Occupational exposure to cisplatin/oxaliplatin during Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)?

INTRODUCTION: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a new promising treatment for patients with peritoneal carcinomatosis. It is supposed to provide a higher local drug concentration and deeper penetrate into the tumor tissue compared to systemic chemotherapy or hyperthermic intraperitoneal chemotherapy perfusion (HIPEC). Due to the application of cytotoxic drug aerosols within the operating room (OR), concern has been raised regarding the occupational exposure risk of the involved OR staff. MATERIALS AND METHODS: In this study, an OR workplace monitoring was performed during 14 PIPAC procedures in two hospitals by collecting air samples (n = 14) during PIPAC and wipe samples (n = 223) before and after PIPAC: 56 samples from the OR floor, 84 from the injector, 28 from trocars and 55 from gloves. All samples were analyzed for platinum (Pt). RESULTS: While air Pt concentrations were below 3.1 pg/m³, surface contaminations widely varied between 0.01 pg/cm2 and 1733 pg/cm2 (median 1.04 pg/cm2), with substantial Pt concentrations on injector parts (i.e. syringe holder) and trocars. Floors and particularly injectors were often higher contaminated before compared to after PIPAC, probably due to inefficient cleaning or cross-contamination. Glove samples taken after different tasks ranged between 0.04 and 423 pg/cm2 (median 0.58 pg/cm2). CONCLUSION: Contamination on various OR surfaces widely ranged and can lead to a distribution of cytotoxic drug residues. However, the air contamination was very low. The results indicate that PIPAC performance seems to be possible with low occupational exposure risk, but adequate safety and cleaning standards for PIPAC must be developed and monitored.

Environmental and biological monitoring on an oncology ward during a complete working week.

Workplace exposure to antineoplastic drugs (AD) is still of evident concern to all occupationally exposed persons in the healthcare sector as residues in relevant concentrations continue to be present. With respect to the carcinogenic and mutagenic potential of ADs and their toxicity on reproduction, occupational exposure should be kept as low as reasonably achievable (ALARA). In the oncology patient care, the medical staff is involved both in chemotherapy administration and handling of AD-contaminated body fluids of the patients. For this purpose, in this study, surface monitoring on an oncology ward and concurrent urine monitoring of the complete healthcare staff was performed during five consecutive days for 5-fluorouracil (5-FU), cyclophosphamide (CP) and platinum (Pt). Contamination was detected on all surfaces in various ranges (5-FU 0.7-12,600 pg/cm2, Pt 0.2-181,800 pg/cm2, CP (

Antineoplastic drug residues inside homes of chemotherapy patients.

Chemotherapy treatment of cancer patients has shifted from inpatient to outpatient administration. Thus, family members are potentially exposed to cytotoxic drug residues from patients' excretions inside their homes. The study's aim was to evaluate the surface contamination and the potential uptake of antineoplastic drug residues by family members at home of chemotherapy patients. Overall, 265 wipe samples from 13 homes were taken at two times after chemotherapy from different surfaces (toilet, bathroom, kitchen). 62 urine samples were collected from patients and family members on three days. Samples were analyzed for cyclophosphamide, 5-fluorouracil (urine: FBAL) and platinum (as marker for cis-, carbo- and oxaliplatin). Substantial contamination was found on every surface type (PT: 0.02-42.5pg/cm2, 5-FU: ND-98.3pg/cm2, CP: ND-283.3pg/cm2) with highest concentrations on toilet and bathroom surfaces. While patients' urinary drug concentrations often were elevated for more than 48h after administration, no drug residues were detectable in the family members' urine. This study provided an insight in the exposure situation against antineoplastic drug residues at home of chemotherapy patients. As contamination could be found on various surfaces adequate hygienic and protective measures are necessary to minimize the exposure risk for cohabitants.

Environmental contamination by cyclophosphamide preparation: Comparison of conventional manual production in biological safety cabinet and robot-assisted production by APOTECAchemo.

