The plungers of the eight syringes tested were contaminated with cyclophosphamide (Table 1) (mean value, 71.5 ng; range, 3.7-445.7 ng). Cyclophosphamide concentration in the solution was 20 mg/mL, which corresponds to a mean volume of 3.6 nL (0.2-22.3 nL).
Contamination reached 50 ng or more in one of three syringes, and about 5 ng in two of three syringes. No relationship was found between the number of in-and-out movements of the plunger and the quantity of cyclophosphamide on the plunger.
The results of the second phase are shown in Tables 2 and 3. Almost no contamination was found when labelled water was used (A). Contamination remained under 1 nL, even after 10 in-and-out pushes, although a slight increase was noted when the number of plunges increased. The contamination of the plungers was consistently greater with the solution of radiolabelled cyclophosphamide than with the pure radiolabelled solution, regardless of the test or the number of in-and-out pushes. This difference became obvious after the first use of the syringe, whether the operator touched the plunger with gloves or not; however, the total contamination of the plungers was more important after the operator had touched the plunger than otherwise, but this difference disappeared after 10 plunges.
Upper and lower surfaces of the plungers (E1 and E2). The contamination of the upper and lower surfaces of the plungers corresponds to the amount of contaminant that could come into contact with the gloves of operators.
- Almost none (90 pL, Table 2) was found with radiolabelled water, regardless of the number of inand-out plunges.
- Contamination increased after only five in-and-out plunges in the test with no contact with the plunger. Little contamination was seen after the first in-and-out plunge, but the amount increased rapidly as a function of the number of plunges; a 50-fold increase was noted between one and 10 plunges (from 0.08 to 3.99 nL).
Our results show that cyclophosphamide infiltrates onto the plungers of syringes, suggesting that the general procedure for the manipulation of cytotoxic agents should be modified. Syringes should not be used throughout the day, but should often be replaced with new ones. Systematic replacement after each manipulation is not justified, as we have shown that leakage onto the plunger occurs only after a syringe has been used several times.
These results also call into question the use of twopiece syringes for reconstituting antineoplastic drugs, as these syringes are less watertight than three-part syringes. This study may lead, as was the case for gloves, to establishing recommendations for the use of certain syringes for the manipulation of cytotoxic agents.
The infiltration onto the plunger is higher with the cyclophosphamide solution than with labelled water, and the quantity increases with the number of uses of the syringe. We suppose that the cyclophosphamide solution itself reacts with the joint or the syringe to ease its way onto the plunger. Initial investigations have shown that the acid pH of the cyclophosphamide solution may affect the silicone used to lubricate the syringe.
The finding that cyclophosphamide infiltrates onto the plungers of syringes further accounts for the contamination of gloves, as well as flasks, during drug manipulation,5,6 even when no handling error is made. The different amounts deposited on the upper and lower surfaces of the plunger in the various tests (either when operators touched the plunger on sampling cyclophosphamide or when they did not) indicate that up to 10.2-53.4 ng of the drug may contaminate the gloves of operators after 5-10 in-and-out plunges (Table 3). This contamination, when repeated all day and going unrecognized, or when not efficiently dealt with, might contribute to the occupational exposure of operators.