Antineoplastic Agents Risk Factors

Overview of risk factors

The adverse health effects associated with antineoplastic agents (cancer chemotherapy and cytotoxic drugs) in patients are well documented. The very nature of antineoplastic agents makes them harmful to healthy cells and tissues as well as the cancerous cells.

Healthcare workers at risk

For cancer patients with a life-threatening disease, there is great benefit to treatment with antineoplastic agents. However, for healthcare workers exposed to antineoplastic agents on the job, precautions are important to eliminate or reduce exposure.

Pharmacists or nurses who prepare and/or administer these drugs have the highest potential for exposure to antineoplastic agents. Other healthcare workers at risk include:

• Physicians and operating room personnel.
• Shipping/receiving, custodial, laundry, and waste workers.
• Veterinary oncology workers.

Health impacts

In addition to acute or short-term effects related to treatment with antineoplastic agents, the following long-term or chronic effects have been documented:

• Liver and kidney damage.
• Bone marrow damage.
• Lung and heart damage.
• Infertility (temporary and permanent).
• Effects on reproduction and the developing fetus in pregnant women.
• Hearing impairment.
• Cancer.

The International Agency for Research on Cancer (IARC) found a number of antineoplastic agents are associated with cancer in patients. IARC currently lists:

• Eleven agents and two combined therapies as Group 1 (human carcinogens).
• Twelve agents as Group 2A (probable human carcinogens).
• Eleven agents as Group 2B (possible human carcinogens).

Identifying exposures

A number of studies have documented environmental and worker exposure to antineoplastic agents in healthcare settings. In addition, analytical methods, such as measuring the drugs and/or their metabolites in worker urine, help document worker exposure.

Worker exposures

Some of the following biological endpoints are used to evaluate worker exposure:

• Urine mutagenicity.
• Chromosomal damage.
• Sister chromatid exchange.
• Micronuclei induction.
• DNA damage.
• HPRT mutations.
• Thioether excretion.

Environmental exposures

Similar analytical methods measure the level of environmental contamination in the workplace. Although limited studies on air sampling exist, there have been numerous studies published on environmental wipe sampling for these drugs.

Preventing exposures

In September 2004, The National Institute for Occupational Safety and Health (NIOSH) published an Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings, 2004, (DHHS (NIOSH) Publication No. 2004-165). This topic page is an expanded bibliography of related publications drawn from the published literature related to the Alert.

Additional information on this topic can be found on the NIOSH Hazardous Drug Exposures in Healthcare page.

Resources

In addition to the resources below, you can explore the NIOSH Hazardous Drugs Resources page or see the NIOSHTIC-2 database search results on Antineoplastic Agents/Chemotherapy. NIOSHTIC-2 is a database of occupational safety and health publications funded in whole or in part by NIOSH.

Decontamination and deactivation

Several reports have dealt with methods for the decontamination and/or deactivation of antineoplastic agents. Although bleach (hypochlorite) is often recommended for the decontamination purposes, it is not effective with all classes of agents. Therefore, it cannot be assumed that cleaning with bleach solutions will destroy all types of antineoplastic agents.

• AIHA Healthcare Working Group Hazardous Drugs Project Team. Chemotherapy hood decommissioning for disposal or recycling. Fact sheet. Approved by AIHA Board: October 17, 2016. Falls Church, VA: American Industrial Hygiene Association (AIHA).
• Anastasi M, Rudaz S, Lamerie TQ, Odou P, Bonnabry P and Fleury-Souverain S. Efficacy of two cleaning solutions for the decontamination of 10 antineoplastic agents in the biosafety cabinets of a hospital pharmacy. Ann Occup Hyg. 2015; 59:895-908.
• Cox J, Speed V, O’Neal S, Hasselwander T, Sherwood C, Eckel SF and Zamboni WC. Development and evaluation of a novel product to remove surface contamination of hazardous drugs. J Oncol Pharm Pract. 2017; 23:103-115.
• Gohma H, Inoue Y, Asano M and Sugiura SI. Testing the degradation effects of three reagents on various antineoplastic compounds. J Oncol Pharm Practice. 2014; (Epub ahead of print) DOI: 10.1177/1078155214530175.
• Hon CY, Chua PPS, Danyluk Q and Astrakianakis G. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study. J Oncol Pharm Practice. 2014; 20:210-216.

Effects of occupational exposure

There is a limited amount of evidence in the literature concerning occupational cancer related to antineoplastic agents.

