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.

Findings from this cross-sectional study indicate a need for expanded training in safe handling practices. 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. CONCLUSIONS: 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.

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.

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.

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.

The National Institute for Occupational Safety and Health (NIOSH) and ASCO cohosted the Workshop on the Safe Handling of Hazardous Drugs on November 13, 2015, in Alexandria, Virginia. NIOSH is the US federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. ASCO is a national organization representing nearly 40,000 physicians and other health care professionals specializing in cancer treatment, diagnosis, and prevention. | The Workshop focused on the history of guidance development for safe handling of hazardous drugs and challenges in development of guidance for worker safety. The goal was to promote information sharing and collaboration among stakeholders, including experts in occupational health, drug management and safety, cancer care, and research. | Thomas Connor, PhD, from NIOSH and Robin Zon, MD, Chair of ASCO’s Task Force on Safe Handling of Chemotherapy, served as Workshop co-chairs. Participating organizations included the American Nurses Association, American Society of Health-System Pharmacists, ASCO, NIOSH/Centers for Disease Control and Prevention, Hematology Oncology Pharmacy Association, Oncology Nursing Society (ONS), Occupational Safety and Health Administration, US Pharmacopeial Convention, and the Department of Veterans Affairs. A full list of Workshop participants is included in the Appendix (online only).

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 the 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.

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.

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 cm2 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 cm2 (0.1 ng/cm2) using the electronic reader and 25 ng/100 cm2 (0.25 ng/cm2) 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.

Pharmacists, nurses, and other health care personnel who handle antineoplastic (chemotherapy) drugs require appropriately tested gloves that protect them from dermal exposure, but there is confusion about which gloves provide adequate protection. The American society for Testing and Materials (ASTM) currently has two standards for testing the permeation of glove materials by chemicals: ASTM F739-99a (F739), which is the Standard Test Method for Resistance of Protective Clothing Materials to Permeation by Liquids or Gases Under Conditions of continuous Contact, and ASTM D6978-05 (D6978), which is the Standard Practice for Assessment of Resistance of Medical Gloves to Permeation by Chemotherapy Drugs. Because of the highly toxic nature of chemotherapy agents, the National Institute for Occupational Safety and Health (NIOSH), the American Society of Heath-system Pharmacists (ASHP), the Oncology Nursing Society (ONS), and the United States Pharmacopeial Convention (USP) state that health care workers who handle antineoplastic and other hazardous drugs (HDs) should wear gloves that have been tested for permeation by the more robust D6978 standard rather than the standard used for other chemicals-F739.

NIOSH estimates that approximately 8 million healthcare workers may be exposed to hazardous drugs (HDs). Healthcare workers might not be aware that they may be harming their health when they handle HDs, which are known to cause serious side effects in patients and are capable of causing cancer, organ toxicity, fertility problems, genetic damage, and birth defects in healthcare workers.

Due to concerns about exposure of health care workers to hazardous drugs, The National Institute for Occupational Safety and Health (NIOSH) convened a Hazardous Drug Working Group in 2000 in Washington, DC. The primary output of the group, which disbanded in 2007, was the 2004 publication of the NIOSH Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Healthcare Settings. This alert included a definition of hazardous drugs that was modified from a definition proposed by the American Society of Hospital Pharmacists (currently the American Society of Health-System Pharmacists). The 2004 alert included a sample, non-all-inclusive list of 136 drugs that should be handled as hazardous. It comprised lists being used at that time by four institutions: The National Institutes of Health, Johns Hopkins University, University of Michigan, and Northside Hospital in Atlanta. It also included a list generated by the Pharmaceutical Research and Manufacturers of America (PhRMA). At the time the 2004 Alert was published, NIOSH acknowledged that it would update the hazardous drug list as needed. After deciding on an approach and a mechanism to perform these updates, NIOSH reviewed all new drugs approved by the FDA and all new warnings on existing drugs from 2004 to 2007, to determine whether they qualified as hazardous under the NIOSH definition. This resulted in the official update that was published in 2010, which contained 31 additions to the original list. The list was updated a second time in 2012 with 33 additions and 15 removals. The Latest Update: The process of updating the hazardous drug list includes a number of steps and takes about two years to complete; therefore, the list is about two to three years out of date when it is published. Currently, the expert review panel is made up of at least 10 members representing pharmacy and nursing organizations (ASHP, Hematology/Oncology Pharmacy Association, Oncology Nursing Society, American Nurses Association), government (Food and Drug Administration, Department of Veterans Affairs, Occupational Safety and Health Administration), industry (Biological Industry Organization, drug manufacturers), and academia.

