Reducing the particles generated by flushing institutional toilets.

Airborne particles play a significant role in the transmission of SARS-CoV-2, the virus that causes COVID-19. A previous study reported that institutional flush-O-meter (FOM) toilets can generate 3-12 times as many droplets as other toilets by splashing (large droplets) and bubble bursting (fine droplets). In this study, an aerosol suppression lid was evaluated to measure the reduction of particles by size using three metrics; number, surface area, and mass concentrations. To quantify toilet flush aerosol over time, detailed particle size distributions (from 0.016-19.81 µm across 152 size bins) were measured from a FOM toilet in a controlled-environment test chamber, without ventilation, with and without use of the suppression lid. Prior to each flushing trial, the toilet bowl water was seeded with 480 mL fluorescein at 10 mg/mL. A high-speed camera was used to record the large droplet movements after flushing. An ultraviolet-visible spectrophotometer was used to analyze the wipe samples to evaluate the contamination on the lid. The particle number, surface area, and mass concentrations without a lid were elevated compared to a lid in the first 90 sec. Overall, the lid reduced 48% of total number concentration, 76% of total surface area concentration, and 66% of total mass concentration, respectively. Depending on the particle size, the number concentration reduction percentage ranged from 48-100% for particles larger than 0.1 µm. Large droplets created by splashing were captured by the high-speed camera. Similar studies can be used for future particle aerodynamic studies. The fluorescein droplets deposited on the lid back sections, which were closer to the FOM accounted for 82% of the total fluorescein. Based on two-way ANOVA analysis, there were significant differences among both the experimental flushes (p = 0.0185) and the sections on the lid (p = 0.0146). Future work should explore the aerosolization produced by flushing and the performance of the lid in real restroom environments, where feces and urine exist in the bowl water and the indoor ventilation system is in operation.

Meta-analysis of chromosomal aberrations as a biomarker of exposure in healthcare workers occupationally exposed to antineoplastic drugs.

Many antineoplastic drugs used to treat cancer, particularly alkylating agents and topoisomerase inhibitors, are known to induce genetic damage in patients. Elevated levels of chromosomal aberrations, micronuclei, and DNA damage have been documented in cancer patients. Elevations in these same biomarkers of genetic damage have been reported in numerous studies of healthcare workers, such as nurses and pharmacists, who routinely handle these drugs, but results vary across studies. To obtain an overall assessment of the exposure effect, we performed a meta-analysis on data obtained from peer-reviewed publications reporting chromosomal aberration levels in healthcare workers exposed to antineoplastic drugs. A literature search identified 39 studies reporting on occupational exposure to antineoplastic drugs and measurement of chromosomal aberrations in healthcare workers. After applying strict inclusion criteria for data quality and presentation, data from 17 studies included in 16 publications underwent meta-analysis using Hedges' bias-corrected g and a random-effects model. Results showed the level of chromosomal aberrations in healthcare workers exposed to antineoplastic drugs was significantly higher than in controls. The standardized mean differences (difference of means divided by within sd) from all studies were pooled, yielding a value 1.006 (unitless) with p<0.001. Thus, in addition to the documented genotoxic effects of antineoplastic drugs in cancer patients, this meta-analysis confirmed a significant association between occupational exposure to antineoplastics during the course of a normal work day and increases in chromosomal aberrations in healthcare workers. Based on the studies reviewed, we were unable to accurately assess whether appropriate use of protective measures might reduce the incidence of genetic damage in healthcare workers. However, given the potential for increased cancer risk linked to increases in chromosomal aberrations, the results of this study support the need to limit occupational exposure of healthcare workers to antineoplastic drugs as much as possible.

Survey of guidelines and current practices for safe handling of antineoplastic and other hazardous drugs used in 24 countries.

