Cyclophosphamide - CAREX Canada

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					 CARCINOGEN PROFILE


Cyclophosphamide                                                         Main Uses
CAS No. 50-18-0                                                        •	 Cyclophosphamide	is	a	drug	used	to	treat	cancer	and	other	
                                                                          medical conditions (2).
                                                                       	 •	 It	may	be	used	alone	or	in	combination	with	other	
                                                                            chemotherapy medications (2).

                                                                         Use in Canada
                                                                       •	 In	Canada,	cyclophosphamide	is	marketed	for	human	use	as	
                                                                          an intravenous injection or tablets for oral consumption (7).
                                                                       •	 In	2007,	a	study	of	cancer	risks	among	nurses	in	British	
                                                                          Columbia found cyclophosphamide to be the most frequently
                                                                          used alkylating agent (a type of chemotherapeutic drug).
                                                                       	 •	 Of	the	units	polled	in	this	research,	44%	of	oncology,	80%	
                                                                             of	pharmacies	and	5%	of	other	departments	reported	using	
                                                                             cyclophosphamide	(8).
Wikimedia Commons Photo: Cyclophosphamide (1)                          Searches of the MSDS and Health Canada Drug Product databases
IARC Monograph Vol. 26, Supplement 7 (1987)                            yielded the following results on current usage of cyclophosphamide
(Group 1)                                                              in Canada:


                                                                         DAtAbASe            SeARCh teRM               ReSult
General Information
                                                                         CCOHS (9)           ‘cyclophosphamide’        4 MSDS
Cyclophosphamide is the generic name for a drug used in
chemotherapy and exists as a white crystalline powder (2). It may
also be referred to by its trade names, such as Cytoxan or Neosar        DIStRIbutoR         loCAtIoN                  MANufACtuRe
(3). There are numerous other synonyms and product names; see            (7)                                           loCAtIoN
HSDB for more information (3).                                           1. Bristol-Myers    Montreal, QC              Unconfirmed*
                                                                         Squibb Canada
Cyclophosphamide has been classified by IARC as a Group 1
carcinogen (4), with a well-established link to leukemia and bladder     2. Baxter           Mississauga, ON           Unconfirmed*
                                                                         Corporation
cancer in humans (2). Other health effects experienced by patients
taking cyclophosphamide include digestive problems and nausea,         *Manufacturing locations were deemed private by the company.
hair loss, temporary sterility, and bone marrow suppression (3).

CAREX Canada ranks cyclophosphamide as a Group A (immediate              Occupational Exposures
high priority) for occupational settings, targeting people who may     •	 Occupational	exposure	to	cyclophosphamide	may	occur	via	
be exposed to the drug at work (i.e. nurses and pharmacists),             inhalation or dermal exposure (2).
rather than those who are prescribed the drug for therapeutic use.     •	 Probable	exposure	scenarios	in	Canada	are	in	hospitals	and	are	
Prioritization for pharmaceuticals was based on the carcinogenicity       limited to handling in wholesale pharmacies, patient handling,
of the substance (only IARC Group 1 and 2A drugs were considered),        sanitary	and	similar	services,	research,	and	education	(8).
and whether the drug is registered for use in Canada.
                                                                       Nurses
Regulations and Guidelines                                             •	 In	2006,	CIHI	(the	Canadian	Institute	for	Health	Information)	
No occupational exposure limits for Canada or any other                   estimated	that	68	Licensed	Practical	Nurses	(LPNs)	and	2,975	
international bodies were located.                                        Registered Nurses (RNs) worked in the oncology areas of
                                                                          Canadian hospitals (10) and thus may have been exposed
Canadian Agencies/Organizations
                                                                          to chemotherapeutic drugs (including cyclophosphamide).
  AGeNCy             DeSIGNAtIoN /PoSItIoN            yeAR              The number of nurses potentially exposed to cyclophosphamide
                                                       (Ref)              by province is shown in the following table.
  Health Canada       DSL – high priority                2004
                      substance (added under             (5)
                      the Food and Drug Act)*
   CEPA               Not included                       (6)


*Cyclophosphamide and several other pharmaceuticals were added to
the DSL via an amendment in 2004 (5).
Nursing Oncology Workforce by Province/Territory 2006 (10)                               Preliminary estimates of the number of BC and ON workers
                                                                                         exposed to cyclophosphamide were prepared in a pilot phase
                            RN                      lPN                                  of the current project.
  Canada                    2,975                   68
  NL                        63                      0                                    CAREX Canada Pilot Project Estimates
  PE                        **                      *
                                                                                                               NuMbeR of
  NS                        206                     **                                         PRoVINCe                             PRIMARy
                                                                                                               woRkeRS
                                                                                                                                    INDuStRy
  NB                        128                     12                                                         exPoSeD
  QC                        1,345                   0
                                                                                               ON                 900
  ON                        0                       0                                                                               Health Care
  MB                        139                     0                                          BC                 300
  SK                        174                     18
                                                                                               exPoSuRe DeSCRIPtIoN
  AB                        511                     8
  BC                        396                     15                                         Exposures likely in hospital settings
  YT                        *                       0
                                                                                               Handling in wholesale pharmacies, handling by nurses
  NT                        0                       0                                          (mixing, administering to patient, patient handling, disposal
  NU                        ^                       ..                                         of waste, accidental spills), sanitary and similar services
                                                                                               (waste collection and disposal), research and education
* Value suppressed for privacy; cell value is from 1 to 4.                                     (research purposes)
** Value suppressed for privacy; cell value is ≥5.
^ NT and NU data are combined for 2006.
.. Data not currently collected
Values expressed as “0” may be due to classification differences                                 SouRCeS

