Contamination of Syringe Plungers During the Sampling of Cyclophosphamide Solutions
Institution: Journal of Oncology Pharmacy Practice
Year Published: 2005
Syringe Plunger Contamination by Hazardous Drugs: A Comparative Study
Institution: Journal Oncology Pharmacy Practice
Year Published: 2015
Evaluation of Syringes Used for Compounding Hazardous Drugs and the Contamination Risks to Healthcare Personnel
Institution: FASHP Nebraska Methodist Hospital, USA
Year Published: 2014
Comparative Study of Syringe Contamination by Hazardous Drugs
Comparative Study of Syringe Contamination by Hazardous Drugs
- Dr. Kiffmeyer, Head of Department of Environmental Hygiene performed this study during 2009,
- at the Institute of Energy and Environmental Technology, in Duisburg Germany in cooperation with Dr. Favier of of Léon-Bérard Cancer Center,
- Léon France.
Abstract
Aim – The purpose of this study was to compare surface contamination resulting from standard syringe plungers and cylinders compared to using the
EQUASHIELD® Syringe Unit.
Method – the contamination level of standard syringes was compared to that of EQUASHIELD® Syringe Units, after repeated pharmaceutical manipulations using an antineoplastic (Cyclophosphamide) drug.
Results – Significant levels of up to 0.5 milligrams contamination were found on all sampled standard syringe plungers and cylinders. Significantly lower contamination levels were found on EQUASHIELD’s fully enclosed Syringe Units.
Method – the contamination level of standard syringes was compared to that of EQUASHIELD® Syringe Units, after repeated pharmaceutical manipulations using an antineoplastic (Cyclophosphamide) drug.
Results – Significant levels of up to 0.5 milligrams contamination were found on all sampled standard syringe plungers and cylinders. Significantly lower contamination levels were found on EQUASHIELD’s fully enclosed Syringe Units.
Since the late 1970s numerous studies have documented the potential health risks associated with exposure to hazardous drugs in healthcare settings. Evidence has indicated that exposure to these dangerous substances can lead to acute and long term health complications such as infertility, miscarriage, birth defects, leukemia and other types of cancer. It has been clearly demonstrated that workers are in danger of exposure to these drugs at all contact stages, including drug manufacture, transport, distribution, receipt, storage, preparation, administration, waste handling, and equipment repair and maintenance (ASHP, 2006).
Identifying and quantifying possible sources of contamination is of great importance, as it can contribute to a better understanding of the issues involved in the safe handling of hazardous drugs, as well as to constant improvement of drug handling methods, the development of more effective protective equipment, and the establishment of better pharmacy and bedside compounding and administration safety policies and regulations.
The National Institute for Occupational Safety and Health (NIOSH, 2004) has recommended the use of an effective closed-system drug transfer device (CSTD) in order to facilitate safe, enclosed drug transfers and minimize the exposure to hazardous drugs and their adverse effects.
When examining surface contamination, studies using CSTDs have shown a significant reduction in contamination levels, yet detectable levels of hazardous substances were still found, suggesting that the systems are not entirely safe and that environmental contamination still places healthcare workers at risk of exposure.
In 2005, a study using a surface monitoring technique further explored environmental contamination, when it specifically examined the possibility of syringe plunger contamination during routine drug preparations at hospital pharmacies. Contamination by yclophosphamide was confirmed, quantified, and localized on a standard syringe plunger, in order to determine what quantity of the Cytotoxic agents come into contact with the operators’ gloves (Favier, Gilles, Latour, Desage and Giammarile, 2005). Thus, results revealed a previously undetected route of exposure whereby drug residuals on the syringe plunger contaminate gloves and the work environment, and most alarmingly, place unprotected hospital staff who handle the syringe outside of the safety cabinet, at great danger.
The current study was designed to provide further evidence regarding the surface contamination on standard syringe plungers and barrels during routine drug preparation, using the prevalent Cyclophosphamide. The same agent was also used to quantify drug residuals detected on the inner wall of the syringe cylinders.
