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Pharmaceutisch Weekblad

, Volume 12, Issue 6, pp 217–227 | Cite as

The risks of handling cytotoxic drugs

I. Methods of testing exposure
  • G. P. Kaijser
  • W. J. M. Underberg
  • J. H. Beijnen
Reviews

Abstract

Results of various biological and physical/chemical tests of the urines or blood of health-care personnel working with cytotoxic drugs are discussed. The outcomes of these tests are conflicting and inconclusive. The physical/chemical tests seem to be an alternative method. However, until now it has not been possible to establish the threshold concentration in urine or blood beneath which no effect has to be expected. Therefore, the interpretation of the concentration of cytotoxic drugs and/or the metabolites in the urine or blood is difficult. As long as one will not be able to provide conclusive data on the health hazards when working with cytotoxic drugs, protective measures have to be taken in order to lower the risk as much as possible.

Keywords

Antineoplastic agents Drug compounding Drug contamination Exposure, occupational Health-care personnel Mutagenicity tests Occupational health Protective devices 

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References

  1. 1.
    Anonymous. Occupational hazards of cytostatic agents. Hospital pharmacists' discussion. Pharm J 1977;219:335.Google Scholar
  2. 2.
    Anonymous. How real is the hazard? Lancet 1984;1:203.Google Scholar
  3. 3.
    Anonymous. Hazards of cancer chemotherapy. Lancet 1982;2:1317–8.Google Scholar
  4. 4.
    Anonymous. Curbing cancer drugs' risks to nurses. Am J Nurs 1987;87:765–6.Google Scholar
  5. 5.
    Ballentine R. Cancerphobia — or whatever happened to red M & M's? Drug Intell Clin Pharm 1982;16:60–1.PubMedGoogle Scholar
  6. 6.
    Bingham E. Hazards to health workers from antineoplastic drugs. N Engl J Med 1985;313:1173–8.PubMedGoogle Scholar
  7. 7.
    Briggs KM. Caring for cytotoxic drug handlers. Occup Health 1983;35:273–81.Google Scholar
  8. 8.
    Delaney RA. Guidelines needed for handling of carcinogenic antineoplastics. Am J Hosp Pharm 1981;38:166.PubMedGoogle Scholar
  9. 9.
    Dumont D. Risques encourus par les personnels soignants manipulant des cytostatiques. Arch Mal Prof 1989;50:109–25.Google Scholar
  10. 10.
    Hamilton CW. Risk to personnel admixing cancer chemotherapy. US Pharm 1982;7:H1-H8.Google Scholar
  11. 11.
    Jacobs JY. Work hazards from drug handling. Pharm J 1984;233:195–6.Google Scholar
  12. 12.
    LeJeuness J. Precautions for preparing cytotoxic agents. Parenterals 1983;1(4):1–5.Google Scholar
  13. 13.
    Macek C. Hospital personnel who handle anticancer drugs may face risks. JAMA 1982;247:11–2.CrossRefPubMedGoogle Scholar
  14. 14.
    Ng LM. Possible hazards of handling antineoplastic drugs. Pediatrics 1970;46:648–9.PubMedGoogle Scholar
  15. 15.
    Sorsa M, Hemminki K, Vainio H. Occupational exposure to anticancer drugs. Potential and real hazard. Mut Res 1985;154:135–49.Google Scholar
  16. 16.
    Stellman JM, Zoloth SR. Cancer chemotherapeutic agents as occupational hazards: a literature review. Cancer Invest 1986;4:127–35.PubMedGoogle Scholar
  17. 17.
    Verwey SL, Simonetti GPC. Verpleegkundigen ondergaan risico's bij het omgaan met cytostatica [Health-care personnel who handle cytostatic drugs face risks]. Tijdschr Kanker 1987;5:148–50.Google Scholar
  18. 18.
    Wagener DJTh. Beroepsrisico's bij het omgaan met chemotherapeutische middelen [Occupational risks of handling chemotherapeutic drugs]. Ned Tijdschr Geneeskd 1986;130:2292–4.PubMedGoogle Scholar
  19. 19.
    Williams CJ. Handling cytotoxics. Br Med J 1985;291:1299–300.Google Scholar
  20. 20.
    Zellmer WA. Reducing occupational exposure to potential carcinogens in hospitals. Am J Hosp Pharm 1981;38:1679.PubMedGoogle Scholar
  21. 21.
