Cytotoxic Drugs Guide

2021

saskatchewan.ca
 PLEASE NOTE
Consult the legislation for all purposes of
interpretation and application of the law.
Table of Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Reasons for concern. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Sources of exposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Responsibilities for controlling exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Guidelines for controlling exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
The written program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2
Receiving, Storage and Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3
Preparation of parenteral cytotoxic drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4
Approved Biological Safety Cabinets (BSCs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5
Using and maintaining the Biological Safety Cabinet. . . . . . . . . . . . . . . . . . . . . . . . 5
Respiratory protection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6
Approved respiratory devices. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Use and maintenance of respirators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Other personal protective equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6
Gloves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7
Protective gown and shoe covers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Face and eye protection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Supplies and equipment for drug preparation, administration, waste disposal and spills. 8
Preparing Cytotoxic Drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Work procedures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Additional protection for pregnant workers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Resources. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Appendix 1: Antineoplastic drugs classified by the International Agency for
Research on Cancer (IARC). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Appendix 2: Class II and Class III Biological Safety Cabinets. . . . . . . . . . . . . . . . . . . 14
The Class II BSC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Class II, Type A1 BSC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Class II, Type A2 BSC (Formerly called A/B3) . . . . . . . . . . . . . . . . . . . . . . . . . . . .16
Class II, Type B1 BSC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Class II, Type B2 BSC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Class II, Type C1 BSC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
The Class III BSC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Occupational Health and Safety

Introduction
Cytotoxic drugs include any drug that inhibits or prevents the function of cells. Cytotoxic
drugs include drugs used to treat cancer and other medical conditions such as arthritis or
autoimmune disorders (e.g., psoriasis). This guide explains the duty of an employer in a
health care facility to protect workers who are likely to be exposed to cytotoxic drugs. Such
worker exposure may occur at health care facilities such as:
• hospitals;
• special care and personal care homes;
• cancer and other medical clinics;
• in home care situations; and
• veterinary clinics and animal hospitals.

Reasons for concern

There is a potential for cytotoxic drugs to harm workers who are likely to be exposed to
them. This includes workers who prepare, administer, or handle the drugs, waste products,
contaminated surfaces or materials. The concern is based on:
• toxic side effects seen in patients treated with these drugs;
• evidence that these drugs can produce chromosome changes, cancer and reproductive
abnormalities in animal experiments; and
• adverse effects in workers exposed to them.

Sources of exposure
Worker exposure occurs by inhalation of drug dust or aerosol, absorption through the skin,
injection by accidental skin puncture and ingestion through contact with contaminated food,
drink, or cigarettes. Exposure may occur through activities like:
• counting, crushing or breaking powdered tablets;
• mixing cytotoxic drugs into intravenous fluids;
• preparing or administering cytotoxic drugs. (e.g., while breaking open ampules,
withdrawing needles from drug vials, transferring drugs with syringes or expelling air
from a drug- filled syringe);
• handling any material that has been in contact with cytotoxic drugs like needles,
syringes, IV bags, tubing, incontinence products, soiled linens, used personal protective
equipment, drug packaging and waste, or;
• cleaning areas where cytotoxic drugs are used.

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 Cytotoxic Drugs Guide

Responsibilities for controlling exposure

Section 31-5 of The Occupational Health and Safety Regulations, 2020, requires employers in
health care facilities to take all practicable steps to minimize worker exposure to cytotoxic
drugs or materials, or equipment contaminated with cytotoxic drugs.1 Where workers are
required to prepare, administer, handle, or use cytotoxic drugs or are likely to be exposed to
them, the employer must prepare and implement a written program. The program includes
written procedures and other precautions to ensure the health and safety of workers. The
employer must train workers on the content of the program and its procedures when
implementing the program.
Where workers prepare parenteral cytotoxic drugs on a frequent and continuing basis,
the employer must provide and maintain an approved biological safety cabinet (BSC) and
ensure it is used safely. The regulations also place duties on workers to co-operate with the
employer and use the safe work procedures and protective equipment referred to in the
written program.

Guidelines for controlling exposures

The following guidelines explain the employer’s duties under section 31-5of the Regulations
and are intended to assist the employer in developing the written program. The program
is especially important because there are no established contamination limits for cytotoxic
drugs. The goal of the written program is to keep exposures as low as reasonably achievable
(ALARA) given the potential for severe health hazards associated with cytotoxic drugs.