As all but one currently available CSTD use standard syringes, this study is significant in establishing the efficiency of these systems in minimizing exposure to hazardous drugs. are only CSTD that has addressed this route of exposure is a new device called EQUASHIELD®.
EQUASHIELD® is a new airtight, leak-proof closed system drug transfer device that prohibits the escape of hazardous drugs and vapors into the surrounding environment through an innovative pressure equalization mechanism. EQUASHIELD® addresses the issue of contamination through the syringe:
1. EQUASHIELD’s Syringe Unit has a double jacket enclosure that seals the syringe barrel and isolates the syringe plunger’s rod. Thus, EQUASHIELD’s design ensures that contaminants remain fully contained, preventing any possibility of plunger and cylinder contact or exposure.
2. There is no direct contact between EQUASHIELD’s plunger rod and the syringe cylinder.
3. The plunger rod’s surface area in EQUASHIELD® is much smaller than that of a standard syringe plunger.
4. EQUASHIELD’s plunger rod can never be detached from the syringe, whereas in standard syringes, the plunger can be pulled out of the barrel.
In order to assess its effectiveness in reducing plunger contamination and aerosol evaporation of drug residuals compared to standard syringes used by other CSTDs, surface contamination of standard syringe plungers and inner walls (barrels) were compared with EQUASHIELD® surface contamina- tion during routine drug preparation procedures.
Identifying and quantifying possible sources of contamination is of great importance, as it can contribute to a better understanding of the issues involved in the safe handling of hazardous drugs, as well as to constant improvement of drug handling methods, the development of more effective protective equipment, and the establishment of better pharmacy and bedside compounding and administration safety policies and regulations.
The National Institute for Occupational Safety and Health (NIOSH, 2004) has recommended the use of an effective closed-system drug transfer device (CSTD) in order to facilitate safe, enclosed drug transfers and minimize the exposure to hazardous drugs and their adverse effects.
When examining surface contamination, studies using CSTDs have shown a significant reduction in contamination levels, yet detectable levels of hazardous substances were still found, suggesting that the systems are not entirely safe and that environmental contamination still places healthcare workers at risk of exposure.
In 2005, a study using a surface monitoring technique further explored environmental contamination, when it specifically examined the possibility of syringe plunger contamination during routine drug preparations at hospital pharmacies. Contamination by yclophosphamide was confirmed, quantified, and localized on a standard syringe plunger, in order to determine what quantity of the Cytotoxic agents come into contact with the operators’ gloves (Favier, Gilles, Latour, Desage and Giammarile, 2005). Thus, results revealed a previously undetected route of exposure whereby drug residuals on the syringe plunger contaminate gloves and the work environment, and most alarmingly, place unprotected hospital staff who handle the syringe outside of the safety cabinet, at great danger.
The current study was designed to provide further evidence regarding the surface contamination on standard syringe plungers and barrels during routine drug preparation, using the prevalent Cyclophosphamide. The same agent was also used to quantify drug residuals detected on the inner wall of the syringe cylinders.
As all but one currently available CSTD use standard syringes, this study is significant in establishing the efficiency of these systems in minimizing exposure to hazardous drugs. are only CSTD that has addressed this route of exposure is a new device called EQUASHIELD®.
EQUASHIELD® is a new airtight, leak-proof closed system drug transfer device that prohibits the escape of hazardous drugs and vapors into the surrounding environment through an innovative pressure equalization mechanism. EQUASHIELD® addresses the issue of contamination through the syringe:
1. EQUASHIELD’s Syringe Unit has a double jacket enclosure that seals the syringe barrel and isolates the syringe plunger’s rod. Thus, EQUASHIELD’s design ensures that contaminants remain fully contained, preventing any possibility of plunger and cylinder contact or exposure.
2. There is no direct contact between EQUASHIELD’s plunger rod and the syringe cylinder.
3. The plunger rod’s surface area in EQUASHIELD® is much smaller than that of a standard syringe plunger.
4. EQUASHIELD’s plunger rod can never be detached from the syringe, whereas in standard syringes, the plunger can be pulled out of the barrel.
