Identification of Knowledge Gaps Regarding Healthcare Workers' Exposure to Antineoplastic Drugs: Review of Literature, North America versus Europe

We have been examining the issue of healthcare workers' exposure to antineoplastic drugs for nearly a decade and have observed that there appears to be more publications on the subject matter originating from Europe than from North America. The concern is that findings from Europe may not be generalizable to North America because of differences in handling practices, regulatory requirements, and training. Our objective was to perform a literature review to confirm our observation and, in turn, identify gaps in knowledge that warrants addressing in North America. Using select keywords, we searched for publications in PubMed and Web of Science. All papers were initially classified according to the originating continent and then categorized into one or more subject categories (analytical methods, biological monitoring, occupational exposure, surface contamination, and probability of risk/exposure). Our review identified 16 papers originating from North America and 55 papers from Europe with surface contamination being the subject matter most often studied overall. Based on our results, we are of the opinion that North American researchers need to further conduct dermal and/or urinary drug contamination studies as well as assess the exposure risk faced by healthcare workers who handle antineoplastic drugs. Trends in exposure levels should also be explored

Pilot Evaluation of Dermal Contamination by Antineoplastic Drugs among Hospital Pharmacy Personnel

ABSTRACTBackground: It is believed that health care workers are exposed to antineoplastic drugs primarily via dermal contact. However, levels of occupational dermal contamination in Canada have not been formally investigated.Objective: To determine the potential dermal exposure to antineoplastic drugs among hospital pharmacy personnel in a metropolitan area in British Columbia.Methods: Six hospital pharmacies in the Vancouver area participated in this pilot study. Three pharmacy workers (a technician responsible for preparing drugs, a pharmacist responsible for checking drugs before administration, and a technician not responsible for preparing drugs but working in the pharmacy department) were selected from each site, for a total of 18 participants. Each worker’s hands were wiped with a premoistened tissue (one wipe per person), and the wipes were subsequently analyzed by high-performance liquid chromatography tandem mass spectrometry to determine levels of both cyclophosphamide and methotrexate (total of 36 analyses).Results: At 3 of the 6 sites, at least one hand-wipe sample was above the analytical detection limit. Of the 18 analyses from the 3 “positive” sites, 5 (28%) had measurable levels of cyclophosphamide and methotrexate. Cyclophosphamide was detected in 3 samples (geometric mean 0.98 ng, geometric standard deviation 2.72 ng, range from below limit of detection to 3.96 ng) and methotrexate in 2 samples (geometric mean 0.27 ng, geometric standard deviation 2.57 ng, range from below limit of detection to 0.27 ng).Conclusions: The results of this pilot study suggest that hospital pharmacy workers in Metro Vancouver are probably exposed to antineoplastic drugs, given that detectable levels of drug were found on the hands of some personnel. Further studies are recommended to confirm these findings.RÉSUMÉContexte : D’aucuns croient que les travailleurs de la santé sont exposés aux agents anticancéreux principalement par voie cutanée. Cependant, les taux de contamination professionnelle par voie cutanée au Canada n’ont pas fait l’objet d’études officielles.Objectif : Déterminer l’exposition cutanée potentielle aux agents anticancéreux du personnel des pharmacies d’hôpitaux dans une région métropolitaine de Colombie-Britannique.Méthodes : Six pharmacies d’hôpitaux de la région de Vancouver ont participé à cette étude pilote. Trois membres du personnel de la pharmacie (un technicien responsable de la préparation des médicaments; un pharmacien responsable de la vérification des médicaments avant leur administration; et un technicien non responsable de la préparation des médicaments, mais travaillant dans le service de pharmacie) ont été choisis dans chaque centre, pour un total de 18 sujets. Les mains de chaque sujet ont été essuyées au moyen d’une lingette (une par sujet), puis les lingettes ont été analysées par chromatographie liquide haute performance couplée à la spectrométrie de masse en tandem afin de déterminer les concentrations de cyclophosphamide et de méthotrexate, pour un total de 36 analyses.Résultats : Dans trois centres, au moins un échantillon de lingette présentait une concentration supérieure à la limite de détection analytique. Des 18 analyses provenant de ces trois centres, cinq (28 %) ont révélé des concentrations mesurables de cyclophosphamide ou de méthotrexate. On a détecté de la cyclophosphamide dans trois échantillons (moyenne géométrique de 0,98 ng, écart-type géométrique de 2,72, plage allant d’une valeur sous la limite de détection à 3,96 ng) et du méthotrexate dans deux échantillons (moyenne géométrique de 0,27 ng, écart-type géométrique de 2,57, plage allant d’une valeur sous la limite de détection à 0,27 ng).Conclusions : Les résultats de cette étude pilote suggèrent que les membres du personnel des pharmacies d’hôpitaux de Metro Vancouver sont probablement exposés à des agents anticancéreux, étant donné les concentrations détectables de médicaments trouvées sur les mains de certains employés. D’autres études sont recommandées afin de confirmer ces résultats