The written program

The employer is required to consult with the occupational health committee when
developing the written program. The program must include:
1. A list of all cytotoxic drugs that are used on site.
2. Identify workers that are at risk for exposure to cytotoxic drugs based on the work
activities completed.
3. An explanation of how cytotoxic drugs, supplies and equipment contaminated with
cytotoxic drugs will be:
a) identified;
b) stored;
c) prepared, transported, administered, handled and used (including the means to
minimize the risk of aerosolization);
d) maintained (supplies and equipment); and
e) discarded – this section must identify means to:
¯ contain and label cytotoxic drug wastes;
¯ describe how the wastes will be transported per the Transportation of Dangerous
Goods Regulations; and
“Practicable” means possible given current knowledge, technology and invention.
1

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¯ identify the collection or disposal site, which must be approved by

Saskatchewan’s Ministry of Environment.
4. Emergency procedures to use:
a) when a cytotoxic drug spills or leaks, (e.g., from a damaged package); or
b) when a worker is exposed to cytotoxic drugs as a result of:
¯ a skin puncture;
¯ contact with intact skin;
¯ contact with the eye;
¯ accidental inhalation of drug dust or aerosol; or
¯ swallowing a substance contaminated with a cytotoxic drug.
5. An explanation of how to maintain or dispose of equipment that becomes contaminated
with cytotoxic drugs.
6. The use of:
a) engineering controls (e.g., general or local exhaust ventilation);
b) work practices;
c) hygiene practices (e.g., personal hygiene standards). These standards should include
a ban on eating, drinking, smoking, applying cosmetics or storing food in or near the
preparation area;
d) hygiene facilities (e.g., personal wash facilities);
e) approved respiratory protective devices, approved eye or face protectors and other
appropriate personal protective equipment; and
f) decontamination materials and equipment that are appropriate in the circumstances.
7. The use of an approved BSC for preparing cytotoxic drugs and methods of maintaining
the cabinet.
Once prepared, the program must be implemented. Workers must be trained on the program
and a written copy of the program must be made readily available to workers. The program
must be reviewed annually and revised as needed.
The following sections describe protective measures to minimize workers’ exposure.

Receiving, Storage and Transport

All workers who receive deliveries of cytotoxic drugs should be trained on how to properly
handle them. The integrity of the external package should be inspected upon receipt.
If packaging is broken or damaged and likely to cause a leak or spill, the spill protocol
developed as part of the emergency procedures must be initiated. Delivery containers should
be taken immediately to the pharmacy department or other dedicated storage area. Since
packaging can have high levels of contamination, there should be an unpacking area in the
pharmacy to limit exposure risks. Workers should wear a protective gown and two pairs
of gloves to unpack cytotoxic drugs. A receptacle for cytotoxic waste must be available in
the unpacking area for the disposal of secondary packaging. Once unpackaged, all drug

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 Cytotoxic Drugs Guide

containers should be cleaned to reduce external contamination. It is important to ensure

that the cleaning process does not damage the container or make it difficult to read the
label.
Areas where cytotoxic drugs are stored should be separated from regular storage and clearly
marked. Engineering controls (e.g., locks, limited access card systems) should be in place
to prevent unauthorized workers from entering the storage area. The list of the cytotoxic
drugs on site should be kept in the room, along with instructions for cleaning spills. Where
possible, other drugs should not be stored with cytotoxic drugs. Clear warning labels should
be used to identify the cytotoxic drugs. The 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 must only be handled by trained workers wearing
appropriate personal protective equipment. Broken containers and contaminated packing
materials must all be placed in the appropriate labeled puncture proof container and
disposed of as cytotoxic biological waste.
Any transport of cytotoxic drugs must be done in containers designed to contain leakage and
spills. The containers must be clearly labeled as containing hazardous drugs.

Preparation of parenteral cytotoxic drugs

Before preparing the written program, determine whether the facility will be equipped to
prepare parenteral cytotoxic drugs.
The employer must make a determination of whether the health care facility will prepare
parenteral cytotoxic drugs on a frequent and continuing basis. To make this determination,
the employer needs to examine the present situation at the facility. Consider the size of the
population being served the size of the facility, how frequently parenteral cytotoxic drugs
have been prepared in the past and the location of the nearest facility with an approved
BSC. The employer should also consider any intended changes to the current situation. For
example, are there going to be changes in the size of the population being served or other
reasons that might increase the frequency of cytotoxic (parenteral) drug preparations?
An approved BSC must be provided to workers when it is determined that parenteral
cytotoxic drugs will be prepared on a frequent and continuing basis in the facility. If it is
determined that parenteral cytotoxic drugs will not be prepared on a regular basis in the
facility, the employer must make this intention clear to the occupational health committee
and the workers and should also explain the alternate arrangements to clients.
An alternative arrangement may be made with another facility. These drugs could be
prepared at a nearby facility that has an approved BSC and then transported to the facility
where the drugs will be administered to patients. Alternately, the patient may travel to
another nearby health care facility that is suitably equipped to prepare parenteral cytotoxic
drugs.
Parenteral cytotoxic drugs may be prepared on an occasional or interim basis at a health
care facility that does not have an approved BSC, where:

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• exceptional circumstances arise;

• alternative arrangements prove impractical to use; or
• the employer has planned for, but not yet received, the BSC.
In such cases, the employer must determine what arrangements can be made in the facility
to minimize worker exposure to parenteral cytotoxic drugs being prepared. The arrangement
must include measures to protect the worker preparing the drug as well as other workers in
the vicinity. The arrangement must also prevent the spread of drug contamination from the
immediate vicinity of the preparation area.