In order to assess its effectiveness in reducing plunger contamination and aerosol evaporation of drug residuals compared to standard syringes used by other CSTDs, surface contamination of standard syringe plungers and inner walls (barrels) were compared with EQUASHIELD® surface contamina- tion during routine drug preparation procedures.
Method
The study examined two sources of contamination: the first test examined plunger contamination levels, whereas the second test examined the prevalence of syringe barrel residuals that can evaporate into the environment.
Plunger Contamination Test
A total of 24 syringes were used to test plunger contamination levels: 12 standard Becton Dickinson 60cc syringes, and 12 EQUASHIELD® 60cc syringes. Similarly, 24 sealable sampling cups, one for each syringe, were prepared according to the laboratory’s recommendation. All syringes and sampling cups were marked in advance with matching labels that included the following information: the syringe type (BD or ES); the number of manipulations (2M, 4M, or 8M); the serial number (1 to 12 for BD and 1-12 for ES); and an empty space to mark the CP serial number.
All syringes and sampling cups were marked in advance with matching labels that included the following information: the syringe type (BD or ES); the number of manipulations (2M, 4M, or 8M); the serial number (1 to 12 for BD and 1-12 for ES); and an empty space to mark the CP serial number.
Cyclophosphamide dry substance (Baxter) was admixed in original containers with sodium chlorine solution according to standard procedure, resulting in stock solutions with a concentration of 20mg/ml. pH values were measured for all solutions. All vials filled with Cyclophosphamide were marked with serial numbers.
A trained person performed 2, 4 or 8 manipulations with each of the standard and EQUASHIELD® syringes. In each manipulation 50cc Cyclophosphamide were aspired from the vial into the syringe, and then emptied back into the vial.
All manipulations were performed in a safety cabinet dedicated to the preparation of antineoplastic drugs, using paper sheets to cover the work area. After the completion of manipulations with each specific syringe, the paper sheet was replaced, gloves were changed and the work area was wiped with 0.1M NaOH followed by 2 Isopropanol before working with the next syringe.
After the designated number of manipulations with each syringe was completed, the syringe was moved to a second safety cabinet and placed on a paper sheet. Special care was taken to prevent one syringe from touching another. A KimWipe saturated with 1ml water pH adjusted to 3.0 with HCl was applied to the plunger surfaces as illustrated in Figure 1 in order to determine the contamination level on each syringe plunger.
A total of 3 wipes were taken from each plunger and stored at -18ºC until analysis. No longer than 40 minutes elapsed between the time a syringe was manipulated and the time it was wiped. After wiping was completed, syringes were placed in a closed disposal bin and the gloves and paper sheet were replaced. The pH values of the Cyclophosphamide in each vial was measured and recorded.
Recovery rates (101% for the wiping tests and 72% for the rinsing procedure) and standard deviation of the wiping process were determined in precursory validation of the process using syringes spiked with known amounts of Cyclophosphamide.
Recovery rates (101% for the wiping tests and 72% for the rinsing procedure) and standard deviation of the wiping process were determined in precursory validation of the process using syringes spiked with known amounts of Cyclophosphamide.
Figure 1
Cylinder Contamination Test
The second test, that was designed to evaluate contamination levels on the exposed inner walls of standard syringe barrels, used a total of 21 syringes of 3 different types from 2 manufacturers: 9 standard Becton Dickinson 20cc syringes, 9 standard Becton Dickinson 60cc syringes (Manufacturer A), and 3 standard Terumo 60cc syringes (Manufacturer B).
EQUASHIELD® cylinders were not tested for contamination because their syringe units are fully enclosed, presenting no risk of vapor and aerosol evaporation.
Manipulations using Cyclophosphamide were performed in the exact same manner as in the first test (see above description). Once the designated number of manipulations with each syringe was com- pleted, 5ml of pH3 water was dripped into each of the four standard syringe quarters, and then poured into a flask that was then sealed and frozen at -18°C until analysis (see Figure 2 where colored water was used to demonstrate the actual procedure).
