HAZARDOUS DRUG EXPOSURES IN HEALTHCARE

Since most antineoplastic agents and/or their metabolites are excreted in the urine and a large percentage of them are mutagenic, the analysis of the urine of workers handling antineoplastic agents is a means to document exposure. However, relatively high doses are needed in order to detect an effect and, because the assays are nonspecific, confounding factors must be controlled for. Concentrated urine from workers is usually tested with a bacterial mutagenicity assay (Ames test) that is sensitive to many of the antineoplastic agents and/or their metabolites and the results compared to a control population.

• Anderson RW, Puckett WH, Dana WJ, Nguyen TV, Theiss JC and Matney TS. Risk of handling injectable antineoplastic agents. Am J Hosp Pharm. 1982;39:1881-87.
• Barale R, Sozzi G, Toniolo P, Borghi O, Reali D, Loprieno N and Della Porta G. Sister-chromatid exchanges in lymphocytes and mutagenicity in urine of nurses handling cytostatic drugs. Mutat Res. 1985;157:235-40.
• Benhamou S, Callais F, Sancho-Garnier H, Min S, Courtois YA and Festy B. Mutagenicity in urine from nurses handling cytostatic agents. Eur J Cancer Clin Oncol. 1986;22:1489-93.
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• Caudell KA, Vredevoe DL, Dietrich MF, Caudell TP, Hoban MJ and Block JB. Quantification of urinary mutagens in nurses during potential antineoplastic agent exposure:A pilot study with concurrent environmental and dietary control. Cancer Nurs. 1988;11:41-50.
• Cloak MM, Connor TH, Stevens KR, Theiss JC, Alt JM, Matney TS and Anderson RW. Occupational exposure of nursing personnel to antineoplastic agents. Oncol Nurs Forum. 1985;12:33-39.
• Connor TH, Theiss JC Anderson RW, Puckett WH and Matney TS. Re-evaluation of urine mutagenicity of pharmacy personnel exposed to antineoplastic agents. Am J Hosp Pharm. 1986;43:1236-39.
• Courtois YA, Beaubestre C, Benhamou S, Min S, Callais F, Sancho-Carnier HS and Festy B. Determination de la génotoxicité urinaire:Application au dépistage de l’exposition tabagique et/ou professionnelle. Ann Pharmaceutiques Francaises. 1987;45:289-300.
• DeMeó MP, Mérono S, DeBaille AD, Botta A, Laget M, Guiraud H and DumJnil G. Monitoring exposure of hospital personnel handling cytostatic drugs and contaminated materials. Int Arch Occup Environ Health. 1995;66:363-68.
• Falck K, Gröhn P, Sorsa M, Vainio H, Heinonen E and Holsti LR. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet. 1979;1:1250-51.
• Friederich U, Molko F, Hofmann V, Scossa D, Würgler FE and Senn HJ. Limitations of the salmonella/mammalian microsome assay (Ames test) to determine occupational exposure to cytostatic drugs. Eur J Cancer Clin Oncol. 1986;22:567-75.
• Gibson JF, Gompertz D and Hedworth-Whitty RB. Mutagenicity of urine from nurses handling cytotoxic drugs. Lancet. 1984;1:100-01.
• Hama T, Aoyama T, Shirai T, Higuchi S, Yokokawa T and Sugimoto Y. Environmental Contamination due to preparation of cyclophosphamide and exposure to pharmacists to it. Jpn J Pharm Health Care Sci. 2009; 35: 693-700.
• Hoffman DM. Lack of urine mutagenicity of nurses administering pharmacy prepared doses of antineoplastic agents. Am J Intravenous Ther Clin Nutrition. 1983;28-31.
• Kolmodin-Hedman B, Hartvig P, Sorsa M and Falck K. Occupational handling of cytostatic drugs. Arch Toxicol. 1983;54:25-33.
• Krepinsky A, Bryant DW, Davison L, Heddle J, McCalla DR, Douglas G and Michalko K. Comparison of three assays for genetic effects of antineoplastic drugs on cancer patients and their nurses. Environ Mol Mutagen. 1990;15:83-92.
