Initial assessment of multi-compound antineoplastic drug surface contamination in Argentinean healthcare centers: Insights into occupational exposures in South America.

INTRODUCTION: Antineoplastic drug contamination can result in severe health effects for healthcare workers exposed to them. Despite the worldwide growing concern regarding these drugs and sustained monitoring efforts in developed countries, there is almost no data about surface contamination levels in Argentina, in particular, and South America, in general. METHODS: Antineoplastic drug contamination was measured in three Argentinean public hospitals (pharmacy and daycare center areas) by surface wiping and liquid chromatography coupled with tandem mass spectrometry. RESULTS AND DISCUSSION: Eleven drugs were detected, in 51 of 58 sampled surfaces, in variable concentrations from 0.00064 to 7.3 ng cm-2, with cyclophosphamide, gemcitabine, and paclitaxel as the most prevalent drugs. This highly variable antineoplastic distribution reflects differences in facility layout, number of patients, antineoplastic drug use, etc., at each hospital. Values exceeding the 1 ng cm-2 threshold were detected in 13 surfaces of the two hospitals handling the largest amounts of antineoplastic drugs. The cyclophosphamide 75th percentile averaged 0.030 ng cm-2 comparable to the high values reported more than 10 years ago for developed countries, emphasizing the potential of reducing antineoplastic contamination by implementing routine monitoring and improved cleaning and handling procedures. CONCLUSION: This study is the first survey of multi-compound surface antineoplastic contamination in Argentinean (and South American) hospitals, providing a baseline against which future studies can be compared. Widespread antineoplastic contamination has been detected on numerous surfaces, with concentrations surpassing suggested threshold exposure levels (1 ng cm-1) for some surfaces in two of the sampled hospitals.

Developing wipe sampling strategy guidance for assessing environmental contamination of antineoplastic drugs.

Surveillance for environmental contamination of antineoplastic drugs has been recommended by authoritative bodies such as the United States Pharmacopeia and the National Association of Pharmacy Regulatory Authorities. Clear guidance is needed on how to develop sampling strategies that align with surveillance objectives efficiently and effectively. We conducted a series of simulations using previously collected surveillance data from nine cancer treatment centers to evaluate different sampling strategies. We evaluated the impact of sampling 2, 5, 10, or 20 surfaces, at monthly, quarterly, semi-annual, and annual frequencies, while employing either a random or sentinel surface selection strategy to assess contamination by a single antineoplastic drug (AD) or by a panel of three ADs. We applied two different benchmarks: a binary benchmark of above or below the limit of detection and AD-specific hygienic guidance values, based on 90th percentile values as quantitative benchmarks. The use of sentinel surfaces to evaluate a three-drug panel relative to 90th percentile hygienic guidance values (HGVs) resulted in the most efficient and effective surveillance strategy.

Personal and household PM2.5 and black carbon exposure measures and respiratory symptoms in 8 low- and middle-income countries.

BACKGROUND: Household air pollution (HAP) from cooking with solid fuels has been associated with adverse respiratory effects, but most studies use surveys of fuel use to define HAP exposure, rather than on actual air pollution exposure measurements. OBJECTIVE: To examine associations between household and personal fine particulate matter (PM2.5) and black carbon (BC) measures and respiratory symptoms. METHODS: As part of the Prospective Urban and Rural Epidemiology Air Pollution study, we analyzed 48-h household and personal PM2.5 and BC measurements for 870 individuals using different cooking fuels from 62 communities in 8 countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Self-reported respiratory symptoms were collected after monitoring. Associations between PM2.5 and BC exposures and respiratory symptoms were examined using logistic regression models, controlling for individual, household, and community covariates. RESULTS: The median (interquartile range) of household and personal PM2.5 was 73.5 (119.1) and 65.3 (91.5) µg/m3, and for household and personal BC was 3.4 (8.3) and 2.5 (4.9) x10-5 m-1, respectively. We observed associations between household PM2.5 and wheeze (OR: 1.25; 95%CI: 1.07, 1.46), cough (OR: 1.22; 95%CI: 1.06, 1.39), and sputum (OR: 1.26; 95%CI: 1.10, 1.44), as well as exposure to household BC and wheeze (OR: 1.20; 95%CI: 1.03, 1.39) and sputum (OR: 1.20; 95%CI: 1.05, 1.36), per IQR increase. We observed associations between personal PM2.5 and wheeze (OR: 1.23; 95%CI: 1.00, 1.50) and sputum (OR: 1.19; 95%CI: 1.00, 1.41). For household PM2.5 and BC, associations were generally stronger for females compared to males. Models using an indicator variable of solid versus clean fuels resulted in larger OR estimates with less precision. CONCLUSIONS: We used measurements of household and personal air pollution for individuals using different cooking fuels and documented strong associations with respiratory symptoms.