    Zellmer WA. Fear of anticancer drugs. Am J Hosp Pharm 1984;41:665.PubMedGoogle Scholar
  22. 22.
    Sotaniemi EA, Sutinen S, Arranto AJ, et al. Liver damage in nurses handling cytostatic agents. Acta Med Scand 1983;214:181–9.PubMedGoogle Scholar
  23. 23.
    Selevan SG, Lindbolm ML, Hornung RW, et al. A study of occupational exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med 1985;313:1173–221.PubMedGoogle Scholar
  24. 24.
    Siebert S, Adamson RH. Toxicity of antineoplastic agents in man: chromosomal aberrations, antifertility effects, congenital malformations and carcinogenic potential. Adv Cancer Res 1975;22:57–155.PubMedGoogle Scholar
  25. 25.
    Hemminki K, Kyyronen P, Lindbohm ML. Spontaneous abortions and malformations in the offspring of nurses exposed to cytostatic drugs. J Epidemiol Commun Health 1985;39:141–7.Google Scholar
  26. 26.
    Crudi CB. A compounding dilemma: I've kept the drug sterile but have I contaminated myself? Natl I.V. Ther J 1980;3:77–80.Google Scholar
  27. 27.
    Estryn-Behar M, Prugnaud JL, Sainte-Laudy J. Hypersensibilité immédiate at antimitotiques. Necessité de la protection du personnel soignant. J Pharm Clin 1983;2:131–43.Google Scholar
  28. 28.
    Ladik DF, Stoehr GP, Maurer MA. Precautionary measures in the preparation of antineoplastics. Am J Hosp Pharm 1980;37:1184–6.PubMedGoogle Scholar
  29. 29.
    Reynolds RD, Ignoffo R, Lawrence J, et al. Adverse reactions to AMSA in medical personnel. Cancer Treat Rep 1982;66:1885.PubMedGoogle Scholar
  30. 30.
    Ames BN, McCann J, Yamasaki E. Methods for detecting carcinogens and mutagens withSalmonella test. Mutat Res 1975;31:347–64.PubMedGoogle Scholar
  31. 31.
    Bartsch H, Malaveille C, Camus AM, et al. Validation and comparative studies on 180 chemicals withSalmonella typhimurium strains and V79 hamster cells in the presence of various metabolising systems. Mutat Res 1980;76:1–50.PubMedGoogle Scholar
  32. 32.
    Benedict WF, Baker MS, Harcoun L, et al. Mutagenicity of cancer chemotherapeutic agents inSalmonella/microsome test. Cancer Res 1977;37:2209–13.PubMedGoogle Scholar
  33. 33.
    Dunkel VC, Zeiger E, Brusick D, et al. Reproducibility of microbial mutagenicity assays. II. Testing of carcinogens and noncarcinogens inSalmonella typhimurium andEscherichia coli. Environ Mutagen 1985;7(Suppl 5):1–248.Google Scholar
  34. 34.
    McCann J, Choi E, Yamasaki E, Ames BN. Detection of carcinogens as mutagens in theSalmonella/microsome test: assays of 300 chemicals. Proc Natl Acad Sci USA 1975;72:5135–9.PubMedGoogle Scholar
  35. 35.
    Purchase IFH, Longstaff E, Ashby J, Styles JA, et al. An evaluation of 6 short-term tests for detecting organic chemical carcinogens. Br J Cancer 1978;37:873–959.PubMedGoogle Scholar
  36. 36.
    Rinkus SJ, Legator MS. Chemical characterization of 465 known or suspected carcinogens and their correlation with mutagenic activity in theSalmonella typhimurium system. Cancer Res 1979;39:3289–318.PubMedGoogle Scholar
  37. 37.
    Zeiger E. Carcinogenicity of mutagens: predictive capability of theSalmonella mutagenesis assay for rodent carcinogenicity. Cancer Res 1987;47:1287–96.PubMedGoogle Scholar
  38. 38.
    Marquardt H, Marquardt H. Induction of malignant transformation and mutagenesis in cell cultures by cancer chemotherapeutic agents. Cancer 1977;40:1930–4.PubMedGoogle Scholar
  39. 39.
    Ames BN, Durston WE, Yamasaki E, Lee FD. Carcinogens are mutagens. A simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci USA 1973;70:2281–5.PubMedGoogle Scholar
  40. 40.
