Biological Monitoring of the Oncology Healthcare Staff Exposed to Cyclophosphamide in Two Hospitals in Tehran

Abstract

Background: Antineoplastic drugs as chemotherapy agents are used for various therapeutic purposes. Occupational exposure to antineoplastic drugs is possible through inhalation, skin contact, skin absorption, and digestive or injection. Assessment of occupational exposure of staff working with anti-neoplastic drugs has been a major concern among practitioners and occupational health and safety managers. Objectives: Considering the importance of safeguarding oncology personnel against antineoplastic drugs, the aim of this study was to validate a method for analysing cyclophosphamide (CPA) in urine samples as the biomarker of the exposure of oncology personnel of two hospitals in Tehran. Methods: Standard urine samples were obtained from a healthy man without having any exposure to CPA drug. The standards urine samples of CPA within the concentration range of 0.02 to 50 microgram per liter (µg/L) were prepared by diluting the urine stock solution. Ifosfamide (IFO) was added as an internal standard at a concentration of 20 µg/L. CPA and IFO analysis by gas chromatography-electron capture detector (GC-ECD) in this study was confirmed by gas chromatography-mass spectrometry (GC-MS) for verification of their peak retention times and MS signature at 95% confidence. Results: Urinary CPA concentrations as the biomarker of the exposure of the oncology personnel were detected within the range of 0.52 to 21.4 µg/L. The drug presence in the urine of 31% (10 of 32) of two hospital staff indicate the biological monitoring potential to recognition of worker's exposure. Conclusions: In general, biological monitoring of oncology personnel could be a useful tool for assessing occupational exposure through all routes and efficacy of the current safety measures. Owing to higher values of urinary CPA in this study compared to the studies of their colleagues abroad stringent control measures were deemed necessary.

Exposure to Antineoplastic Drugs in Occupational Settings: A Systematic Review of Biological Monitoring Data

“…Ifosfamide (IP) is an alkylating agent similar to CPA, used in the treatment of several forms of lymphomas, sarcomas, and advanced forms of solid organ tumors [ 51 ]. Different studies have found traces of these ADs in biological matrices, primarily in urine of healthcare workers, and some of these reported proportions of workers or samples with biological contamination [ 2 , 36 , 37 , 47 , 48 ].…”

“…Furthermore, in the second repeated series of samples, only the control subject that briefly visited such workplace area during the 24-h study period tested positive for urinary CPA. Rezazadeh Azari et al [ 36 ], measuring the urinary CPA concentrations in the oncology personnel in two hospitals in Tehran, found that 10 out of 32 urine samples (31%) had detectable concentrations and nurses were the category with the most positive samples. Santos et al [ 34 ] found higher levels of CPA in pharmacists and nurses with respect to unexposed controls from the hospital staff.…”

“…However, a great deal of variability with respect both to AD concentrations (when available), and percentages of positive samples emerged. Some studies reported no drugs determined [ 10 , 13 , 32 , 38 , 39 , 40 , 41 , 44 , 45 ], while others demonstrated that up to 55% of the analyzed urine samples exceeded the LOD [ 2 , 30 , 35 , 36 , 37 , 47 , 48 ]. These results are in line with those retrieved in previous reviews reporting that, even when technical and PPE was used, a remarkable uptake of ADs could be observed, as percentages of positive urinary samples ranged from 0% to 88.9% in the hospital personnel [ 21 ].…”

“…In regard to the investigated populations, in the literature, these were mainly selected among staff members considered at risk of exposure, particularly staff whose work consisted of handling ADs, in compounding or administration phases, i.e., nurses, pharmacy technicians, oncology healthcare workers, that resulted also in the most frequently contaminated categories [ 2 , 36 , 37 ]. However, in some studies, participants from departments/areas where drug preparation and administration did not take place (shipping/receiving, transport, nutrition, and materials management) had also detectable [ 29 , 48 ] and, in some cases, higher average drug concentration levels [ 47 ] than those workers directly involved in preparing/handling/administering chemotherapy.…”

“…Overall, this prevents extrapolation into definite conclusions on qualitative and quantitative types of exposure per job category or suitable comparisons and needs to be overcome in future investigations. Moreover, the increasing application of ADs in innovative surgical procedures, such as the HIPEC and PIPAC, as well as the employment of such drugs also for non-malignant diseases, may increase the likelihood for healthcare occupational exposure [ 28 , 36 , 42 ]. Particularly, the exposure for healthcare workers to ADs during open abdomen HIPEC is a subject of concern since healthcare workers in the operating room generally have no experience in handling these drugs.…”