Biological monitoring of cyclophosphamide and ifosfamide in urine of hospital personnel occupationally exposed to cytostatic drugs.

Abstract

The occupational exposure of 21 nurses and pharmacy personnel from eight hospitals to cyclophosphamide and ifosfamide was determined by quantifying the amount of the drugs handled and by measuring the urinary excretion of the unmetabolised substances. Preparing antineoplastic drugs for intravenous treatment was the major task of all study participants. Twenty four hour urine was collected on days when cyclophosphamide andlor ifosfamide were mixed, on average 3900 mg cyclophosphamide and/or 5900 mg ifosfamide. The analyses were performed by gas chromatography with electron capture, detection limit 2' p5g124 hour urine. Despite standard safety precautions, including a vertical laminar air flow safety cabinet and gloves, cyclophosphamide was detected in 12 of 31 and ifosfamide in four of 21 urine samples on days when the drugs were handled. Excretion of cyclophosphamide ranged from 3*5 to 38 og124 h (mean ,ug/24 h) urine, ifosfamide from 5 to 12-7 ug/24 h (mean 9 ug/24 h) urine. Based on an excretion rate of 11'3% unmetabolised cyclophosphamide, the average amount excreted corresponded to an uptake of 101 pg cyclophosphamide. For ifosfamide the mean quantity incorporated was 20 pg assuming that 45% of the drug was excreted. Pertaining to the doses handled, the uptake of cyclophosphamide and ifosfamide was estimated to be approximately 0*0025% and 0-0004% respectively.Despite time-consuming purification procedures, gas chromatographic analysis is a suitable method for monitoring personnel occupationally exposed to cyclophosphamide and ifosfamide and is a major contribution to the evaluation of potential health risks of exposed personnel. (Occup Environ Med 1994;51:229-233)

Evaluation of Environmental Contaminations and Occupational Exposures Involved in Preparation of Chemotherapeutic Drugs

“…Ensslin 11) estimated that 0.0025％ and 0.00045％ of handled CP and IF were taken up, and possible precautions such as wearing proper protective clothing, safely handling drugs, and vertical laminar ‰ow cabinet should be adopted.…”

Development and validation of methods for environmental monitoring of cyclophosphamide in workplaces

“…Absorption of antineoplastic drugs occurs mainly through skin or through inhalation of gases or particles. Occupationally exposed workers have earlier been studied and the levels of antineoplastic drugs or their metabolites in both urine [1][2][3][4][5] and blood 6 have been monitored. Cyclophosphamide (2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide; CP), a very common antineoplastic drug, was introduced in the 1950s.…”

Environmental Contaminations and Occupational Exposures Involved in Preparation of Chemotherapeutic Drugs

“…Previously, in studies of external exposures [Sessink et al,1992;Minoia et al,1998;Sabatini et al,2005;Hedmer et al,2008] and studies in internal exposures [Hirst et al,1984;Sessink et al,1992Sessink et al, , 1994Sessink et al, , 1995Ensslin et al,1994;Burgaz et al,1999;Pethran et al,2003], cyclophosphamide was frequently used as a marker of occupational exposures because of its slight volatility and human genotoxicity [Connor et al,2000], reproductive toxicity [Anderson et al,1995], carcinogenicity [IARC,1981], and ease of detection [Turci et al,2002;Barbieri et al,2006].…”