Effects of wound dressings containing silver on skin and immune cells.

Wound dressings with silver have been shown to be cytotoxic in vitro. However, the extrapolation of this cytotoxicity to clinical settings is unclear. We applied dressings with various forms of silver on porcine skin ex vivo and investigated silver penetration and DNA damage. We assessed antimicrobial efficacy, cytotoxicity to skin cells, and immune response induced by the dressings. All dressings elevated the DNA damage marker γ-H2AX and the expression of stress-related genes in explanted skin relative to control. This corresponded with the amount of silver in the skin. The dressings reduced viability, induced oxidative stress and DNA damage in skin cells, and induced the production of pro-inflammatory IL-6 by monocytes. The oxidative burst and viability of activated neutrophils decreased. The amount of silver released into the culture medium varied among the dressings and correlated with in vitro toxicity. However, antimicrobial efficiencies did not correlate strongly with the amount of silver released from the dressings. Antimicrobial efficiency and toxicity are driven by the form of silver and the construction of dressings and not only by the silver concentration. The damaging effects of silver dressings in ex vivo skin highlight the importance of thorough in vivo investigation of silver dressing toxicity.

Association of surface contamination by antineoplastic drugs with different working conditions in hospital pharmacies.

This study investigates the surface contamination levels of cyclophosphamide and platinum (a marker of platinum-containing drugs) in storage and preparation areas of hospital pharmacies and their relationship to working conditions surveyed by questionnaire. In total, 259 wipe samples were collected in 13 hospital pharmacies over 4 sampling campaigns. After sample extraction with acetate buffer, cyclophosphamide and platinum were determined using high-performance liquid chromatography-tandem mass spectroscopy (HPLC-MS/MS) and inductively coupled plasma mass spectrometry (ICP-MS). Depending on the sampling spot and campaign, median concentrations ranged from <2 to 61 pg/cm(2) and from <0.2 to 6.9 pg/cm(2) for cyclophosphamide and platinum, respectively. Statistical evaluation of monitoring data revealed that the contamination level was significantly influenced by laboratory throughput (expressed as number of chemotherapies prepared per week), personnel expertise (ie, participation of pharmacists with academic education in drug admixture activities), and surface material.

Evaluation of the efficacy of additional measures introduced for the protection of healthcare personnel handling antineoplastic drugs.

OBJECTIVES: Due to their adverse effects, antineoplastic drugs are considered as a potential health risk to healthcare personnel. The objective of the study was to compare the surface contamination level of the conventional preparation room and outpatient clinic before and after the implementation of a set of additional protective measures. METHODS: The measures were targeted at eliminating potential sources of environmental contamination, and modification of the cleaning procedure. The measures introduced into the preparation room consisted of (i) the introduction of manual cleaning of drug vials before they enter the preparation room, (ii) the modification of the routine cleaning procedure performed at the end of each working day (i.e. shifting the cleaning of the isolators as the most contaminated objects from the beginning of the cleaning process to the end), and (iii) the introduction of regular cleaning of the work table every 2 h. The measures introduced into the outpatient clinic consisted of (i) replacement of the standard infusion sets with multichannel sets for safe drug administration, (ii) the introduction of self-cleaning seats to the patient lavatories supporting hygienic and contamination-free seated urination, and (iii) replacement of standard infusion stands with wall-mounted stands, supporting the regular and proper cleaning of the floor beneath. To determine the surface contamination level with antineoplastic drugs, cyclophosphamide and platinum were determined in wipe samples with high performance liquid chromatography with tandem mass spectrometry and inductively coupled plasma mass spectrometry. RESULTS: In the preparation room, depending on the sampling spot and analyte, median concentrations ranged from 5 to 267 pg cm(-2) and from 2 to 368 pg cm(-2) before and after implementation of the measures, respectively. In the outpatient clinic, median concentrations ranged from 5 to 5310 pg cm(-2) and from <0.2 to 574 pg cm(-2) before and after implementation of the measures, respectively. Depending on the sampling spot, median contamination of the outpatient clinic with cyclophosphamide and platinum was reduced by 57-99% and 61-98%, respectively. CONCLUSIONS: The measures implemented in the outpatient clinic were shown to reduce workplace contamination effectively. Therefore, they can be recommended also for other workplaces where antineoplastic drugs are administered. In contrast, measures implemented in the preparation room, where relatively strict regulations had already been adopted before the study, were less effective. To decrease the actual contamination of the preparation room, other protective measures (e.g. closed-system transfer devices) should be considered.

[Determination of airborne and surface contamination with cyclophosphamide at the Masaryk Memorial Cancer Institute, Brno, Czech Republic]. / Sledování prítomnosti cyklofosfamidu ve vnitrním ovzdusí a na povrchu materiálního vybavení Masarykova onkologického ustavu.

