Editing Chemotherapy (section)

== Occupational exposure and safe handling ==
{{how-to|section|date=June 2023}}
In the 1970s, antineoplastic (chemotherapy) drugs were identified as hazardous, and the [[American Society of Health-System Pharmacists]] (ASHP) has since then introduced the concept of [[hazardous drugs]] after publishing a recommendation in 1983 regarding handling hazardous drugs. The adaptation of federal regulations came when the U.S. [[Occupational Safety and Health Administration]] (OSHA) first released its guidelines in 1986 and then updated them in 1996, 1999, and, most recently, 2006.<ref>{{cite journal | vauthors = Sorsa M, Hämeilä M, Järviluoma E | title = Handling anticancer drugs: from hazard identification to risk management? | journal = Annals of the New York Academy of Sciences | volume = 1076 | issue = 1 | pages = 628–34 | date = September 2006 | pmid = 17119240 | doi = 10.1196/annals.1371.008 | bibcode = 2006NYASA1076..628S | s2cid = 7081365 }}</ref>

The [[National Institute for Occupational Safety and Health]] (NIOSH) has been conducting an assessment in the workplace since then regarding these drugs. Occupational exposure to antineoplastic drugs has been linked to multiple health effects, including infertility and possible carcinogenic effects. A few cases have been reported by the NIOSH alert report, such as one in which a female pharmacist was diagnosed with papillary transitional cell carcinoma. Twelve years before the pharmacist was diagnosed with the condition, she had worked for 20 months in a hospital where she was responsible for preparing multiple antineoplastic drugs.<ref name=":0">{{Cite journal|url=http://theoncologypharmacist.com/top-issues/2014-issues/february-2014-vol-7-no-1/16084-chemotherapy-biomarkers-of-exposure-effect-reproductive-hazards-and-cancer|title=Chemotherapy: Biomarkers of Exposure, Effect, Reproductive Hazards, and Cancer|journal=The Oncology Pharmacist|date=March 2014|last1=Thomas h. Connor|first1=PhD|access-date=22 November 2018|archive-date=25 June 2021|archive-url=https://web.archive.org/web/20210625164339/http://theoncologypharmacist.com/top-issues/2014-issues/february-2014-vol-7-no-1/16084-chemotherapy-biomarkers-of-exposure-effect-reproductive-hazards-and-cancer|url-status=dead}}</ref> The pharmacist did not have any other risk factor for cancer, and therefore, her cancer was attributed to the exposure to the antineoplastic drugs, although a cause-and-effect relationship has not been established in the literature. Another case happened when a malfunction in biosafety cabinetry is believed to have exposed nursing personnel to antineoplastic drugs. Investigations revealed evidence of genotoxic biomarkers two and nine months after that exposure.

=== Routes of exposure ===
Antineoplastic drugs are usually given through [[Intravenous therapy|intravenous]], [[Intramuscular injection|intramuscular]], [[Intrathecal administration|intrathecal]], or [[Subcutaneous injection|subcutaneous]] administration. In most cases, before the medication is administered to the patient, it needs to be prepared and handled by several workers. Any worker who is involved in handling, preparing, or administering the drugs, or with cleaning objects that have come into contact with antineoplastic drugs, is potentially exposed to hazardous drugs.<ref name="cancer.org">{{cite web|url=https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/chemotherapy-safety.html|title=Chemotherapy Safety|publisher=[[Cancer.org]]|language=en|access-date=2021-08-10|archive-date=2021-08-10|archive-url=https://web.archive.org/web/20210810165723/https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/chemotherapy-safety.html|url-status=live}}</ref> Health care workers are exposed to drugs in different circumstances, such as when pharmacists and pharmacy technicians prepare and handle antineoplastic drugs and when nurses and physicians administer the drugs to patients. Additionally, those who are responsible for disposing antineoplastic drugs in health care facilities are also at risk of exposure.<ref name=":1">{{cite document|title=Personal protective equipment for health care workers who work with hazardous drugs |date=October 2008 |doi=10.26616/NIOSHPUB2009106|publisher=NIOSH |doi-access=free }}</ref>

Dermal exposure is thought to be the main route of exposure due to the fact that significant amounts of the antineoplastic agents have been found in the gloves worn by healthcare workers who prepare, handle, and administer the agents. Another noteworthy route of exposure is inhalation of the drugs' vapors. Multiple studies have investigated inhalation as a route of exposure, and although air sampling has not shown any dangerous levels, it is still a potential route of exposure. Ingestion by hand to mouth is a route of exposure that is less likely compared to others because of the enforced hygienic standard in the health institutions. However, it is still a potential route, especially in the workplace, outside of a health institute. One can also be exposed to these hazardous drugs through injection by [[Needlestick injury|needle sticks]]. Research conducted in this area has established that occupational exposure occurs by examining evidence in multiple urine samples from health care workers.<ref>{{Cite book|title=Antineoplastic drugs: Occupational exposure and health risks | year=2006|isbn=978-90-393-4331-9}}</ref>