All samples were analyzed using a HPLC-MS/MS system consisting of an 1100 binary pump with a HTS-PAL autosampler equipped with a stack cooler for sample storage at 4°C until injection of 20µL. As previously mentioned, this step was validated using spiked syringes to determine recovery rates and standard deviation of the process (Tuerk, Kiffmeyer, Kuss, Hahn, Stuetzer, Hadtstein, Heinemann, and Eickmann, 2010).
EQUASHIELD® cylinders were not tested for contamination because their syringe units are fully enclosed, presenting no risk of vapor and aerosol evaporation.
Manipulations using Cyclophosphamide were performed in the exact same manner as in the first test (see above description). Once the designated number of manipulations with each syringe was com- pleted, 5ml of pH3 water was dripped into each of the four standard syringe quarters, and then poured into a flask that was then sealed and frozen at -18°C until analysis (see Figure 2 where colored water was used to demonstrate the actual procedure).
All samples were analyzed using a HPLC-MS/MS system consisting of an 1100 binary pump with a HTS-PAL autosampler equipped with a stack cooler for sample storage at 4°C until injection of 20µL. As previously mentioned, this step was validated using spiked syringes to determine recovery rates and standard deviation of the process (Tuerk, Kiffmeyer, Kuss, Hahn, Stuetzer, Hadtstein, Heinemann, and Eickmann, 2010).
Figure 2
Results
The results of the first test indicated significant levels of contamination on standard syringe plungers; contamination levels on EQUASHIELD® syringe plungers were mostly negligible (see Table 1 and Figure 3). Contamination levels were not related to the number of manipulations performed with each syringe and could be detected as soon as after one manipulation.
Table 1 – Cyclophosphamide Plunger Total Contamination Levels (ng)
- 2, 4 and 8 are the number of manipulations.
- U/D-Undetectable contamination levels.
Sample analysis revealed significantly greater levels of contamination on standard syringe plungers.
Figure 3: Cyclophosphamide Plunger Contamination Levels (ng)
Plunger Contamination Levels (ng)
Standard (STD) syringes compared to EQUASHIELD® (ES) Syringe Units during routine drug preparation with Cyclophosphamide
The second test which was performed separately, revealed Cyclophosphamide contamination on all tested syringe barrels (see Table 2 and Figure 4), with greater contamination levels found on the 60cc syringes compared to the 20cc syringes.
Table 2 – Cyclophosphamide Cylinder Contamination Levels (ng)
All the tested syringe cylinders were contaminated with Cyclophosphamide. the values appearing in the table are the detected values divided by 72%, which was the recovery rate.
Figure 4: Cyclophosphamide Cylinder Contamination Levels (ng)
Discussion
Results revealed Cyclophosphamide residuals on the standard syringe plungers and barrels, supporting previous studies that suggest that syringe plunger contamination is an additional route of exposure that may contaminate gloves and work areas during hazardous drug routine preparation and administration at pharmacies and patient bedsides.
These findings may also explain surface contamination, as the contaminated plungers come into con-tact with healthcare workers’ gloves, and consequently, with work surfaces, chairs, tabletops and so forth, despite various precautions such as the use of gloves, safety cabinets and the like. Similarly, aero- sols and vapors from the syringe barrels may contribute to air contamination when evaporating into the environment or condensing upon work surfaces.
Furthermore, as standard syringe plungers are used with all but one currently available closed system drug transfer device (CSTD), it is important to alert healthcare workers to the dangers of using these systems that may present a neglected safety concern, which is particularly alarming when considering the unprotected personnel who handle the syringe outside the safety cabinet.
Finally, it is important to note that the contamination levels found on the EQUASHIELD® CSTD’s plungers is inconsequential, indicating the effectiveness of a fully enclosed syringe unit. This informa- tion may contribute to the development of more effective CSTDs and the enforcement of better poli- cies and regulations concerning the handling of hazardous drugs.
Results indicate that plunger and barrel contamination of common syringes used for drug preparation are a significant source of exposure that requires further investigation and consideration. One possible solution is the use of a fully enclosed syringe such as EQUASHIELD® that has proven to result in significantly lower contamination levels.
