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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 (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. . Ann Occup Hyg. 2015; 59:895-908.
• Cox J, Speed V, O’Neal S, Hasselwander T, Sherwood C, Eckel SF and Zamboni WC. . J Oncol Pharm Pract. 2017; 23:103-115.
• Gohma H, Inoue Y, Asano M and Sugiura SI. . J Oncol Pharm Practice. 2014; (Epub ahead of print) DOI: 10.1177/1078155214530175.
• Hon CY, Chua PPS, Danyluk Q and Astrakianakis G. . 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. . Regul Toxicol Pharmacol.2014; 70:122-124.
• Fransman W, Kager H, Meijster T, Heederik D, Kromhout H, Portengen L and Blaauboer BJ. . 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. . 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. . Clin J Oncol Nurs. 2014; 18:497-500.
• Krämer I, Federici M. Kaiser V and Thiesen J. . J Oncol Pharm Pract. 2016; 22:195-204.
• Landeck L, Gonzalez E and Koch OM. ? 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. . 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. . 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. . Intern Med J. 2014; 44:1018-1026.
• Anon. . 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. . Toxicol Sci. 2016; 151:2-9.
• Bayraktar-Ekincioglu A, Korubük G and Demirkan K. . J Oncol Pharm Pract 2018; 24:563-573.
• Bohlandt A, Groeneveld S, Fischer E and Schierl R. . 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. . J Chromatogr B. 2016; 1038:109–117.
• Celano P, Fausel CA, Kennedy EB, Miller TM, Oliver TK, Page R, Ward JC and Zon RT. . 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. . Mansur J, contributing editor. 2016. Joint Commission Resources (www.jcrinc.comexternal icon).
• Crul M and Simons-Sanders K. . J Oncol Pharm Pract 2018; 24:483-489.
• Elshaer NS. . J Egypt Public Health Assoc 2017; 92:144-155.
• Forshay CM, Streeter SO, Salch SA and Eckel SF. . 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. . J Occup Environ Hyg. 2015; 12:669-677.
• Johnson TM. . The Consultant Pharmacist. 2017; 32:74–83.
• Kibby T. . J Occup Environ Hyg. 2017; 14:159–174.
• Klahn S. . Bet Clin Small Anim. 2014; 44:941-963.
• Lecordier J, Plivard C, Gardeux M, Daouadi K and Lehet J-J. . J Oncol Pharm Pract. 2014. (epub. DOI: 10.1177/1078155214565125)
• McGowan D. . 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. . 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. . 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. . J Infus Nurs. 2016; 39:307–313.
• Poupeau C, Tanguay C, Caron NJ and Bussières J-F. . J Oncol Pharm Pract 2018; 24:9-17.
• Ramphal R, Bains T, Vaillancourt R, Osmond MH and Barrowman N. . J Occup Environ Med. 2014; 56:304-312.
• Redic KA, Fang K, Christen C and Chaffee BW. . 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. . Am J Health-Sys Pharm. 2015; 72:396-407.
• Salman D, Barton S and Gebara SN. . 2014; 20:236.
• Siden R, Kem R, Ostrenga A, Nicksy D, Bernhardt B and Bartholomew J. . J Oncol Pharm Practice. 2014; 20:217-224.
• Trovato, JA and Tuttle LA. . J Oncol Pharm Pract. 2014; 20:88-92.
• U.S. Pharmacopeia (USP) Revised Chapter (797) .
• Umemura, M., Itoh, A., Ando, Y., Yamada, K., Wakiya, Y, and Nabeshima, T. . Journal of Oncology Pharmacy Pract. 2015; 21(4): 243-248.
• Vyas N, Yiannakis D, Turner A and Sewell GJ. . 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. . 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. . Medycyna Pracy 2018; 69:589-604.
• Fabrizi G, Fioretti M and Rocca LM. . 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. . Oxid Med Cell Longev. 2014; http://dx.doi.org/10.1155/2014/858604.
• Koller M, Böhlandt A, Haberl C, Nowak D and Schierl R. . 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. . J Oncol Pharm Pract. 2017; 23:323–332.
• Ramphal R, Bains T, Goulet G and Vaillancourt R. . 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. . Toxicol Letters 2018; 298:164-170
• Villarinia M, Gianfredia V, Levoratoa S, Vannini S, Salvatori T and Moretti M. . Mutat Res. 2016; 770(Pt A):35–45.