PURPOSE: A survey of guidelines and current practices was conducted to examine the safe handling procedures for antineoplastic and other hazardous drugs that are used in 24 countries including the Americas, Europe, the Mideast, Far East, and Australia. METHODS: Subject experts were asked to complete a brief survey regarding safe handling guidelines and practices for hazardous drugs in their countries. Questions addressed practices for handling monoclonal antibodies, the use of closed-system transfer devices, medical surveillance practices, and measurements of compliance with existing guidelines. RESULTS: Responses from 37 subject experts representing 24 countries revealed considerable variation in the content and scope of safe handling guidelines and pharmacy practices among the participating countries. Guidelines in the majority of countries used the term "cytotoxics," while others referred to "hazardous" or "antineoplastic" drugs. The International Society of Oncology Pharmacy Practice standard was cited by six countries, and five cited the National Institute for Occupational Safety and Health Alert. Others cited international guidelines other than International Society of Oncology Pharmacy Practice, or they have created their own guidelines. Approximately half reported that their guidelines were mandatory under federal, state, or provincial legislation. Only 11 countries reported that monoclonal antibodies were covered in their guidelines. Closed-system drug-transfer devices are widely used, but were not specifically recommended in four countries, while one country required their use. Medical surveillance programs are in place in 20 countries, but only in The Netherlands is surveillance mandatory. Nine countries reported that they have completed recent updates or revisions of guidelines, and the measures for their adoption have been initiated. CONCLUSIONS: Although the overall goals in the participating countries were similar, the approaches taken to assure safe handling of hazardous drugs varied considerably in some cases.

CE: Original Research: Antineoplastic Drug Administration by Pregnant and Nonpregnant Nurses: An Exploration of the Use of Protective Gloves and Gowns.

: Background: Many antineoplastic (chemotherapeutic) drugs are known or probable human carcinogens, and many have been shown to be reproductive toxicants in cancer patients. Evidence from occupational exposure studies suggests that health care workers who have long-term, low-level occupational exposure to antineoplastic drugs have an increased risk of adverse reproductive outcomes. It's recommended that, at minimum, nurses who handle or administer such drugs should wear double gloves and a nonabsorbent gown to protect themselves. But it's unclear to what extent nurses do. PURPOSE: This study assessed glove and gown use by female pregnant and nonpregnant nurses who administer antineoplastic drugs in the United States and Canada. METHODS: We used data collected from more than 40,000 nurses participating in the Nurses' Health Study 3. The use of gloves and gowns and administration of antineoplastic drugs within the past month (among nonpregnant nurses) or within the first 20 weeks of pregnancy (among pregnant nurses) were self-reported via questionnaire. RESULTS: Administration of antineoplastic drugs at any time during their career was reported by 36% of nonpregnant nurses, including 27% who reported administering these drugs within the past month. Seven percent of pregnant nurses reported administering antineoplastic drugs during the first 20 weeks of pregnancy. Twelve percent of nonpregnant nurses and 9% of pregnant nurses indicated that they never wore gloves when administering antineoplastic drugs, and 42% of nonpregnant nurses and 38% of pregnant nurses reported never using a gown. The percentage of nonpregnant nurses who reported not wearing gloves varied by type of administration: 32% of those who administered antineoplastic drugs only as crushed pills never wore gloves, compared with 5% of those who administered such drugs only via infusion. CONCLUSION: Despite longstanding recommendations for the safe handling of antineoplastic and other hazardous drugs, many nurses-including those who are pregnant-reported not wearing protective gloves and gowns, which are considered the minimum protective equipment when administering such drugs. These findings underscore the need for further education and training to ensure that both employers and nurses understand the risks involved and know which precautionary measures will minimize such exposures.

A review of high performance liquid chromatographic-mass spectrometric urinary methods for anticancer drug exposure of health care workers.

This review describes published high performance liquid chromatography/mass spectrometry (HPLC-MS) methods for the determination of anticancer drugs in human urine as non-invasive tool for monitoring of health care worker exposure to antineoplastic and cytotoxic drugs. HPLC-MS is a sensitive and specific method for analysis of anticancer drugs and their metabolites in biological fluids. In this review, a tabular summary and overview of published HPLC-MS methods are presented, as well as future trends and limitations in this area of research.

Safe handling of oral antineoplastic medications: Focus on targeted therapeutics in the home setting.