• Labuhn K, Valanis B, Schoeny R, Loveday K and Vollmer WM. Nurses’ and pharmacists exposure to antineoplastic drugs:Findings from industrial hygiene scans and urine mutagenicity tests. Cancer Nursing. 1998;21:79-89.
• Lovejoy N, Powers L, Flessel P, Lecocq G, Guirguis G and Chang K. Mutagenicity in urine of hospital workers who prepare and administer chemotherapy agents. EMS Abstracts. 1985;7.
• Newman MA, Valanis BG, Schoeny RS and Hee SQ. Urinary biological monitoring markers of anticancer drug exposure in oncology nurses. Am J Pub Health. 1994;84:852-55.
• Nguyen TV, Theiss JC and Matney TS. Exposure of pharmacy personnel to mutagenic antineoplastic drugs. Cancer Res. 1982;42:4792-96.
• Pohlová H, Cerná M and Rössner P. Chromosomal aberrations, SCE and urine mutagenicity in workers occupationally exposed to cytostatic drugs. Mutat Res. 1986;174:213-17.
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• Ratcliffe JM. Occupational exposure to cancer chemotherapeutic agents in pharmacists and nurses. NIOSH (Industry-wide study E:-80-41) Washington, DC, General Printing Office, 1983.
• Rogers B and Emmett EA. Handling antineoplastic agents: Urine mutagenicity in nurses. Image: J of Nurs Scholar. 1987;19:108-13.
• Rössner P, Cerná M, Pokorána D, Hájek V and Petr J. Effect of ascorbic acid prophylaxis on the frequency of chromosome aberrations, urine mutagenicity and nucleolus test in workers occupationally exposed to cytostatic drugs. Mutat Res. 1988;208:149-53.
• Sabatini L, Barbieri A, Lodi V and Violante FS. Biological monitoring of occupational exposure to antineoplastic drugs in hospital settings. Med Lav. 2012;103(5):394-401.
• Sorsa M, Pyy L, Salomaa S, Nyland L and Yager JW. Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals. Mutat Res. 1988;204:465-79.
• Stiller A, Obe G, Boll I and Pribilla W. No elevation of the frequencies of chromosomal alterations as a consequence of handling cytostatic drugs: Analyses with peripheral blood and urine of hospital personnel. Mutat Res. 1983;121:253-59.
• Stücker I, Hirsch A, Doloy T, Bastie-Sigeac, I and Hémon D. Urine mutagenicity, chromosomal abnormalities and sister chromatid exchanges in lymphocytes of nurses handling cytostatic drugs. Int Arch Occup Environ Health. 1986;57:195-205.
• Thiringer G, Granung G, Holmén A, Hogstedt B, Jarvhom B, Jonsson D, Persson L, Wahlstrom J and Westin J. Comparison of methods for the biomonitoring of nurses handling antitumor drugs. Scand J Work Environ Health. 1991;17:133-38.
• Venitt S, Crofton-Sleigh C, Hunt J, Speechley V and Briggs K. Monitoring exposure of nursing and pharmacy personnel to cytotoxic drugs: Urinary mutation assays and urinary platinum as markers of absorption. Lancet. 1984;1:74-77.
• 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.

Chromosomal aberrations represent damage to DNA that is visible in stained cells. Usually, lymphocytes are obtained from exposed populations and examined for various types of chromosomal damage. This methodology has been applied to numerous occupational and environmental exposures to chemicals and radiation in addition to extensive animal studies. A number of chromosomal aberration studies have demonstrated an increase in chromosomal damage in the lymphocytes of nurses and pharmacists handling antineoplastic agents.

• Anwar WA, Salama SI, Serafy MM, Hermida S and Hafez AS. Chromosomal aberrations and micronucleus frequency in nurses occupationally exposed to cytotoxic drugs. Mutagenesis. 1994;9:315-317.
• Boughattas AB, Bouraoui S, Debbabi F, El Ghazel H, Saad A and Mrizak N. Genotoxic risk assessment of nurses handling antineoplastic drugs. Ann Biol Clin (Paris). 2010; 68:545-553.