    Yamasaki E, Ames BN. Concentration of mutagens from urine by absorption with the non-polar resin XAD2: cigarette smokers have mutagenic urine. Proc Natl Acad Sci USA 1977;74:3555–9.PubMedGoogle Scholar
  41. 41.
    Minnich V, Smith VE, Thompson D, et al. Detection of mutagenic activity in human urine. Cancer 1976;38:1253–8.PubMedGoogle Scholar
  42. 42.
    Tuffnell PG, Gannon MT, Dong A, et al. Limitations of urinary mutagen assays for monitoring occupational exposure to antineoplastic drugs. Am J Hosp Pharm 1986;43:344–8.PubMedGoogle Scholar
  43. 43.
    Hirst M, Tse S, Mills DG, et al. Occupational exposure to cyclophosphamide. Lancet 1984;1:186–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Venitt S, Crofton-Sleigh C, Hunt J, et al. Monitoring exposure of nursing and pharmacy personnel to cytotoxic drugs: urinary mutation assays and urinary platinum as markers of absorption. Lancet 1984;1:74–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Friederich U, Molko F, Hofmann V, et al. Limitations of theSalmonella/mammalian microsome assay (Ames test) to determine occupational exposure to cytostatics. Eur J Cancer Clin Oncol 1986;22:567–75.CrossRefPubMedGoogle Scholar
  46. 46.
    Connor ThH, Theiss JC, Anderson RW, et al. Am J Hosp Pharm 1986;43:1236–9.PubMedGoogle Scholar
  47. 47.
    Rubin H. Carcinogenicity tests. Science 1976;191:241.Google Scholar
  48. 48.
    Ames BN. Dietary carcinogens and anticarcinogens. Science 1983;221:1256–64.PubMedGoogle Scholar
  49. 49.
    Baker R, Arlauskas A, Bonin A, et al. Detection of mutagenic activity in human urine following fried pork or bacon meals. Cancer Lett 1982;16:81–9.CrossRefPubMedGoogle Scholar
  50. 50.
    Hayatsu H, Kasai H, Yokoyama S, et al. Mutagenic metabolites in urine and faeces of rats fed with 2-amino-3,8-dimethyl-imidazo(4,5-f)quinoxoline, a carcinogenic mutagen present in cooked meat. Cancer Res 1987;47:791–4.PubMedGoogle Scholar
  51. 51.
    Sugimura T. Mutagens, carcinogens, and tumor promotors in our daily food. Cancer 1982;49:1970–84.PubMedGoogle Scholar
  52. 52.
    Sugimura T, Salo S. Mutagens—carcinogens in food. Cancer Res 1983;43:2415–21.Google Scholar
  53. 53.
    Caudell KA, Vredevoe DL, Dietrich MF. Quantification of urinary mutagens in nurses during potential antineoplastic agent exposure. Cancer Nurs 1988;11(1):41–50.PubMedGoogle Scholar
  54. 54.
    Kriebel D, Commoner B, Bollinger D, et al. Detection of occupational exposure to genotoxic agents with urinary mutagen assay. Mutat Res 1983;108:67–79.PubMedGoogle Scholar
  55. 55.
    Dolara P, Mazzoli S, Rosi D. Exposure to carcinogenic chemicals and smoking increases urinary excretion of mutagens in humans. J Tox Environ Health 1981;8:95–103.Google Scholar
  56. 56.
    Falck K. Urinary mutagenicity caused by smoking. In: Mutagens in our environment. New York: Alan R. Liss, 1982:387–400.Google Scholar
  57. 57.
    Hannan MA, Recio L, Deluca PP, Enoch H. Co-mutagenic effects of 2-aminoanthracene and cigarette smoke condensate or smoker's urine in the AmesSalmonella assay system. Cancer Lett 1981;13:203.CrossRefPubMedGoogle Scholar
  58. 58.
    Trichopolous D, Kalandide A, Sparros L, MacMahan B. Lung cancer and passive smoking. Int J Cancer 1981;27:1–4.PubMedGoogle Scholar
  59. 59.
    Van Doorn R, Bos RP, Leigdeckers CM. Thioether concentration and mutagenicity of urine from cigarette smokers. Int Arch Occup Environ Health 1979;43:159–66.CrossRefPubMedGoogle Scholar
  60. 60.
