Chemical contamination is defined as the unintended exposure of a healthcare professional to hazardous drugs.
The American National Institute for Occupational Safety and Health (NIOSH) defines a hazardous drug as any drug identified by at least one of the following criteria: carcinogenicity, teratogenicity or developmental toxicity, reproductive toxicity in humans, organ toxicity at low doses in humans or animals, genotoxicity, or new drugs that mimic existing hazardous drugs in structure or toxicity.1
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Kromhout and others have noted that the exact cause or pathway of this exposure is unclear2, but two primary routes can be found in the literature: a dermal3 and an aerosol route.2
There are many areas where contamination has been found and which have been identified as leading to dermal, or ‘touch’, contamination. These include:
- contact with the surface of vials4
- contact with the surface of drug boxes5
- preparation of drugs such as cyclophosphamide6
- the priming of IV sets
- handling outside of the pharmacy1
- handling bodily fluids of patients undergoing cytostatic treatment.2,6
The presence of contamination in these areas suggests that preparing cytostatics as well as handling vials, boxes and bodily fluids is a cause of contamination. Other causes of contamination, discussed by regulatory bodies such as the NIOSH, are poorly decontaminated spills, the priming of IV sets, handling outside of the pharmacy and poor product choice.1
Aerosol contamination during preparation and delivery is possible and a number of studies have measured airborne concentrations of antineoplastic drugs in health care settings.
In most cases, the percentage of air samples containing measurable airborne concentrations of hazardous drugs was low, and the actual concentrations of the drugs, when present, were quite low.1 Recently published experimental trials confirmed these results.7,8
Nevertheless, Huang et al. found significant 5-FU concentrations measured on the outer and inner of surgical masks.7 Sessink et al. also reported that 5-FU could be detected on a mask after a technician had preparation a large quantity of 5-FU.9
The consequences of chemical contamination depend on the drug in question. For this reason, a differentiation between toxic and non-toxic contamination seems appropriate.
Exposure to non-toxic medications such as certain antibiotics is not without consequences and has been shown to lead to dermatitis10 and hypersensitivity11 which can reduce working efficiency.
- Acute symptoms
Drug SPCs are the principle source of information regarding undesirable effects and should be consulted regulary.
Paclitaxel, for example, is said to lead to acute symptoms such as nausea, alopecia (hair loss) and bradycardia.12 Studies show a significant increase in similar acute symptoms between control cases and cases exposed to antineoplastic agents (e.g. chronic cough, dizziness, headache, eye irritation, hair loss and allergic reactions).13 However, the main acute symptom is mutagenicity. Studies have found various mutagenicity indicators such as sister chromatid exchange or aberrations.13 Since chromosomal mutagenicity following exposure is stochastic in nature14, as little as one molecule could cause a mutation. For this reason, regulatory bodies do not quote threshold levels under which exposure is acceptable.
- Chronic Symptons - Carcinogenicity
Mutagenicity, while being an acute symptom in itself, can lead to the chronic disease cancer. The link between exposure to high dose cytotoxic medication and secondary malignant neoplasia has also been shown, and has led to the International Agency for Research on Cancer (IARC) classifying many antineoplastic drugs as group10 (carcinogenic to humans) compounds. The stochastic nature of carcinogenicity makes even low doses, such as those found during a contamination, a risk. Studies showing such a link are subject to certain statistical challenges due to the low occurrence of cancer in the population and limited sample sizes. However, Sessink calculated that the theoretical lifetime risk that a healthcare worker suffers from leukemia was 95-475 per million.15 Skov shows an increased risk of leukemia and non-Hodgkin’s lymphoma in hospital workers.16
- Reproductive effects
Studies show an increased occurrence of fetal loss as well as teratogenicity.17
- Other chronic effects
As further possible consequences, Sotaniemi shows chronic liver damage and fibrosis as a result of exposure to toxic drugs.18
Common standard operating procedures (SOPs) in hospitals as well as published guidelines state that healthcare workers exposed to contamination must thoroughly rinse the exposed area with water for ten minutes. If the eyes are contaminated, an ophthalmologist is to be consulted.20 Added to this lost productivity, there are some hardware costs for washes, ointments, bandages and medication to ease the symptoms of any acute consequences such as diarrhea.