• Bouraoui S, Brahem A, Tabka F, Mrizek N, Saad A and Elghezal H. Assessment of chromosomal aberrations, micronuclei and proliferation rate index in peripheral lymphocytes from Tunisian nurses handling cytotoxic drugs. Environ Tox and Pharm. 2011; 31:250-257.
• Brumen V, Horvat D and Trošic I. Potential genotoxic risk related to simultaneous exposure to radionuclides and cytostatics. Am J Ind Med. 1995;27:871-876.
• Burgaz S, Karahalil B, Canhi Z, Terzioglu F, Ancel G, Anzion RB, Bos RP and Huttner E. Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations. Hum Exp Tox. 2002; 21:129-135.
• Cavallo D, Usini CL, Perniconi B, Di Francesco A, Giglio M, Rubino FM, Marinaccio A, Iavicoli S. Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees. Mutat Res. 2005; 587:45-51.
• Cavallo D, Ursini CL, Omodeo-Salé E and Iavicoli S. Micronucleus induction and FISH analysis in buccal cells and lymphocytes of nurses administering antineoplastic drugs. Mutat Res. 2007; 628:11-18.
• Cooke J, Williams J, Morgan RJ, Cooke P and Calvert RT. Use of cytogenetic methods to determine mutagenic changes in the blood of pharmacy personnel and nurses who handle cytotoxic agents. Am J Hosp Pharm. 1991;48:1199-1205.
• Ferguson LR, Everts R, Robbie MA, Harvey V, Tempel D, Mak D and Gerred AJ. The use within New Zealand of cytogenetic approaches to monitoring of hospital pharmacists for exposure to cytotoxic drugs: report of a pilot study in Auckland. Aust J Hosp Pharm. 1988; 18:228-233.
• Fucic A, Jazbec A, Mijic A, Seso-Simic D and Tomek R. Cytogenetic consequences after occupational exposure to antineoplastic drugs. Mutat Res. 1998;416:59-66.
• Gianfredi V, Salvatori T, Nucci D, Villarini M and Moretti M. Rischio genotossico da manipolazione di farmad chemioterapid antiblastid negli operatori sanitari professionalmente esposti: revisione sistematica della letteratura e meta-analisi. Recenti Prog Med 2017; 108:511-520. (Italian with English abstract)
• Goloni-Bertollo EM, Tajara EH, Manzato AJ and Varella-Garcia M. Sister chromatid exchanges and chromosome aberrations in lymphocytes of nurses handling antineoplastic drugs. Int J Cancer. 1992;50:341-344.
• Grummt T, Grummt H-J and Schott G. Chromosomal aberrations in peripheral lymphocytes of nurses and physicians handling antineoplastic drugs. Mutat Res. 1993; 302: 19-24.
• Harris PE, Connor TH, Stevens KR and Theiss JC. Cytogenetic assessment of occupational exposure of nurses to antineoplastic agents. J Occup Med Toxicol. 1992;1:243-254.
• Jakab MG, Major J and Tompa A. Follow-up genotoxicological monitoring of nurses handling antineoplastic drugs. J Toxicol Environ Health. 2001; 62:307-318.
• Karelová J, Jablonická A, Gavora J and Hano Lubomír. Chromosome and sister-chromatid exchange analysis in peripheral lymphocytes and mutagenicity of urine in anesthesiology personnel. Int Arch Occup Environ Health. 1992;64:303-306.
• Kopjar N, Garaj-Vrhovac V, Kašuba V, Rozgaj R, Ramić S, Pavlica V and Želježić D. Assessment of genotoxic risks in Croatian health care workers occupationally exposed to cytotoxic drugs: A multi-biomarker approach. Int J Hyg Environ Health. 2009; 212:414-431.
• Kopjar N, Graj-Vrhovac V and Milas I. Acute cytogenetic effects of antineoplastic drugs on peripheral blood lymphocytes in cancer patients [sic] chromosome aberrations and micronuclei. Tumori. 2002; 88:300-312.
• Krepinsky A, Bryant DW, Davison L, Heddle J, McCalla DR, Douglas G and Michalko K. Comparison of three assays for genetic effects of antineoplastic drugs on cancer patients and their nurses. Environ Mol Mutagen. 1990;15:83-92.