Estimating national-level exposure to antineoplastic agents in the workplace: CAREX Canada findings

Objectives: Occupational exposure to antineoplastic agents occurs in various environments and is associated with increased cancer risk and adverse reproductive outcomes. National-level information describing the location and extent of occupational exposure to antineoplastic agents is unavailable in Canada and most other countries. CAREX Canada aimed to estimate the prevalence and relative levels of occupational exposures to antineoplastic agents across work setting, occupation, and sex. Methods: 'Exposure' was defined as any potential for worker contact with antineoplastic agents. Baseline numbers of licensed workers were obtained from their respective professional bodies. For unlicensed workers, Census data or data extrapolated from human resources reports (e.g., staffing ratios) were used. Prevalence was estimated by combining population estimates with exposure proportions from peer-reviewed and grey literature. Exposure levels (classified as low, moderate, and high) by occupation and work setting were estimated qualitatively by combining estimates of contact frequency and exposure control practices. Results: Approximately 75 000 Canadians (0.42% of the total workforce) are estimated as occupationally exposed to antineoplastic agents; over 75% are female. The largest occupational group exposed to antineoplastic agents is community pharmacy workers, with 30 200 exposed. By work setting, 39 000 workers (52% of all exposed) are located in non-hospital settings; the remaining 48% are exposed in hospitals. The majority (75%) of workers are in the moderate exposure category. Conclusions: These estimates of the prevalence and location of occupational exposures to antineoplastic agents could be used to identify high-risk groups, estimate disease burden, and target new research and prevention activities. The limited secondary data available for developing these estimates highlights the need for increased quantitative measurement and documentation of antineoplastic agent contamination and exposure, particularly in work environments where use is emerging

Evidence of a paradoxical relationship between endotoxin and lung cancer after accounting for left truncation in a study of Chinese female textile workers

INTRODUCTION: Occupational exposure to endotoxin, found in Gram-negative bacteria in organic material, has been associated predominantly with a reduced risk of lung cancer among workers. An inverse exposure–response gradient among women textile workers in Shanghai, China, has been reported previously. In this case–cohort study, we investigated the influence of left truncation, which can itself induce a downward trend, on the observed association. METHODS: Subjects were enrolled between 1989 and 1991 and followed until 1998. The data were left-truncated as all subjects were hired before baseline. An analysis was performed with 3038 subcohort members and 602 cases of incident lung cancer. To evaluate left truncation, we compared lung cancer rates in those hired longer ago with those hired more recently among unexposed subjects. Cox proportional hazards modelling was used to estimate incident rate ratios (IRRs) and 95% CIs. RESULTS: Among those who were never exposed to workplace endotoxin, we compared lung cancer rates in those hired >35 years before enrolment with workers hired ≤35 years before enrolment and observed a reduced risk in the former group, IRR=0.74, 95% CI (0.51 to 1.07). After accounting for this downward bias from left truncation, the reduced risk associated with endotoxin remained among those hired ≤50 years before enrolment. In contrast, there was suggestion of an increased risk of lung cancer among those hired >50 years ago. CONCLUSIONS: After examination of left truncation bias, an inverse dose–response between endotoxin and lung cancer remained for all subjects except those hired longest ago