Cytotoxic DrugsMay 3, 2011 10:08 AM
What are cytotoxic drugs?
Cytotoxic drugs include any drug that inhibits or prevents the function of cells. Cytotoxic drugs include drugs that are primarily used to treat cancer, frequently as part of a chemotherapy regime. Recently, their uses have expanded to treatment for certain skin conditions (e.g., psoriasis) and are sometimes used in the treatment of rheumatoid and juvenile rheumatoid arthritis, as well as steroid-resistant muscle conditions. The most common forms of cytotoxic drugs are known as antineoplastic, and sometimes these terms are used reversibly.
Cytotoxic drugs have an effect of preventing the rapid growth and division (mitosis) of cancer cells. However, cytotoxic drugs also affect the growth of other quick dividing cells in the body such as hair follicles and the lining of the digestive system. As a result of the treatment, many normal cells are damaged along with the cancer cells.
There are no exposure limits set for cytotoxic drugs. It is the opinion of CUPE that even low-level exposure to cytotoxic drugs should be avoided. The only safe occupational exposure to cytotoxic drugs is no exposure.
What are the risks of occupational exposure to cytotoxic drugs?
The toxicity of cytotoxic drugs potentially makes them a very dangerous substance for the people who handle them. During the past 30 years, the health effects of working with these drugs have been well documented. Studies have shown that there are frequently detectable levels of cytotoxic drugs in the air of hospital areas where cytotoxic drugs are prepared without the use of proper biological safety cabinets. As well, health care workers preparing the drugs without adequate precautions have been identified with various cytotoxic drugs in their urine. It has been reported that exposure to cytotoxic drugs have caused an increased frequency of chromosome damage in exposed workers.1 Cytotoxic drugs can also produce some acute effects in workers including skin, eyes, and mucous membrane irritations, as well as symptoms including nausea, headache, and dizziness. Working with cytotoxic drugs has also been associated with negative health effects for developing fetuses including higher incidences of spontaneous abortions, congenital malformations, low birth weight, and infertility. As part of any cytotoxic exposure reduction plan, protective reassignment for a worker who is pregnant, breastfeeding or intends to conceive a child must be put in place. Repeated, long term occupational exposure to small amounts of cytotoxic drugs has not been scientifically identified as an actual cause of cancer.
However, many cytotoxic drugs are known to be:
Genotoxic – a substance that damages DNA. Such damage can lead to the growth of a malignant tumor.
Carcinogenetic – a substance that may cause mutations leading to the development of tumors in otherwise healthy cells.
Mutagenic – a substance that alters the DNA of a living being, increasing the likelihood of a mutation.
Teratogenic – a substance that may cause malformations of an embryo or fetus (birth defects).
Who is at risk?
Anyone who works with patients receiving cytotoxic drugs are at risk of exposure, and must be protected at all times while working with cytotoxic drugs. Exposure may occur when preparing, administering, or transporting drugs, handling patient waste, transporting and disposing of waste, and cleaning spills.
If at any time there is skin contact with any cytotoxic drug, the affected worker should thoroughly wash the affected area with soap and water. It should be noted that the worker should not scrape or abrade the skin by using a scrub brush as this could increase the exposure. If eye contact has occurred, flush the affected eye(s), while holding back the eyelid(s), with copious amounts of water for atleast 15 minutes. After any type of exposure, it is always recommended to seek a medical evaluation by a physician.
Training and information
All staff who have the potential to handle cytotoxic drugs or the waste by-products created by their use, including physicians, nurses, assistants, pharmacists, stores and receiving personnel, housekeeping and maintenance, should receive sufficient and relevant training. Management, in conjunction with the health and safety committee should develop specific pre-employment worker training procedures for the proper handling, mixing, and disposal of cytotoxic drugs and waste by-products. These training procedures should:
be written, posted, and available to all employees;
include how training will be developed, delivered, and evaluated;
include descriptions of the roles of supervisors to ensure that all proper regulations are followed.
A completer training program must encompass the following topics:
The full hazards of cytotoxic drugs.
Methods of preparation.
Use and disposal procedures.