Manipulation with cytotoxic drugs (CDs) during the preparation and administration of chemotherapy to cancer patients can potentially lead to contamination of working areas and consequently to occupational exposure of hospital staff. This study aimed to assess the potential of inhalation and dermal contact with CDs. For this purpose, distribution of the marker drug (cyclophosphamide, CP) in the working environment of the Masaryk Memorial Cancer Institute (Czech Republic) was studied. The study determined airborne and surface contamination of the hospital pharmacy and the outpatient clinic. Determination of airborne contamination was based on active stationary sampling of air using a PTFE filter, an impinger filled with distilled water and two solid sorbent tubes (Anasorb 708 and Strata-X) as sampling devices. Surface contamination was determined by the wipe sampling method. The airborne contamination was rare and the concentrations were many times lower than the maximal value calculated from the vapour pressure (0.36 mg/m3 at 20 degrees C). Detectable airborne CP was found in Strata-X samples collected at the outpatient clinic (n = 5, all samples positive at concentrations from 0.3 to 4.3 ng/m3). Surface contamination was determined at 75% of wipe samples (n = 65) with a median concentration of 750 ng/m2. In conclusion, inhalation of CDs seems to be of low importance at our hospital, which is up to the standard specified by current legislation (drug preparation performed in a clean room equipped with negative pressure isolators). The main proportion of contamination was present on the surfaces at all workplaces studied. Consequently, attention should be given to the elimination of the sources of surface contamination and to the prevention of dermal contact with contaminated material.

Utilization of the solid sorbent media in monitoring of airborne cyclophosphamide concentrations and the implications for occupational hygiene.

The main objective of the study was to evaluate the applicability of two solid sorbent media (Anasorb 708 and Strata X), the impinger filled with distilled water and PTFE filters for determination of airborne cyclophosphamide (CP) in the hospital working environment. For this purpose, air contamination of Masaryk Memorial Cancer Institute (Czech Republic) was monitored using the sampling apparatus containing the samplers described above. In addition, the surface contamination was also determined using the wipe sampling technique. During the monitoring, contamination of three different workplaces (storage room, preparation room and outpatient clinic) was studied. Using Strata X solid sorbent tubes, airborne CP was determined in all (n = 5) samples collected at the outpatient clinic over a 5 day monitoring period (concentration range: 0.3-4.3 ng m(-3)). Other samplers (including PTFE filters) did not collect any detectable amount of CP (the limit of detection, LOD ≤ 0.1 ng m(-3)). Negative results detected at filter samples indicate that CP determined at Strata X samples was most probably of gaseous origin. Surface contamination ranged from <2 to 19, <8 to 418 and 133-15,500 pg cm(-2) at the storage room, preparation room and outpatient clinic, respectively. The study showed that evaporation of antineoplastic drugs should not be neglected, albeit the concentrations determined in our study are relatively low. Therefore, proper monitoring of airborne contamination should involve simultaneous sampling of both particle-bonded and gaseous phases. In this way, Strata X sorbent tubes seem to be an effective tool for the sampling of gaseous CP in the indoor air.

Ecotoxicity and genotoxicity assessment of cytostatic pharmaceuticals.

The fate and effects of cytostatic (anticancer or antineoplastic) pharmaceuticals in the environment are largely unknown, but they can contaminate wastewater treatment effluents and consequently aquatic ecosystems. In this paper, we have focused on five cytostatic compounds used in high amounts (cyclophosphamide, cisplatin, 5-fluorouracil, doxorubicin, and etoposide), and we have investigated their ecotoxicity in bacterial Pseudomonas putida growth-inhibition test, algal Pseudokirchneriella subcapitata growth-inhibition test, and Dapnia magna acute immobilization test. Genotoxicity also was assessed with Escherichia coli SOS-chromotest (with and without metabolic activation) and the GreenScreen Assay using yeast S. cerevisiae. All tested compounds showed significant effects in most of the assays with lowest-observed-effect concentrations and concentrations causing 50% effects (EC50s) values ranging within microg/L to mg/L. The most toxic compound was 5-fluorouracil in the assays with P. putida (EC50 = 0.027 mg/L) and P. subcapitata (EC50 = 0.11 mg/L), although cisplatin and doxorubicin were the most toxic to D. magna (EC50 = 0.64 and 2.0 mg/L, respectively). These two chemicals were also the most genotoxic in the SOS-chromotest (minimum genotoxic concentrations [MGC] = 0.07-0.2 mg/L), and 5-fluorouracil was the most genotoxic in the eukaryotic yeast assay (MGC = 0.02 mg/L). Our investigation seems to indicate generally lower risks of acute effects at concentrations expected in the environment. However, some effective concentrations were relatively low and chronic toxicity of cytostatics (and/or their transformation products), as well as specific sources of human pharmaceuticals such as hospital effluents, require research attention.