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Cytotoxic agents are used primarily in patient therapy by nurses and physicians. However, they are also occasionally prepared and used in lab or animal studies. These agents interfere with the growth and proliferation of cells and neoplasms. Because they are primarily used in therapy, they are also frequently called chemotherapeutic drugs.

12.12.1 Authorization for Use

An investigator planning to use cytotoxic agents for purposes other than patient therapy must be authorized to do so with a Chemical Carcinogen Memorandum of Understanding and Agreement (CMUA). See Section 4.

The PI, supervisor, or LSC contacts the CHO to record information needed in the CMUA. The CHO verifies that the necessary safety training, procedures, and equipment are in place, or provides instructions for fulfilling safety requirements.

12.12.2 Routes of Exposure

Exposure via inhalation can occur during improper drug preparation, administration and disposal. For example, aerosols can be generated when inserting needles into or withdrawing them from vials without protection; when expelling air from syringes into the air of the room; and when cytotoxic waste is not closed in plastic bags. Exposure via skin absorption may occur when cytotoxic agents are spilled during preparation, administration or disposal. Exposures may also result from contact with urine of patients or experimental animals being treated with cytotoxic agents.

12.12.3 Hazards of Cytotoxic Agents

All cytotoxic agents are either known or suspected to be carcinogenic, mutagenic, and/or teratogenic. To prevent exposures, cytotoxic agents and materials contaminated with them require special handling. Contaminated materials include body fluids, particularly urine, from patients undergoing chemotherapy and also from experimental animals receiving cytotoxic agents.

12.12.4 Carcinogenic Effects

Therapeutic doses of cytotoxic agents are associated with an increased incidence of malignant tumors (IARC 1981). Cyclophosphamide, cyclosporin, and several others are listed as carcinogens by NTP and/or IARC.

12.12.5 Teratogenic Effects

Human evidence suggests that cyclophosphamide is a teratogen. Many other cytotoxic agents show evidence of teratogenicity in experimental animals.

12.12.6 Toxic & Reproductive Effects

The following effects have been observed in patients treated with cytotoxic agents: lack of sperm production, reduced sperm counts, amenorrhea, and adverse effect on the bone marrow, heart, central nervous system, liver, skin, ears, pancreas, lungs, kidneys, and endocrine glands.

12.12.7 Acute Effects

Acute effects can be severe, as exemplified in the accidental pricking of a patient's finger which eventually resulted in the patient's loss of use of the hand (Duvall and Baumann, 1980). Some cytotoxic agents are strong vesicants that can cause varying degrees of local tissue necrosis upon direct contact.

12.12.8 Chronic Effects

Selevan et al. (1985) observed a statistically significant association between fetal loss and occupational exposure of nurses to cytotoxic agents. Soteniemi et al. (1983) documented liver damage in three oncology nurses who had handled cytotoxic agents over a number of years. Light-headedness, dizziness, nausea, headache, skin and mucous membrane reactions, hair loss, cough, and possible allergic reactions have been reported by nurses handling chemotherapy agents (Crudi, 1980). These symptoms experienced by nurses are the same as those noted by patients undergoing chemotherapy.

12.12.9 Handling Procedures for Cytotoxic Agents: Preparation and Use

Whenever possible, procure cytotoxic agents prepared by the manufacturer. When it cannot be avoided, the preparation of such agents must be performed following the procedures below based on guidelines printed in the NIH publication Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings (NIOSH Publication #2004-165) and recommendations from OSHA's Controlling Occupational Exposures to Hazardous Drugs. The use of any drug listed as a select carcinogen for a purpose other than patient therapy requires that a Chemical Carcinogen Memorandum of Understanding and Agreement (CMUA) be completed by the principal investigator (PI),supervisor, or lab safety coordinator (LSC).