• Barle EL, Winkler GC, Ulrich P, Perino C, Kuster M, Probst A, Thielen S and Bechter R. Cancer risk of immunosuppressants in manufacturing. Regul Toxicol Pharmacol.2014; 70:122-124.
• Fransman W, Kager H, Meijster T, Heederik D, Kromhout H, Portengen L and Blaauboer BJ. Leukemia from dermal exposure to cyclophosphamide among nurses in the Netherlands: quantitative assessment of the risk. Ann Occup Hyg. 2014; 58:271-282.

Evaluation of protective equipment

The most often used type of protective equipment for handling antineoplastic agents is gloves. Typically, latex and other materials have been employed for this use. However, with the concern over latex allergies, newer materials are being marketed and evaluated for use with these agents. Protective gowns are another piece of equipment that is commonly used in the handling of antineoplastic agents.

• Alexander K, Northrup N, Clarke D, Lindell H and Laver T. Engineering controls in veterinary oncology: a survey of 148 ACVIM board-certified oncologists and environmental surveillance in 20 specialty hospitals. Vet Comp Oncol 2018; 16:385-391.
• Douglas K, Richter A, Dorey M and Rizvi I. Refining PPE usage for HD compounding: Part 1. Pharm Pract Prod. 2017; February 2017 14 (2):18-21.
• Hennessy KA and Dynan J. Improving compliance with personal protective equipment use through the model for improvement and staff champions. Clin J Oncol Nurs. 2014; 18:497-500.
• Krämer I, Federici M. Kaiser V and Thiesen J. Media-fill simulation tests in manual and robotic aseptic preparation of injection solutions in syringes. J Oncol Pharm Pract. 2016; 22:195-204.
• Landeck L, Gonzalez E and Koch OM. Handling chemotherapy drugs – Do medical gloves really protect? Int J Cancer, 137: 1800-1805.
• Ledford A and Wetzel B. Constructing an oncology pharmacy. Pharm Purch Prod. May 2017; 14 (5):10-15.
• Tomas ME, Kundrapu S, Thota P, Sunkesula VCK, Cadnum JL, Mana TSC, Jencson A, O’Donnell M, Zabarsky TF, Hecker MT, Ray AJ, Wilson BM and Donskey CJ. Contamination of health care personnel during removal of personal protective equipment. JAMA Intern Med. 2015; 175 (12): 1904-1910.
• Wagner JT. Ensure safe use of CAIs and CACIs. Pharm Purchasing and Products. 2014; 11 (12):12,14.

Handling guidelines, recommendations, and regulations

Since it was first recognized that occupational exposure to antineoplastic agents posed a potential health risk to workers exposed to these agents, various groups, institutions and agencies around the world have developed and published guidelines or recommendations for handling antineoplastic agents.

