Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals

Sorsa, Marja; Pyy, Lauri; Salomaa, Sisko; Nylund, L.; Yager, Janice W.

doi:10.1016/0165-1218(88)90042-0

Cited by 104 publications

(43 citation statements)

References 17 publications

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“…10,11,13,[17][18][19] These methods have been used to study air concentrations of CP at different workplaces. In previous studies different types of filters have been used to collect particles of CP.…”

Section: Introductionmentioning

confidence: 99%

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

2004

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Methods to monitor contamination of workplaces with antineoplastic drugs have been developed and validated. Cyclophosphamide (CP) was used as a model compound as it is one of the most commonly used antineoplastic drugs. A wipe sampling method to detect contamination with CP at surfaces was developed. A personal air sampling method to sample gas and vapour on solid sorbent tubes and particles with filters was also developed. Wipe and filter samples were extracted and sorbent samples were eluted, all with ethyl acetate. The samples were analysed with liquid chromatography tandem mass spectrometry.2 H 6 -labelled cyclophosphamide was used as an internal standard. The between-day precision was 2-5% for wipe samples, 4-6% for sorbent samples and 3-8% for filter samples. The limit of detection was 0.02 ng CP per sample for the wipe and filter methods and 0.03 ng CP per sample for the solid sorbent method. Wipe sampling on surfaces made of different materials resulted in mean recoveries between 78-106%. The desorption recovery was between 97-102% for the wipe samples, 97% for the sorbent samples and 101% for the filter samples. Samples were stable for up to 2 months at 5 1C and À20 1C and for about 2 d at room temperature. The developed methods were applied to the measurement of contamination with CP in a hospital pharmacy. Trace amounts of CP, 1.3 and 1.4 ng, were detected on surfaces in the pharmacy.

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Section: Introductionmentioning

confidence: 99%

“…Limits of detection of the developed methods in this study were much lower compared with earlier studies for wipe and air methods. [10][11][12][13][14][15][16][17][18][19] Precision. The within-day precision of the methods was evaluated by analysing six wipe, solid sorbent and filter samples containing 5 ng CP.…”

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confidence: 99%

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

2004

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“…Another exposure, which usually produces elevations in chromosome aberrations and sister chromatid exchanges, but not in MN, is smoking (4,5,(11)(12)(13)16 (20) were able to show a statistically significant difference in MN levels between smokers and nonsmokers, the overall impression that one gets from the few studies available is that the CB MN assay does not detect smoking as efficiently as the analysis of chromosome aberrations does. (4,6,8,11,12,14,16,19) have demonstrated that age affects the MN frequency of cultured human lymphocytes, the effect being steeper for women than for men.…”

Section: Is Exposure To Aneuploidogens Detected?mentioning

confidence: 95%

“…Since the first human biomonitoring study (11,12) using Cyt-B -which did show elevated MN levels among cyclophosphamide process workers and oncology nurses exposed to cytostatics -biomonitoring studies with a positive MN outcome from exposures to chemical genotoxins (other than cytostatics in cancer therapy) have been rare. In Finland, investigations of exposure to styrene in the reinforced plastics industry (13,14), power-line workers exposed to electric and magnetic fields (15), and formaldehyde-exposed industry workers (Table 1) have all yielded a negative outcome for MN.…”

Section: Is Exposure To Aneuploidogens Detected?mentioning

confidence: 99%

Micronucleus Assay in Lymphocytes as a Tool to Biomonitor Human Exposure to Aneuploidogens and Clastogens

Norppa¹,

Heikanen²,

Roth³

et al. 1993

Environmental Health Perspectives

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The analysis of micronuclei (MN) in cultured human lymphocytes is, in principle, able to detect exposure to clastogens and aneuploidogens alike. There is, however, no clear evidence from human biomonitoring studies or animal experiments showing that in vivo exposure of resting lymphocytes to an aneuploidogen could actually be expressed as MN in cultured lymphocytes. In vitro, a pulse treatment of human lymphocytes with vinblastine, an aneuploidogen, did result in MN induction even if performed before mitogen stimulation, although a much more pronounced effect was obtained in actively dividing lymphocyte cultures. On the other hand, it is probable that a considerable portion of "spontaneous" MN contain whole chromosomes, their contribution increasing with age. It also seems that cytochalasin B, used for the identification of second cell cycle interphase cells in the MN assay, is able to slightly increase the level of MN with whole chromosomes. If MN harboring chromosome fragments represent a minority of the total MN frequency, there may be difficulties in detecting a weak effect in this fraction of MN against the background of MN with whole chromosomes. This would reduce the sensitivity of the assay in detecting clastogens, unless MN with whole chromosomes and chromosome fragments are distinguished from each other. That a problem may exist in sensitivity is suggested by the difficulty in demonstrating MN induction by smoking, an exposure capable of inducing chromosome aberrations. The sensitivity ofthe lymphocyte MN assay could be increased by detecting kinetochore or centromere in MN, or by automation, allowing more cells to be analyzed.

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“…Some of these studies have been particularly useful, as they have allowed direct comparison of the CBMN assay with other cytogenetic end points. These investigations included occupational exposure to styrene (31,32), chemicals in tannery industries (33), cyclophosphamide (34), and intervention trials with paracetamol (35). In three of these studies (32,33,35), increases in chromatid-type aberrations were reported; however, there was no corresponding increase in the MN index.…”

Section: Chemicalsmentioning

confidence: 99%

The Cytokinesis-Block Micronucleus Technique and Its Application to Genotoxicity Studies in Human Populations

Fenech¹

1993

Environmental Health Perspectives

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The development of the cytokinesis-block (CB) technique has made the human lymphocyte micronucleus assay (MN) a reliable and precise method for assessing chromosome damage. Recent studies in our laboratory have confirmed that this method is a sensitive indicator of in vivo radiation exposure in patients undergoing fractionated partial-body radiotherapy and rodents exposed to uniform whole-body irradiation, thus supporting the application of the cytokinesis-block micronucleus (CBMN) assay for biological dosimetry. To further define the use of this assay in biomonitoring, we have also undertaken extensive studies to determine the spontaneous level of MN in normal human populations and its relationship to various lifestyle factors. During the past year, we have also developed a new variation to the CBMN assay that enables the conversion of excision-repairable lesions to MN within one cell-cycle using cytosine arabinoside. With this method the slope of the in vitro dose-response curves was increased by a factor of 1.8 for X-rays, 10.3 for ultraviolet (254 nm) radiation, and approximately 40-fold for methylnitrosourea. Consequently, the CBMN assay can now be used not only to measure whole chromosome loss or chromosome breaks but also excision repair events. The versatility and simplicity of the CBMN assay together with new developments in automation should enable its successful application in monitoring exposed populations as well as identifying mutagen-sensitive individuals within a population.

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Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals

Cited by 104 publications

References 17 publications

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

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

Micronucleus Assay in Lymphocytes as a Tool to Biomonitor Human Exposure to Aneuploidogens and Clastogens

The Cytokinesis-Block Micronucleus Technique and Its Application to Genotoxicity Studies in Human Populations

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