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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.
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.
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.
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.
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.
Human evidence suggests that cyclophosphamide is a teratogen. Many other cytotoxic agents show evidence of teratogenicity in experimental animals.
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.
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.
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.
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).
Excreta from animals should be considered contaminated up to 48 hours following drug administration.
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.
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.
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.
Refer to Chapter VI, Section 4.5 for the proper disposal procedure for cytotoxic agents.
Direct skin or eye contact should be treated as follows: