Antineoplastic Agents Profile

OTHERS  MULTIPLE CLASSIFICATIONS (IARC 1, 2A, 2B)

Numerous IARC Monographs (details under General Information)

Antineoplastic Agents Profile

QUICK SUMMARY

  • A group of drugs that are used to treat various cancers
  • Associated cancers: Cancers of the breast, lung, ovary, liver, and bladder; cancers of the hematopoietic system
  • Most important routes of exposure: Inhalation, skin contact, ingestion, needle stick injury
  • Uses: Prevent the growth and spread of tumor cells
  • Occupational exposures: Approx. 75,000 Canadians are exposed at work, primarily pharmacy staff (pharmacists, technicians, and assistants) and nurses
  • Environmental exposures: Via drinking water, results are inconclusive; also from cancer treatment for patients
  • Fast fact: Antineoplastic agents are increasingly used as treatments for cancer and other conditions.

General Information

Antineoplastic agents, also referred to as chemotherapy drugs or cytotoxic drugs, are the most common type of systemic drug therapy to treat cancer.[1] These drugs interfere with cancer cells’ ability to grow and spread in a variety of ways. They are administered to treat chemo-sensitive cancers (e.g. testicular cancer), as adjuvant therapy (i.e. in conjunction with surgery or radiation), as maintenance therapy (i.e. to prevent relapse and improve survival), or as palliative treatment (i.e. to reduce symptoms and improve quality of life).[1]

Different antineoplastic agents have been classified by the International Agency for Research on Cancer (IARC) as Group 1 (carcinogenic to humans), Group 2A (probably carcinogenic to humans), or Group 2B (possibly carcinogenic to humans) based on varying strengths of evidence of carcinogenicity in animal and human studies, as well as mechanistic considerations.[2,3,4,5,6,7]

A number of adverse health effects are associated with exposure to antineoplastic agents in humans and animals. These include gastrointestinal problems, kidney damage, neurotoxicity, bone marrow suppression, hair loss, and reproductive problems after long-term use.[8]

In addition, patients receiving antineoplastic agents as therapeutic treatments are at increased risk of cancer and other health outcomes. CAREX Canada does not review this exposure circumstance because these treatments are often a necessary medical intervention with tangible benefits for patients. Conversely, workers handling antineoplastic agents are at risk of adverse health outcomes with no positive impact on their well-being.

IARC Classification of antineoplastic agents[9,10]

IARC Classification Group Antineoplastic Agent
1 (Carcinogenic to humans) Arsenic trioxide
Melphalan 
Thiotepa 
Busulfan
Chlorambucil 
Cyclophosphamide
Etoposide
Tamoxifen
2A (Probably carcinogenic to humans) Azacitidine
Cisplatin
Procarbazine
Teniposide
Carmustine
Adriamycin
Lomustine
2B (Possibly carcinogenic to humans) Amsacrine
Streptozotocin
Daunomycin
Bleomycin
Mitomycin
Mitoxantrone

Regulations and Guidelines

Occupational Exposure Limits (OEL)

No occupational exposure limits for Canada or any other international bodies were located.

Classifications under the Canadian Environmental Protection Act (CEPA)

Agent Designation Date added
Adriamycin DSL* – high priority substance with lowest potential for exposure 2006[11]
Chlorambucil DSL* – high priority substance 2004[11]
Cisplatin NDSL** 1998[11]
Cyclophosphamide DSL* – high priority substance 2004[11]
Melphalan DSL* – high priority substance 2004[11]
*The Domestic Substances List (DSL) is an inventory of approximately 23,000 substances manufactured in, imported into, or used in Canada on a commercial scale. The DSL is the sole standard against which a substance is judged to be “new” to Canada.[12,13]

**The Non-Domestic Substances List (NDSL) is an inventory of substances included in the EPA’s Toxic Substances Control Act (TSCA), but not on Canada’s DSL.[13]

Adriamycin, chlorambucil, cisplatin, cyclophosphamide, and melphalan were not included in other Canadian government chemical listings reviewed.[14]