Introduction With the growing number of oral targeted therapies being approved for use in cancer therapy, the potential for long-term administration of these drugs to cancer patients is expanding. The use of these drugs in the home setting has the potential to expose family members and caregivers to them either through direct contact with the drugs or indirectly by exposure to the parent compounds and/or their active metabolites in contaminated patients' waste. Methods A systematic literature review was performed and the known adverse health effect of 32 oral targeted therapeutics is summarized. In particular, the carcinogenicity, genotoxicity, and embryo-fetal toxicity, along with the route of excretion were evaluated. Results Carcinogenicity testing has not been performed on most of the oral targeted therapeutics and the genotoxicity data are mixed. However, the majority of these drugs exhibit adverse reproductive effects, some of which are severe. Currently, available data does not permit the possibility of a health hazard from inappropriate handling of drugs and contaminated patients waste to be ignored, especially in a long-term home setting. Further research is needed to understand these issues. Conclusions With the expanding use of targeted therapies in the home setting, family members and caregivers, especially those of reproductive risk age, are, potentially at risk. Overall basic education and related precautions should be taken to protect family members and caregivers from indirect or direct exposure from these drugs. Further investigations and discussion on this subject are warranted.

Surface wipe sampling for antineoplastic (chemotherapy) and other hazardous drug residue in healthcare settings: Methodology and recommendations.

Surface wipe sampling for various hazardous agents has been employed in many occupational settings over the years for various reasons such as evaluation of potential dermal exposure and health risk, source determination, quality or cleanliness, compliance, and others. Wipe sampling for surface residue of antineoplastic and other hazardous drugs in healthcare settings is currently the method of choice to determine surface contamination of the workplace with these drugs. The purpose of this article is to review published studies of wipe sampling for antineoplastic and other hazardous drugs, to summarize the methods in use by various organizations and researchers, and to provide some basic guidance for conducting surface wipe sampling for these drugs in healthcare settings. Recommendations on wipe sampling methodology from several government agencies and organizations were reviewed. Published reports on wipe sampling for hazardous drugs in numerous studies were also examined. The critical elements of a wipe sampling program and related limitations were reviewed and summarized. Recommendations and guidance are presented concerning the purposes of wipe sampling for antineoplastic and other hazardous drugs in the healthcare setting, technical factors and variables, sampling strategy, materials required, and limitations. The reporting and interpretation of wipe sample results is also discussed. It is recommended that all healthcare settings where antineoplastic and other hazardous drugs are handled consider wipe sampling as part of a comprehensive hazardous drug "safe handling" program. Although no standards exist for acceptable or allowable surface concentrations for these drugs in the healthcare setting, wipe sampling may be used as a method to characterize potential occupational dermal exposure risk and to evaluate the effectiveness of implemented controls and the overall safety program. A comprehensive safe-handling program for antineoplastic drugs may utilize wipe sampling as a screening tool to evaluate environmental contamination and strive to reduce contamination levels as much as possible, using the industrial hygiene hierarchy of controls.

Detection and measurement of surface contamination by multiple antineoplastic drugs using multiplex bead assay.

OBJECTIVES: Contamination of workplace surfaces by antineoplastic drugs presents an exposure risk for healthcare workers. Traditional instrumental methods to detect contamination such as liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) are sensitive and accurate but expensive. Since immunochemical methods may be cheaper and faster than instrumental methods, we wanted to explore their use for routine drug residue detection for preventing worker exposure. METHODS: In this study we examined the feasibility of using fluorescence covalent microbead immunosorbent assay (FCMIA) for simultaneous detection and semi-quantitative measurement of three antineoplastic drugs (5-fluorouracil, paclitaxel, and doxorubicin). The concentration ranges for the assay were 0-1000 ng/ml for 5-fluorouracil, 0-100 ng/ml for paclitaxel, and 0-2 ng/ml for doxorubicin. The surface sampling technique involved wiping a loaded surface with a swab wetted with wash buffer, extracting the swab in storage/blocking buffer, and measuring drugs in the extract using FCMIA. RESULTS: There was no significant cross-reactivity between these drugs at the ranges studied indicated by a lack of response in the assay to cross analytes. The limit of detection (LOD) for 5-fluorouracil on the surface studied was 0.93 ng/cm(2) with a limit of quantitation (LOQ) of 2.8 ng/cm(2), the LOD for paclitaxel was 0.57 ng/cm(2) with an LOQ of 2.06 ng/cm(2), and the LOD for doxorubicin was 0.0036 ng/cm(2) with an LOQ of 0.013 ng/cm(2). CONCLUSION: The use of FCMIA with a simple sampling technique has potential for low cost simultaneous detection and semi-quantitative measurement of surface contamination from multiple antineoplastic drugs.