These findings may also explain surface contamination, as the contaminated plungers come into con-tact with healthcare workers’ gloves, and consequently, with work surfaces, chairs, tabletops and so forth, despite various precautions such as the use of gloves, safety cabinets and the like. Similarly, aero- sols and vapors from the syringe barrels may contribute to air contamination when evaporating into the environment or condensing upon work surfaces.
Furthermore, as standard syringe plungers are used with all but one currently available closed system drug transfer device (CSTD), it is important to alert healthcare workers to the dangers of using these systems that may present a neglected safety concern, which is particularly alarming when considering the unprotected personnel who handle the syringe outside the safety cabinet.
Finally, it is important to note that the contamination levels found on the EQUASHIELD® CSTD’s plungers is inconsequential, indicating the effectiveness of a fully enclosed syringe unit. This informa- tion may contribute to the development of more effective CSTDs and the enforcement of better poli- cies and regulations concerning the handling of hazardous drugs.
Results indicate that plunger and barrel contamination of common syringes used for drug preparation are a significant source of exposure that requires further investigation and consideration. One possible solution is the use of a fully enclosed syringe such as EQUASHIELD® that has proven to result in significantly lower contamination levels.
References
Acampora A., Castiglia L., Miraglia N., Pieri M., Soave C., Liotti F., Sannolo N. A Case Study:
Surface Contamina tion of Cyclophosphamide due to Working Practices and Cleaning Procedures in Two
Italian Hospitals. Ann. occup. Hyg., Vol. 49, No. 7, pp. 611–618, 2005
ASHP Council on Professional Affairs. ASHP Guidelines on Handling Hazardous Drugs. American Journal of Health System Pharm. 2006; 63:1172-93.
Connor TH, Shults, M. And Fraser, MP, Determination of the vaporization of solutions of mutagenic antineoplastic agents at 23 and 37°C using a desiccators technique. Environmental and Occupational Health, University of Texas-Houston Health Science Center, 19 July 2000. Available online 11 September 2000.
Connor TH, Anderson, RW, Sessink, PJ, and Spivey, SM. Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and infosfamide in an i.v. admixture area. American Journal Health-Syst Pharm.; 59: 68-72, 2002.
Ensslin AS, Pethran A, Schierl R et al. Urinary platinum in hospital personnel occupationally exposed to platinum containing antineoplastic drugs. Int Arch Occup Environ Health; 65: 339–42, 1994
Favier B., Gilles L., Latour J. F., Desage M., Giammarile F. Contamination of syringe plungers during the sampling of cyclophosphamide solutions. J Oncol Pharm Practice 11: 1-/5, 2005
Fransman W., Vermeulen R., Kromhout H. Occupational Dermal Exposure to Cyclophosphamide in Dutch Hospitals: A Pilot Study. Ann. occup. Hyg., Vol. 48, No. 3, pp. 237–244, 2004
Goloni-Bertollo EM, Tajara EH, Manzato AJ, Varella-Garcia M. Sister chromatid exchanges and chromosome aberrations in lymphocytes of nurses handling antineoplastic drugs. Int J Cancer; 50: 341–4, 1992.
Hedmer M., Georiadi A., Ramme Bremberg E., Jonsson B. A. G., Eksborg S. Surface Contamination of Cyclophos phamide Packaging and Surface Contamination with Antineo plastic Drugs in a Hospital Pharmacy in Sweden. Ann. occup. Hyg., Vol. 49, No. 7, pp. 629–637, 2005.
Hedmer M., Tinnerberg H., Axmon A., Jonsson B.A.G. Environmental and Biological Monitoring of Antineoplastic Drugs in Four Working Places in a Swedish Hospital. Int Arch Occup Environ Health 81:899-911, 2008.
Kromhout H, Hoek F, Uitterhoeve R, Huijbers, R., Overmars, R. F., Anzion, R. & Vermeulen, R. (2000) Postulatinga 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; 44: 551–60.