• Major J, Jakab MG and Tompa A. The frequency of induced premature centromere division in human populations occupationally exposed to genotoxic chemicals. Mutat Res. 1998; 445:241-249.
• McDevitt MA, Condon M, Stamberg J, Karp JE and McDiarmid M. Fluorescent in situ hybridization (FISH) in bone marrow and peripheral blood of leukemia patients: Implications for occupational surveillance. Mutat Res. 2007; 629:24-31.
• McDiarmid MA, Oliver MS, Roth TS, Rogers B. and Escalante CP. Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs. J Occup Environ Med. 2010; 52:1028-1034.
• McDiarmid MA, Rogers B and Oliver MS. Chromosomal effects of non-alkylating drug exposure in oncology personnel. Environ Mol Mutagen. 2014; 55:369-374.
• Milkovic-Kraus S and Horvat D. Chromosomal abnormalities among nurses occupationally exposed to antineoplastic drugs. Am J Ind Med. 1991;19:771-774.
• Milkovic-Kraus S, Kraus O, Kršnjavi H and Kubelka D. Environmental effects on chromosomes in oncology and radiology department personnel. Preventive Med. 1992;21:498-502.
• Moretti M, Grollino MG, Pavanello S, Bonfiglioli R, Villarini M, Appolloni M, Carrieri M, Savatini L, Dominici L, Stronati L, Mastrangelo G, Barbieri A, Fatigoni C, Bartolucci GB, Ceretti E, Mussi F and Monarca S. Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach. Int Arch Occup Environ Health. 2015; 88:683-695.
• Mušák L, Polakova V, Halasova E, Osina O, Vodickova L, Buchancova J, Hudeckova H and Vodicka P. Effect of occupational exposure to cytostatics and nucleotide excision repair polymorphism on chromosomal aberrations frequency. Interdisc Toxicol. 2009; 2:13-17.
• Nikula E, Kiviniitty K, Leisti J and Taskinen PJ. Chromosome aberrations in lymphocytes of nurses handling cytostatic agents. Scand J Work Environ Health. 1984;10:71-74.
• Oestreicher U, Stephan G and Glatzel M. Chromosome and SCE analysis in peripheral lymphocytes of persons occupationally exposed to cytostatic drugs handled with and without use of safety covers. Mutat Res. 1990;242:271-277.
• Pohlová H, Cerná M and Rössner P. Chromosomal aberrations, SCE and urine mutagenicity in workers occupationally exposed to cytostatic drugs. Mutat Res. 1986;174:213-217.
• Roussel C, Witt KL, Shaw PB and Connor TH. Meta-analysis of chromosomal aberrations as a biomarker of exposure in healthcare workers occupationally exposed to antineoplastic drugs. Mutation Research: Reviews in Mutation Research 2017, http://dx.doi.org/10.1016/j.mrrev.2017.08.002external icon.
• Rössner P, Cerná M, Pokorána D, Hájek V and Petr J. Effect of ascorbic acid prophylaxis on the frequency of chromosome aberrations, urine mutagenicity and nucleolus test in workers occupationally exposed to cytostatic drugs. Mutat Res. 1988;208:149-153.
• Roth S, Norppa H, Järventaus H, Kyyrönen P, Ahonen M, Lehtomäki J, Sainio H and Sorsa M. Analysis of chromosomal aberrations, sister chromatid exchanges and micronuclei in peripheral lymphocytes of pharmacists before and after working with cytostatic drugs. Mutat Res. 1994;325:157-162.
• Roussel C, Witt KL, Shaw PB and Connor TH. Meta-analysis of chromosomal aberrations as a biomarker of exposure in healthcare workers occupationally exposed to antineoplastic drugs. Mutation Research/Reviews in Mutation Research. 2017; https://doi.org/10.1016/j.mrrev.2017.08.002external icon.
• Rubeš J, Kucharová S, Vozdová M, Musilová P and Zudová Z. Cytogenetic analysis of peripheral lymphocytes in medical personnel by means of FISH. Mutat Res. 1998 412:293-298.
• Sarto F, Trevisan A, Tomanin R, Canova A and Fiorentino M. Chromosomal aberrations, sister chromatid exchanges and urinary thioethers in nurses handling antineoplastic drugs. Am J Ind Med. 1990;18:689-695.