    Bos R, Thews J, Henderson P. Excretion of mutagens in human urine after passive smoking. Cancer Lett 1983;19:85–90.CrossRefPubMedGoogle Scholar
  61. 61.
    Alper T. Elkind recovery and ‘sub-lethal damage’. A misleading association? Br J Radiol 1977;50:459–67.PubMedGoogle Scholar
  62. 62.
    Maugh TH. Chemical carcinogens. How dangerous are low doses? Science 1978;202:37–41.PubMedGoogle Scholar
  63. 63.
    Everson RB, Ratcliffe JM, Flack PM, et al. Detection of low levels of urinary mutagen excretion by chemotherapy workers which was not related to occupational drug exposures. Cancer Res 1985;45:6487–97.PubMedGoogle Scholar
  64. 64.
    Poyen D, De Méo MP, Botta A, et al. Handling of cytostatic drugs and urine mutagenesis. Int Arch Occup Environ Health 1988;61:183–8.CrossRefPubMedGoogle Scholar
  65. 65.
    Sasson IM, Coleman DT, Lavoie EJ, et al. Mutagens in human urine; effect of cigarette smoking and diet. Mutat Res 1985;158:149–57.PubMedGoogle Scholar
  66. 66.
    Burnet FM. Immunological aspects of malignant disease. Lancet 1967;1:1171–4.CrossRefPubMedGoogle Scholar
  67. 67.
    Gatti RA, Good RA. Occurrance of malignancy in immunodeficiency diseases. A literature review. Cancer 1971;28:89.PubMedGoogle Scholar
  68. 68.
    Anderson RW, Puckett WH Jr, Dana WJ, et al. Risk of handling injectable antineoplastic agents. Am J Hosp Pharm 1982;39:1881–7.PubMedGoogle Scholar
  69. 69.
    Barale R, Sozzi G, Toniolo P, et al. Sister chromatid exchanges in lymphocytes and mutagenicity in urine of nurses handling cytostatic drugs. Mutat Res 1985;157:235–40.PubMedGoogle Scholar
  70. 70.
    Bos RP, Leenaars AO, Theuws JL, et al. Mutagenicity of urine from nurses handling cytostatic drugs: influence of smoking. Int Arch Occup Environ Health 1982;50:359–69.CrossRefPubMedGoogle Scholar
  71. 71.
    Palck K, Grohn P, Sorsa M, et al. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet 1979;1:1250–1.CrossRefPubMedGoogle Scholar
  72. 72.
    Gibson JF, Gompertz D, Hedworth-Whitty RB. Mutagenicity of urine from nurses handling cytotoxic drugs. Lancet 1984;1:100–1.CrossRefPubMedGoogle Scholar
  73. 73.
    Nguyen TV, Theiss JC, Matney TS. Exposure of pharmacy personnel to mutagenic antineoplastic drugs. Cancer Res 1982;42:4792–6.PubMedGoogle Scholar
  74. 74.
    Signori O, Palchaudhuri S. Observations on the occupational exposure of health care workers to chemotherapeutic agents [Abstract]. Proc Am Soc Clin Oncol 1983;4:23.Google Scholar
  75. 75.
    Staiano N, Gallelli JF, Adamson RH, et al. Lack of mutagenic activity in urine from hospital pharmacists admixing antitumor drugs. Lancet 1981;1:1615–6.Google Scholar
  76. 76.
    Stucker I, Hirsch A, Doloy T, Bastie-Sigeac I, Hemon 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.CrossRefPubMedGoogle Scholar
  77. 77.
    Theiss JC, et al. Results of a study presented at an international colloquium on cancer sponsored by the M.D. Anderson Hospital and Tumor Institute in Houston [Abstract]. JAMA 1982;247:11–2.CrossRefPubMedGoogle Scholar
  78. 78.
    Wilson JP. Solimando DA. Antineoplastics: a safety hazard? Am J Hosp Pharm 1981;38:624.PubMedGoogle Scholar
  79. 79.
    Benhamou S, Callais F, Sancho-Garnier H, et al. Mutagenicity in urine from nurses handling cytostatic agents. Eur J Cancer Clin Oncol 1986;22:1489–93.CrossRefPubMedGoogle Scholar
  80. 80.