Sludge-based activated carbon and its application in the removal of perfluoroalkyl substances: A feasible approach towards a circular economy.

This study explores the recovery of resources and energy from sewage sludge through the production of sludge-based activated carbon (SBAC) considering circular economy principles. The SBAC production costs were estimated under three scenarios considering various sludge dewatering/drying schemes to determine the production feasibility and its role in the circular economy. SBAC was tested in the removal of a mixture of nine commonly detected poly- and perfluoroalkyl substances (PFASs) in environmentally relevant concentrations of ∽50 µg/L in comparison to commercially available activated carbon (AC) using 5 mg of sorbent and 5 mL of a nine-PFAS mixture in deionised water. SBAC can be produced at approximately 1.2 US $/kg, which is substantially lower than the average production cost of commercial AC of >3 US $/kg. A net revenue ranging from 2 to 7 US $/kg SBAC was estimated by recycling the produced non-condensable gases and bio-oil to produce energy and selling the SBAC. Batch adsorption tests showed that the PFASs removal of SBAC was superior to that of granular AC and similar to that of powdered AC, reaching >91% to below the detection limit. The kinetics tests revealed that adsorption by SBAC and AC occurred within 15 min. The overall results demonstrate the potential of SBAC as an effective sorbent for PFASs, achieving waste-to-resources circular economy via resource and energy recovery from sewage sludge, eliminating sludge disposal and contaminant-leaching to the environment, and in enhancing the quality of wastewater effluent before discharge.

Spatial and Temporal Variability in Antineoplastic Drug Surface Contamination in Cancer Care Centers in Alberta and Minnesota.

The health risks of exposure to antineoplastic drugs (ADs) are well established, and healthcare professionals can be exposed while caring for cancer patients receiving AD therapy. Studies conducted worldwide over the past two decades indicate continuing widespread surface contamination by ADs. No occupational exposure limits have been established for ADs, but concerns over exposures have led to the development of guidelines, such as United States Pharmacopeia (USP) General Chapter <800> Hazardous Drugs-Handling in Healthcare. While recommending regular surveillance for surface contamination by ADs these guidelines do not provide guidance on sampling strategies. Better characterization of spatial and temporal variability of multidrug contamination would help to inform such strategies. We conducted surface-wipe monitoring of nine cancer care centers in Alberta, Canada and Minnesota, USA, with each center sampled eight times over a 12-month period. Twenty surfaces from within pharmacy and drug administration areas were sampled, and 11 drugs were analyzed from each wipe sample. Exposure data were highly left-censored which restricted data analysis; we examined prevalence of samples above limit of detection (LOD), and used the 90th percentile of the exposure distribution as a measure of level of contamination. We collected 1984 wipe samples over a total of 75 sampling days resulting in 21 824 observations. Forty-five percent of wipe samples detected at least one drug above the LOD, but only three of the drugs had more than 10% of observations above the LOD: gemcitabine (GEM) (24%), cyclophosphamide (CP) (16%), and paclitaxel (13%). Of 741 wipe samples with at least one drug above LOD, 60% had a single drug above LOD, 19% had two drugs, and 21% had three drugs or more; the maximum number of drugs found above LOD on one wipe was 8. Surfaces in the compounding area of the pharmacy and in the patient area showed the highest prevalence of samples above the LOD, including the compounding work surface, drug fridge handle, clean room cart, passthrough tray, and hazardous drug room temperature storage, the IV pump keypad, patient washroom toilet handle, patient washroom door handle, nurses' storage shelf/tray, and patient side table. Over the course of the study, both 90th percentiles and prevalence above LOD varied without clear temporal patterns, although some centers appeared to show decreasing levels with time. Within centers, the degree of variability was high, with some centers showing changes of two to three orders of magnitude in the 90th percentile of drug concentrations month to month. A clear difference was observed between the six centers located in Alberta and the three in Minnesota, with Minnesota centers having substantially higher percentages of samples above the LOD for CP and GEM. Other factors that were associated with significant variability in exposures were drug compounding volume, size of center, number of patients seen, and age of the center. We hope that demonstrating variability associated with drug, surface, clinic-factors, and time will aid in a better understanding of the nature of AD contamination, and inform improved sampling strategies.