Protective equipment and how to use it properly.
Maintenance of the facilities and equipment.
The department responsible for cytotoxic drugs should maintain a record of information on the toxicity, exposure treatment procedures, solubility, stability, and general description of the appearance for all cytotoxic drugs that are used in the facility. This record should be easily accessible at all times of day, and available to all staff involved with the use of cytotoxic drugs.
A summary of all work procedures should be posted in all appropriate locations. The complete policy and program manual should be available to all workers, and reviewed by workers who interact with the cytotoxic drugs during the training time. The following sections outline a minimum set of recommended procedures for working with cytotoxic drugs, for which all relevant staff should be trained.
Drug preparation and reconstitution
Cytotoxic drugs should only be prepared by personnel with the proper training in a centralized dedicated location. The hierarchy of hazard control should be put into effect to control the hazard as much as possible.
1. Engineering controls
The following engineering controls should be put in place where cytotoxic medications are being used:
A minimum of a Class II biological safety cabinet with HEPA filter exhaust systems that does not allow air to be circulated back into the room should be used while manipulating cytotoxic drugs.
The preparation area within the cabinet should be covered with a plastic backed, absorbent material to reduce dispersion and facilitate the clean-up of any spilled medication.
Medications should be isolated and locked out in such a manner that only those properly trained have access to the storage location.
CSA approved, puncture proof containers for the disposal of needles, syringes and vials must be provided. As well, labelled, sealable refuse bags for the puncture proof containers should be available in the preparation area. Contaminated needles, syringes, and vials should be disposed of intact.
Negative pressure rooms that prevent any spilled medication from leaving the room are also recommended.
2. Personal Protective Equipment (PPE)
While handling any cytotoxic drugs, all workers should use:
Protective gloves made of vinyl or nitrile rubber. Gloves should be changed frequently, or immediately if punctured, cut, or torn. It is also recommended that workers wear two pairs at a time for additional protection.
A moisture resistant, long sleeved gown with elastic cuffs.
Chemical splash goggles,and if necessary, full-face protection.
In cases where there is a possibility of the medication becoming airborne, a powered air purifying respirator is recommended.
To prevent the spread of medication, protective clothing should not be worn outside of the preparation area.
3. Additional controls
Special controls are required for the housekeeping and custodial staff regarding the potential hazards involved in handling laundry or other materials that may be contaminated with biological fluids contaminated with cytotoxic drugs. Safe work procedures for handling these materials should be developed and taught to all affected staff. Proper signage informing all employees that cytotoxic drugs are present and their hazards must be developed and displayed in locations that will be easily seen by all. Eating, drinking, smoking, applying makeup and the storage of food should be completely prohibited in the preparation area. As mentioned previously, workers who are planning to conceive children or women who are currently pregnant or breastfeeding must be placed on protective reassignment and given a position that does not expose them to the cytotoxic drugs.
Caring for patients
Personal care workers that could be potentially exposed to any biological fluid from a patient who has received cytotoxic drugs within the previous 48 hours, and workers handling potentially contaminated linen, should wear protective gloves and disposable gowns that are discarded after use. It is up to management to ensure that all staff are informed as to when and where cytotoxic drugs are being used so appropriate measures can be taken to protect the workers.
Plastic bags that are at least 2mm thick (if polypropylene) or 4mm thick (if polyethylene) should be used to collect the puncture proof plastic containers, gloves, gowns, alcohol wipes and all other potentially contaminated materials. The bags should be color coded to distinguish them from regular rubbish, and labelled with a cytotoxic warning label. All sharps should be placed in puncture proof containers before bagging. All workplaces should have a policy for segregation of waste materials resulting from the use of cytotoxic drug preparation and administration. These plans must meet or exceed the provincial regulations for hazardous waste disposal.
Housekeeping should wear protective gloves while handling waste containers. They should also be trained as to the hazards of cytotoxic waste and the proper methods of handling it. Cytotoxic wastes must be handled differently than regular garbage and must be disposed according to provincial regulations. In cases wherethe waste is to be incinerated, it should be noted that completely sealed (airtight) containers that could build pressure and explode must be avoided. Temperatures of 1,000° to 1,600° C should be used to render the cytotoxic drugs harmless.
