Summary
The exposure of 11 pharmaceutical plant workers to methotrexate (MTX) was studied. Personal air samples were taken during the different manufacturing processes: drug compounding, vial filling, and tablet preparation. The uptake of MTX was established by the determination of MTX in urine. MTX was analyzed using the fluorescence polarization immunoassay (FPIA), a method that is frequently used for monitoring serum levels in patients treated with MTX. The FPIA method was modified in such a way that MTX could be measured quickly and efficiently in air and urine samples. MTX was detected in air samples of all workers except for those involved in the vial filling process (range: 0.8–182 μg/m3; median: 10 μg/m3). The highest concentrations were observed for workers weighing MTX (118 and 182 μg/m3). MTX was detected in urine samples of all workers. The mean cumulative MTX excretion over 72–96 h was 13.4 μg MTX-equivalents (range: 6.1–24 μg MTX-equiva μg MTX-equivalents (range: 6.1–24 μg MTX-equivalents). lents). A significantly lower background level of 10.2 μg A significantly lower background level of 10.2 μg MTX-equivalents was measured in urine of 30 control persons (range: 4.9–21 μg MTX-equivalents).
Similar content being viewed by others
References
Black DJ, Livingston RB (1990) Antineoplastic drugs in 1990. A review (part 1). Drugs 39:489–501
Blecka LJ (1983) Fluorescence polarization immunoassay: a review of methodology and applications. American Association for Clinical Chemistry, therapeutic drug monitoring, continuing education and quality control program. Supplement of Clinical Chemistry, March 1983, pp 1–6
Chen ML, Chiou WL (1981) Sensitive and rapid high-performance liquid chromatographic method for the simultaneous determination of methotrexate and its metabolites in plasma, saliva and urine. J Chromatogr 226:125–134
Colligan SA, Horstman SW (1990) Permeation of cancer chemotherapeutic drugs through glove materials under static and flexed conditions. Appl Occup Environ Hyg 5:848–852
Fairris GM, Dewhurst AG, White JE, Campbell MJ (1989) Methotrexate dosage in patients aged over 50 with psoriasis. BMJ 298:801–802
Furst DE, Kremer JM (1988) Methotrexate in rheumatoid arthritis. Arthritis Rheum 31:305–313
International Agency for Research on Cancer (1981) IARC monographs on the evaluation of the carcinogenic risk to humans, vol 26. Some antineoplastic and immunosuppressive agents. Lyon, France
International Agency for Research on Cancer (1987) IARC monographs on the evaluation of the carcinogenic risk to humans, supplement 7. Overall evaluations of carcinogenicity. An updating of IARC monographs volume 1 to 42. Lyon, France
Mullarkey MF, Blumenstein BA, Andrade WP, Bailey GA, Olason I, Wetzel CE (1988) Methotrexate in the treatment of corticosteroid-dependent asthma: a double blind crossover study. N Engl J Med 318:603–607
Pesce MA, Bodourian SH (1986) Evaluation of a fluorescence polarization immunoassay procedure for quantitation of methotrexate. Ther Drug Monit 8:115–121
Rieche K (1984) Carcinogenicity of antineoplastic agents in man. Cancer Treat Rev 11:39–67
So N, Chandra DP, Alexander IS, Webster VJ, O'Gorman Hughes DW (1985) Determination of serum methotrexate and 7-hydroxymethotrexate concentrations. Method evaluation showing advantages of high-performance liquid chromatography. J Chromatogr 337:81–90
Stoikes ME, Carlson JD, Farris FF, Walker PR (1987) Permeability of latex and polyvinyl chloride gloves to fluorouracil and methotrexate. Am J Hosp Pharm 44:1341–1346
Slevin ML, Ang LM, Johnston A, Turner P (1984) The efficiency of protective gloves used in the handling of cytotoxic drugs. Cancer Chemother Pharmacol 12:151–153
Staubforschung Institute (1973) Recommendations for the determination of Health-Damaging Particulate Matter. Staub Reinhalt Luft 3:1–3
Tjaden UR, de Bruijn EA (1990) Chromatographic analysis of anticancer drugs. J Chromatogr 531:235–294
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sessink, P.J.M., Friemèl, N.S.S., Anzion, R.B.M. et al. Biological and environmental monitoring of occupational exposure of pharmaceutical plant workers to methotrexate. Int Arch Occup Environ Health 65, 401–403 (1994). https://doi.org/10.1007/BF00383251
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00383251