Occupational handling of antineoplastic drugs and cancer risk

Status:

completed 12/2000

Aims:

In observance of the recommended protective measures, antineoplastic drugs must be prepared, administered and disposed of in the health care sector. Although to a small extent, these activities nevertheless imply exposure of the concerned personnel to the handled substances by way of inhalation or dermal contact. As the majority of antineoplastic drugs are carcinogens with a mutagenic mode of action, it is impossible to fix a threshold value for their carcinogenic activity. To decide on the necessity of additional protective measures it is therefore necessary to carry out a quantitative risk assessment.

Activities/Methods:

A literature review was employed for an estimation of the specific cancer risk for the following selected antineoplastic drugs: cyclophosphamide, melphalan, methotrexate, 5-fluorouracil, cisplatin and etoposide. The quantitative risk assessment based upon the available data from animal experiments was performed using established analysis methods employed by the US Environmental Protection Agency. Parallel to the risk assessment, numerous epidemiological studies were evaluated concerning the occurrence of secondary tumours following treatment with antineoplastic drugs. The results obtained in animal experiments were applied to human beings on the assumption that test animals and humans exhibit the same sensitivity to the same carcinogenic concentrations in environmental media under long-term exposure conditions.

Results:

Specific risk values in the order of 2x10^-6 mg^-1 were derived consistently for cyclophosphamide, the drug for which the greatest useful information is available, by a clear margin. In other words, an excess lifetime tumour risk of 2:1,000,000 may be anticipated per milligram of total cyclophosphamide intake. The carcinogenic potency lifetime tumour risk of melphalan is estimated to be at least ten times this value. Unsufficient literature data indicate that the lifetime tumour risk of methotrexate and 5-fluorouracil is lower than that of cyclophosphamide; it remains unclear, however, whether 5-fluorouracil and methotrexate do in fact present a carcinogenic risk. The epidemiological data available for cisplatin are not sufficient to permit risk assessment. The few animal experiments performed with cisplatin indicate, with a high degree of uncertainty, that its carcinogenic potency lifetime tumour risk is higher than that of cyclophosphamide. The epidemiological research performed with etoposide permits calculation of an approximate value of 2-5x10^-6 mg^-1 for the specific risk. Measurements of the cyclophosphamide discharged in the urine of hospital staff appeared to be a suitable basis for calculation of exposure at the workplace. These measurements yield an excess tumour risk of between 2x10^- 5 (2:1,000,000) and 7x10^-4 (7:10,000) for daily contact at the workplace over a period of 35 years. Full exploitation of the TRK values (technical exposure limits for atmospheric values applicable in Germany) for certain carcinogenic agents certainly brings with it increased risks. Close attention should nevertheless be paid in hospitals and pharmacies and at similar workplaces to minimizing the exposure to antineoplastic drugs.

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