Household and personal air pollution exposure measurements from 120 communities in eight countries: results from the PURE-AIR study.

BACKGROUND: Approximately 2·8 billion people are exposed to household air pollution from cooking with polluting fuels. Few monitoring studies have systematically measured health-damaging air pollutant (ie, fine particulate matter [PM2·5] and black carbon) concentrations from a wide range of cooking fuels across diverse populations. This multinational study aimed to assess the magnitude of kitchen concentrations and personal exposures to PM2·5 and black carbon in rural communities with a wide range of cooking environments. METHODS: As part of the Prospective Urban and Rural Epidemiological (PURE) cohort, the PURE-AIR study was done in 120 rural communities in eight countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Data were collected from 2541 households and from 998 individuals (442 men and 556 women). Gravimetric (or filter-based) 48 h kitchen and personal PM2·5 measurements were collected. Light absorbance (10-5m-1) of the PM2·5 filters, a proxy for black carbon concentrations, was calculated via an image-based reflectance method. Surveys of household characteristics and cooking patterns were collected before and after the 48 h monitoring period. FINDINGS: Monitoring of household air pollution for the PURE-AIR study was done from June, 2017, to September, 2019. A mean PM2·5 kitchen concentration gradient emerged across primary cooking fuels: gas (45 µg/m3 [95% CI 43-48]), electricity (53 µg/m3 [47-60]), coal (68 µg/m3 [61-77]), charcoal (92 µg/m3 [58-146]), agricultural or crop waste (106 µg/m3 [91-125]), wood (109 µg/m3 [102-118]), animal dung (224 µg/m3 [197-254]), and shrubs or grass (276 µg/m3 [223-342]). Among households cooking primarily with wood, average PM2·5 concentrations varied ten-fold (range: 40-380 µg/m3). Fuel stacking was prevalent (981 [39%] of 2541 households); using wood as a primary cooking fuel with clean secondary cooking fuels (eg, gas) was associated with 50% lower PM2·5 and black carbon concentrations than using only wood as a primary cooking fuel. Similar average PM2·5 personal exposures between women (67 µg/m3 [95% CI 62-72]) and men (62 [58-67]) were observed. Nearly equivalent average personal exposure to kitchen exposure ratios were observed for PM2·5 (0·79 [95% 0·71-0·88] for men and 0·82 [0·74-0·91] for women) and black carbon (0·64 [0·45-0·92] for men and 0·68 [0·46-1·02] for women). INTERPRETATION: Using clean primary fuels substantially lowers kitchen PM2·5 concentrations. Importantly, average kitchen and personal PM2·5 measurements for all primary fuel types exceeded WHO's Interim Target-1 (35 µg/m3 annual average), highlighting the need for comprehensive pollution mitigation strategies. FUNDING: Canadian Institutes for Health Research, National Institutes of Health.

The application of novel field measurement and field evaluation protocols for assessing health care workers' exposure risk to antineoplastic drugs.