Detection of 5-fluorouracil surface contamination in near real time.

OBJECTIVES: Contamination of workplace surfaces by antineoplastic drugs presents an exposure risk for healthcare workers. Traditional instrumental methods to detect contamination such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) are sensitive and accurate but expensive and incapable of producing results in real time. This limits their utility in preventing worker exposure. We are currently developing monitors based on lateral flow immunoassay that can detect drug contamination in near real time. In this report, we describe the laboratory performance of a 5-fluorouracil (5-FU) monitor. METHODS: The monitor was evaluated by spiking ceramic, vinyl, composite, stainless steel, and glass surfaces of 100 cm(2) area with 5-FU masses of 0, 5, 10, 25, 50, and 100 ng. The surface was sampled with a wetted cotton swab, the swab was extracted with buffer, and the resulting solution was applied to a lateral flow monitor. Two ways of evaluating the response of these monitors were used: an electronic method where a lateral flow reader was used for measuring line intensities, and a visual method where the intensity of the test line was visually compared to the control line. RESULTS: The 5-FU monitor is capable of detecting 10 ng/100 cm(2) (0.1 ng/cm(2)) using the electronic reader and 25 ng/100 cm(2) (0.25 ng/cm(2)) using the visual comparison method for the surfaces studied. The response of the monitors was compared to LC-MS/MS results for the same samples for validation and there was good correlation of the two methods but some differences in absolute response, especially at higher spiking levels for the surface samples.

New approaches to wipe sampling methods for antineoplastic and other hazardous drugs in healthcare settings.

PURPOSE: At the present time, the method of choice to determine surface contamination of the workplace with antineoplastic and other hazardous drugs is surface wipe sampling and subsequent sample analysis with a variety of analytical techniques. The purpose of this article is to review current methodology for determining the level of surface contamination with hazardous drugs in healthcare settings and to discuss recent advances in this area. In addition it will provide some guidance for conducting surface wipe sampling and sample analysis for these drugs in healthcare settings. METHODS: Published studies on the use of wipe sampling to measure hazardous drugs on surfaces in healthcare settings drugs were reviewed. These studies include the use of well-documented chromatographic techniques for sample analysis in addition to newly evolving technology that provides rapid analysis of specific antineoplastic. RESULTS: Methodology for the analysis of surface wipe samples for hazardous drugs are reviewed, including the purposes, technical factors, sampling strategy, materials required, and limitations. The use of lateral flow immunoassay (LFIA) and fluorescence covalent microbead immunosorbent assay (FCMIA) for surface wipe sample evaluation is also discussed. CONCLUSIONS: Current recommendations are that all healthcare settings where antineoplastic and other hazardous drugs are handled include surface wipe sampling as part of a comprehensive hazardous drug-safe handling program. Surface wipe sampling may be used as a method to characterize potential occupational dermal exposure risk and to evaluate the effectiveness of implemented controls and the overall safety program. New technology, although currently limited in scope, may make wipe sampling for hazardous drugs more routine, less costly, and provide a shorter response time than classical analytical techniques now in use.

Reproductive health risks associated with occupational exposures to antineoplastic drugs in health care settings: a review of the evidence.

OBJECTIVES: Antineoplastic drugs are known reproductive and developmental toxicants. Our objective was to review the existing literature of reproductive health risks to workers who handle antineoplastic drugs. METHODS: A structured literature review of 18 peer-reviewed, English language publications of occupational exposure and reproductive outcomes was performed. RESULTS: Although effect sizes varied with study size and population, occupational exposure to antineoplastic drugs seems to raise the risk of both congenital malformations and miscarriage. Studies of infertility and time to pregnancy also suggested an increased risk for subfertility. CONCLUSIONS: Antineoplastic drugs are highly toxic in patients receiving treatment, and adverse reproductive effects have been well documented in these patients. Health care workers with long-term, low-level occupational exposure to these drugs also seem to have an increased risk of adverse reproductive outcomes. Additional precautions to prevent exposure should be considered.

Sampling and mass spectrometric analytical methods for five antineoplastic drugs in the healthcare environment.