• Santovito A, Cervella P and Delpero M. Chromosomal damage in peripheral blood lymphocytes from nurses occupationally exposed to chemicals. Hum Exp Toxicol. 2012; 33:897-903.
• Sessink PJM, Cerná M, Rössner P, Pastorkova A, Bavarova H, Frankova K, Anzion RB and Bos RP. Urinary cyclophosphamide excretion and chromosomal aberrations in peripheral blood lymphocytes after occupational exposure to antineoplastic agents. Mutat Res. 1994;309:193-199.
• Stiller A, Obe G, Boll I and Pribilla W. No elevation of the frequencies of chromosomal alterations as a consequence of handling cytostatic drugs: Analyses with peripheral blood and urine of hospital personnel. Mutat Res. 1983;121:253-259.
• Stücker I, Hirsch A, Doloy T, Bastie-Sigeac, I and Hémon D. Urine mutagenicity, chromosomal abnormalities and sister chromatid exchanges in lymphocytes of nurses handling cytostatic drugs. Int Arch Occup Environ Health. 1986;57:195-205.
• Testa A, Giachelia M, Palma S, Appolloni M, Padua L, Tranfo G, Spagnoli M, Trindelli D and Cozzi R. Occupational exposure to antineoplastic agents induces a high level of chromosome damage. Lack of an effect of GST polymorphisms. Tox and Appl Pharmacol. 2007; 223:46-55.
• Thulin H, Sundberg E, Hansson K, Cole J and Hartley-Asp B. Occupational exposure to nor-nitrogen mustard: Chemical and biological monitoring. Toxicol Ind Health. 1995;11:89-97.
• Tompa A, Jakab M, Biro A, Magyar B, Fodor Z, Klupp T and Major J. Chemical safety and health conditions among Hungarian hospital nurses. Ann NY Acad Sci. 2006; 1076:635-648.
• Waksvik H, Klepp O and Brøgger A. Chromosome analyses of nurses handling cytostatic agents. Cancer Treat Rep. 1981;65:607-610.
• Yang D-P, Xu S-J and Wang J-X. Study on chromosomal damage among nurses occupationnaly exposed to antineoplastic drugs in an oncology department. Biomed Environ Sci. 2002; 15:268-270.

Although Sister Chromatid Exchanges (SCEs) are typically measured in lymphocytes, similar to chromosomal aberrations and micronuclei, they are involved with DNA repair. This endpoint has been used extensively in other occupational settings as a marker for agents that may damage DNA, thus resulting in its repair. Several studies of workers exposed to antineoplastic agents have shown an increase in their frequency as compared to control populations.

• Barale R, Sozzi G, Toniolo P, Borghi O, Reali D, Loprieno N and Della Porta G. Sister-chromatid exchanges in lymphocytes and mutagenicity in urine of nurses handling cytostatic drugs. Mutat Res. 1985;157:235-240.
• Brumen V and Horvat D. Work environment influence on cytostatics-induced genotoxicity in oncologic nurses. Am J Indus Med. 1996;30:67-71.
• Brumen V, Horvat D and Trošic I. Potential genotoxic risk related to simultaneous exposure to radionuclides and cytostatics. Am J Ind Med. 1995;27:871-876.
• Evelo CTA, Bos RP, Peters JGP and Henderson PT. Urinary cyclophosphamide assay as a method for biological monitoring of occupational exposure to cyclophosphamide. Int Arch Occup Environ Health. 1986;58:151-155.
• Ferguson LR, Everts R, Robbie MA, Harvey V, Tempel D, Mak D and Gerred AJ. The use within New Zealand of cytogenetic approaches to monitoring of hospital pharmacists for exposure to cytotoxic drugs: report of a pilot study in Auckland. Aust J Hosp Pharm. 1988; 18:228-233.
• Fucic A, Jazbec A, Mijic A, Seso-Simic D and Tomek R. Cytogenetic consequences after occupational exposure to antineoplastic drugs. Mutat Res. 1998;416:59-66.
• Goloni-Bertollo EM, Tajara EH, Manzato AJ and Varella-Garcia M. Sister chromatid exchanges and chromosome aberrations in lymphocytes of nurses handling antineoplastic drugs. Int J Cancer. 1992;50:341-344.