=== Hazards ===
Hazardous drugs expose health care workers to serious health risks. Many studies show that antineoplastic drugs could have many side effects on the reproductive system, such as fetal loss, congenital malformation, and infertility. Health care workers who are exposed to antineoplastic drugs on many occasions have adverse reproductive outcomes such as spontaneous abortions, stillbirths, and congenital malformations. Moreover, studies have shown that exposure to these drugs leads to menstrual cycle irregularities. Antineoplastic drugs may also increase the risk of learning disabilities among children of health care workers who are exposed to these hazardous substances.<ref>{{Cite journal |last1=Connor |first1=Thomas H. |last2=Lawson |first2=Christina C. |last3=Polovich |first3=Martha |last4=McDiarmid |first4=Melissa A. |date=2014 |title=Reproductive Health Risks Associated with Occupational Exposures to Antineoplastic Drugs in Health Care Settings: A Review of the Evidence |journal=Journal of Occupational and Environmental Medicine |volume=56 |issue=9 |pages=901–910 |doi=10.1097/JOM.0000000000000249 |issn=1076-2752 |pmc=4569003 |pmid=25153300}}</ref>

Moreover, these drugs have [[carcinogen]]ic effects. In the past five decades, multiple studies have shown the carcinogenic effects of exposure to antineoplastic drugs. Similarly, there have been research studies that linked alkylating agents with humans developing leukemias. Studies have reported elevated risk of breast cancer, nonmelanoma skin cancer, and cancer of the rectum among nurses who are exposed to these drugs. Other investigations revealed that there is a potential [[Genotoxicity|genotoxic]] effect from anti-neoplastic drugs to workers in health care settings.<ref name=":0" />

=== Safe handling in health care settings ===
As of 2018, there were no [[occupational exposure limit]]s set for antineoplastic drugs, i.e., OSHA or the [[American Conference of Governmental Industrial Hygienists]] (ACGIH) have not set workplace safety guidelines.<ref name=":2">{{Cite web|url=https://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf |archive-url=https://web.archive.org/web/20040913063413/http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf |archive-date=2004-09-13 |url-status=live|title=preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings }}</ref>

==== Preparation ====
NIOSH recommends using a [[Engineering controls|ventilated cabinet]] that is designed to decrease worker exposure. Additionally, it recommends training of all staff, the use of cabinets, implementing an initial evaluation of the technique of the safety program, and wearing protective gloves and gowns when opening drug packaging, handling vials, or labeling. When wearing [[personal protective equipment]], one should inspect gloves for physical defects before use and always wear double gloves and protective gowns. Health care workers are also required to wash their hands with water and soap before and after working with antineoplastic drugs, change gloves every 30 minutes or whenever punctured, and discard them immediately in a chemotherapy waste container.<ref>{{Cite web|url=https://www.lni.wa.gov/Safety/Topics/AtoZ/HazardousDrugs/ProgramGuides.asp|title=Hazardous Drugs Program Guides|website=lni.wa.gov|access-date=2018-11-22|archive-date=27 October 2019|archive-url=https://web.archive.org/web/20191027005510/http://www.lni.wa.gov/Safety/Topics/AtoZ/HazardousDrugs/ProgramGuides.asp|url-status=dead}}</ref>

The gowns used should be disposable gowns made of polyethylene-coated polypropylene. When wearing gowns, individuals should make sure that the gowns are closed and have long sleeves. When preparation is done, the final product should be completely sealed in a plastic bag.<ref>{{Cite journal |last=Kilinc |first=F. Selcen |date=2015 |title=A Review of Isolation Gowns in Healthcare: Fabric and Gown Properties |journal=Journal of Engineered Fibers and Fabrics |volume=10 |issue=3 |pages=180–190 |doi=10.1177/155892501501000313 |issn=1558-9250 |pmc=4791533 |pmid=26989351}}</ref>

The health care worker should also wipe all waste containers inside the ventilated cabinet before removing them from the cabinet. Finally, workers should remove all protective wear and put them in a bag for their disposal inside the ventilated cabinet.<ref name=":1" />

==== Administration ====
Drugs should only be administered using protective medical devices such as needle lists and closed systems and techniques such as priming of IV tubing by pharmacy personnel inside a ventilated cabinet. Workers should always wear personal protective equipment such as double gloves, goggles, and protective gowns when opening the outer bag and assembling the delivery system to deliver the drug to the patient, and when disposing of all material used in the administration of the drugs.<ref name=":2" />