1. Spill kit
A clearly labelled cytotoxic spill kit should be kept wherever cytotoxic medications are being prepared, stored, administered or received (shipping). The kit should contain:
Fit tested NIOSH certified respirators for anyone that would potentially be working in these areas.
At least two sets of surgical gloves
Disposable eye protection
Scoop and scraper
Two large plastic disposal bags (minimum of 4mm thick)
Decontamination agent (i.e. a basic detergent of pH 8-9 and water)
Puncture and leak resistant waste container
Two sheets at least 30 cm square of absorbent material
A spill needs to be cleaned by members of the staff that have received the appropriate training and have the appropriate protective equipment; other members should vacate the area as soon as it is safe to do so until the spill is cleaned. Any person at the workplace who may potentially handle a cytotoxicdrug should receive this training. All spills should be immediately marked with a warning sign to prevent exposure to other workers. Glass should never be handled by hand; always use a scoop. The cleanup should be reduced to as few people as feasible, but there should be at least two people involved.
2. Small spill cleanup
Small spills (less than 5ml, or 5mg) that occur outside of a biological safety cabinet should be cleaned immediately by personnel wearing gowns and doubled protective gloves and eye protection.
Small amounts of liquids should be wiped with absorbent pads, while solids should be wiped with a wet absorbent gauze. Spill areas should be cleaned at least three times with the detergent (described above). Broken glass should be placed in a small container and placed in the disposal bags. All contaminated materials should also be placed in the garbage bags.
Unbroken glassware or reusable items that have been contaminated should be placed in a plastic bag and washed, following the procedures for cleaning reusable items that have been developed for the workplace.
3. Large spill cleanup
For spills that are larger than 5ml or 5mg, the cleaner’s initial concern (after personal protection) should be limiting the spread of cytotoxic drugs through the work environment. The first step should be to cover the spill with an absorbent sheet or spill control pads. If the drug is in powder form, a wet or damp cloth should be used. For large spills, protective clothing should be worn with the addition of the respirator to protect against any airborne powder or aerosols. The use of chemical inactivates is not recommended as they may create a hazardous by-product. As with small spills, all contaminated areas should be cleaned a minimum of three times, and all contaminated products and equipments should be disposed of or cleaned in an appropriate manner.
4. Spills in biological safety cabinet
After the procedures described above are followed, the interior of the hood may also require cleaning. If the HEPA filter has been contaminated, the unit must be labelled – Contaminated, DO NOT USE. The filter must then be changed and disposed of as soon as possible by trained personnel who are wearing the appropriate protective clothing. Protective goggles (if not disposed of) should be thoroughly cleaned with an alcohol wipe after cleanup.
Storing and transport
Areas where cytotoxic drugs are stored should be separated from regular storage, and clearly marked. Engineering controls (locks, limited access key card systems) should be in place to prevent unauthorized personnel from entering the storage area. An inventory of the cytotoxic drugs that is frequently confirmed should be kept in the room, along with instructions for cleaning spills. Where possible, other drugs should notbe stored with cytotoxic drugs. Clear warning labels should be used to identify the cytotoxic drugs and point out their hazards. Shelves should also be fitted with a ‘lip’ or back slope that prevents the drugs from falling to the floor.
When a damaged container is found, it should only be handled by trained personnel with personal protective equipment described previously. Broken containers and contaminated packing material should all be placed in the appropriate puncture proof container and disposed of as cytotoxic biological waste.
Cytotoxic drugs should be securely capped and sealed and should be packed in impervious packing material. Labels of all boxes, containers and vials should indicate that the substance is a cytotoxic drug.
Legislation regarding cytotoxic drugs in Canada
Most jurisdictions do not specifically cover cytotoxic drugs in legislation or regulations. However, in all Canadian jurisdictions it is the general duty of the employer to keep the workplace safe and eliminate foreseeable hazards. This includes the three basic worker rights in workplace safety: the right to refuse unsafe work, the right to knowledge about all hazards in the workplace, and the right to participate in the planning and development of procedures to protect workers from harm. For more information on your rights and how to develop safer workplaces, please refer to the CUPEGuideline, Effective Health and Safety Programs.