• Gulten T, Evke E, Ercan I, Evrensel T, Kurt E and Manavoglu O. Lack of genotoxicity in medical oncology nurses handling antineoplastic drugs: effect of work environment and protective equipment. Work. 2011; 39:485-489.
• Ikeda K, Yagi Y, Tkegami M, Lu Y, Morimoto K and Kurokawa N. Efforts to ensure safety of hospital pharmacy personnel occupationally exposed to antineoplastic drugs during a preparation task. Hosp Pharm. 2007; 42:209-218.
• Jakab MG, Major J and Tompa A. Follow-up genotoxicological monitoring of nurses handling antineoplastic drugs. J Toxicol Environ Health. 2001; 62:307-318.
• Jordan DK, Patil SR, Jochimsen PR, Lachenbruch PA and Corder MP. Sister chromatid exchange analysis in nurses handling antineoplastic drugs. Cancer Invest. 1986;4:101-107.
• Karelová J, Jablonická A, Gavora J and Hano Lubomír. Chromosome and sister-chromatid exchange analysis in peripheral lymphocytes and mutagenicity of urine in anesthesiology personnel. Int Arch Occup Environ Health. 1992;64:303-306.
• Kasuba V, Rozgaj R and Garak-Vrhovac V. Analysis of sister chromatid exchange and micronuclei in peripheral blood lymphocytes of murses handling cytostatic drugs. J Appl Toxicol. 1999;19:401-404.
• Kevekordes S, Gebel TW, Hellwig M, Dames W and Dunkelberg H. Human effect monitoring in cases of occupational exposure to antineoplastic drugs: A method comparison. Occup Environ Med. 1998;55:145-149.
• Kolmodin-Hedman B, Hartvig P, Sorsa M and Falck K. Occupational handling of cytostatic drugs. Arch Toxicol. 1983;54:25-33.
• Kopjar N, Garaj-Vrhovac V, Kašuba V, Rozgaj R, Ramić S, Pavlica V and Želježić D. Assessment of genotoxic risks in Croatian health care workers occupationally exposed to cytotoxic drugs: A multi-biomarker approach. Int J Hyg Environ Health. 2009; 212:414-431.
• Krepinsky A, Bryant DW, Davison L, Heddle J, McCalla DR, Douglas G and Michalko K. Comparison of three assays for genetic effects of antineoplastic drugs on cancer patients and their nurses. Environ Mol Mutagen. 1990;15:83-92.
• Lambert B, Bredberg A, McKenzie W and Sten M. Sister chromatid exchange in human populations:the effect of smoking, drug treatment and occupational exposure. Cytogenet Cell Genet. 1982;33:62-67.
• Lanza A, Robustelli della Cuna FS, Zibera C, Pedrazzoli P and Robustelli della Cuna G. Somatic mutations at the T-cell antigen receptor in antineoplastic drug-exposed populations: comparison with sister chromatid exchange frequency. Int Arch Environ Health. 1999;72:315-322.
• Mader RM, Kokalj A, Kratochvil E, Pilger A and Rudiger HW. Longitudinal biomonitoring of nurses handling antineoplastic drugs. J Clin Nurs. 2008; 18:263-269.
• McDiarmid MA, Kolodner K, Humphrey F, Putman D and Jacobson-Kram D. Baseline and phosphoramide mustard-induced sister-chromatid exchanges in pharmacists handling anti-cancer drugs. Mutat Res. 1992;279;199-204.
• McDiarmid MA, Kolodner K, Humphrey F, Putman D and Jacobson-Kram D. Baseline and mutagen-induced sister chromatid exchanges in lymphocytes of pharmacists handling anticancer drugs. Environ Epidemol Tox. 2000; 2:254-260.
• Milkovic-Kraus S and Horvat D. Chromosomal abnormalities among nurses occupationally exposed to antineoplastic drugs. Am J Ind Med. 1991;19:771-774.
• Mrđanović J, Jungić S, Šolajić S, Bogdanović V and Jurišić V. Effects of orally administered antioxidants on micronuclei and sister chromatid exchange frequency in workers professionally exposed to antineoplastic agents. Food Chem Toxicol. 2012; 50:2937-2744.