CONTEXT: Healthcare worker exposure to antineoplastic drugs continues to be reported despite safe handling guidelines published by several groups. Sensitive sampling and analytical methods are needed so that occupational safety and health professionals may accurately assess environmental and biological exposure to these drugs in the workplace. OBJECTIVE: To develop liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analytical methods for measuring five antineoplastic drugs in samples from the work environment, and to apply these methods in validating sampling methodology. A single method for quantifying several widely used agents would decrease the number of samples required for method development, lower cost, and time of analysis. METHODS: for measuring these drugs in workers' urine would also be useful in monitoring personal exposure levels. RESULTS: LC-MS/MS methods were developed for individual analysis of five antineoplastic drugs in wipe and air sample media projected for use in field sampling: cyclophosphamide, ifosfamide, paclitaxel, doxorubicin, and 5-fluorouracil. Cyclophosphamide, ifosfamide, and paclitaxel were also measured simultaneously in some stages of the work. Extraction methods for air and wipe samples were developed and tested using the aforementioned analytical methods. Good recoveries from the candidate air and wipe sample media for most of the compounds, and variable recoveries for test wipe samples depending on the surface under study, were observed. Alternate LC-MS/MS methods were also developed to detect cyclophosphamide and paclitaxel in urine samples. CONCLUSIONS: The sampling and analytical methods were suitable for determining worker exposure to antineoplastics via surface and breathing zone contamination in projected surveys of healthcare settings.

A pilot study of workplace dermal exposures to cypermethrin at a chemical manufacturing plant.

Exposure during the manufacture of pesticides is of particular concern due to their toxicity and because little is known about worker exposure, since most studies have focused on end-use application within agriculture or buildings. Even though dermal exposure can be expected to dominate for pesticides, little is known about workplace dermal exposures or even appropriate methods for their assessment. The current study begins to address this gap by evaluating alternative methods for assessing dermal exposure at a chemical manufacturing plant. For this pilot study, eight workers were recruited from a U.S. plant that produced the pesticide cypermethrin. Exposure was evaluated using three approaches: (1) survey assessment (questionnaire), (2) biological monitoring, and (3) workplace environmental sampling including ancillary measurements of glove contamination (interior and exterior). In each case, cypermethrin was quantified by enzyme-linked immunosorbent assay (ELISA). Environmental measurements identified two potential pathways of cypermethrin exposure: glove and surface contamination. Workplace exposure was also indicated by urine levels (specific gravity adjusted) of the parent compound, which ranged from 35 to 253 µg/L (median of 121 µg/L) with no clear trend in levels from pre- to post-shift. An exploratory analysis intended to guide future studies revealed a positive predictive association (Spearman correlation, p ≤ 0.10) between post-shift urine concentrations and a subset of survey questions evaluating worker knowledge, attitudes, and perceptions (KAP) of workplace dermal hazards, i.e., personal protective equipment self-efficacy, and inverse associations with behavior belief and information belief scales. These findings are valuable in demonstrating a variety of dermal exposure methods (i.e., behavioral attributes, external contamination, and biomarker) showing feasibility and providing measurement ranges and preliminary associations to support future and more complete assessments. Although these pilot data are useful for supporting design and sample size considerations for larger exposure and health studies, there is a need for validation studies of the ELISA assay for quantification of cypermethrin and its metabolites in urine.

Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device.

PURPOSE: Surface contamination with the antineoplastic drugs cyclophosphamide, ifosfamide, and 5-fluorouracil was compared in 22 US hospital pharmacies following preparation with standard drug preparation techniques or the PhaSeal® closed-system drug transfer device (CSTD). METHODS: Wipe samples were taken from biological safety cabinet (BSC) surfaces, BSC airfoils, floors in front of BSCs, and counters and analyzed for contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil. Contamination was reassessed several months after the implementation of the CSTD. Surface contamination (ng/cm(2)) was compared between the two techniques and evaluated with the Signed Rank Test. RESULTS: Using the CSTD compared to the standard preparation techniques, a significant reduction in levels of contamination was observed for all drugs (cyclophosphamide: p < 0.0001; ifosfamide: p < 0.001; 5-fluorouracil: p < 0.01). Median values for surface contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil were reduced by 95%, 90%, and 65%, respectively. CONCLUSIONS: Use of the CSTD significantly reduces surface contamination when preparing cyclophosphamide, ifosfamide, and 5-fluorouracil as compared to standard drug preparation techniques.