Approved Biological Safety Cabinets (BSCs)

Class II BSC: B1, B2, or B3; and Class III BSC that meet the current standard of NSF/ANSI
49-2019 (See the Resources section) are approved for the purposes of preparing parenteral
cytotoxic drugs. (More information can be found in the Centres for Disease Control and
Prevention (CDC) publication Biosafety in Microbiological and Biomedical Laboratories
(BMBL) 6th Edition, which can be downloaded at no charge from the CDC. Relevant
information from that publication can also be found in Appendix 2 of this guide.)
Class II Type A BSCs exhaust HEPA-filtered cabinet air into the workroom. They are also
approved if:
A. they are used with a canopy or thimble hood that captures air released from the BSC
and exhausts the air out of the building; or
B. there are means to ensure that the HEPA filter is functioning effectively before each
use (e.g., by reading a properly installed pressure differential gauge) and the exterior
surface of the HEPA filter is protected from damage.
Option A is the recommended approach.
Preference should be given to Type B-BSCs, which do not exhaust any cabinet air into the
workroom.
See the Resources section for more information on BSC.
Using and maintaining the Biological Safety Cabinet
The BSC must be inspected and certified by a competent person at least annually and when
the cabinet is moved. The BSC must be cleaned, maintained, and used according to the
manufacturer’s recommendations.
The exhaust blower on the BSC should be operated continuously — even when the BSC is
not in use. The cabinet should be cleaned daily with 70 percent alcohol and decontaminated
weekly or whenever spills occur. Decontamination should consist of surface cleaning
with an alkaline detergent followed by thorough rinsing. Personal protective equipment as
described later in this document should be used while decontaminating the cabinet. The
ductwork attached to the cabinet should be labelled to reflect its hazardous content.
If a risk assessment determines that a BSC is not required, designate a centralized area for

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 Cytotoxic Drugs Guide

the preparation of cytotoxic drugs. The area should be a work area that is quiet, uncluttered,
and well ventilated. The ventilation system, fans or air conditioning unit should not blow air
directly at the preparation area. The area should be clearly posted with a sign identifying it
as a cytotoxic drug preparation area.

Respiratory protection
Approved respiratory protection must be provided by the employer and worn by workers
who may be exposed to cytotoxic drug dusts or aerosols. This type of exposure may occur
when workers:
• prepare cytotoxic drugs on a counter or some other place that is outside of an approved
BSC;
• clean up spilled cytotoxic drugs; or
• decontaminate a BSC that has the sash raised.
Approved respiratory devices
Approved respiratory protective devices include a reusable facemask with filter cartridges, or
a disposable filter mask. The filter cartridges or the filter mask must provide high efficiency
particulate air (HEPA) filtration and carry the National Institute for Occupational Safety and
Health (NIOSH) label with either the N100, P100, or R100 rating.
These respirators are available from most safety equipment suppliers. Surgical masks are
neither suitable nor adequate to protect the worker.
Use and maintenance of respirators
Workers must be trained to use their respirator properly. Training should include how
to ensure a proper fit and how to prevent the contamination of the inner surface of the
respirator. Workers must also be fit tested to ensure the respirator is the right size and will
provide effective protection. Employers must ensure that workers can make an effective
seal to their facial skin (e.g., clean shaven) during every use. Reusable facemasks must be
cleaned and inspected after each day’s use. The cartridge must be replaced according to
manufacturer’s recommendations. When not in use, respirators be stored in a dust-proof,
sanitary location.

Other personal protective equipment

Personal protective equipment must be provided for and used by workers preparing or
administering the drugs. The equipment must include well-fitted disposable gloves, an
appropriate protective gown, shoe covers, face and eye protection. Workers must also be
trained in the proper donning and doffing of protective equipment to ensure that they do not
contaminate their skin, clothing or the work environment.
If an accidental spill or splash occurs, contaminated clothing and personal protective
equipment should be removed immediately. Contaminated skin or eyes should be flushed
immediately with copious amounts of running water to effectively cleanse the area. Specific
emergency response information can be found on the safety data sheet for the drug(s) being
used.