Contamination of multiple antineoplastic drugs (ADs) on work surfaces presents an exposure concern for health care workers. Surface wipe sampling is a recognized method to evaluate the degree of contamination present. Our research team has previously reported on wipe sampling and analytical methods to simultaneously detect 10 commonly used ADs from a single wipe. Our objectives here were: to field test a protocol consisting of the wipe sampling method and an accompanying wipe sample collection tool kit and confirm this protocol can be effectively used by health care workers to assess drug contamination levels in their facilities; and, to confirm the potential for simultaneous exposure to multiple antineoplastic drugs. Three facilities within one health authority in British Columbia, Canada participated in this field study. In collaboration with the site health and safety advisors, up to 25 surfaces within each facility were considered for sampling. Collected wipe samples were analyzed using HPLC-MS/MS to quantify the 10 analyte, resulting in 750 potential analyses. Following the sampling, each of the three facilities' safety advisors provided feedback regarding the usability of the protocols. Among the 72 wipe samples actually collected (or 720 analyses conducted), detectable levels and simultaneous contamination of work surfaces of five of the 10 analytes were found at all three participating sites: 5-fluorouracil, cyclophosphamide, vincristine, paclitaxel, and methotrexate; (range < LoD to 33.0 ng/cm2) with 5-fluorouracil having the highest concentration in every instance. Drug contamination was found on a variety of different work surfaces in pharmacies and patient care areas among all three sites. Users of the sampling protocols were generally satisfied with the wipe sample collection toolkit with some minor suggestions for improvement. Our findings support the hypothesis that health care workers may be simultaneously at risk of exposure to several ADs. Our toolkit was found to be user-friendly and manageable by those who were not experienced in collecting wipe samples to monitor contamination of ADs on the work surfaces in their facilities.

Wipe Sampling Method and Evaluation of Environmental Variables for Assessing Surface Contamination of 10 Antineoplastic Drugs by Liquid Chromatography/Tandem Mass Spectrometry.

This paper describes a novel wipe sampling and high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method capable of simultaneously detecting 10 antineoplastic drugs (5-fluorouracil, oxaliplatin, methotrexate, vindesine, ifosfamide, cyclophosphamide, vincristine, vinblastine, docetaxel, and paclitaxel). The good overall recoveries and sensitivity values of this method along with the comparatively short run time (8 min) allows for its use in routine monitoring in health care facilities. The long-term behavior of the studied drugs on contaminated surfaces and the effect of surface roughness on drug recoveries were studied to gain insights about how these environmental variables influence the detection, cleaning, and occupational exposure of these drugs. Surfaces with higher roughness parameter (Ra) values (rougher) had the lowest recoveries while those with lower Ra (smoother) presented the highest recoveries. Long-term assessments evidence distinctive drug behaviors with oxaliplatin, vindesine, vincristine, and vinblastine being the less persistent drugs (~20% was recovered after 24 h) and docetaxel and paclitaxel the most persistent drugs with recoveries of 40% and 80% after 1 month. This information indicates the importance of collecting ancillary information about drug usage (throughput, timing, cleaning procedures, etc.) to interpret the results in the context of potential exposure. Finally, the method was successfully applied to evaluate trace surface contamination down to the single picogram per square centimeter in multiple work areas within three local health care centers on Vancouver Island, Canada.

A surface wipe sampling and LC-MS/MS method for the simultaneous detection of six antineoplastic drugs commonly handled by healthcare workers.

An effective wipe sampling and LC-MS/MS method was developed to simultaneously analyze six commonly administered antineoplastic drugs in stainless steel surface. The analyzed drugs were methotrexate, paclitaxel, cyclophosphamide, 5-fluorouracil, vincristine, and oxaliplatin, a frequently prepared antineoplastic drug that has not been included among any of the published simultaneous detection methods. The established method was used to evaluate the recoveries of antineoplastic drugs on brand new and worn stainless steel surfaces by wiping the plates with a Whatman filter paper wetted with 0.5 mL of water/methanol (20:80) with 0.1% formic acid followed by LC-MS/MS before desorbing the filter with a water/methanol (50:50) solution. A significant decrease in the recovery of all evaluated drugs was found when worn plates were used. Additionally, the inter-personnel variability on drug recoveries during wiping procedures was evaluated. Significantly higher recoveries were achieved by the personnel with more training and experience versus personnel without prior experience. Finally, a laboratory stability test was developed to assess the degradation of the antineoplastic drugs during replicated shipping conditions. With the exception of vincristine sulfate which exhibited a significant (p < 0.05) degradation after 48 h, all evaluated drugs were stable during the first 24-48 h. However, after 144 h, an increase in the degradation of all evaluated drugs was observed, with oxaliplatin and 5-fluorouracil exhibiting the most degradation.