Two provinces that do specifically cover cytotoxins are British Columbia and Saskatchewan. British Columbia (sections 6.42-6.58 of the Occupational Health and Safety Regulation) legislates that the employermust “develop and implement an exposure control plan…” The legislation also ensures that employees should be aware of information regarding the(a) acute and chronic toxicity, including any potential reproductive hazard, (b) acute exposure treatment, (c) safe handling of, and (d) the proper labeling of cytotoxic drugs and their storage areas. Safe work procedures must also be developed for the receiving, preparation, administration, storage, disposal and waste handling.
In Saskatchewan, law (section 471 of the Occupational Health and Safety Regulations), the employer shall “take all practicable steps to minimize the exposure of workers to cytotoxic drugs or to materials or equipment contaminated with cytotoxic drugs”. As well, the legislation covers: (a) installation and maintenance of the biological safety cabinets, (b) development of a program to protect the workers from exposure, (c) emergency procedures in case of exposure, (d) the disposal of cytotoxic drugs, and (e) the equipment used to administer the drugs.
As mentioned above, it is the position of CUPE that there is no “safe” exposure level for any carcinogen, including cytotoxic drugs. In the case of these types of drugs, all steps must be taken to remove the hazard at the source to ensure the safest and healthiest workplaces possible. Some cytotoxic drugs are mutagens that may damage the DNA in sperm of male workers and the ova of female workers. While the only way to protect workers is to prevent exposure, protective re-assignment with no loss of pay or benefits is the minimum that CUPE locals and their H&S committees should demand from their employers, especially for those workers who are pregnant or considering reproduction.
The information contained in this fact sheet relates to the minimal requirements for cytotoxic drug administration and use, and should be considered only as a basic starting point in the development of healthy work practices.
For more information, please contact:
1. Preventing Occupational Exposures to Antineoplastic Drugs in Health Care Settings, Thomas H. Connor and Melissa A. McDiarmid, CA Cancer Journal for Clinicians 2006;56;354-365
2. NIOSH Alert, Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings. DHHS (NIOSH) Publication No. 2004–165.
3. Cytotoxic Drugs and Related Waste Guide (2008) Prepared by the cytotoxic drugs working party for WorkCover, New South Wales Government, Australia.
4. NIOSH Occupational Exposure to Antineoplastic Agents. United States National Institute for Occupational Safety and Health. http://www.cdc.gov/niosh/topics/antineoplastic/. Retrieved 2009-12-24.
5. Cytotoxic Drugs, (Nov 1999) Occupational Health and Safety Division, Government of Saskatchewan, http://www.labour.gov.sk.ca/Default.aspx?DN=2427f860-f7f5-4b5f-91e0-4ecd26ff6ef8 2009-12-24.
6. Guidelines for the Safe Handling of Cytotoxic Drugs and Related Waste, Occupational Safety and Health Service, Department of Labour, Wellington, New Zealand, 1997.
7. White, S.K.; Stephens, A.D.; Dowjat, B.; Sugarbaker, P.H. (1996) Safety considerations in the use of intraoperative intraperitoneal chemotherapy. Cancer treatment and research; 82:311-6.
8. Recommendations for the Safe Use of Handling of Cytotoxic Drugs, Office of Research Services, U.S. Dept of Health and Human Services. http://dohs.ors.od.nih.gov/pdf/Recommendations_for_the_Safe_Use_of_Handling_of_Cytotoxic_Drugs.pdf Retrieved on 2010-2-24.
9. Province of British Columbia, Worksafe BC, OHS Regulation, Guidelines Part 6, http://www2.worksafebc.com/Publications/OHSRegulation/GuidelinePart6.asp?reportID=19259 Retrieved 2009-12-24
10. Province of Saskatchewan, The Occupational Health and Safety Regulations, 1996 http://www.qp.gov.sk.ca/documents/English/Regulations/Regulations/O1-1R1.pdf Retrieved 2009-12-24