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Gloves
The gloves used to handle cytotoxic drugs should meet with ASTM standard D-6978-05
(2019) Standard Practice for Assessment of Resistance of Medical Gloves to Permeation by
Chemotherapy Drugs and be powder free. Nitrile, polyurethane or neoprene gloves are
recommended. Vinyl gloves should not be used. Latex gloves are not recommended as they
are known to cause latex allergies in workers. It is recommended that workers wear two
pairs of gloves for additional protection. The first pair of gloves should be put on prior to
donning the gown. The second pair should fit over the cuff of the protective gown. Hands
must be washed both before and after gloving.
Gloves should be changed frequently (approximately every hour). They must be removed
and changed immediately if they are punctured, cut, torn or visibly contaminated with
a cytotoxic drug. Great care should be taken in the removal of gloves to prevent the
contamination of the skin. Double gloving is recommended for cleaning up spills. Potentially
contaminated gloves must not be worn outside of the work area.
Protective gown and shoe covers
Gowns used for handling cytotoxic drugs should:
• be disposable;
• be made of lint free and low-permeability fabric;
• have long sleeves with tight fitting cuffs; and
• fasten in the back.
Gowns must be changed in the event of contamination, spillage, or rips, as well as at the
end of the procedure. Avoid touching the outside of the gown when removing it to prevent
contamination of the hands. Potentially contaminated gowns must not be worn outside of
the work area.
Disposable shoe covers should be worn to prevent contamination of the workers’ shoes.
They should be worn in the sterile preparation room or in the event of a spill. Shoe
covers must be removed immediately when leaving the sterile preparation room to avoid
contamination of other areas.
Face and eye protection
Eye protection, such as a face shield or splash goggles, must be made available for use in
any situation where there is a risk of splashes, sprays, or aerosols onto the face or into the
eyes. Face or eye protection must also be used when cleaning up spills. A risk assessment
by a competent person is required to determine the level of protection required to ensure
adequate worker safety.

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 Cytotoxic Drugs Guide

Supplies and equipment for drug preparation, administration, waste

disposal and spills
Preparing Cytotoxic Drugs
Standard operating procedures for parenteral preparations should be documented and
emphasize the need to:
• contain excess drug solutions and air when priming;
• use techniques that avoid the generation of pressure differentials; and
• avoid using cytotoxic drugs supplied in glass ampoules. If glass ampoules must be used,
open with an ampoule breaker or a low-linting swab.
Tablets, capsules and topical creams should be prepared under the same conditions as
parenteral cytotoxic drug preparations.
Specific additional standard operating procedures for non-parenteral preparations include:
• using purpose-dedicated equipment;
• making mixtures by dispersing tablets in water;
• not crushing tablets in an open mortar;
• not counting tablets or capsules by machine; and
• cleaning equipment immediately after use.
Specific handling techniques and procedures incorporating suitable equipment (designed to
reduce the risk of exposure) should be used and include:
1. Drug preparation equipment
Equipment used for preparing drugs should incorporate a closed system where possible, and
reduce the potential for generating high pressure.
Note: Closed systems are not an acceptable substitute for appropriate ventilation or
engineering controls (e.g., class II or III biological safety cabinets) used along with personal
protective equipment. Specific methods of control may include:
• use of Luer-lock syringes and fittings to keep connections together;
• use of Luer-slip syringes (only if Luer-lock connections are incompatible) such as
intrathecal needles;
• use of syringe-to-syringe connectors when transferring solutions from one syringe to
another;
• use of wide bore needles to reconstitute and draw-up cytotoxic drugs;
• use of filter needles only when the cytotoxic drug has been removed from a glass
ampoule, or if particulate matter is visible, for example if coring of a vial rubber has
occurred; and
• use of air-venting devices to equalize pressures and to prevent the passage of powder,
aerosols and liquids.

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2. Waste disposal
Plastic bags that are 2 mm thick (if polypropylene) or 4 mm thick (if polyethylene) should
be used to collect potentially contaminated materials. The outer container or bag must be
colour coded and labeled with a cytotoxic warning label. All sharps should be placed in
puncture-proof containers. All workplaces where cytotoxic drugs may be present should
have a policy for segregating waste materials resulting from cytotoxic drug preparation and
administration.
Housekeeping staff should be trained on how to safely handle waste materials and wear
protective gloves while handling waste containers. Cytotoxic waste must be handled
differently than regular garbage and must be disposed of according to provincial regulations
at facilities approved for cytotoxic waste disposal.
3. Spill kits
A spill management kit should be available in all areas where cytotoxic drugs are stored,
transported, handled and administered. All staff should know where the kit is located and
the names of individuals who are trained to clean a spill. Spills must be cleaned by workers
who have received appropriate training and have appropriate protective equipment. Others
should vacate the area as soon as it is safe to do so and should not return until the spill
is cleaned. They should remove any clothing or personal protective equipment that may
be contaminated. All spills should be marked with a warning sign to prevent exposure to
others. Glass must never be handled by hand, only with a scoop.
The spill kit should contain the following items:
• procedure for spill clean-up;
• protective disposable gowns (preferably lint free, low permeability fabric), hair and shoe
covers;
• goggles/face shield;
• at least two pairs of chemotherapy gloves or thick quality disposable gloves such as
nitrile or neoprene;
• approved respirator (when there is risk of inhaling drug aerosols);
• absorbent backed sheets or spill pads;
• decontaminating agent;
• puncture-resistant container labeled for cytotoxic waste;
• scoop;
• warning signs;
• any additional items identified by a risk assessment of the facility; and
• incident report forms.

