Research paper
Monitoring of occupational exposure to cytostatic anticancer agents

https://doi.org/10.1016/0027-5107(96)00031-0Get rights and content

Abstract

Many anticancer agents have been shown to be carcinogenic, mutagenic and teratogenic in experimental animals and in in vitro test systems. Epidemiological data on the association of second neoplasms with a specific chemotherapy treatment is available on some 30 agents, and in the case of 10 compounds the overall evidence on human carcinogenicity has been evaluated to be conclusive (Group 1: IARC, 1987 and 1990). The primary source of human exposure to anticancer drugs is from their use in therapy of cancer. However, persons employed in the manufacture, preparation and administration of the drugs to patients and in nursing patients may also be exposed. Safe handling of anticancer drugs, since the introduction of various general handling guidelines, is now good practice in hospitals, pharmacies and drug manufacturing companies of most developed countries. Careless handling of cancer chemotherapeutic agents may lead to exposure of the personnel in amounts detectable with chemical or biological methods in the body fluids or cell samples of the subjects. The exposure is typically to mixed compounds over long-term and to low exposure levels with accidental peaks. Therefore, the use of biological exposure markers is appropriate for the monitoring of such exposure patterns. The biological markers/methods for exposure assessment are either non-specific (e.g., cytogenetic damage, point mutations or 32P-post-labelling adducts in peripheral blood lymphocytes, urinary mutagenicity) or specific for a given compound (immunological methods for DNA adducts, specific analytical methods). Studies have revealed minor amounts of cyclophosphamide in the urine of pharmacy technicians and nurses handling the drug even when taking special safety precautions (Sessink et al. (1994a) J. Occup. Med., 36, 79; Sessink et al. (1994b) Arch. Env. Health, 49, 165). Another study showed surface wipe samples with measurable cyclophosphamide even away from the handling site (McDevitt et al. (1993) J. Occup. Med., 5, 57). These studies strongly implicate the importance of skin absorption as an exposure route. Also accidental spillage is never completely avoidable (Sorsa et al. (1988) Mutation Res., 204, 465–479). The potential confounders (smoking etc.), toxicokinetics of the agent(s) to be assessed and individual working practices should be carefully considered in any exposure assessment studies using human body fluid samples. Environmental monitoring on indicator cytostatics should be combined into studies designed to identify potential occupational exposure situations to anticancer agents. A properly performed study should also include dissemination of information to the workers to create a psychologically positive atmosphere for this important work.

References (56)

  • M.L Kleinberg et al.

    Airborne drug levels in a laminar flow hood

    Am. J. Hosp. Pharm.

    (1981)
  • W Popp et al.

    DNA protein cross-links and sister chromatid exchanges frequencies in lymphocytes and hydroxyethylmercapturic acid in urine of ethylene oxide-exposed hospital workers

    Int. Arch. Occup. Environ. Health

    (1994)
  • P.J.M Sessink et al.

    Assessment of occupational exposure of pharmaceutical plant workers to 5-fluorouracil

    J. Occup. Med.

    (1994)
  • M Sorsa et al.

    Induction of sister chromatid exchanges among nurses handling cytostatic drugs

  • J.M Stellman

    Assessment of potential exposure to anti-neoplastic agents in the health care setting

    Prev. Med.

    (1984)
  • M Tortorici

    Precautions followed by personnel involved with the preparation of parenteral anti-neoplastic medications

    Hosp. Pharm.

    (1980)
  • H Vainio et al.

    Bacterial mutagenicity assay in monitoring exposure to mutagens and carcinogens

  • I.B Weinstein

    The origins of human cancer: Molecular mechanisms of carcinogenesis and their implications for cancer prevention and treatment

    Cancer Res.

    (1988)
  • Anderson, D., A. Dhawan, T.W. Yu and M.J. Plewa. An investigation of bone marrow and testicular cells in vivo using the...
  • C Betti et al.

    Microgel electrophoresis assay (COMET test) and SCE analysis in human lymphocytes from 100 normal subjects

    Mutation Res.

    (1994)
  • R.P Clark et al.

    The potassium iodide method for determining protection factors in open-fronted microbiological safety cabinets

    J. Appl. Biol.

    (1981)
  • A Chrysostomou et al.

    Mutation frequency in nurses and pharmacists working with cytotoxic drugs

    Aust. NZ J. Med.

    (1984)
  • N.A de Werk et al.

    Exposure of hospital workers to airborne anti-neoplastic agents

    Am. J. Hosp. Pharm.

    (1983)
  • L Ferguson

    Occupational health and staff monitoring: a genetic toxicologists viewpoint

    J. Oncol. Pharm. Practice

    (1995)
  • A.M.J Fichtinger-Schepman et al.

    CIS-Diaminedichloroplatinum (II)-induced DNA adducts in peripheral leukocytes from seven cancer patients: quantitative immunochemical detection of the adduct induction and removal after a single dose of CIS-diaminedichloroplatinum (II)

    Cancer Res.

    (1987)
  • J Hansen et al.

    Cancer morbidity among Danish female pharmacy technicians

    Scand. J. Work Environ. Health

    (1994)
  • K Hemminki et al.

    Spontaneous abortions and malformations in the offspring of nurses exposed to anaesthetic gases, cytostatic drugs and other potential hazards in hospitals based on registered information of outcome

    J. Epidemiol. Commun. Health

    (1985)
  • Cited by (0)

    View full text