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/cm2 with a limit of quantitation (LOQ) of 2.8 ng/cm2, the LOD for paclitaxel was 0.57 ng/cm2 with an LOQ of 2.06 ng/cm2, and the LOD for doxorubicin was 0.0036 ng/cm2 with an LOQ of 0.013 ng/cm2. 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.

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.

This is the last article of a 4-part series on the toxic effects and safe handling of hazardous drugs by Roussel and Connor.1-3 The previous 3 articles have covered the adverse health effects of hazardous drugs, contamination of the workplace, and biomarkers of effect and exposure. The present article addresses several emerging issues that healthcare providers will need to be aware of, including hazardous drug assessment, use of antineoplastic drugs in nonon- cology settings, oral chemotherapy, decontamination/cleaning, state legislative activities, and US Pharmacopeial Convention (USP) Chapter 800.4

This article discusses approaches that have been used to examine potentially adverse outcomes in healthcare professionals who work with or are exposed to chemotherapy drugs: (1) the use of biomarkers to evaluate genotoxic damage; (2) adverse reproductive outcomes; and (3) the association of cancer with exposure to chemotherapy drugs. Biomarkers of exposure and effect have been used extensively to monitor both healthcare professionals who work with antineoplastic(3-5) and other hazardous drugs, and workers in other occupational settings who may be exposed to genotoxic chemicals. In general, biomarkers are based on mutagenic or other end points of genotoxicity of the drugs. As most of the first generation of antineoplastic drugs were genotoxic in one test system or another, they were ideal candidates for use in exposed worker populations. However, these end points are typically nonspecific in nature and can result from exposure to any genotoxic compound, certain types of radiation, and possibly viral infections. Therefore, studies of worker populations must be carefully designed to rule out extraneous factors such as smoking history, diet, age, and other variables that may compromise test results. Nevertheless, more than half of the 100-plus published studies in the literature have reported a statistically significant association between exposure to antineoplastic drugs and the end point being investigated. Most of these studies have originated outside the United States, and they often have been conducted in countries where safety precautions may not be as rigorous as in the United States.

In February 2010, the National Institute for Occupational Safety and Health (NIOSH) received a confidential employee request for a Health Hazard Evaluation (HHE) at a veterinary teaching hospital that provides routine care and oncology services to large and small animals. Canines and felines constitute the majority of the oncology department’s patients. Veterinary hospital employees were concerned about adverse health effects from the use of chemotherapy drugs in the oncology department. | In 2004, NIOSH released an Alert regarding occupational exposures to antineoplastic and other hazardous drugs that are used in health care settings. Hazardous drugs were defined in the NIOSH Alert as having “specific health effects (such as skin rashes, cancer, and reproductive effects) and high toxicity at low doses.”(1) The NIOSH Alert also described best practices for handling, storage, disposal, and decontamination procedures and was updated in 2010 and 2012 to include an expanded list of hazardous drugs.(2,3) Also in 2010, NIOSH released a Workplace Solutions document to increase awareness of occupational safety and health issues in veterinary health care workers who work with antineoplastic and hazardous drugs.(4)

We read with interest the article by Traynor1 that appeared in the September 1 issue of AJHP and would like to clarify a potential misconception—that the National Institute for Occupational Safety and Health (NIOSH) recommends all hazardous drugs be handled in the same manner, regardless of dosage form. The 2004 NIOSH alert on this topic recommends a “universal” or “standard” precautions approach to safe handling but does not recommend that all formulations be handled in the same manner.2 | The NIOSH alert reflects an understanding that many factors affect the determination of handling procedures for hazardous drugs. The purpose of the list of hazardous drugs provided in the alert, updated in 2010 and 2012, is to identify hazardous drugs and assist health care facilities in developing their own risk management procedures based on the drugs and formulations used in their facility. The most recent update to the hazardous-drugs list states the following3: | Some drugs defined as hazardous may not pose a significant risk of direct occupational exposure because of their dosage formulation (for example, coated tablets or capsules—solid, intact medications that are administered to patients without modifying the formulation). Uncoated tablets may present a risk of exposure from dust by skin contact and/or inhalation when the tablets are counted and if solid drug formulations are altered, such as by crushing tablets or making solutions from them.

