Occupational Exposure to Antineoplastic Agents

Urinary Mutagenicity

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. 

Bos RP, Leenaars AO, Theuws JLG and Henderson PT. Mutagenicity of urine from nurses handling cytostatic drugs, influence of smoking. Int Arch Occup Environ Health. 1982;50:359-69.

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.

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.

Poyen D, DeMeó MP, Botta A, Gouvernet J and Duménil G. Handling of cytostatic drugs and urine mutagenesis. Int Arch Occup Environ Health. 1988;61:183-88.

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.

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.

Chromosomal Aberrations

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.

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., Ursini CL, Omodeo-Salé E, 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.

Fucic A, Jazbec A, Mijic A, Seso-Simic and Tomek R. Cytogenetic consequences after occupational exposure to antineoplastic drugs. Mutat Res. 1998;416:59-66.

McDevitt MA, Condon M, Stamberg J, Karp JE, 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.

Testa A, Giachelia M, Palma S, Appolloni M, Padua L, Tranfo G, Spagnoli M, Trindelli D, 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.

Yang D-P, Xu S-J, 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.

Sister Chromatid Exchanges

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.

Fucic A, Jazbec A, Mijic A, Seso-Simic 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.

Ikeda K, Yagi Y, Tkegami M, Lu Y, Morimoto K, 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.

Yang D-P, Xu S-J, 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

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.

Burgaz S, Karahal2l B, Bayrak P, TaÕk2n L, Yavuzaslan F, B`kesoy 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., Ursini CL, Omodeo-Salé E, Iavicoli S. Micronucleus induction and FISH analysis in buccal cells and lymphocytes of nurses administering antineoplastic drugs. Mutat Res. 2007; 628:11-18.

Deng H, Lou, J, Zhang M, Wu W, Jin J, Chen S, Zheng W, Wang B, He J. Detecting the cytogenetic effects in workers occupationally exposed to vincristin with four genetic tests. Mutat Res. 2006; 599:152-159.

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.

Hessel H, Radon K, Pethran A, Maisch B, Grobmair S, Sautter I, Fruhmann G. The genotoxic risk of hospital, pharmacy and medical personnel occupationally exposed to cytostatic drugs-evaluation by the micronucleus assay. Mutat Res. 2001; 497:101-109.

Kasuba V, Rozgaj R and Garak-Vrhovac V. Analysis of sister chromatid exchange and micronuclei in peripheral blood lymphocytes of nurses handling cytostatic drugs. J Appl Toxicol. 1999;19:401-404.

Laffon B, Teixeira JP, Silva S, Loureiro J, Torres J, Pásaro E, Méndez, Mayan O. Genotoxic effects in a population of nurses handling antineoplastic drugs, and relationship with genetic polymorphisms in DNA repair enzymes. Am J Ind Med. 2005; 48:128-136.

Machado-Santelli GM, Cerqueira EM, Oliveira CT and de Braganca Peira CAA. Biomonitoring of nurses handling antineoplastic drugs. Mutat Res. 1994;332:203-208.

Maluf SW and Erdtmann B. Evaluation of occupational genotoxic risk in a Brazilian hospital. Genetics Mol Biol. 2000; 23: 485-488.

Maluf SW and Erdtmann. Follow-up study of the genetic damage in lymphocytes of pharmacists and nurses handling antineoplastic drugs evaluated by cytokinesis-block micronuclei analysis and single cell gel electrophoresis assay. Mutat Res. 2000; 471: 21-27.

Pethran A, Hauff K and Hessel H . Biological, cytogenetic and ambient monitoring of exposure to antineoplastic drugs. J Oncol Pharm Practice. 1998;4:57.

Pilger A, Kohler I, Stettner H, Mader RM, Rizovski B, Terkola R, Diem E, Franz-Hainzl E, Konnaris C, Valic E, 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.

Rekhadevi PV, Sailaja N, Chandrasekhar M, Mahboob M, Rahman MF, Grover P. Genotoxicity assesment in oncology nurses handling anti-neoplastic drugs. Mutagenisis. 2007; 1-7.

Rombaldi F, Cassini C, Salvador M, Saffi J, Erdtmann B. Occupational risk assessment of genotoxicyty and oxidative stress in workers handeling anti-neoplastic drugs during a work week. Mutagenesis. 2008; 1-6.

DNA Damage

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.

Balcarová O, Zavázal V, Seberová E, Kuklová D, Halík J. The risk of work with cytostatics and immunomodulation compounds. Pracov Lék. 1993; 45:195-201. (English abstarct)

Deng H, Lou, J, Zhang M, Wu W, Jin J, Chen S, Zheng W, Wang B, He J. Detecting the cytogenetic effects in workers occupationally exposed to vincristin with four genetic tests. Mutat Res. 2006; 599:152-159.