Kiffmeyer TK, Kube C, Opiolka S, Schmidt KG, Schöppe G, Sessink PJM [2002]. Vapor pressures, evaporation behaviour and airborne concentrations of hazardous drugs: implications for occupational safety. Pharmeaceut J 268:331–337
National Institute for Occupational Safety and Health Alert. Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Healthcare Settings. Atlanta, GA: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupa tional Safety and Health, DHHS (NIOSH) Publication No 2004-165; 2004.
Nygren O, Lundgren C. (1997) Determination of platinum in workroom air and in blood and urine from nursing staff attending patients receiving cisplatin chemotherapy. Int Arch Occup Environ Health; 70: 209–14.
Otto T, Rubben H. (2004) Prevention of bladder cancer. Urologe A; 43: 56–4. Pethran A, Schierl R, Hauff K et al. (2003) Uptake of antineoplastic agents in pharmacy and hospital personnel. Part I: monitoring of urinary concentrations. Int Arch Occup Environ Health; 76: 5–10.
Selevan SG, Lindbohm ML, Hornung RW, Hemminki K. A study of occupational exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med;1985 313: 1173 8.
Sessink PJM, Cerna M, Rossner P et al. Urinary cyclophosphamide excretion and chromosomal aberrations in peripheral blood lymphocytes after occupational exposure to antineoplastic agents. Mutat Res; 309: 193–9. 1994a.
Sessink PJM, Kerkhof MCvd, Anzion RBM, Noordhoek J, Bos RP. 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; 49: 165–9, 1994b.
Sessink PJM, Bos RP. Drugs hazardous to healthcare workers. Evaluation of methods for monitor ing occupational exposure to cytostatic drugs. Drug Safety 20:346-59, 1999;
Touzin K., Bussie J. F., Lannglois E., Lefebvre M, Gallant C. Cyclophosphamide Contamination Observed on the External Surfaces of Drug Vials and the Efficacy of Cleaning on Vial Contamination. Ann. Occup. Hyg., Vol. 52, No. 8, pp. 765–771, 2008
Tuerk, J. Kiffmeyer, T. K. Kuss, Hahn, H.M. Stuetzer, M. H. Hadtstein, C. Heinemann, A., Eickmann U. Develop ment, validation and application of an LC-MS/MS procedure for environmental monitoring of cytostatic drugs. International Journal of Environmental Analytical Chemistry. Accepted for publication 2010
Turci R, Sottani C, Ronchi A et al. (2002) Biological monitoring of hospital personnel occupationally exposed to antineoplastic agents. Toxicol Lett; 134: 57–64.
Vandenbroucke, J. And Robays, H. How to protect environment and employees against cytotoxic agents, the UZ Ghent experience. Journal of Oncol Pharm Pract 2001; 6; 146.
Wick, C., Slawson, M. H., Jorgenson, J. A., and Tyler, L. S. (2003) Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. American Journal of Health-System Pharmacists, Vol. 60, Nov. issue, pp. 2314-2320.
ASHP Council on Professional Affairs. ASHP Guidelines on Handling Hazardous Drugs. American Journal of Health System Pharm. 2006; 63:1172-93.
Connor TH, Shults, M. And Fraser, MP, Determination of the vaporization of solutions of mutagenic antineoplastic agents at 23 and 37°C using a desiccators technique. Environmental and Occupational Health, University of Texas-Houston Health Science Center, 19 July 2000. Available online 11 September 2000.
Connor TH, Anderson, RW, Sessink, PJ, and Spivey, SM. Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and infosfamide in an i.v. admixture area. American Journal Health-Syst Pharm.; 59: 68-72, 2002.
Ensslin AS, Pethran A, Schierl R et al. Urinary platinum in hospital personnel occupationally exposed to platinum containing antineoplastic drugs. Int Arch Occup Environ Health; 65: 339–42, 1994
Favier B., Gilles L., Latour J. F., Desage M., Giammarile F. Contamination of syringe plungers during the sampling of cyclophosphamide solutions. J Oncol Pharm Practice 11: 1-/5, 2005
Fransman W., Vermeulen R., Kromhout H. Occupational Dermal Exposure to Cyclophosphamide in Dutch Hospitals: A Pilot Study. Ann. occup. Hyg., Vol. 48, No. 3, pp. 237–244, 2004
Goloni-Bertollo EM, Tajara EH, Manzato AJ, Varella-Garcia M. Sister chromatid exchanges and chromosome aberrations in lymphocytes of nurses handling antineoplastic drugs. Int J Cancer; 50: 341–4, 1992.
