Biological and environmental monitoring of occupational exposure of pharmaceutical plant workers to methotrexate.
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 micrograms/m3; median: 10 micrograms/m3). The highest concentrations were observed for workers weighing MTX (118 and 182 micrograms/m3). MTX was detected in urine samples of all workers. The mean cumulative MTX excretion over 72-96 h was 13.4 micrograms MTX-equivalents (range: 6.1-24 micrograms MTX-equivalents). A significantly lower background level of 10.2 micrograms MTX-equivalents was measured in urine of 30 control persons (range: 4.9-21 micrograms MTX-equivalents).
Sessink
P J
PJ
Department of Toxicology, Faculty of Medical Sciences, University of Nijmegen, The Netherlands.
Friemèl
N S
NS
Anzion
R B
RB
Bos
R P
RP
D000328:Adult; D000395:Air Pollutants, Occupational / Q000009:adverse effects / Q000493:pharmacokinetics; D004339:Drug Compounding; D004345:Drug Industry; D004784:Environmental Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000493:pharmacokinetics; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced* / Q000652:urine; D016273:Occupational Exposure / Q000009:adverse effects*; D011481:Protective Clothing
D000395:Air Pollutants, Occupational; D008727:Methotrexate