    Kolmodin-Hedman B, Hartvig P, Sorsa M, et al. Occupational handling of cytotoxic drugs. Arch Toxicol 1983;54:25–33.CrossRefPubMedGoogle Scholar
  81. 81.
    Green MHL, Muriel WJ, Bridges BA. Use of a simplified fluctuation test to detect low levels of mutagens. Mutat Res 1976;38:33–42.PubMedGoogle Scholar
  82. 82.
    Gibson JF, Baxter PJ, Hedworth-Whitty RB, et al. Urinary mutagenicity assays: XAD2-prepared urine concentrates. Carcinogenesis 1983;4:1471–6.PubMedGoogle Scholar
  83. 83.
    Aesbacher HU, Finot PA, Wolleb U. Interactions of histidine containing test substances and extraction methods with the Ames mutagenicity test. Mutat Res 1983;113:103–46.PubMedGoogle Scholar
  84. 84.
    De Mitchell IG. Microbial essays for mutagenicity. Mutat Res 1978;54:1–16.PubMedGoogle Scholar
  85. 85.
    Kato H. Induction of sister chromatid exchange by chemical mutagens and its possible relevance to DNA repair. Exp Cell Res 1974;85:239–47.CrossRefPubMedGoogle Scholar
  86. 86.
    Knudson AG. Mutation and human cancer. Adv Cancer Res 1973;17:317–52.Google Scholar
  87. 87.
    Kurvink K, Bloomfield CD, Cerrenka J. Sister chromatid exchange in patients with viral disease. Exp Cell Res 1978;113:450.CrossRefPubMedGoogle Scholar
  88. 88.
    Kato H. Induction of sister chromatid exchanges by UV light and its inhibition by caffeine. Exp Cell Res 1973;82:383–90.CrossRefPubMedGoogle Scholar
  89. 89.
    Norman A, Sasaki M, Ottoman RE, Veomett RC. Chromosome aberrations in radiation workers. Radiat Res 1964;23:282–9.PubMedGoogle Scholar
  90. 90.
    Lambert B, Bredberg A, McKenzie W, Sten M. Sister chromatid exchange in human populations: the effect of smoking, drug treatment and occupational exposure. Cytogen Cell Genet 1982;33:62–7.Google Scholar
  91. 91.
    Murthy Bala Krishna P, Prema K. Sister chromatid exchanges in oral contraceptive users. Mutat Res 1979;68:149–52.PubMedGoogle Scholar
  92. 92.
    Knuutila S, Mäki-Paakkanen J., Kahkonen M, Hokkanen E. An increased frequency of chromosomal changes in cultured blood lymphocytes of 12 subjects vaccinated against smallpox. Human Genet 1978;41:89–96.CrossRefGoogle Scholar
  93. 93.
    Kucerova M, Polivkova Z, Matowek V. Chromosomal aberrations and SCE in lymphocytes of children revaccinated against smallpox. Mutat Res 1980;71:263–7.PubMedGoogle Scholar
  94. 94.
    Schürer CC, Manojlovic N, Seemayer NH. Induction of sister chromatid exchanges in human cellsin vitro by the mutagenic effect of city-smog extract. Mutat Res 1980;74:164–5.Google Scholar
  95. 95.
    Obe C, Göbel D, Engeln H, Herha J, Natarajan AT. Chromosomal aberrations in peripheral lymphocytes of alcoholics. Mutat Res 1980;73:377–86.PubMedGoogle Scholar
  96. 96.
    Husum B, Wulf HC, Niebuhr E. Normal sister chromatid exchanges in oral contraceptive users. Mutat Res 1980;103:161–4.CrossRefGoogle Scholar
  97. 97.
    Benedict WF, Banerjee A, Kanalingam KK, et al. Increased sister chromatid exchange in bone-marrow cells of mice exposed to whole cigarette smoke. Mutat Res 1984;136:73–80.PubMedGoogle Scholar
  98. 98.
    Husgafvel-Pursiainen K, Mäki-Paakkanen J, Norrpa J, Sorsa M. Smoking and SCE. Hereditas 1980;92:247–50.PubMedGoogle Scholar
  99. 99.
    Lambert B, Lindblad A, Nordenskjöld M, et al. Increased frequency of sister chromatid exchanges in cigarette smokers. Hereditas 1978;88:147–9.PubMedGoogle Scholar
  100. 100.
    Obe G, Herha J. Chromosomal aberrations in heavy smokers. Hum Genet 1978;41:259–63.CrossRefPubMedGoogle Scholar
  101. 101.
