0.14 (0.140.14) 0.14 (9.3511.85) p 1.04

0.07 (0.070.07) 2.01 (1.632.41) 2.09 (1.842.54) 10.37 (1.252.18) p < 0.05

MTX

2.49 (2.232.69) 3.06 (2.424.31) 4.96 (2.786.35) 1.71 (8.9810.37) p < 0.05

CP

0.07 (0.070.07) 2.15 (1.812.49) 1.55 (1.221.75) 9.70 (0.681.02) p < 0.05

MTX

Discussion
In this pilot study, we examined various factors associated with cleaning to determine their inuence on the eectiveness of removing antineoplastic drug residual from drug preparation surfaces (stainless steel). None of the four cleaning agents tested, CaviCide , Phenokil IITM, household bleach or chlorhexidine, proved to be 100% eective in removing the antineoplastic drug residual. We found that the method of cleaning agent application, either indirectly to a wipe or directly onto the contaminated surface, had minimal eect on the residual levels. Our results also indicate that the use of IPA after the application of cleaning agent lowered the residual levels of MTX and CP further. This additional IPA application generally resulted in a statistically signicant reduction of drug residual (compared with no IPA usage) and, in some instances, essentially removed all of the contamination from the stainless steel surfaces. However, we need to be cautious with this nding, as we cannot state with certainty that this was independent of the mechanical action of cleaning (discussed further). The use of cleaning agents to reduce the amount of surface contamination on non-porous surfaces has been investigated in several studies.5,23,24 Common cleaning agents investigated include sodium hypochlorite, hydrogen peroxide, Fenton reagent, chlorhexidine and potassium permanganate. Most of these studies found

with IPA afterwards

CP

Mean% (range) Mean% (range)

0.00 (0.000.00) 0.56 (0.070.81) 1.08 (0.851.30) 3.05 (0.140.14) p < 0.05 Bleach CaviCide Phenokil IITM Chlorhexidine ANOVA 0.05 (0.000.07) 2.35 (1.143.00) 2.60 (2.332.75) 11.37 (2.633.60) p < 0.05 4.28 (3.065.02) 2.75 (0.144.15) 4.00 (1.905.11) 3.15 (2.553.41) p 0.63

MTX

Downloaded from opp.sagepub.com at Universiti Teknologi MARA (UiTM) on September 8, 2013

IPA: isopropyl alcohol; MTX: methotrexate; CP: cyclophosphamide.

Cleaning agent applied onto wipe

without IPA afterwards

Cleaning agent

Mean% (range)

MTX

Mean% (range)

CP

Hon et al.

Table 2. p-values following paired t-tests comparing amount of drug residual by cleaning application method with and without the use of isopropyl alcohol (statistical significance set at p < 0.1). Comparison following use of IPA Comparison by cleaning agent application method (no IPA) Cleaning agent Bleach CaviCide Phenokil IITM Chlorhexidine MTX 0.423 0.649 0.116 0.377 CP 0.116 0.815 0.023 0.120 Applied onto wipe MTX 0.184 0.145 0.027 0.004 CP 0.026 0.184 0.067 0.009 Applied onto surface MTX N/A 0.737 0.297 0.250 CP 0.014 0.059 0.079 0.035

IPA: isopropyl alcohol; MTX: methotrexate; CP: cyclophosphamide.

that the cleaning agents and associated cleaning practices were successful in reducing the amount of antineoplastic drug contaminant on surfaces, but amounts of antineoplastic agents were still detectable. A recent Canadian study investigated the eectiveness of chlorhexidine and Surface Safe (a sodium hypochloritebased commercial product) on removing CP residual from the working surface of a stainless steel biological safety cabinet found that contamination remained, despite the rigorous cleaning techniques evaluated.25 Lamerie et al.26 reported that all tested decontamination agents reduced antineoplastic drug residual on stainless steel surface to some extent, but none removed the contamination completely. They concluded that sodium hypochlorite (i.e. bleach) was the most eective cleaning agent, whereas IPA, on its own, was the least eective. With respect to method of application, Le et al.27 found that spraying cleaning agent onto surface was more eective than applying using a wipe; however, the authors performed their experiments on platinum-containing compounds. In the current study, we also found that bleach was an eective cleaning agent, especially for MTX; however, handling precautions should be practiced due to its oxidative nature as well as the adverse respiratory eects associated with exposure.28 In addition, there are concerns about the formation of mutagenic residues following the interaction of sodium hypochlorite with cytotoxic agents.26 Upon review, many of the cleaning protocols employed at the participating facilities are strikingly similar to hospital cleaning regimens designed to combat environmental infection control, i.e. microbial contamination.10 As such, we suspect that current antineoplastic drug cleaning protocols are simply an extension of infection control practices, rather than being based on their eectiveness at removing drug contamination, and may provide an explanation as to why measureable levels of antineoplastic drugs were found even after cleaning had been performed.18

