Contaminations chimiques par les anticancéreux en pharmacie hospitalière : Italie
Postes de Sécurité Biologique - Flux laminaires (Italie)
Healthcare personnel handling cytostatic antineoplastic agents may be exposed to these drugs. Exposure may occur through inhalation, skin contact, skin absorption, ingestion, or injection during preparation, administration, and disposal. Since the late ‘70s, occupational exposure to these drugs has been recognized as a potential health hazard.
Since then, several countries have published guidelines and recommendations with the objective to improve operating procedures and safety workplace, and keep exposure levels as low as possible. As a consequence, operating procedures have been improved,biological and environmental monitoring have been used to assess contamination and exposure levels, and a lot of analytical methods have been developed and validated.
In general, the strategy used to prevent or minimize occupational exposure applies a combination of interventions, such as engineering controls, administrative and work practice controls, and personal protective equipment.
In Italy, the National Institute for Occupational Health and Prevention, which is a public reasearch body dealing with occupational and environmental health, has established a Working Group on Antineoplastic Drugs Safe Handling in 1997. Two years later, after further revision and update, that work resulted in the official Italian guidelines, which are consistent with international guidelines.
The main points are :
- the implementation of handling procedures
- use of specialized equipment
- wearing personal protective equipment
- training and education of workers handling ADs or at risk of exposure
- health surveillance
- exposure assessment
- establishment of a registry of hospital personnel exposed to ADs.
Our laboratory mainly works on exposure assessment. Over the last decade, our research activities have focused on the development and validation of new analytical methods for the determination of antineoplastic agents in both biological and environmental samples. A lot of surveys were carried out in several hospitals.
In seven hospitals located in Central Italy, periodic assessments were scheduled to verify continuing compliance with guidelines over a four-years period.
A detailed questionnaire was completed by the personnel working in each department to collect important information about their occupational history, work practices, use of protective measures, etc.
In all hospitals, all therapies were prepared in one central area. An anteroom protected the preparation room. Biological Safety Cabinets (BSCs) with HEPA filters were used. Periodic engineering controls were carried out. Additional equipment, such as closed-system drug-transfer devices, glove bags and needle-less systems were used. Proper personal protective equipment (PPE) was used.
In addition, written safe working policies and procedures were developed in consultation with health and safety representatives. Job instruction, information and training have been provided.
As regards biological monitoring, urine samples were collected at the beginning and at the end shift. When possible, samples were collected in the middle of the shift. All the samples were found to be below the limit of quantitation.
But this doesn’t necessarily mean absence of contamination.
The possible reasons why biological samples are negative are mainly related to pharmacokinetics and metabolism of the investigated drug and to the sensitivity of the analytical method. Some drugs are metabolized so rapidly that we cannot find the parent drug in urine. So, we should search for its metabolite. Nevertheless, metabolites are often unstable or the standards for the analytical measurement are not commercially available, and this puts a limit on our work.
This is the reason why there’s conflicting opinion regarding the value of routine biological tests in this field. It is true that results from biomonitoring are difficult to interpret especially without environmental monitoring data.
We could say that biological monitoring can tell us if contamination occurred, while environmental monitoring can tell us how contamination occurred.
For this reason, the results from both environmental and biological monitoring must be combined.
As regards environmental monitoring, adherence to guidelines has resulted in very low-level exposure. Significant contamination was found on the working tray inside the BSC, as expected, (up to 20.55 microg/dm2 5-FU) and on the outside of drug vials (156 microg/dm2).
Forearm and chest pads were found to be slightly contaminated for CP and 5-FU.
In some departments, low levels were detected on the floors and on the working trays inside the BSC as well as outside the preparation area.
In general, contamination was mainly found on pumps and i.v. tubing in the preparation area.
No air samples was found to be positive.
These results confirm that a cost- effective monitoring regime, including :
- fast and simple sample pre-treatment procedure
- simultaneous determination of the analytes and their metabolites
(e.g. four anthracyclines, gemcitabine + 2,2’- dFdU)
- validated procedure and uncertainty evaluation
- periodic surveys,
is the adequate approach for the collection of reliable exposure data and thus for effective intervention.