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 mug/L (median of 121 mcg/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.

The Journal of Oncology Pharmacy Practice(JOPP)was first published in June 1995 as the official journalof the International Society of Oncology PharmacyPractitioners (ISOPP). In a supplement to that issue,as part of a review of the ISOPP IV symposium presen-tations, an article by Professor Graham Sewell wasincluded titled ‘Pharmaceutical issues: preparationand handling’.1This article raised concerns aboutvarious aspects of quality and safety associated withcytotoxic drug reconstitution. It discussed the use ofcytotoxic safety cabinets versus isolators, the use ofearly ‘closed systems’ and even the possible future useof robotics. In the 15 years since that first publication,interest in the handling of hazardous drugs used to treatcancer patients has not waned. At the recent ISOPP XIIsymposium held in Prague in May 2010, ten presenta-tions and seven submitted abstracts on the topic of safehandling were included. From the highly technical useof robotics and the use of specialized closed systems tothe basic use of personal protective equipment (PPE) inunder-resourced countries, this subject remains highlytopical.One reason for the interest in this topic is the inabil-ity to quantify the occupational risk of handling anti-cancer drugs. It is well recognized that patients treatedwith therapeutic doses of these drugs may developsecond cancers years later. However, the risk associatedwith long-term very low level exposure to these agentsis not currently measurable. A basic tenet of employ-ment is the provision of a safe workplace. It may beimpossible to remove all risk but it is imperative thatrisk is minimized. Large pharmaceutical companiesmanufacturing anti-cancer drugs do so in totallyenclosed environments with workers wearing full respi-rator suits reminiscent of movies of outbreaks of adeadly virus. But it is financially completely beyondindividual hospitals, institutions and clinics to supplysuch protective equipment. The smaller the preparationfacility, the less viable it is to introduce expensiveprotective measures

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((R)) 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.

When NIOSH first published the alert Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings in September 2004, the driving motivator was to provide health care workers, and their employers, with information on the risks of working with hazardous drugs, as well as measures they could take to protect their health. In the 2004 alert, it was proposed that the list be revised on an annual basis in order to continually provide the most up-to-date information to those workers who may come in contact with hazardous drugs throughout the process of receiving, handling, administration, and disposal. Although annually revising the list has proven untenable, an update to the original listing of NIOSH-designated hazardous drugs was released this past September.

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.

OBJECTIVE: This study evaluated health care worker exposure to antineoplastic drugs. METHODS: A cross-sectional study examined environmental samples from pharmacy and nursing areas. A 6-week diary documented tasks involving those drugs. Urine was analyzed for two specific drugs, and blood samples were analyzed by the comet assay. RESULTS: Sixty-eight exposed and 53 nonexposed workers were studied. Exposed workers recorded 10,000 drug-handling events during the 6-week period. Sixty percent of wipe samples were positive for at least one of the five drugs measured. Cyclophosphamide was most commonly detected, followed by 5-fluorouracil. Three of the 68 urine samples were positive for one drug. No genetic damage was detected in exposed workers using the comet assay. CONCLUSIONS: Despite following recommended safe-handling practices, workplace contamination with antineoplastic drugs in pharmacy and nursing areas continues at these locations.

Over the past 30 years, we have been investigating the risks hazardous drugs pose to health care workers to determine how to minimize them. With current analytical techniques, we can assess the level of environmental contamination for about 10% of the hazardous drugs currently in use. Several dozen studies have shown that workplace contamination is common with these drugs. We can extrapolate that the other 90% of hazardous drugs handled in the same manner, although not yet measured, probably pose the same risk. Until safer drugs become the mainstay, health care workers need to be vigilant about their work practices for their protection and the protection of their coworkers.