• Ahmad N, Simanovski V, Hertz S, Klaric G, Kaizer L and Krzyzanowska MK. Oral chemotherapy practices at Ontario cancer centres. J Oncol Pharm Pract. 2015; 21(4): 249-257.
• Alexander M, King J, Bajel A, Doecke C, Fox P, Lingaratnam S, Mellor JD, Nicholson L, Roos I, Saunders T, Wilkes J, Zielinski R, Byrne J, MacMillan K, Mollo A, Kirsa S and Green M. Australian consensus guidelines for the safe handling of monoclonal antibodies for cancer treatment by healthcare personnel. Intern Med J. 2014; 44:1018-1026.
• Anon. Practice fined for health and safety record. Vet Rec. 2014; 175:418.
• ASTM D666-01 “Standard Practice for Field Collection of Organic Compounds from Surface Using Wipe Sampling,” ASTM International.
• Barle EL, Winkler GC, Glowienke S, Elhajouji A, Nunic J and Martus HJ. Setting occupational exposure limits for genotoxic substance in the pharmaceutical industry. Toxicol Sci. 2016; 151:2-9.
• Bayraktar-Ekincioglu A, Korubük G and Demirkan K. An evaluation of chemotherapy drug preparation process in hospitals in Turkey: a pilot study. J Oncol Pharm Pract 2018; 24:563-573.
• Bohlandt A, Groeneveld S, Fischer E and Schierl R. Cleaning Efficiencies of three cleaning agents on four different surfaces after contamination by Gemcitabine and 5-fluorouracile. J Occup Environ Hyg. 2015; 12:384-392.
• Canal-Raffin M, Khennoufa K, Martinez B, Goujon Y, Folch C, Ducint D, Titier K, Brochard P, Verdun-Esquer C, Molimard M. Highly sensitive LC-MS/MS methods for urinary biological monitoring of occupational exposure to cyclophosphamide, ifosfamide, and methotrexate antineoplastic drugs and routine application. J Chromatogr B. 2016; 1038:109–117.
• Celano P, Fausel CA, Kennedy EB, Miller TM, Oliver TK, Page R, Ward JC and Zon RT. Safe handling of hazardous drugs: ASCO standards. J Clin Oncol 2019; DOI: 10.1200/JCO.18.01616.
• Connor TH, Douglass K, Eisenberg S, Kastango ES, Kienle PC, Massoomi F and Parsad SD. Improving safe handling practices for hazardous drugs: toolkit. Mansur J, contributing editor. 2016. Joint Commission Resources (www.jcrinc.comexternal icon).
• Crul M and Simons-Sanders K. Carry over of antineoplastic drug contamination in Dutch hospital pharmacies. J Oncol Pharm Pract 2018; 24:483-489.
• Elshaer NS. Adverse health effects among nurses and clinical pharmacists handling antineoplastic drugs: adherence to exposure control methods. J Egypt Public Health Assoc 2017; 92:144-155.
• Forshay CM, Streeter SO, Salch SA and Eckel SF. Application of the 2015 proposed NIOSH vapor containment performance protocol for closed system transfer devices used during pharmacy compounding and administration of hazardous drugs. J Oncol Pharm Pract 2018; July, doi: 10.1177/1078155218787256external icon.
• Ho KV, Edwards MS, Solimando DA Jr, Johnson AD. Determination of extended sterility for single-use vials using the Phaseal closed-system transfer device. J Hematol Oncol Pharm. 2016; 6:46-50.
• Hon CY, Teschke K and Shen H. Healthcare workers’ knowledge, perceptions and behaviors regarding antineoplastic drugs: survey from British Columbia, Canada. J Occup Environ Hyg. 2015; 12:669-677.
• Johnson TM. Long-term care: safe drug handling of oral chemotherapy. The Consultant Pharmacist. 2017; 32:74–83.
• Kibby T. A review of surface wipe sampling compared to biologic monitoring for occupational exposure to antineoplastic drugs. J Occup Environ Hyg. 2017; 14:159–174.
• Klahn S. Chemotherapy safety in clinical veterinary oncology. Bet Clin Small Anim. 2014; 44:941-963.
• Lecordier J, Plivard C, Gardeux M, Daouadi K and Lehet J-J. To create a cleanroom controlled environement using a mobile air decontamination unit for the preparation of antineoplastic drugs. J Oncol Pharm Pract. 2014. (epub. DOI: 10.1177/1078155214565125)
• McGowan D. Safe handling and administration of MABS: the guidance. Brit J Nurs. 2015; 24:S14-20.
• Müller-Ramírez C, Squibb K and McDiarmid M. Accessible analytical methodology for assessing workplace contamination of antineoplastic drugs in limited-resource oncology health-care settings. J Anal Sci and Technol. 2016; 7:11.
• Murashov V and Howard J. Risks to health care workers from nano-enabled medical products. J Occup Environ Hyg. 2015; 12:D75-D85.
• Nurgat ZA , Lawrence M , Elhassan TA , Al Nahedh M , Ashour M , Alaboura D , Al-Jazairi AS and Al-jedai A. Comparison of closed system transfer devices for turnaround time and ease of use. J Oncol Pharm Pract 2018. DOI: 10.1177/1078155218781900.
• Polovich M, Olsen M and LeFebvre K (eds.) 2014. Chemotherapy and biotherapy guidelines and recommendations for practice. Pittsburgh, PA: Oncology Nursing Society.
• Polovich M. Minimizing occupational exposure to antineoplastic agents. J Infus Nurs. 2016; 39:307–313.
• Poupeau C, Tanguay C, Caron NJ and Bussières J-F. Multicenter study of environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in 48 Canadian hospitals. J Oncol Pharm Pract 2018; 24:9-17.
• Ramphal R, Bains T, Vaillancourt R, Osmond MH and Barrowman N. Occupational exposure to cyclophosphamide in nurses at a single center. J Occup Environ Med. 2014; 56:304-312.
• Redic KA, Fang K, Christen C and Chaffee BW. Surface contamination of hazardous drug pharmacy storage bins and pharmacy distributor shipping containers. J Oncol Pharm Pract 2018; 24:91-97.
• Ricci MS, Fazier M, Moore J, Cromwell M, Galush WJ, Patel AR, Adler M, Altenburger U, Grauschopf U, Goldbach P, Fast JL, Kramer I and Mahler HC. In-use physicochemical and microbiological stability of biological parenteral products. Am J Health-Sys Pharm. 2015; 72:396-407.
• Salman D, Barton S and Gebara SN. Improving the stability of anticancer drugs. J Oncol Pharm Practice. 2014; 20:236.
• Siden R, Kem R, Ostrenga A, Nicksy D, Bernhardt B and Bartholomew J. Templates of patient brochures for the preparation, administration and safe-handling of oral chemotherapy. J Oncol Pharm Practice. 2014; 20:217-224.
• Trovato, JA and Tuttle LA. Oral chemotherapy handling and storage practices among Veterans Affairs oncology patients and caregivers. J Oncol Pharm Pract. 2014; 20:88-92.
• U.S. Pharmacopeia (USP) Revised Chapter (797) Pharmaceutical Compounding-Sterile Preparations.
• Umemura, M., Itoh, A., Ando, Y., Yamada, K., Wakiya, Y, and Nabeshima, T. Effects of outside air temperature on the preparation of antineoplastic drug solutions in biological safety cabinets. Journal of Oncology Pharmacy Pract. 2015; 21(4): 243-248.
• Vyas N, Yiannakis D, Turner A and Sewell GJ. Occupational exposure to anti-cancer drugs: A review of effects of new technology. J Oncol Pharm Pract. 2014; 20:278-287.
• Yuki M, Takase K, Sekine S and Ishida T. Evaluation of surface contamination with cyclophosphamide in the home setting of outpatients on cancer chemotherapy. J Nurs Educ Prac. 2014; 4:16-23.
• Zhang J, Bao J, Wang R, Geng Z, Chen Y, Xie XY, Jiang L, Deng Y, Liu G, Xu R and Miao L. A multicenter study of biological effects assessment of pharmacy workers occupationally exposed to antineoplastic drugs in pharmacy intravenous admixture services. J Haz Mat. 2016; 315: 86–92.