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 Cytotoxic Drugs Guide

Work procedures
Written safe work procedures or specific instructions are a part of the written plan. They
should be formulated or otherwise adapted from existing written/published procedures. The
employer must implement and train workers on the procedures and make them available to
all personnel involved in the mixing and/or administration of the drugs. There are several
written/published procedures available such as the U.S. Occupational Health and Safety
Administration Guidelines, Center for Disease Control and Prevention and The National
Institute of Health, etc. One or more of these documents should be obtained and adapted to
the workplace (See the Resources section).

Training
The employer must ensure workers are:
• informed of the hazards of cytotoxic drugs and risks of exposure;
• instructed on proper precautions;
• trained on safe work procedures; and
• supervised to make sure they follow safe work procedures.
Pre-job training must be given to all personnel involved in the mixing and/or administration
of cytotoxic drugs.
The training must include housekeeping, laundry, and janitorial staff. They must receive
training on the potential hazards of handling laundry, excreta, etc., contaminated with
cytotoxic drugs, and safe work procedures when handling these materials.
The training should be continually assessed and reinforced.2 The written program must
address how training will be developed, delivered and evaluated.

Additional protection for pregnant workers

A pregnant worker who may be exposed to hazardous amounts of cytotoxic drugs may
notify the employer that they are pregnant. In this situation, the employer must minimize
this worker’s exposure (section 21-7of the Regulations), or, on the worker’s request, the
employer must transfer a pregnant worker to duties that do not involve handling cytotoxic
drugs, where such duties are available.
A policy covering any personnel who are actively trying to conceive a child and breast-
feeding workers should also be established.

2
“Train” means to give information and explanation to a worker with respect to a particular subject-matter
and require a practical demonstration that the worker has acquired knowledge or skill related to the subject-
matter.

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Resources
CAREX Canada
CAUT Cytotoxic Drugs Health and Safety Fact Sheet
Occupational Health and Safety Administration, (2016, August 1). Controlling Occupational
Exposure to Hazardous Drugs.
Primary Containment for Biohazards: Selection, Installation and Use of Biological Safety
Cabinets. Center for Disease Control and Prevention and The National Institute of Health.
PHONE: (404) 639-3311.
Safe Handling of Cytotoxic Drugs in Home Chemotherapy. Seminars in Oncology Nursing
(502), Suppl. 1, 1989, pp 15-20.
Safe handling of Hazardous Drugs in Healthcare
Safe Handling of Parental Cytotoxics: Recommendations for Ontario. American Society of
Clinical Oncology. September 2009.
NSF/ANSI 49-2019 Biosafety Cabinetry: Design, Construction, Performance, and Field
Certification Informative Annex 1 (formerly Annex E)

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 Cytotoxic Drugs Guide

Appendix 1: Antineoplastic drugs classified by the International

Agency for Research on Cancer (IARC)
Antineoplastic or anti-cancer drugs are used to treat cancer. Most antineoplastic drugs are
also cytotoxic.
The following is a list of antineoplastic drugs that have been classified by the International
Agency for Research on Cancer (IARC) as known, probable, or possible cancer-causing
agents.
It is not a complete listing of all carcinogenic antineoplastic drugs, since not all
antineoplastic drugs have been reviewed and classified by IARC.
Some of the following antineoplastic drugs that are classified as potentially carcinogenic
are not cytotoxic. Despite this, the precautions outlined in this guide and guides on
antineoplastic drugs should be used.
Group 1 – Drugs which are carcinogenic (sufficient human evidence of carcinogenesis)3
• Arsenic trioxide
• Azathioprine (Imuran)
• Busulfan (Myleran)
• Methoxsalen, plus UV radiation (Oxsoralen, Oxsoralen-Ultra, UltraMOP)
• Chlorambucil (Leukeran)
• Cyclophosphamide (Cytoxan, Procytox)
• Etoposide
• Melphalan (Alkeran)
• Thiotepa
• Tamoxifen citrate (Apo-Tamox, Gen-Tamoxifen, Nolvadex, Nolvadex-D, Novo-Tamoxifen,
Tamofen, Tamone)
• Diethylstilbestrol sodium diphosphate (Honvol)
Group 2A – Drugs which are probably carcinogenic to humans (generally, limited human
evidence, but sufficient animal evidence)4
• Adriamycin
• Azacitidine
• Certain combined chemotherapy for lymphomas: (e.g., procarbazine, vincristine,
prednisone and nitrogen mustard)
• Bischloroethyl nitrosourea or carmustine (BiCNU)
• Carmustine
• 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea or lomustine (CeeNU)
3
Source: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Supplement 7, 2000.
4
Source: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Supplement 7, 2000.