Our ndings result in several potential policy implications. Because none of the cleaning agents was 100% eective in removing drug contamination, healthcare workers may continue to be at risk of exposure. These workers may treat the cleaned surface as uncontaminated and place objects on them, and thus serve as a fomite for further exposure. This residual contamination and potential exposure risk should be communicated to personnel who work within the drug preparation area. Furthermore, departmental and facility policies advocating exposure control, including use of personal protective equipment, must be stringently complied with to reduce the risk of worker exposure. As this was a pilot study, we faced a number of challenges. We attempted to simulate cleaning actions that would occur within acute care hospital pharmacies. Aspects taken into consideration include the pharmacy contamination patterns in biological safety cabinets as well as typical cleaning patterns and procedures used by pharmacy technicians for the cleaning of stainless steel work surface after drug preparations. We were unable to replicate exactly the contamination patterns on the stainless steel swatches that result from drug preparation but were able to approximate concentrations of antineoplastic drug contamination. In order to overcome the issue of diering pressures and cleaning patterns practiced between individuals, the same individual was tasked to conduct all the cleaning of the swatches. It is assumed that increased pressure would cause more antineoplastic drug contamination to be removed from the stainless steel surfaces. Other limitations of our study include the fact that only two antineoplastic drugs were examined. Pharmacy technicians handle a variety of antineoplastic drugs and, often more than one at a time, and our study did not examine this aspect or the potential interaction between drugs. In addition, we did not include a control cleaning agent such as deionized water to test the independent eect of IPA to conrm that the reduced levels were not just due to the additional mechanical

Downloaded from opp.sagepub.com at Universiti Teknologi MARA (UiTM) on September 8, 2013

6 action of cleaning. We also only evaluated cleaning from stainless steel surfaces. Although drug preparation is mainly performed on stainless steel, drug contamination may occur on other surface types, generally more porous, and therefore the results likely do not apply to these other surfaces.

Journal of Oncology Pharmacy Practice 0(0)

6. Kiffmeyer TK, Tuerk J, Hahn M, et al. Application and assessment of a regular environmental monitoring of the antineoplastic drug contamination level in pharmacies the MEWIP project. Ann Occup Hyg 57: 444455, http:// annhyg.oxfordjournals.org/cgi/doi/10.1093/annhyg/ mes081 (2013, accessed 9 November 2012). 7. Hon C-Y, Teschke K, Chu W, et al. Antineoplastic drug contamination of surfaces throughout the hospital medication system in Canadian hospitals. J Occup Environ Hyg 2013; 10: 374383. 8. 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 Chromatogr B Analyt Technol Biomed Life Sci 2003; 789: 169209. 9. Fransman W, Vermeulen R and Kromhout H. Occupational dermal exposure to cyclophosphamide in Dutch hospitals: a pilot study. Ann Occup Hyg 2004; 48: 237244. 10. CSHP: Products and Publications. http://www. cshp.ca/productsServices/officialPublications/subject_e. asp (accessed 4 February 2013). 11. Anonymous. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm 1990; 47: 1033. 12. WorkSafeBC. Regulation part 6 substance specific requirements cytotoxic drugs, http://www2.worksafebc. com/Publications/OHSRegulation/Part6.asp?report ID18230 (2012, accessed 9 January 2012). 13. ServiceOntario. Occupational health and safety act O. Reg. 67/93, http://www.e-laws.gov.on.ca/html/regs/english/ elaws_regs_930067_e.htm#BK20 (1993, accessed 4 February 2013). 14. Green E, Johnston M, Trudeau M, et al. Safe handling of parenteral cytotoxics: recommendations for Ontario. J Oncol Pract 2009; 5: 245249. 15. Anonymous. Summary of BCCA pharmacy practice standards for hazardous drugs, http://www.bccancer. bc.ca/NR/rdonlyres/D0AB44C4-4505-49BA-9F8867F65015C3BE/35055/8StandardsSummary.pdf (2009, accessed 4 February 2012). 16. Sessink PJ, Timmersmans JL, Anzion RB, et al. Assessment of occupational exposure of pharmaceutical plant workers to 5-fluorouracil. Determination of alphafluoro-beta-alanine in urine. J Occup Med 1994; 36: 7983. 17. Kromhout H, Hoek F, Uitterhoeve R, et al. Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys. Ann Occup Hyg 2000; 44: 551560. 18. Chu WC, Hon C-Y, Danyluk Q, et al. Pilot assessment of the antineoplastic drug contamination levels in British Columbian hospitals pre- and post-cleaning. J Oncol Pharm Pract 2012; 18: 4551. 19. Crauste-Manciet S, Sessink PJ, Ferrari S, et al. Environmental contamination with cytotoxic drugs in healthcare using positive air pressure isolators. Ann Occup Hyg 2005; 49: 619628.