The dermatitis and hypersensitivity caused by repeated exposure to medication has not been investigated with regard to cost, but Mälkönen found that healthcare workers with an occupational skin disease had to take sick leave (21%) or change occupation (21%).21 The reduction of the working efficiency of staff who stay, and the training of new staff to replace those who leave, are two cost factors that must not be forgotten.
Another case where a complication leads to loss of productivity is cancer; for example, in the UK, patients are allocated up to 28 weeks statutory sick leave with a sick pay of 79.15 £ (90 €) per day.22
In a similar way, hospital costs associated with the reproductive complications such as fetal loss, are caused when compassionate sick leave is granted to the healthcare worker. While this will certainly vary significantly, the legal minimum leave for the loss of a 1st degree relative for many industries in Germany is 2 days.23
Potential Risk Associated Cost
The Fig. 2 shows the results of a calculation based on the costs factors that are split into the cost to society and the cost to the healthcare institutions.
Depending on the country one can imagine, that if any of these health problems can be traced back to poor safety procedures, there may be costly legal consequences for a healthcare institution.
The following bodies (among others) publish recommendations for the prevention of chemical contamination:
- The National Institute for Occupational Safety and Health (NIOSH), USA
- Centers for Disease Control and Prevention (CDC), USA
- International Society of Pharmacovigilance (ISOP)
- German Society for Oncology Pharmacy (DGOP), Germany
- Swedish Work Environment Authority (AFS), Sweden.
Preventive strategies are often recommended by national bodies and focus on reducing exposure. The main precautions are:
- Prevent contamination caused by handling errors by centralizing preparation.13 This allows medication to be handled by specially trained personnel.
- Prevent release of toxic contamination by using “safety” devices.1 These aim to reduce aerosol contamination (e.g. aerosol filters) as well as drip contamination (e.g. needle free devices).
Some causes of contamination such as the vial surface, however, are difficult to prevent and so must be contained (Fig. 5):
- Any aerosol contamination which is formed is contained by using laminar air flow (LAF) or isolator cabinets.19
- Any drip contamination which is formed is prevented from being absorbed by using protective coverings such as gowns, masks and gloves.13
- In addition, regular controls such as blood tests are recommended in order to monitor exposure levels. If systematic protective measures are put in place, exposure can be reduced.13
Highlight Safety Products
Mini-Spike® 2 Chemo
Vented dispensing pin with swabable needlefree access valve (0,2µm air filter and 5µm particle filter).
Single-use, sterile infusion system for administration of different cytotoxic drugs via one single closed line-system by gravity or pressure
1 NIOSH. (2004) Preventing Occupational Exposures to Antineoplastic and other Hazardous Drugs in Healthcare Settings.
2 Kromhout H, Hoek F, Uitterhoeve R, Huijibers R, Overmars RF, Anzion R, Vermeulen R. (2000) 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; 44(7):551-60
3 Schierl R, Böhlandt A, Nowak D. (2009) Guidance Values Surface Monitoring of Antineoplastic Drugs in German Pharmacies. Occup Hyg; 53(7): 703-711
4 Mason HJ, Morton J, Garfitt SJ, Igbal S, Jones K. (2003) Cytotoxic drug contamination on the outside of vials delivered to a hospital pharmacy. Ann Occup Hyg; 47(8):681-5
5 Schmaus G, Schierl R, Funck S. (2002) Monitoring surface contamination by antineoplastic drugs using gas chromatography-mass spectometry and voltammetry. Am J Health Syst Pharm; 59(10):956-61
6 Fransman W, Vermeulen R, Kromhout H. (2004) Occupational dermal exposure to cyclophosphamide in Dutch hospitals: a pilot study. Ann Occup Hyg; 48(3):237-44