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• Cisplatin (Platinol)
• Doxorubicin (Adriamycin)
• Lomustine
• Nitrogen mustard (Mustargen)
• Procarbazine (Natulan)
• Teniposide
Group 2B – Drugs which are possibly carcinogenic to humans (generally, limited human
evidence, but absence of animal evidence)5
• Amsacrine
• Bleomycin sulfate (Blenoxane)
• Dacarbazine (DTIC)
• Daunomycin
• Mitomycin (Mutamycin)
• Mitoxantrone
• Streptozocin (Zanosar)
• Daunorubicin (Cerubidine)
• Medroxyprogesterone acetate (Alti-MPA, Depo-Provera, Provera) – cancer, hormone
Drugs with evidence of carcinogenicity which, at present, are not used clinically in Canada
• Chlornaphazine (Group 1)
• 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-l-nitrosourea or Methyl-CCNU (Group 1)
• Treosulphan (Group 1)
• Aminouracil mustard or Uracil mustard (Group 2B)
• Nitrogen mustard, n-oxide (Group 2B)
• Azacitidine (Group 2A)
• Chlorozotocin (Group 2A)
• Trichlormethine (Group 2B)

5
IBID.

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 Cytotoxic Drugs Guide

Appendix 2: Class II and Class III Biological Safety Cabinets

This information was developed by The Centers for Disease Control and Prevention (CDC),
The full publication Biosafety in Microbiological and Biomedical Laboratories (BMBL), 6th
Edition is available as a free download from the CDC website.
This information is provided for educational and illustration purposes only.
The Class II BSC
The Class II (Types A1, A2, B1, B2, and C1) BSCs provide personnel, environmental, and
product protection. Airflow is drawn into the front grille of the cabinet, providing personnel
protection. In addition, the downward flow of HEPA-filtered air provides product protection
by minimizing the chance of cross-contamination across the work surface of the cabinet.
Because cabinet exhaust air is passed through a certified HEPA filter, it is particulate-free
(environmental protection), and may be recirculated to the laboratory (Type A1, A2, and C1
BSCs) or discharged from the building through a canopy (formerly thimble) connected to
the building exhaust.
It is possible to exhaust the air from a Type A1, A2, or C1 cabinet outside of the building.
When using volatile toxic chemicals, removal of the exhaust from the laboratory is required.
However, it must be done in a manner that does not alter the balance of the cabinet
exhaust system, thereby disturbing the internal cabinet airflow. The proper method of
connecting a Type A1, A2, or C1 cabinet to the building exhaust system is through use of a
canopy connection, which provides a small opening or air gap (usually one inch) around
the cabinet exhaust filter housing (Figure 4). The airflow of the building exhaust must be
sufficient to maintain the flow of room air into the gap between the canopy unit and the
filter housing. The canopy must be removable or be designed to allow for operational testing
of the cabinet and must have an alarm to indicate insufficient airflow through the canopy.
Class II, Type A1 or A2 cabinets should never be direct-connected to the building exhaust
system. Fluctuations in air volume and pressure that are common to all building exhaust
systems can make it difficult to match the airflow requirements of the cabinet.
Type B cabinets must be direct-connected, preferably to a dedicated, independent exhaust
system. Fans for laboratory exhaust systems should be located at the terminal end of the
ductwork to avoid pressurizing the exhaust ducts. A failure in the building exhaust system
may not be apparent to the user, as the supply blowers in the cabinet will continue to
operate. A pressure-independent monitor and alarm must be installed to provide a warning
and shut off the BSC supply fan, should a failure in exhaust airflow occur. Since this feature
is not supplied by all cabinet manufacturers, it is prudent to install a sensor such as a flow
monitor and alarm in the exhaust system as necessary. To maintain critical operations,
laboratories using Type B BSCs should connect the exhaust blower to the emergency power
supply.
HEPA filters are effective at trapping particulates, and thus infectious agents, but do not
capture volatile chemicals or gases. Only canopy-connected Type A1, A2, and C1 or Types
B1 and B2 BSCs should be used when working with volatile, toxic chemicals, but amounts
must be limited.

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The mechanical design and air balance testing of the laboratory exhaust system for Class
IIB BSCs must use Concurrent Balance Values (CBV) as published in the NSF/ANSI 49
Standard—a standard that describes the requirements for the construction and function of
a Class II BSC. When a BSC is certified to NSF/ ANSI 49-2018, the standard method is to
set the inflow velocities using a direct inflow measurement (DIM) hood. When the HVAC
system air balance is set, it is typically done based on duct traverse air measurements taken
at some point in the ductwork. The two groups are attempting to measure and set the BSC
inflows, but each is using a different type of instrument and taking airflow measurements at
different locations. There can be a difference in air volume measurements between the two.
The CBV provides each discipline the information they require to properly test or certify the
BSC.
All Class II cabinets are designed for work involving microorganisms assigned to Risk
Groups (RG) 1–4. Class II BSCs provide the microbe-free work environment necessary
for cell culture propagation and also may be used for the formulation of nonvolatile
antineoplastic or chemotherapeutic drugs. Class II BSCs may be used with organisms
requiring BSL-4 containment in a BSL-4 suit laboratory by a worker wearing a positive-
pressure protective suit. Maximum containment potential is achieved only through strict
adherence to proper practices and procedures.
Class II, Type A1 BSC
An internal fan (Figure 3) draws sufficient room air through the front grille to maintain
a minimum calculated or measured average inflow velocity of at least 75 lfm at the face
opening of the cabinet. The supply air flows through a HEPA filter and provides particulate-
free air to the work surface. Airflow provided in this manner reduces turbulence in the work
zone and minimizes the potential for cross-contamination.
 Cytotoxic Drugs Guide