  1. Cytotoxic drug preparation must be performed in a Class II Type A2, B1, or B2, or Class III biological safety cabinet exhausted outside the building. If this type of cabinet is not available, a chemical fume hood may be used.
  2. Employees preparing the drugs must wear two pairs of Safeskin Purple Nitrile gloves or other suitable chemotherapy gloves, and a disposable closed-front gown made of polyethylene-coated polypropylene material with elastic cuffs and disposable arm sleeves. Gloves should be changed every 30 minutes, or immediately when contaminated, torn, or punctured. Protective clothing must not be worn outside the preparation area.
  3. Hands and arms must be washed thoroughly with soap and water before donning and after removing gloves.
  4. Vials containing drugs to be reconstituted should be vented to reduce internal pressure. This can be done by using a 0.22-micron hydrophobic filter or a chemotherapy dispensing pin. This reduces spraying and spilling of the agent.
  5. If a chemotherapy pin is not used, a sterile alcohol pad should be carefully placed around the needle and vial top during withdrawal from the septum.
  6. External surfaces contaminated with the drug must be cleaned with 2% sodium hypochlorite or Surface Safe wipes prior to transfer or transport.
  7. Glass ampules must be wrapped with an alcohol pad and snapped at the break to reduce the possibility of injury and to contain the aerosol produced. Use a 5-micron filter needle to remove the drug solution.
  8. Syringes and IV bottles containing cytotoxic drugs must be labeled and dated unless they are being used immediately.
  9. Wipe down the interior of the safety cabinet with 2% sodium hypochlorite using disposable towels or Surface Safe wipes after drug preparation is complete. All wastes are considered contaminated and must be packaged and labeled for EH&S pickup.

12.12.10 Administration of Cytotoxic Agents

  1. Safeskin Purple Nitrile or other chemotherapy gloves should be worn. Change gloves as recommended above in Section 12.11.9. Hands must be thoroughly washed before gloves are donned and after gloves are removed.
  2. Disposable closed-front gowns with elastic cuffs should be worn. Gowns should be made of polyethylene-coated polypropylene material.
  3. If bubbles are removed from syringes or IV tubing, an alcohol pad should be placed carefully over the tip in order to collect any of the cytotoxic drugs that may be inadvertently discharged. Care must be taken not to prime sets or syringes into the sink or any open receptacle.
  4. If administering the drug directly into an animal, hold a sterile pad at the injection site to absorb any drug discharged while infusing or withdrawing the needle.

12.12.11 Animal Studies: Cleaning Cages and Bedding

Excreta from animals should be considered contaminated up to 48 hours following drug administration.

Dogs:

Animal handlers must wear rubber boots and aprons while cleaning cages. Care should be taken when cleaning the cages to avoid creating an aerosol. This can be done by rinsing water down the cage room wall or backsplash to dilute the excreta prior to spraying the area directly to clean the cages.

Small rodents:

When cleaning rodent cages, wet the bedding to minimize dust and dispose of it with other bedding. Cages should be cleaned and disinfected as usual.

12.12.12 Storage of Cytotoxic Agents

Cytotoxic agents kept in the lab must be labeled with a warning label and clearly identified as a cytotoxic agent or as a suspect or known carcinogen.

Areas where cytotoxic agents are stored should be posted with a warning sign. Segregate the agents in a tray; label, and store the tray behind closed doors.

12.12.13 Disposal of Cytotoxic Agents

Refer to Chapter VI, Section 4.5 for the proper disposal procedure for cytotoxic agents.

12.12.14 Emergency Response: Exposure

Direct skin or eye contact should be treated as follows:

  1. Immediately remove contaminated gloves or gown.
  2. Wash affected skin area immediately with soap (non-germicidal) and water for fifteen minutes. For eye exposure, immediately flood affected eye with water or isotonic eyewash designated for that purpose for at least fifteen minutes. Seek medical attention immediately.
  3. Call the EH&S.
  4. Complete an Accident-Illness Form as soon as possible and mail to the EH&S at J3-200.

12.12.15 Emergency Response: Spills

  1. Spills of less than 50 ml or 5 g should be cleaned up immediately by staff wearing gowns, double gloves, and safety glasses.
  2. Wipe liquids with absorbent material. Wipe solids with wet absorbent material. Clean spill area three times with detergent solution, then rinse with clean water.
  3. Glass fragments or other contaminated sharps must be disposed of in a red sharps container and labeled as cytotoxic waste. All contaminated materials used for spill cleanup must be bagged and labeled as cytotoxic waste.
  4. Spills of more than 50 ml or 5 g outside a chemical fume hood must be cleaned up by staff wearing respirators. In the event of such a spill, evacuate the lab and contact EH&S or contact security after hours.