Laffon B, Teixeira JP, Silva S, Loureiro J, Torres J, Pásaro E, Méndez, Mayan O. Genotoxic effects in a population of nurses handling antineoplastic drugs, and relationship with genetic polymorphisms in DNA repair enzymes. Am J Ind Med. 2005; 48:128-136.

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.

Mäki-Paakkanen J, Walles S, Osterman-Golkar S and Norppa H. Single-strand breaks, chromosome aberrations, sister-chromatid exchanges and micronuclei in blood lymphocytes of workers exposed to styrene during the production of reinforced plastics. Environ Mol Mutagen. 1991;17:27-31.

Maluf SW and Erdtmann B. Follow-up study of the genetic damage in lymphocytes of pharmacists and nurses handling antineoplastic drugs evaluated by cytokinesis-block micronuclei analysis and single cell gel electrophoresis assay. Mutat Res. 2000; 471:21-27.

Mucci, N, Ianni A, Ursini CL, Orsini M, Arzani D, Romano-Spica V. Cytostatic drugs and health risks for exposed personnel: Search for New biomarkers. Anticancer Res. 2000; 20:2995-3000.

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Rekhadevi PV, Sailaja N, Chandrasekhar M, Mahboob M, Rahman MF, Grover P. Genotoxicity assesment in oncology nurses handling anti-neoplastic drugs. Mutagenisis. 2007; 1-7.

Rombaldi F, Cassini C, Salvador M, Saffi J, Erdtmann B. Occupational risk assessment of genotoxicyty and oxidative stress in workers handeling anti-neoplastic drugs during a work week. Mutagenesis. 2008; 1-6.

Sasaki M, Dakeishi M, Hoshi S, Ishii N, Murata K . Assessment of DNA damage in Japanese nurses handeling antineoplastic drugs by the comet assay. J Occup Health. 2008; 50:7-12.

Ündeger Ü, Basaran, Kars A and Güç D. Assessment of DNA damage in nurses handling antineoplastic drugs by the alkaline COMET assay. Mutat Res. 1999;439:277-285.

Ursini CL, Cavallo D, Colombi A, Giglio M, Marinaccio A, Iavicoli S. Evaluation of early DNA damage in healthcare workers handeling antineoplastic drugs. Int Arch Occup Environ Health. 2006; 80:134-140.

Yang D, Xu S, Wang J. Study of DNA damage of peripheral lymphocytes in the nurses occupationally exposed to anticancer drugs. Zhonghua Laodong Weisheng Zhiyebing Zazhi. 2002; 20:197-199.

Yoshida J, Kosaka H, Tomika K, Kumagai S. Genotoxic Risks to nurses from contamination of the work enviroment with antineoplastic drugs in Japan. J Occup Health; 2006; 48:517-522.

HPRT Mutations

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.

Chrysostomou A, Seshadri R and Morley AA. Mutation frequency in nurses and pharmacists working with cytotoxic drugs. Aust NZ J Med. 1984;14;831-834.

Deng H, Zhang M, He J, Wu W, Jin L, Zheng W, Lou J, Wang B. Investigating genetic damage in workers occupationally exposed to methotrexate using three genetic end-points. Mutagenesis. 2005; 20:351-357.

Dubeau H, Zazi W, Baron C and Messing K. Effects of lymphocyte subpopulations on the clonal assay of HPRT mutants: Occupational exposure to cytostatic drugs. Mutat Res. 1994;321:147-157.

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Thioether Excretion

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.

Bayhan A, Burgaz S and Karakaya AE. Urinary thioether excretion in nurses at an oncologic department. J Clin Pharm Ther. 1987;12:303-306.

Burgaz S, Özdamar YN and Karakaya AE. A signal assay for the detection of genotoxic compounds:Applications on the urines of cancer patients on chemotherapy and of nurses handling cytotoxic drugs. Hum Toxicol. 1988;7:557-560.

Deng H, Lou, J, Zhang M, Wu W, Jin J, Chen S, Zheng W, Wang B, He J. Detecting the cytogenetic effects in workers occupationally exposed to vincristin with four genetic tests. Mutat Res. 2006; 599:152-159.

Jagun O, Ryan M and Waldron HA. Urinary thioether excretion in nurses handling cytotoxic drugs. Lancet. 1982;2:443-444.

Rombaldi F, Cassini C, Salvador M, Saffi J, Erdtmann B. Occupational risk assessment of genotoxicyty and oxidative stress in workers handeling anti-neoplastic drugs during a work week. Mutagenesis. 2008; 1-6.

Urinary Excretion of Antineoplastic Agents

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.

Bos RP, Weissenberger BFJ and Anzion RBM. a-Fluoro-8-alanine in urine of workers occupationally exposed to 4-fluorouracil in a 5-flourouracil-producing factory. Biomarkers. 1998;3:81-87.

Burgaz S, Karahal2l B, Bayrak P, TaÕk2n L, Yavuzaslan F, B`kesoy 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.