The downward moving air splits as it approaches the work surface; the fan draws part of
the air to the front grille and the remainder to the rear grille. Although there are variations
among different cabinets, this split generally occurs about halfway between the front and
rear grilles and two to six inches above the work surface.
The air is drawn through the front and rear grilles by the internal fan and pushed into the
space between the supply and exhaust filters. Due to the relative size of these two filters,
approximately 30% of the air passes through the exhaust HEPA filter and 70% recirculates
through the supply HEPA filter back into the work zone of the cabinet. Most Class II, Type
A1, and A2 cabinets have dampers to modulate this division of airflow.
Since 2010, a Class II A1 cabinet may not have a potentially contaminated positively
pressurized plenum that is not surrounded by a negatively pressurized plenum. This change
has minimized the difference between an A1 and A2 cabinet to the inflow velocity.
Class II, Type A2 BSC (Formerly called A/B3)
Only when this BSC (Figure 3) is ducted to the outdoors does it meet the requirements of
the former Class II, Type B3. The designation Class II B3 is no longer used. The Type A2
cabinet has a minimum calculated or measured inflow velocity of 100 lfm. All positive-
pressure contaminated plenums within the cabinet are surrounded by a negative air pressure
plenum thus ensuring that any leakage from a contaminated plenum will be drawn into the
cabinet and not released to the environment. Small quantities of volatile toxic chemicals
or radionuclides can be used in a Type A2 cabinet only if it exhausts to the outside via a
properly functioning canopy with exhaust alarm.

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Occupational Health and Safety

Class II, Type B1 BSC

Some biomedical research requires the use of small quantities of toxic volatile chemicals,
such as organic solvents or carcinogens. Carcinogens used in cell culture or microbial
systems require both biological and chemical containment.
The Class II, Type B cabinet originated with the National Cancer Institute (NCI)-designed
Type 212 (later called Type B) BSC (Figure 5a) and was designed for manipulations of small
quantities of toxic volatile chemicals with in vitro biological systems. The NSF/ANSI 49-2018
definition of Type B1 cabinets8 includes this classic NCI design Type B; cabinets without a
supply HEPA filter located immediately below the work surface (Figure 5b); and those with
exhaust/recirculation downflow ratios other than 70/30%.

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 Cytotoxic Drugs Guide

The cabinet supply blower draws room air (plus a portion of the cabinet’s recirculated
air) through the front grille and through the supply HEPA filter located immediately below
the work surface. This particulate-free air flows upward through a plenum at each side of
the cabinet and then downward to the work area through a backpressure plate. In some
cabinets, there is an additional supply HEPA filter to remove particulates that may be
generated by the blower-motor system.
Room air is drawn through the face opening of the cabinet at a minimum measured inflow
velocity of 100 lfm. As with the Type A1 and A2 cabinets, there is a split in the down-
flowing air stream just above the work surface. In the Type B1 cabinet, approximately 70%
of the downflow air exits through the rear grille, passes through the exhaust HEPA filter, and
is discharged from the building. The remaining 30% of the downflow air is drawn through
the front grille. Since the air that flows to the rear grille is discharged into the exhaust
system, activities that may generate toxic volatile chemical vapors or gases should be
conducted toward the rear of the cabinet work area.
Class II, Type B2 BSC
This BSC is a total-exhaust cabinet; no air is recirculated within it (Figure 6). This cabinet
provides simultaneous primary biological and chemical (small quantity) containment.
Consideration must be given to the chemicals used in BSCs as some chemicals can destroy
the filter medium, housings, and/or gaskets causing loss of containment. The supply blower
draws either room or outside air in at the top of the cabinet, passes it through a HEPA
filter and down into the work area of the cabinet. The building exhaust system draws air
through both the rear and front grilles, capturing the supply air plus the additional amount
of room air needed to produce a minimum calculated or measured inflow face velocity of
100 lfm. All air entering this cabinet is exhausted and passes through a HEPA filter (and

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Occupational Health and Safety

perhaps some other air-cleaning device, such as a carbon filter, if required, for the work
being performed prior to discharge to the outside). This cabinet exhausts as much as 1,200
cubic feet per minute of conditioned room air making this cabinet expensive to operate.
The higher static air pressure required to operate this cabinet also results in additional costs
associated with heavier gauge ductwork and higher capacity exhaust fan. Therefore, the
need for a Class II, Type B2 should be justified by the risk assessment of the research to be
conducted.