Pharmacists and Pharmacy Technicians                                                     1.      Wikimedia Commons Photo: Cyclophosphamide
                                                                                                 http://upload.wikimedia.org/wikipedia/commons/a/aa/
•	 Pharmacists	and	pharmacy	technicians	are	potentially	exposed	to	
                                                                                                 Cyclophosphamide-3D-balls.png
   chemotherapeutics when they prepare the drugs for patient use.
•	 A	report	by	Eli	Lilly	on	hospital	pharmacies	in	Canada	(for	2005/06)	                 2.      NTP 11th report on carcinogens for Cyclophosphamide (2005)
   reports the number of hospitals with in-house pharmacies                                      http://ntp-server.niehs.nih.gov/ntp/roc/eleventh/profiles/s052cycl.pdf

   performing hematology and oncology functions for the whole                            3.      Hazardous Substances Database
   country (11). This data is presented in the table below.                                      http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB (Search term:
                                                                                                 ‘cyclophosphamide’)
Number of Pharmacies with clinical Hematology/
Oncology Services 2005/6 (11)                                                            4.	     IARC	monograph	summary,	Volume	26	Supplement	7	(1987)
                                                                                                 http://monographs.iarc.fr/ENG/Monographs/suppl7/suppl7.pdf
                                      ReGIoNS of CANADA                                  5.      Health Canada’s Prioritization of the DSL (2004)
                                                                                                 http://www.hc-sc.gc.ca/ewh-semt/contaminants/existsub/categor/_
                           All       bC        PR        oN        QC     Atl                    result_substance/index-eng.php
  All hospitals             142      20        20        45        42      15            6.      CEPA List of Toxic Substances (1999)
  surveyed                                                                                       http://www.ec.gc.ca/TOXICS/EN/mainlist.cfm?par_actn=s2
  Outpatient                118      17        14        32        40      15
                                                                                         7.      Health Canada Drug Product Database
  pharmacy*^
                                                                                                 http://205.193.93.51/dpdonline/startup.do?applanguage=en_CA
  Inpatient                 116      16        15        34        39      12                    (Search Term: cyclophosphamide as active ingredient)
  pharmacy
                                                                                         8.	     Ward	et	al.	2007.	Mortality	and	Cancer	Incidence	in	a	cohort	of	
                                                                                                 Registered Nurses From British Columbia, Canada. American Journal
Note: YK, NT, and NU were not included in the report.
                                                                                                 of	Industrial	Medicine.	50:892–900.	
PR = Prairie provinces (AB, SK, MB)
                                                                                                 http://www3.interscience.wiley.com/cgi-bin/fulltext/116317545/
ATL = Atlantic provinces (NB, NS, NL, PE)
                                                                                                 PDFSTART
* Inpatients are patients who are admitted to hospital. Outpatients visit the hospital
for treatment, but are not admitted. There could be minor differences in the types of    9.      MSDS database of the CCOHS
drugs prepared by workers in these different pharmacies (i.e. IV drugs are likely used           http://ccinfoweb.ccohs.ca/msds/search.html
more for inpatients), therefore we differentiate this information in the table.
^ Some hospitals employ either a pharmacist or a pharmacy tech or both.                  10.     CIHI, 2006. 2006 Workforce Trends Health Human Resources Database
                                                                                                 http://secure.cihi.ca/cihiweb/dispPage.jsp?cw_page=statistics_results_
•	 The	same	Eli	Lilly	report	found	that,	across	Canada,	there	were	                              topic_nurses_e&cw_topic=Health%20Human%20Resources&cw_
   94 pharmacists working in hematology/oncology outpatient                                      subtopic=Nurses

   pharmacies, and 91 in inpatient pharmacies.                                           11.     Eli Lilly Canada. 2007. 2005/06 Hospital Pharmacy in Canada Report.
•	 Pharmacy	technicians	compose	approximately	47%	of	the	                                        http://www.lillyhospitalsurvey.ca/hpc2/content/2006_report/2005_
   average	hospital	pharmacy	staff,	ahead	of	pharmacists	at	40%	                                 06_full2.pdf
   (11). Therefore, the number of pharmacy technicians exposed
   to chemotherapeutic drugs can be estimated as being slightly
   higher than the number of pharmacists.



CARCINOGEN PROFILE: Cyclophosphamide
Published January 2009
updated february 2010


We are CAREX Canada, a research unit based in the School of
Environmental Health in the University of British Columbia and funded by
Health Canada through the Canadian Partnership Against Cancer. We are
developing estimates of the number of Canadians exposed to carcinogens
in workplace and community environments. These estimates have been
compiled to the best of our ability using the data, the facilities and other
resources available to us and are for general information only. While every
effort has been made to ensure that this information is accurate and current,
we assume no responsibility for errors, omissions or outdated information
provided on this fact sheet. This information is not intended to serve as
medical advice, diagnosis, treatment nor care, and should not replace proper
consultation with healthcare professionals. Consult a qualified healthcare
professional before making medical decisions or if you have questions about
your individual medical situation. The views expressed herein represent the
views of CAREX Canada.




CAREX Canada
School of Environmental Health
University of British Columbia
3rd Floor — Library Processing Center
2206 East Mall
Vancouver, BC, V6T 1Z3
Canada

T.	 604-822-0837	
F.	 604-822-9588	
E. info@carexcanada.ca

www.carexcanada.ca




CARCINOGEN PROFILE: Cyclophosphamide

				
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