Deschamps F, Marinutti-Liberge and Lamiable D. Biological monitoring of occupational exposure to cytostatic drugs with platinum. Cancer Detect Prev Online. Available: http://www.cancerprev.org/Journal/Issues/26/101/1193/4393

Ensslin AS, Huber R, Pethran A, Pethran A, Rommelt H, Schelerl, Kulka U and Fruhmann G. Biological monitoring of hospital pharmacy personnel occupationally exposed to cytostatic drugs: urinary excretion and cytogenetics studies. Int Arch Occup Environ Health 1997 70:205-208.

Ensslin AS, Pethran A, Schierl R and Fruhmann G. Urinary platinum in hospital personnel occupationally exposed to platinum-containing antineoplastic drugs. Int Arch Occup Environ Health. 1994a; 65:339-342.

Ensslin AS, Stoll Y, Pethran A, Pfaller A, Rommelt H and Fruhmann G. Biological monitoring of cyclophosphamide and ifosfamide in urine of hospital personnel occupationally exposed to cytostatic drugs. Occup Environ Med 1994;51:229-233.

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.

Favier B, Gilles L, Gesage M and Latour JF. Analysis of cyclophosphamide in the urine of antineoplastic drug handlers. Bull Cancer. 2003; 90:905-909.

Hedmer M, Tinnerberg H, Axmon A, Joensson BAG. Environmental and biologocal monitoring of antineoplastic drugs in four workplaces in a Swedish hospital. Int Arch Occup Environ Health. 2008; 81:899-911

Ikeda K, Yagi Y, Tkegami M, Lu Y, Morimoto K, 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.

Mason HJ, Blair S, Sams C, Jones K, Garfitt SJ, Cuschieri MJ, Baxter PJ. Exposure to antineoplastic drugs in two UK hospital pharmacy units. Ann Occup Hyg. 2005; 49:603-610.

Minoia C, Turci R, Sottani C, Schiavi A, Perbellini L, Angeleri S, Draicchio F and Apostoli P. Application of high performance liquid chromatography/tandem mass spectrometry in the environmental and biological monitoring of health care personnel occupationally exposed to cyclophosphamide and ifosfamide. Rapid Commun Mass Spetrom. 1998; 12: 1485-1493.

Minoia C, Turci R, Sottani C, Schiavi A, Perbellini L, Angeleri S, Frigerio F, Draicchio F and Apostoli P. Risk assessment concerning hospital personnel participating in the preparation and administration of antineoplastic drugs. [Italian] Giornale Italiano di Medicina del Lavoro ed Ergonomia. 1999; 21:93-107.

Nygren O and Lundgren C. Determination of platinum in workroom air and in blood and urine from nursing staff attending patients receiving cisplatin chemotherapy. Int Arch Occup Environ Health. 1997;70:209-214.

Nyman H, Jorgenson J, Slawson MH. Workplace Contamination with Antineoplastic Agents in a new cancer hospital using a closed-system drug transfer device. Hosp Pharm. 2007; 42:219-225

Pethran A, Schierl R, Hauff K, Grimm C-H, Boos K-S and Nowak D. Uptake of antineoplastic agents in pharmacy and hospital personnel. Part I: monitoring of urinary concentrations. Int Arch Environ Health. 2003; 76:5-10.

Rekhadevi PV, Sailaja N, Chandrasekhar M, Mahboob M, Rahman MF, Grover P. Genotoxicity assesment in oncology nurses handling anti-neoplastic drugs. Mutagenisis. 2007; 1-7.

Tuerk J, Reinders M, Dryer M, Kiffmeyer TK, Schmidt KG, Kuss HM. Analysis of antibiotics in urine and wipe samples from environmental and biological monitoring- comparison of HPLC with UV-, single MS- and tandem MS-detection. J Chromatog. 2006; 831:72-80.

Turci R, Sottani C, Spagnoli G, Minoia C. Biological and environmental monitoring of hospital personnel exposed to antineoplastic agent: a review of analytical methods. J Chromatog B. 2003; 789:169-209.

Turci R, Sottani C, Schierl R, Minoia C. Validation protocol and analytical quality in biological monitoring of occupational exposure to antineoplastic drugs. Tox Lett. 2006; 162:256-262.

Ursini CL, Cavallo D, Colombi A, Giglio M, Marinaccio A, Iavicoli S. Evaluation of early DNA damage in healthcare workers handeling antineoplastic drugs. Int Arch Occup Environ Health. 2006; 80:134-140.

Wick C, Slawson MH, Jorgenson JA and Tyler LS. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health-Syst Pharm. 2003; 60:2314-2320.

Ziegler E, Mason HJ, Baxter PJ. Occupational exposure to cytotoxic drugs in two UK onkology wards. Occup Environ Med. 2002; 59:608-612.