Occupational monitoring

Over the past several years, the direct measurement of antineoplastic agents in body fluids of healthcare workers has been employed to assess exposure to these agents. Methods for a number of the more common agents are included in the citations on this page. Currently, these techniques are only used in research settings and not for routine monitoring of healthcare workers.

• Dugheri S, Bonari A, Pompilio I, Boccalon P, Tognoni D, Cecchi M, Ughi M, Mucci N and Arcangeli G. Analytical strategies for assessing occupational exposure to antineoplastic drugs in healthcare workplaces. Medycyna Pracy 2018; 69:589-604.
• Fabrizi G, Fioretti M and Rocca LM. Dispersive solid-phase extraction procedure coupled to UPLC-ESI-MS/MS analysis for the simultaneous determination of thirteen cytotoxic drugs in human urine. Biomed Chromatogr. 2016; 30:1297-1308.
• Gómez-Oliván LM, Miranda-Mendoza GD, Cabrera-Galeana PA, Galar-Martínez M, Islas-Flores H, SanJuan-Reyes N, Neri-Cruz N and Garcia-Medina S. Oxidative stress induced in nurses by exposure to preparation and handling of antineoplastic drugs in Mexican Hospitals: A multicentric study. Oxid Med Cell Longev. 2014; http://dx.doi.org/10.1155/2014/858604.
• Koller M, Böhlandt A, Haberl C, Nowak D and Schierl R. Environmental and biological monitoring on an oncology ward during a complete working week. Toxicol Letters 2018; 298:158-163.
• Ladeira C, Viega S, Padua M, Carolino E, Gomes MC and Brito M. Genotoxic assessment in different exposure groups working with antineoplastic agents. Occupational Safety and Hygiene III. Arezes PM, Baptista JS, Barroso MP, Carneiro P, Cordeiro P, Nelson C, Melo RB, Miguel AS and Perestrelo G. London: Taylor and Francis Group. 2015. ISBN 978-1-138-02765-7.
• Poupeau C, Tanguay C, Plante C, Gagne S, Caron N and Bussieres JF. Pilot study of biological monitoring of four antineoplastic drugs among Canadian healthcare workers. J Oncol Pharm Pract. 2017; 23:323–332.
• Ramphal R, Bains T, Goulet G and Vaillancourt R. Occupational exposure to chemotherapy of pharmacy personnel at a single centre. Can J Hosp Pharm. 2015; 68:104-112.
• Soltani C, Grignani E, Zaratin L, Santorelli D, Studioso E, Lonati D, Locatelli CA, Pastoris O, Negri S and Cottica D. A new, sensitive and versatile assay for quantitative determination of α-fluoro-β-alanine (AFBA) in human urine by using the reversed-phase ultrahigh performance-tandem mass spectrometry (rp-UHPLC-MS/MS) system. Toxicol Letters 2018; 298:164-170
• Villarinia M, Gianfredia V, Levoratoa S, Vannini S, Salvatori T and Moretti M. Occupational exposure to cytostatic/antineoplastic drugs and cytogenetic damage measured using the lymphocyte cytokinesis-block micronucleus assay: a systematic review of the literature and meta-analysis. Mutat Res. 2016; 770(Pt A):35–45.