Japanese Multi Center Study on Occupational Exposure to Cyclophosphamide
Risks to Health Professionals from Hazardous Drugs in Japan
In Japan, cytostatic drugs are prepared in the hospital ward and the left over drug is disposed without proper measures being taken. In order to examine the contamination conditions related to this, we examined the exposure situation of medical staff and environmental contamination of cytostatic drugs at 6 hospitals across the nation.
(Enviromental study) Regarding the environmental contamination situation of cyclophosphamide, which is cytotoxic and said to be carcinogenic (WHO classification: Class I), we conducted a wipe off study at 6 sites within 2 divisions each of 6 hospitals that handle these drugs. (Staff exposure study) In the same manner as the environmental study, the volume of the unchanged drug excreted in urine was measured. The targets to be measured were doctors, pharmacists as well as nurses and 7 people were measured at each site irrespective of their job. After measuring the volume of each urination, part of it was collected and measured.
(Environmental study) Contamination from cyclophosphamide was found from 50% of the measurement sites, but there was deviation in the degree of contamination among the hospitals. In 3 hospitals, the contamination concentration was below 0.10ng/cm2, although at the other 3 hospitals it was high (CP > 1.00 ng/cm2). The most contaminated sites were the drug preparation areas of the hospital ward and safety cabinets (air file parts).
(Staff exposure study) 276 urine samples were obtained from 41 medical staff. Cyclophosphamide was detected from 90 urine samples of 23 subjects,. There was a large difference in exposure amount between hospitals. High concentrations of cyclophosphamide were detected from the staff of 3 hospitals which indicated continuous exposure. The volume of cyclophosphamide excreted in urine per staff was from 2.7 to 462.8ng/24hr. The range in excretion among hospitals was between 4.6 to 211.2 ng/24hr.
The environmental contamination condition of hospital wards became evident. However, the outpatient chemotherapy center did not have much contamination, may be due to the facilities being relatively new. Also, it is thought as such because a full-time pharmacist is preparing the cytostatic drugs at these facilities. The contamination of the preparation rooms, hospital wards and patient rooms indicate similar levels of contamination as the study results of foreign countries. The drug preparation table of the hospital wards had the highest concentration of contamination and there was indication of contamination from other cytostatic drugs as well. It is thought that this contamination comes from when drugs are moved from a vial by a syringe or when syringes are used to connect to intravenous sets. Therefore, we think that it is necessary to prevent contamination when preparing the cytostatic drugs within the hospital ward. However, it is not that facilities with high environmental contamination increase the chances of staff exposure, but it is thought that the personal protection, such as wearing gloves, of each individual staff is important. The exposure path of staff is unknown. We think that it is necessary to study air samples in order to clarify the exposure path.
There was contamination risk from cytostatic drugs in many departments of the hospital. Therefore, it is necessary to prevent the spreading of contamination by reviewing the daily operation procedures and follow the anti-cancer drug handling guidelines set by the Japanese Society of Hospital Pharmacists. A closed system that prevents scattering at preparation was introduced domestically but it is expensive and difficult to use under the current reimbursement system. Therefore, the multi-dosing of cytostatic drugs along with being kitted with a closed system is desired.