Conclusions
Under experimental conditions, no one single cleaning agent proved to be eective in eliminating all drug contamination from stainless steel surfaces used for drug preparation. The method of cleaning agent application was not found to be an important factor. When paired with an IPA wipe after use of cleaning agents, there was generally a further reduction of drug residual but measureable levels were still detected in some cases. Acknowledgements
This work was supported by the WorkSafeBC Research Secretariat (RS2006-DG03). We would also like to acknowledge the contributions of Dr Winnie Chu, Tom Barnjak, Leah Butler, and Nicole Watson from the School of Environmental Health at the University of British Columbia.

Funding
This research received no specic grant from any funding agency in the public, commercial, or not-for-prot sectors.

Conflict of interest
None declared.

References
1. CDC NIOSH Publications and Products. Preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings (2004-165), http:// www.cdc.gov/niosh/docs/2004-165/ (2004, accessed 30 November 2011) 2. Connor TH, DeBord DG, Pretty JR, et al. Evaluation of antineoplastic drug exposure of health care workers at three university-based US cancer centers. J Occup Environ Med 2010; 52: 10191027. 3. Siderov J, Kirsa S and McLauchlan R. Surface contamination of cytotoxic chemotherapy preparation areas in Australian hospital pharmacy departments. J Pharm Pract Res 2009; 39: 117. 4. Hedmer M, Tinnerberg H, Axmon A, et al. Environmental and biological monitoring of antineoplastic drugs in four workplaces in a Swedish hospital. Int Arch Occup Environ Health 2008; 81: 899911. 5. Acampora A, Castiglia L, Miraglia N, et al. A case study: surface contamination of cyclophosphamide due to working practices and cleaning procedures in two Italian hospitals. Ann Occup Hyg 2005; 49: 611618.

Downloaded from opp.sagepub.com at Universiti Teknologi MARA (UiTM) on September 8, 2013

Hon et al.
20. Minoia C, Turci R, Sottani C, et al. Application of high performance liquid chromatography/tandem mass spectrometry in the environmental and biological monitoring of health care personnel occupationally exposed to cyclophosphamide and ifosfamide. Rapid Commun Mass Spectrom 1998; 12: 14851493. 21. Sabatini L, Barbieri A, Tosi M, et al. A new high-performance liquid chromatographic/electrospray ionization tandem mass spectrometric method for the simultaneous determination of cyclophosphamide, methotrexate and 5-fluorouracil as markers of surface contamination for occupational exposure monitoring. J Mass Spectrom 2005; 40: 669674. 22. Hornung RW and Reed LD. Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg 1990; 5: 4651. 23. 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: 475484. 24. Touzin K, Bussieres J-F, Langlois E, et al. Cyclophosphamide contamination observed on the

7
external surfaces of drug vials and the efficacy of cleaning on vial contamination. Ann Occup Hyg 2008; 52: 765771. Touzin K, Bussieres JF, Langlois E, et al. Pilot Study comparing the efficacy of two cleaning techniques in reducing environmental contamination with cyclophosphamide. Ann Occup Hyg 2010; 54: 351359. Queruau Lamerie T, Nussbaumer S, Decaudin B, et al. In vitro evaluation of decontamination efficacy of cleaning solutions on stainless steel and glass surfaces contaminated by 10 antineoplastic agents. Ann Occup Hyg 2013; 57: 456-469, http://annhyg.oxfordjournals.org/cgi/doi/ 10.1093/annhyg/mes087 (2012, accessed 28 January 2013). Le LMM, Jolivot PA, Sadou Yaye H, et al. Effectiveness of cleaning of workplace cytotoxic surface. Int Arch Occup Environ Health 2012; 86: 333341. National Library of Medicine HSDB Database. Sodium hypochlorite, http://toxnet.nlm.nih.gov/cgi-bin/sis/search/ f?./temp/$0LVzrR:1 (accessed 4 February 2013).

25.

26.

27.

28.

Downloaded from opp.sagepub.com at Universiti Teknologi MARA (UiTM) on September 8, 2013