• Norppa H, Sorsa M, Vainio H, Grohn P, Heinonen E, Holsti L and Nordman E. Increased sister chromatid exchange frequencies in lymphocytes of nurses handling cytostatic drugs. Scand J Work Environ Health. 1980;6:299-301.
• Oestreicher U, Stephan G and Glatzel M. Chromosome and SCE analysis in peripheral lymphocytes of persons occupationally exposed to cytostatic drugs handled with and without use of safety covers. Mutat Res. 1990;242:271-277.
• Pilger A, Kohler I, Stettner H, Mader RM, Rizovski B, Terkola R, Diem E, Franz-Hainzl E, Konnaris C, Valic E and Rudiger. Long-term monitoring of sister chromatid ecchanges and micronucleus formation in pharmacy personnel occupationally exposed to cytostatic drugs. Int Arch Occup Environ Health. 2000; 73:442-448.
• Pohlová H, Cerná M and Rössner P. Chromosomal aberrations, SCE and urine mutagenicity in workers occupationally exposed to cytostatic drugs. Mutat Res. 1986;174:213-217.
• Roth S, Norppa H, Järventaus H, Kyyrönen P, Ahonen M, Lehtomäki J, Sainio H and Sorsa M. Analysis of chromosomal aberrations, sister chromatid exchanges and micronuclei in peripheral lymphocytes of pharmacists before and after working with cytostatic drugs. Mutat Res. 1994;325:157-162.
• Santovito A, Cervella P and Delpero M. Chromosomal damage in peripheral blood lymphocytes from nurses occupationally exposed to chemicals. Hum Exp Toxicol. 2012; 33:897-903.
• Sarto F, Trevisan A, Tomanin R, Canova A and Fiorentino M. Chromosomal aberrations, sister chromatid exchanges and urinary thioethers in nurses handling antineoplastic drugs. Am J Ind Med. 1990;18:689-695.
• Sorsa M, Pyy L, Salomaa S, Nyland L and Yager JW. Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals. Mutat Res. 1988;204:465-479.
• Stücker I, Hirsch A, Doloy T, Bastie-Sigeac, I and Hémon D. Urine mutagenicity, chromosomal abnormalities and sister chromatid exchanges in lymphocytes of nurses handling cytostatic drugs. Int Arch Occup Environ Health. 1986;57:195-205.
• Thiringer G, Granung G, Holmén A, Hogstedt B, Jarvhom B, Jonsson D, Persson L, Wahlstrom J and Westin J. Comparison of methods for the biomonitoring of nurses handling antitumor drugs. Scand J Work Environ Health. 1991;17:133-138.
• Thulin H, Sundberg E, Hansson K, Cole J and Hartley-Asp B. Occupational exposure to nor-nitrogen mustard: Chemical and biological monitoring. Toxicol Ind Health. 1995;11:89-97.
• Tompa A, Jakab M, Biro A, Magyar B, Fodor Z, Klupp T and Major J. Chemical safety and health conditions among Hungarian hospital nurses. Ann NY Acad Sci. 2006; 1076:635-648.
• Waksvik H, Klepp O and Brøgger A. Chromosome analyses of nurses handling cytostatic agents. Cancer Treat Rep. 1981;65:607-610.
• Yang D-P, Xu S-J and Wang J-X. Study on chromosomal damage among nurses occupationnaly exposed to antineoplastic drugs in an oncology department. Biomed Environ Sci. 2002; 15:268-270.

Micronuclei induction results from exposure to many chemicals that react with DNA. This assay has been employed extensively in animal studies, and to a lesser extent in occupational studies, to determine the ability of a chemical agent to damage DNA resulting in the formation of small fragments of DNA termed micronuclei. Micronuclei are usually measured in peripheral lymphocytes, but also can be evaluated in other cell types.

• Anwar WA, Salama SI, Serafy MM, Hermida S and Hafez AS. Chromosomal aberrations and micronucleus frequency in nurses occupationally exposed to cytotoxic drugs. Mutagenesis. 1994;9:315-317.
