Environmental contamination and assessment of exposure to antineoplastic agents by determination of cyclophosphamide in urine of exposed pharmacy technicians: is skin absorption an important exposure route?
In the Netherlands, special guidelines and safety precautions were introduced about 10 y ago for preparation and administration of antineoplastic agents. However, little is known about the effectiveness of these measures. In this study, occupational exposure to antineoplastic agents of nine pharmacy technicians who were involved in drug preparation was investigated. Cyclophosphamide, 5-fluorouracil, and methotrexate accounted for 95% of the antineoplastic agents prepared; therefore, the presence of these compounds was monitored. During preparation, cyclophosphamide was detected in the air of the work environment (< 0.04-10.1 micrograms/m3). Contamination of and permeation through latex gloves were found for each of the three compounds. The uptake of cyclophosphamide was assessed by the determination of cyclophosphamide in urine. The drug was found in urine samples of six pharmacy technicians, including three persons who were not directly involved in the preparation of cyclophosphamide. The amounts excreted ranged from 0.2 to 19.4 micrograms/24 h. The results strongly suggest that inhalation is of minor importance for internal exposure, compared with other, presumably dermal, routes.
Sessink
P J
PJ
Department of Toxicology, Faculty of Medical Sciences, University of Nijmegen, The Netherlands.
Van de Kerkhof
M C
MC
Anzion
R B
RB
Noordhoek
J
J
Bos
R P
RP
D000042:Absorption; D000328:Adult; D000395:Air Pollutants, Occupational / Q000032:analysis; D003520:Cyclophosphamide / Q000493:pharmacokinetics / Q000652:urine*; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics; D017575:Gloves, Protective; D003368:Gossypium; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000493:pharmacokinetics; D016273:Occupational Exposure / Q000032:analysis*; D010604:Pharmacy; D012408:Rubber; D012867:Skin / Q000378:metabolism*
D000395:Air Pollutants, Occupational; D003520:Cyclophosphamide; D012408:Rubber; D005472:Fluorouracil; D008727:Methotrexate