Hedmer M., Georiadi A., Ramme Bremberg E., Jonsson B. A. G., Eksborg S. Surface Contamination of Cyclophos phamide Packaging and Surface Contamination with Antineo plastic Drugs in a Hospital Pharmacy in Sweden. Ann. occup. Hyg., Vol. 49, No. 7, pp. 629–637, 2005.
Hedmer M., Tinnerberg H., Axmon A., Jonsson B.A.G. Environmental and Biological Monitoring of Antineoplastic Drugs in Four Working Places in a Swedish Hospital. Int Arch Occup Environ Health 81:899-911, 2008.
Kromhout H, Hoek F, Uitterhoeve R, Huijbers, R., Overmars, R. F., Anzion, R. & Vermeulen, R. (2000) Postulatinga 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; 44: 551–60.
Kiffmeyer TK, Kube C, Opiolka S, Schmidt KG, Schöppe G, Sessink PJM [2002]. Vapor pressures, evaporation behaviour and airborne concentrations of hazardous drugs: implications for occupational safety. Pharmeaceut J 268:331–337
National Institute for Occupational Safety and Health Alert. Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Healthcare Settings. Atlanta, GA: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupa tional Safety and Health, DHHS (NIOSH) Publication No 2004-165; 2004.
Nygren O, Lundgren C. (1997) Determination of platinum in workroom air and in blood and urine from nursing staff attending patients receiving cisplatin chemotherapy. Int Arch Occup Environ Health; 70: 209–14.
Otto T, Rubben H. (2004) Prevention of bladder cancer. Urologe A; 43: 56–4. Pethran A, Schierl R, Hauff K et al. (2003) Uptake of antineoplastic agents in pharmacy and hospital personnel. Part I: monitoring of urinary concentrations. Int Arch Occup Environ Health; 76: 5–10.
Selevan SG, Lindbohm ML, Hornung RW, Hemminki K. A study of occupational exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med;1985 313: 1173 8.
Sessink PJM, Cerna M, Rossner P et al. Urinary cyclophosphamide excretion and chromosomal aberrations in peripheral blood lymphocytes after occupational exposure to antineoplastic agents. Mutat Res; 309: 193–9. 1994a.
Sessink PJM, Kerkhof MCvd, Anzion RBM, Noordhoek J, Bos RP. 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; 49: 165–9, 1994b.
Sessink PJM, Bos RP. Drugs hazardous to healthcare workers. Evaluation of methods for monitor ing occupational exposure to cytostatic drugs. Drug Safety 20:346-59, 1999;
Touzin K., Bussie J. F., Lannglois E., Lefebvre M, Gallant C. Cyclophosphamide Contamination Observed on the External Surfaces of Drug Vials and the Efficacy of Cleaning on Vial Contamination. Ann. Occup. Hyg., Vol. 52, No. 8, pp. 765–771, 2008
Tuerk, J. Kiffmeyer, T. K. Kuss, Hahn, H.M. Stuetzer, M. H. Hadtstein, C. Heinemann, A., Eickmann U. Develop ment, validation and application of an LC-MS/MS procedure for environmental monitoring of cytostatic drugs. International Journal of Environmental Analytical Chemistry. Accepted for publication 2010
Turci R, Sottani C, Ronchi A et al. (2002) Biological monitoring of hospital personnel occupationally exposed to antineoplastic agents. Toxicol Lett; 134: 57–64.
Vandenbroucke, J. And Robays, H. How to protect environment and employees against cytotoxic agents, the UZ Ghent experience. Journal of Oncol Pharm Pract 2001; 6; 146.
Wick, C., Slawson, M. H., Jorgenson, J. A., and Tyler, L. S. (2003) Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. American Journal of Health-System Pharmacists, Vol. 60, Nov. issue, pp. 2314-2320.