• Bolognesi C, Nucci MC, Colacci AM, et al. Biomonitoring of nurses occupationally exposed to antineoplastic drugs: the IMEPA Project. Epidemiol Prev. 2005; 29: Suppl:91–95.
• Boughattas AB, Bouraoui S, Debbabi F, El Ghazel H, Saad A and Mrizak N. Genotoxic risk assessment of nurses handling antineoplastic drugs. Ann Biol Clin (Paris). 2010; 68:545-553.
• Bouraoui S, Brahem A, Tabka F, Mrizek N, Saad A and Elghezal H. Assessment of chromosomal aberrations, micronuclei and proliferation rate index in peripheral lymphocytes from Tunisian nurses handling cytotoxic drugs. Environ Tox and Pharm. 2011; 31:250-257
• Burgaz S, Karahalil B, Bayrak P, Taşin L, Yavuzaslan F, Bökesoy I, Anzion RBM, Bos RP and Platin N. Urinary cyclophosphamide excretion and micronuclei frequencies in periperal lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics. Mutat Res. 1999;439:97-104.
• Cavallo D, Usini CL, Perniconi B, Di Francesco A, Giglio M, Rubino FM, Marinaccio A, Iavicoli S. Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees. Mutat Res. 2005; 587:45-51.
• Cavallo D., Ursini CL, Omodeo-Salé E and Iavicoli S. Micronucleus induction and FISH analysis in buccal cells and lymphocytes of nurses administering antineoplastic drugs. Mutat Res. 2007; 628:11-18.
• Cavallo D, Ursini CL, Rondinone B and Iavicoli S. Evaluation of a suitable DNA damage biomarker for human biomonitoring of exposed workers. Environ Mol Mutagen. 2009; 50:781-790.
• Cornetta T, Padua L, Testa A, Ievoli E, Festa F, Tranfo G, Baccelliere L and Cozzi R. Molecular biomonitoring of a population of nurses handling antineoplastic drugs. Mutat Res. 2008; 638:75-82.
• Deng H, Zhang M, He J, Wu W, Jin L, Zheng W, Lou J and Wang B. Investigating genetic damage in workers occupationally exposed to methotrexate using three genetic end-points. Mutagenesis. 2005; 20:351-357.
• Deng H, Lou, J, Zhang M, Wu W, Jin J, Chen S, Zheng W, Wang B and He J. Detecting the cytogenetic effects in workers occupationally exposed to vincristine with four genetic tests. Mutat Res. 2006; 599:152-159.
• Fucic A, Jazbec A, Mijic A, Seso-Simic D and Tomek R. Cytogenetic consequences after occupational exposure to antineoplastic drugs. Mutat Res. 1998;416:59-66.
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A number of methods are available to measure DNA damage directly. These include alkaline elution, and more recently, the Comet assay. These assays have been used in vitro and in animal studies, but only sparingly in occupation exposure studies. They usually measure DNA strand breaks. Since most antineoplastic agents target DNA, this is a sensitive and relevant endpoint to study.

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• Cavallo D, Ursini CL, Perniconi B, Francesco AD and Giglio M, Rubino FM, Marinaccio A, Iavicoli S. Evaluation of gentotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees. Mutat Res. 2005; 587:45-51.
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HPRT mutations are typically measured in lymphocytes and targets mutations in a specific gene. This method had been employed recently in other occupational setting as a marker for exposure to agents which mutate DNA. A small number of studies of occupational exposure to antineoplastic agents has shown an increase in HPRT mutations.

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The excretion of thioethers in the urine has been used in a limited number of occupational studies as a marker for exposure. The method is nonspecific and may be seen with other exposures, including smoking.

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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.

Urinary analysis is the direct measurement of antineoplastic agents and/or their metabolites in the urine of exposed workers by analytical methods. Typically, gas chromatography/mass spectrometry (GC-MS or GC-MS-MS), high performance liquid chromatography (LC-MS or LC-MS-MS) or high performance liquid chromatography with UV detection LC-UV are employed to identify the drugs and/or their metabolites in the urine. For platinum-containing compounds, votammetry or inductively coupled plasma mass spectrometry (ICPMS) are used to determine the presence of platinum in the urine.

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