7 Huang YW, Jian L, Zhang MB, Zhou Q, Yan XF, Hua XD, Zhou Y, He JL. (2012) An investigation of oxidative DNA damage in pharmacy technicians exposed to antineoplastic drugs in two Chinese hospitals using the urinary 8-OHdG assay. Biomed Environ Sci; 25(1):109-16
8 Connor TH, DeBord DG, Pretty JR, Oliver MS, Roth TS, Lees PS, Krieg EF Jr, Rogers B, Escalante CP, Toennis CA, Clark JC, Johnson BC, McDiarmid MA. (2010) Evaluation of antineoplastic drug exposure of health care workers at three university-based US cancer centers. J Occup Environ Med. 2010 Oct; 52(10):1019-27
9 Sessink PJ. Wittenhorst BC, Anzion RB, Bos RP. (1997) Exposure of pharmacy technicians to antineoplastic agents: reevaluation after additional protective measures. Arch Environ Health ; 52(3): 240-4
10 Gielen K, Goossens A. (2001) Occupational allergic contact dermatitis from drugs in healthcare workers. Contact Dermatitis; 45(5): 273-9
11 AFS 2005
12 Placlitaxel SmPC (2010)
13 Boiano JM, Steege AL, Sweeney MH. (2014) Adherence to safe handling guidelines by healthcare workers who administer antineoplastic drugs. J Occup Environ Hyg; 11(11):728-40
14 Health Counsel (1994)
15 Sessink PJ, Kroese ED, van Kranen HJ, Bos RP. (1995) Cancer risk assessment for health care workers occupationally exposed to cyclophosphamide. Int Arch Occup Environ Health; 67(5):317-23
16 Skov T, Maarup B, Olsen J, Rørth M, Winthereik H, Lynge E. (1992) Leukaemia and reproductive outcome among nurses handling antineoplastic drugs. Br J Ind Med; 49(12): 855-61
17 Connor TH, Lawson CC, Polovich M, McDiardmid MA. (2014) Reproductive health risks associated with occupational exposures to antineoplastic drugs in health care settings: a review of evidence. J Occup Environ Med; 56(9):901-10
18 Sotaniemi EA, Sutinen S, Arranto AJ, Sutinen S, Sotaniemi KA, Lehtola J, Pelkonen RO. (1983) Liver damage in nurses handling cytostatic agents. Acta Med Scand; 214(3):181-9
19 Solass W, Giger-Pabst U, Zieren J, Reymond MA. (2013) Pressurized intraperitoneal aerosol chemotherapy (PIPAC): occupational health and safety aspects. Ann Surg Oncol; 20(11):3504-11
20 QuapoS 3 Quality Standard for the Oncology Pharmacy Service with Commentary. Institute for Applied Healthcare Sciences (IFAHS e.V.) for the German Society of Oncology Pharmacy (DGOP e.V.). 2003
21 Mälkönen T, Jolanki R, Alanko K, Luukkonen R, Aalto-Korte K, Lauerma A, Susitaival P. A 6-month follow-up study of 1048 patients diagnosed with an occupational skin disease. Contact Dermatitis 2009; 61(5): 261-8
22 Macmillan cancer support website. A guide to benefits and financial help for people affected by cancer.
23 IGBCE. Manteltarifvertrag 2000 http://www.ncbi.nlm.nih.gov/pubmed/2000
24 Flintoff JP. Thalidomide: the battle for compensation goes on. The Sunday Times. March 23, 2008 http://www.timesonline.co.uk/tol/life_and_style/health/article3602694.ece
25 Horner MJ, Ries LAG, Krapcho M, et al (eds). SEER Cancer Statistics Review, 1975-2006, National Cancer Institute. Bethesda, Md, based on November 2008 SEER data submission, posted to the SEER website, 2009. Table I-21, US Prevalence Counts, Invasive Cancers Only, January 1, 2006, Using Different Tumor Inclusion Criteria. Accessed at http://seer.cancer.gov/csr/1975_2006/results_single/sect_01_table.21_2pgs.pdf on September 3, 2009
26 Based on Uk National Health Service (NHS) pay recommendations: approximate annual salary of 30,000 € (100 € per day) - [NHS 2010]
27 IARC Monographs on the Evaluation of Carcinogenic Risks to Humans - Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs 1987. Supplemen 7; Volumes 1-42
28 US Bureau of Labor Statistics. May 2006 National and Occupational Employment and Wage Estimates. Washington DC: United States Department of Labor, Bureau of Labor Statistics; 2007.
29 Lawson CC, Rocheleau CM, Whelan EA, et al. Occupational exposures among nurses and risk of spontaneous abortion. Am J Obstet Gynecol 2012;206:327.e1-8.