Hospital workers should never remove tubing from an IV bag that contains an antineoplastic drug, and when disconnecting the tubing in the system, they should make sure the tubing has been thoroughly flushed. After removing the IV bag, the workers should place it together with other disposable items directly in the yellow chemotherapy waste container with the lid closed. Protective equipment should be removed and put into a disposable chemotherapy waste container. After this has been done, one should double bag the chemotherapy waste before or after removing one's inner gloves. Moreover, one must always wash one's hands with soap and water before leaving the drug administration site.<ref>{{Cite book|title=Infectious and Medical Waste Management|isbn=9781315894430|last1=Reinhardt|first1=Peter A.|date=29 November 2017|publisher=CRC Press }}{{page needed|date=December 2018}}</ref>

==== Employee training ====
All employees whose jobs in health care facilities expose them to hazardous drugs must receive training. Training should include shipping and receiving personnel, housekeepers, pharmacists, assistants, and all individuals involved in the transportation and storage of antineoplastic drugs. These individuals should receive information and training to inform them of the hazards of the drugs present in their areas of work. They should be informed and trained on operations and procedures in their work areas where they can encounter hazards, different methods used to detect the presence of hazardous drugs and how the hazards are released, and the physical and health hazards of the drugs, including their reproductive and carcinogenic hazard potential. Additionally, they should be informed and trained on the measures they should take to avoid and protect themselves from these hazards. This information ought to be provided when health care workers come into contact with the drugs, that is, perform the initial assignment in a work area with hazardous drugs. Moreover, training should also be provided when new hazards emerge as well as when new drugs, procedures, or equipment are introduced.<ref name=":2" />

==== Housekeeping and waste disposal ====
When performing cleaning and decontaminating the work area where antineoplastic drugs are used, one should make sure that there is sufficient ventilation to prevent the buildup of airborne drug concentrations. When cleaning the work surface, hospital workers should use deactivation and cleaning agents before and after each activity as well as at the end of their shifts. Cleaning should always be done using double protective gloves and disposable gowns. After employees finish up cleaning, they should dispose of the items used in the activity in a yellow chemotherapy waste container while still wearing protective gloves. After removing the gloves, they should thoroughly wash their hands with soap and water. Anything that comes into contact or has a trace of the antineoplastic drugs, such as needles, empty vials, syringes, gowns, and gloves, should be put in the chemotherapy waste container.<ref>{{Cite web|url=http://www.searo.who.int/srilanka/documents/safe_management_of_wastes_from_healthcare_activities.pdf?ua=1|title=Safe management of wastes from health-care activities |website=WHO}}</ref>

==== Spill control ====
A written policy needs to be in place in case of a spill of antineoplastic products. The policy should address the possibility of various sizes of spills as well as the procedure and personal protective equipment required for each size. A trained worker should handle a large spill and always dispose of all cleanup materials in the chemical waste container according to EPA regulations, not in a yellow chemotherapy waste container.<ref>{{cite journal | vauthors = DeJoy DM, Smith TD, Woldu H, Dyal MA, Steege AL, Boiano JM | title = Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses | journal = Journal of Occupational and Environmental Hygiene | volume = 14 | issue = 7 | pages = 485–493 | date = July 2017 | pmid = 28326998 | doi = 10.1080/15459624.2017.1285496 | bibcode = 2017JOEH...14..485D | s2cid = 3879822 }}</ref>

=== Occupational monitoring ===
A [[Workplace health surveillance|medical surveillance]] program must be established. In case of exposure, occupational health professionals need to ask for a detailed history and do a thorough physical exam. They should test the urine of the potentially exposed worker by doing a [[urine dipstick]] or microscopic examination, mainly looking for blood, as several antineoplastic drugs are known to cause bladder damage.<ref name=":0" />

Urinary mutagenicity is a marker of exposure to antineoplastic drugs that was first used by Falck and colleagues in 1979 and uses bacterial mutagenicity assays. Apart from being nonspecific, the test can be influenced by extraneous factors such as dietary intake and smoking and is, therefore, used sparingly. However, the test played a significant role in changing the use of horizontal flow cabinets to vertical flow biological safety cabinets during the preparation of antineoplastic drugs because the former exposed health care workers to high levels of drugs. This changed the handling of drugs and effectively reduced workers' exposure to antineoplastic drugs.<ref name=":0" />

Biomarkers of exposure to antineoplastic drugs commonly include urinary [[platinum]], [[methotrexate]], urinary [[cyclophosphamide]] and [[ifosfamide]], and urinary metabolite of [[5-Fluorouracil|5-fluorouracil]]. In addition to this, there are other drugs used to measure the drugs directly in the urine, although they are rarely used. A measurement of these drugs directly in one's urine is a sign of high exposure levels and that an uptake of the drugs is happening either through inhalation or dermally.<ref name=":0" /> &nbsp;