Should the building exhaust system fail, the cabinet will be pressurized, resulting in a flow
of air from the work area back into the laboratory.
Cabinets built since the early 1980s have an interlock system, installed by the manufacturer,
to prevent the supply blower from operating whenever the exhaust flow is insufficient;
systems can be retrofitted. Exhaust air movement should be monitored by a pressure-
independent device, such as a flow monitor.
Class II, Type C1 BSC
This BSC is similar to a Type B1 BSC in that it has a special region of the work area intended
for work with toxic volatile chemicals that are exhausted from the building (Figure 7a).
However, it also has an internal exhaust blower that allows the BSC to be either room
recirculated if no volatile toxic chemicals or vapors are present or canopy-connected with
an exhaust alarm if volatile toxic chemicals are used. Room air is drawn through the face
opening of the cabinet at a minimum measured inflow velocity of 100 lfm. The down-
flowing air stream just above the work surface is split by a specific grille pattern with a
portion of 70% to be exhausted and the remaining 30% recirculated. If the air that flows

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 Cytotoxic Drugs Guide

over the specific region is discharged into the exhaust system, activities that may generate
toxic, volatile chemicals or gases must only be conducted in that area of the cabinet work
zone if connected to a properly functioning canopy with alarm (Figure 7b). If canopy
connected during a building system failure, the BSC must be either interlocked with the
cabinet blower(s) alarm to shut off the cabinet or, if using a sealed and tested duct system
and if permitted by a chemical risk assessment, may continue to operate for up to five
minutes pressurizing the duct and indicating the time remaining before the BSC is shut off.

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Occupational Health and Safety

Special Applications Class II BSCs can be modified to accommodate special tasks. For
example, the front sash can be modified by the manufacturer to accommodate the eyepieces
of a microscope. The work surface can be designed to accept a carboy, a centrifuge, or
other equipment that may require containment. A rigid plate with openings for the arms
can be added if needed. Good cabinet design, microbiological aerosol tracer testing of the
modification, and appropriate certification are required to ensure that the basic systems
operate properly after modification.
The Class III BSC
The Class III BSC (Figure 8) was designed for work with highly infectious microbiological
agents and the conduct of hazardous operations and provides maximum protection for the
environment and the worker. It is a gas-tight (no leak greater than 1x10-7 cc/sec with 1%
test gas at three inches pressure water gauge) enclosure with a non-opening view window.
Access for passage of materials into the cabinet is through a dunk tank that is accessible
through the cabinet floor or a double-door pass-through box (e.g., antechamber, autoclave)
that can be decontaminated between uses. Reversing that process allows materials to be
removed from the Class III BSC safely. Both supply and exhaust air are HEPA-filtered on a
Class III cabinet. Exhaust air must pass through two HEPA filters, or a HEPA filter and an
air incinerator, before discharge directly to the outdoors. Class III cabinets are not exhausted
through the general laboratory exhaust system. Using a dedicated exhaust system reduces
the risk of outside ventilation influences on Class III containment performance. Airflow is
maintained by an exhaust system exterior to the cabinet, which keeps the cabinet under
negative pressure (minimum of 0.5 in water gauge). This level of negative pressure is
required to minimize risk and maintain containment if a breach occurs such as holes or
tears in the glove system.

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 Cytotoxic Drugs Guide

Long, heavy-duty rubber gloves are attached in a gas-tight manner to ports in the cabinet
to allow direct manipulation of the materials isolated inside. Although these gloves restrict
movement, they prevent the user’s direct contact with the hazardous materials. The trade-
off is clearly on the side of maximizing personal safety. Depending on the design of the
cabinet, the supply HEPA filter provides particulate-free, albeit somewhat turbulent, airflow
within the work environment. Laminar or uniform airflow is optional but not a typical
characteristic of a Class III cabinet.
Several Class III BSCs can be joined together in series to provide a larger work area.
Such cabinet lines are custom-built; the equipment installed in the cabinet series (e.g.,
refrigerators, small elevators, shelves to hold small animal cage racks, microscopes,
centrifuges, incubators) is generally custom-built as well.

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Cytotoxic Drugs Guide 23

Cytotoxic Drugs Guide
2021

For more information, please contact the Ministry of Labour Relations and Workplace Safety
Occupational Health and Safety Division at:

Regina
300 - 1870 Albert Street
REGINA, CANADA S4P 4W1
Saskatoon
8th Floor, 122 3rd Avenue North
SASKATOON, CANADA S7K 2H6
Toll Free
1-800-567-7233

saskatchewan.ca