Main Uses

Antineoplastic agents are drugs used to treat cancer and other conditions such as rheumatoid arthritis and psoriasis.[15]

Canadian Production and Trade

Several companies import antineoplastic agents, including: Janssen Pharmaceutical Inc., Hoffman-La Roche Ltd., and Sanofi-Aventis Canada Inc.[16] The total value of imports is approximately 1.2 billion Canadian dollars.[16]

Occupational Exposures Overview

Occupational exposure to antineoplastic agents may occur directly via dermal contact, inhalation, ingestion, accidental injection, or indirectly via contact with contaminated surfaces and objects.[17] This can occur in hospitals, where antineoplastic agents are handled in shipping and receiving areas, prepared in pharmacies, administered in wards, and contacted through sanitary services such as laundry, cleaning, and waste handling.[18] Exposure can also occur outside of hospitals in workplaces such as community pharmacies, veterinary care facilities, and home care settings.[19]

CAREX Canada estimates that approximately 75,000 Canadians are exposed to antineoplastic agents at work; most exposures occur in the moderate category. In addition, over 75% of exposed workers are female.

Exposure to antineoplastic agents was not estimated by industry per se, but by setting. The largest number of workers exposed were in non-hospital settings, with a substantial proportion working in hospitals.

Occupations at risk of exposure to antineoplastic agents are community pharmacy workers (including pharmacists, technicians, and assistants), hospital nurses (including nurses and licensed nurse practitioners), and hospital pharmacy workers (including pharmacists, technicians, and assistants).

For more information, see the occupational exposure estimate for antineoplastic agents.

Sources

1. Pham T, Holle L. Cancer Therapy: Prescribing and Administration Basics. Burlington, MA: Jones & Bartlett Learning. (2015)
2. International Agency for Research on Cancer (IARC). IARC Monograph, Volume 26 (1987) (PDF)
3. International Agency for Research on Cancer (IARC). IARC Monograph, Volume 100C (2012) (PDF)
4. International Agency for Research on Cancer (IARC). IARC Monograph, Volume 100A (2012) (PDF)
5. International Agency for Research on Cancer (IARC). IARC Monograph, Volume 50 (1990) (PDF)
6. International Agency for Research on Cancer (IARC). IARC Monograph, Supplement 7 (1987) (PDF)
7. International Agency for Research on Cancer (IARC). IARC Monograph, Volume 76 (2000) (PDF)
8. U.S. National Library of Medicine. Hazardous Substances Data Base (HSDB)
9. International Agency for Research on Cancer (IARC). Agents Classified by the IARC Monographs, Volumes 1–117 (2016) (PDF)
10. National Institute for Occupational Safety and Health (NIOSH). List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings (2016)
11. Environment and Climate Change Canada. Domestic Substance list: Search Engine for Chemicals, biochemicals, polymers and biopolymers published in the Canada Gazette (2016) (Search terms: ‘23214-92-8’; ‘305-03-3’; ‘15663-27-1′; ’50-18-0’; ‘148-82-3’)
12. Environment and Climate Change Canada. Domestic Substances List (2015) (PDF)
13. Environment and Climate Change Canada. Search Engine for Chemicals and Polymers (2013) (Search term: “23214-92-8 and 15663-27-1”)
14. Environment and Climate Change Canada. CEPA List of Toxic Substances (1999)
15. National Toxicology Program (NTP). 14th Report on Carcinogens for Chlorambucil (2016)
16. Innovation, Science and Economic Development Canada. Canadian Importers Database (2013)
17. National Institute for Occupational Safety and Health (NIOSH). NIOSH Workplace Safety and Health Topic: Occupational Exposure to Antineoplastic Agents (2015)
18. Hon C-Y, Teschke K, Chu W, Demers P, Venners S. “Antineoplastic drug contamination of surfaces throughout the hospital medication system in Canadian hospitals.” Journ of Occup and Environ Hygiene 2013;10(7):374–83.
19. Meijster T, Fransman W, Veldhof R, Kromhout H. “Exposure to antineoplastic drugs outside the hospital environment.” Ann Occup Hyg 2006;50(7): 657–64.

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