    Obe G, Vogt HJ, Madle S, Fahning A, Heller WD. Double blind study on the effect of cigarette smoking on the chromosomes of human peripheral blood lymphocytesin vivo. Mutat Res 1982;92:309–19.PubMedGoogle Scholar
  102. 102.
    Honeycombe JR. The effects of busulphan on the chromosomes of normal human lymphocytes. Mutat Res 1978;57:35–49.PubMedGoogle Scholar
  103. 103.
    Jordan DK, Patil SR, Jochimsen PR, Lachenbruch PA, Corder MP. SCE analysis in nurses handling antineoplastic drugs. Cancer Invest 1986;4:101–7.Google Scholar
  104. 104.
    Waksvik H, Magnus P, Berg K. The effect of age, sex and genes on SCE. Clin Genet 1981;20:449–54.PubMedGoogle Scholar
  105. 105.
    Evans HJ. Chromosomal mutations in human populations. Cytogenet Cell Genet 1982;33:48–56.PubMedGoogle Scholar
  106. 106.
    Wolff S. Difficulties in assessing the human health effects of mutagenic carcinogens by cytogenetic analysis. Cytogenet Cell Genet 1982;33:7–13.PubMedGoogle Scholar
  107. 107.
    Carrano AV, Minckler JL, Stetka DG, Moore DH. Variation in the baseline SCE frequency in human lymphocytes. Environ Mutagen 1980;2:325–37.PubMedGoogle Scholar
  108. 108.
    Lambert B, Ringborg V, Harper E, Lindblad A. Sister chromatid exchange in lymphocyte culture of patients receiving chemotherapy. Cancer Treat Rep 1978;62:1413–9.PubMedGoogle Scholar
  109. 109.
    Waksvik H, Klepp O., Brøgger A. Chromosome analysis of nurses handling cytostatic drugs. Cancer Treat Rep 1981;65:607–10.PubMedGoogle Scholar
  110. 110.
    Benhamou S, Pot-Deprun J, Sancho-Garnier H, Chouroulinkov I. SCE's and CA's in lymphocytes of nurses handling cytostatic agents. Int J Cancer 1988;41:350–3.PubMedGoogle Scholar
  111. 111.
    Chrysostomou A, Morley AA, Seshadri R. Mutation frequency in nurses and pharmacists working with cytotoxic drugs. Aust NZ J Med 1984;14:831–4.Google Scholar
  112. 112.
    Stiller A, Obe G, Pribilla A. No elevation of the frequencies of chromosomal alterrations as a consequence of handling cytostatic drugs. Mutat Res 1983;121:253–9.CrossRefPubMedGoogle Scholar
  113. 113.
    Lassila O, Toivanen A, Nordman E. Immune function in nurses handling cytostatic agents. Lancet 1980;2:482.CrossRefGoogle Scholar
  114. 114.
    LeRoy AF, Wehling ML, Sponseller HL, et al. Analysis of platinum in biological materials by flameless AAS. Biochem Med 1977;18:184–91.CrossRefPubMedGoogle Scholar
  115. 115.
    Safirstein R, Daye M, Guttenplan JB. Mutagenic activity and identification of excreted platinum in human and rat urine and rat plasma after administration of Cisplatin. Cancer Lett 1983;18:329–38.CrossRefPubMedGoogle Scholar
  116. 116.
    Juma FD, Rogers HJ, Trounce JR, et al. Pharmacokinetics of i.v. cyclophosphamide in man, estimated by gas-liquid chromatography. Cancer Chemother Pharmacol 1978;1:229–31.CrossRefPubMedGoogle Scholar
  117. 117.
    Evelo CTA, Bos RP, Peters JGP, Henderson PTh. Urinary cyclophosphamide assay as a method for biological monitoring of occupational exposure to cyclophosphamide. Int Arch Occup Environ Health 1986;58:151–5.CrossRefPubMedGoogle Scholar
  118. 118.
    Johnson BL, Gross J. Handling methotrexate — a safety problem? Am J Nurs 1982;82:1531.PubMedGoogle Scholar
  119. 119.
    Seutter Berlage F, Van Dorp HL, et al. Urinary mercapturic acid excretion as a biological parameter of exposure to alkylating agents. Int Arch Occup Environ Health 1977;39:41–51.Google Scholar
  120. 120.
