Evaporation behavior of antineoplastic drugs: relevance of gaseous & airborne particle inhalation
1 Hospital
Pharmacy of Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic
(Research Center for Environmental Chemistry and Ecotoxicology), Masaryk University, Kamenice 3, Brno,
Czech Republic
Odraska P.1,2, Dolezalova L.1, Gorna L.1, Vejpustkova R.1 and Blaha L.
2 RECETOX
1,2
Discussion and conclusions
Only minor non-significant evaporation of four of the studied compounds (cisplatin, cyclophosphamide, fluorouracil
and paclitaxel) was observed (Fig. 1).
About 40% of doxorubicin (loaded at 60 ng/cm2) evaporated within 12 hours (Fig. 2).
.
Previous studies focused on evaluation of VP of ADs have shown
that evaporation/sublimation of these agents can be expected (see
comparison in Table 1).
1.0
DX
FU
CP
PX
Figure 1
30%
absorbed
12h
Start
Figure 3A
K25
K7
20°C
7°C
varianta
Ve
nt
i la
te
d
Evaporation of doxorubicin (12 hours)
Substance
Vapour pressure at 20°C
[Pa]
Fig. 3B
20°C
K25
450
350
0h
7°C
varianta
Glass
400
K7
Start
Fig. 3C
12h
20°C
K25
K7
7°C
varianta
lo
se
d
Start
12h
16*10 -2
23*10 2
This experimental study confirms that at least some commonly used
ADs (such as doxorubicin) can evaporate under laboratory
temperatures and conditions. Interestingly, our results do not fully
correspond to the measured vapour pressure values: doxorubicin
(VP = 1 mPa) was expected to evaporate less than for example
paclitaxel (VP = 23 mPa; no evaporation for paclitaxel observed).
Significant absorption of cyclophosphamide by PVC corresponds to
relatively easy permeation of this compound through vinyl material
(e.g. gloves and gowns)3. We propose that PVC and related
materials (e.g. linoleum) should be avoided in oncology wards and
pharmacies. These materials may retain ADs and interfere with
efficient decontamination.
500
C
0h
99*10 -3
Mercury
W ater
550
Ve
nt
il.
350
1-23*10 -3
Diethyl phthalate
600
lo
se
d
ng cm-2
Stain. steel
650
C
400
lo
se
d
7°C
C
se
d
lo
C
Ve
n
ti l
at
ed
20°C
450
Concentration (ng cm-2 )
K7
500
lo
se
d
K25
varianta
550
lo
se
d
12h
600
C
0h
650
C
x ±SD
Ve
nt
il.
x ±SE
ng cm-2
x
Concentration (ng cm-2)
evaporated
Start
Figure 2
x ±SE
x ±SD
0h
40%
x
se
d
CS
C
lo
0.0
650
600
550
500
450
400
350
se
d
0.2
C
lo
0.4
-2
start
20°C / ventilated
20°C / closed
7°C / closed
Concentration (ng cm )
Cyclophosphamide absorption by
PVC
0.6
65
60
55
50
45
40
35
30
Table 1: VP of CDs in comparison with some well-known substances
Antineoplastic drugs
0.8
650
60
60
250
150
ng cm-2 ng cm-2 ng cm-2 ng cm-2 ng cm-2
Concentration
[ng cm-2]
Based on the previous measurements of VPs, here we present
experimental studies of evaporation of selected antineoplastic
agents under controlled laboratory conditions (ventilated BSC
cabinet).
1.2
Concentration
[ng cm-2]
Previous studies have shown frequent contamination of working
areas by ADs including contamination of various surfaces (floor,
tables, vials, telephones etc.). However, air contamination by ADs
has been documented sporadically and dermal uptake is
considered the main route of exposure.
On the other hand, presence of ADs in the ambient air has not
been studied in detail, although vapor pressures (VP) of selected
ADs (such as carmustin, cisplatin, cyclophosphamide,
dacarbazine, doxorubicine, etoposide, fluorouracil and paclitaxel)
has been measured and reach up to 22.5mPa at 20 degrees
Celsius (Table 1). For small particles (d = 1 micrometer), these
values are high enough to expect evaporation time in the range of
several seconds to minutes2.
Specific interaction was found between
cyclophosphamide and PVC that absorbed about 30 %
of loaded cyclophosphamide under the laboratory
temperature (Fig. 3A).
Total loss of CDs during 12
hours
1.4
Relative recovery
Handling of antineoplastic drugs (ADs) has possible side adverse
effects such as mutagenicity, teratogenicity or cancerogenicity1.
Health-care personnel handling such agents may be exposed via
several pathways including dermal contact, inhalation (aerosols
or vapours) or unintentional ingestion.
Results
concentration []
Introduction and Aims
Further indoor fate of ADs and their
possible health impacts on
occupationally exposed health-care
personnel should be studied, and
appropriate preventive and protective
measures should carefully be applied.
Materials and methods
Trace amounts of five ADs (fluorouracil (A), doxorubicin (B), cyclophosphamide (C), cisplatin (D), and paclitaxel
(E)) were experimentally dosed on the surfaces of three diferent materials (stainless steel, PVC, glass) and placed
into the biological safety cabinet for 12 hours. After this period the surfaces were sampled, analyzed by HPLC or
AAS and compared with appropriate controls (closed vials kept at room temperature 20°C and/or in refrigerator).
Significant differences were analyzed by non-parametric statistics (Mann-Whitney test, p < 0.05).
References
[1] IARC. Monographs on the evaluation of cancinogenic risk of chemicals to humans: Pharmaceutical
drugs. Lyon, France. [2] Kiffmeyer T, Kube C, Opiolka S, Schmidt KG, Schoppe G, Sessink PJM. The
Pharmaceutical Journal. 2002; 268: 331-337. [3] Wallemacq PE, Capron A, Vanbinst R, Boeckmans E,
Gillard J, Favier B. American Journal of Health-System Pharmacy. 2006; 63(6): 547-556.
Acknowledgement
The research is supported by the Ministry of Education, Czech Republic, project "CYTO", No. 2B06171.