    Jagun O, Ryan M, Waldrom HA. Urinary thioether excretion in nurses handling cytotoxic drugs. Lancet 1982;2:443–4.CrossRefGoogle Scholar
  121. 121.
    Burgaz S, Ozdamar YM, Karakaya AE. A signal assay for the detection of genetoxic compounds: application on the urines of cancer patients on chemotherapy and of nurses handling cytoxic drugs. Human Toxicol 1988;7:557–60.Google Scholar
  122. 122.
    Ehling UH, Averbeck D, Cerutti PA, et al. Review of the evidence for the presence or absence of thresholds in the induction of genetic effects by genotoxic chemicals. Mutat Res 1983;123:281–341.PubMedGoogle Scholar
  123. 123.
    Truhaut R. The problems of thresholds for chemical carcinogens. Am Ind Hyg Assoc J 1980;41:685–92.PubMedGoogle Scholar
  124. 124.
    Gori GB. The regulation of carcinogenic hazards. Science 1980;208:256–61.PubMedGoogle Scholar
  125. 125.
    Ehrenberg L. In: Boerhaave Committee for Post-graduate Medical Education. Genetic risk of exposure to chemical mutagens and cytostatics. Leiden: Leiden University, 1984:83–98.Google Scholar
  126. 126.
    Rose VE. Standards for controls of carcinogens in the workplace. J Occup Med 1976;18:81–4.PubMedGoogle Scholar
  127. 127.
    Stolar MH, Power LA, Viele CS. Recommendations for handling cytotoxic drugs in hospitals. Am J Hosp Pharm 1983;40:1163–71.PubMedGoogle Scholar
  128. 128.
    Vainio H, Sorsa M, Rantanen J, et al. Biological monitoring in the identification of the cancer risk of individuals exposed to chemical carcinogens. Scand J Work Environ Health 1981;7:241–51.PubMedGoogle Scholar
  129. 129.
    Barry LK, Booker RB. Promoting the responsible handling of antineoplastic agents in the community. Oncol Nurs Forum 1985;12:41–6.Google Scholar
  130. 130.
    Cloak MM, Connor TH, Stevens KR, Theiss JC, et al. Occupational exposure of nursing personnel to antineoplastic agents. Oncol Nurs Forum 1985;12(5):33–9.Google Scholar
  131. 131.
    Hoffman DM. Lack of urine mutagenicity of nurses administering pharmacy prepared doses of antineoplastic agents. Am J IV Ther Clin Nutr 1983;10(8):28–31.Google Scholar
  132. 132.
    Sorsa M, Pyy L, Salomaa S, et al. Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals. Mutat Res 1988;204:465–79.PubMedGoogle Scholar
  133. 133.
    Norrpa H, Sorsa M, Vainio H, et al. Increased sister chromatid exchange frequencies in lymphocytes of nurses handling cytostatic drugs. Scand J Work Environ Health 1980;6:299–301.PubMedGoogle Scholar
  134. 134.
    Szigeti M, Fekete G, Szollar J. The effect of regular cytostatic handling on the SCE's in hospital nurses [Abstract]. Mutat Res 1982;97:227.Google Scholar
  135. 135.
    Nikula E, Kiviniitty K, Leisti J, et al. Chromosome aberrations in lymphocytes of nurses handling cytostatic agents. Scand J Work Environ Health 1984;10:71–4.PubMedGoogle Scholar
  136. 136.
    Bayhan A, Burgaz S, Karakaya AE. Urinary thioether excretion in nurses at an oncology department. J Clin Pharm Ther 1987;12:303–6.PubMedGoogle Scholar
  137. 137.
    Kaijser GP, Underberg WJM, Beijnen JH, The risks of handling cytotoxic drugs. II. Recommendations for working with cytotoxic drugs. Pharm Weekbl [Sci] 1990;12:228–35.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1990

Authors and Affiliations

  • G. P. Kaijser
    • 1
  • W. J. M. Underberg
    • 1
  • J. H. Beijnen
    • 2
    • 3
  1. 1.Pharmaceutical LaboratoryUtrecht UniversityGH Utrechtthe Netherlands
  2. 2.Slotervaart HospitalEC Amsterdamthe Netherlands
  3. 3.Antoni van Leeuwenhoek HospitalCX Amsterdamthe Netherlands

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