OBJECTIVES: The aim of this study was to compare environmental contamination of cyclophosphamide (CP) during 1 week of drug compounding by conventional manual procedure in a biological safety cabinet (BSC) with laminar airflow and a new robotic drug preparation system (APOTECAchemo). METHODS: During four consecutive days, similar numbers of infusion bags with cyclophosphamide were prepared with both techniques in a cross-over design. Wipe samples (49 for BSC, 50 for APOTECAchemo) were taken at several locations (gloves, infusion bags, trays, BSC-benches, floor) in the pharmacy and analyzed for CP concentrations by GC-MSMS (LOD 0.2 ng/sample). RESULTS: The detection rate was 70% in the BSC versus 15% in APOTECAchemo. During manual preparation of admixtures using BSC contamination with CP was below 0.001 ng/cm(2) at most locations, but significant on gloves (0.0004-0.0967 ng/cm(2)) and the majority (70%) of infusion bags (<0.0004-2.89 ng/cm(2)). During robotic preparation by APOTECAchemo, gloves (1 of 8: 0.0007 ng/cm(2)) and infusion bags (3 of 20: 0.0005, 0.0019, 0.0094 ng/cm(2)) were considerably less contaminated. Residual contamination was found on the surfaces under the dosing device in the compounding area (0.0293-0.1603 ng/cm(2)) inside the robotic system. CONCLUSIONS: Compared to outcomes of other studies, our results underline good manufacturing procedures in this pharmacy with low contamination for both techniques (BSC and APOTECAchemo). Comparison of both preparation procedures validated that contamination of infusion bags was much lower by using the robotic system.

Cleaning Efficiencies of Three Cleaning Agents on Four Different Surfaces after Contamination by Gemcitabine and 5-fluorouracile.

Occupational exposure to antineoplastic drugs has been documented for decades showing widespread contamination in preparation and administration areas. Apart from preventive measures, efficient cleaning of surfaces is indispensable to minimize the exposure risk. The aim of this study was to evaluate the efficiency of three cleaning agents after intentional contamination by gemcitabine (GEM) and 5-fluorouracile (5-FU) on four different surface types usually installed in healthcare settings. Glass, stainless steel, polyvinylchloride (PVC), and laminated wood plates were contaminated with 20 ng/µl GEM and 2 ng/µl 5-FU solutions. Wipe samples were analyzed for drug residues after cleaning with a) distilled water, b) aqueous solution containing sodium dodecyl sulfate (10 mM) and 2-propanol (SDS-2P), and c) Incides N (pre-soaked) alcoholic wipes. Quantification was performed by high-performance liquid chromatography (HPLC) for GEM and gas chromato-graphy-tandem mass spectrometry (GCMS/MS) for 5-FU. Recovery was determined and cleaning efficiency was calculated for each scenario. Mean recoveries were 77-89% for GEM and 24-77% for 5-FU and calculated cleaning efficiencies ranged between 95 and 100% and 89 and 100%, respectively. Residual drug amounts were detected in the range nd (not detected) - 84 ng GEM/sample and nd - 6.6 ng 5-FU/sample depending on surface type and cleaning agent. Distilled water and SDS-2P had better decontamination outcomes than Incides N wipes on nearly all surface types, especially for GEM. Regarding 5-FU, the overall cleaning efficiency was lower with highest residues on laminated wood surfaces. The tested cleaning procedures are shown to clean glass, stainless steel, PVC, and laminated wood with an efficiency of 89-100% after contamination with GEM and 5-FU. Nevertheless, drug residues could be verified by wipe samples. Pure distilled water and SDS in an alcoholic-aqueous solution expressed an efficient cleaning performance, especially with respect to GEM. The study results demonstrate the need to adapt cleaning procedures to the variety of drugs and surface types to develop effective decontamination strategies.

Silicone implants--a possible confounder for urinary platinum background concentrations?

INTRODUCTION: Urinary platinum excretion from occupationally unexposed population is very low. Up to now, in Germany, dental noble metal alloys and a platinum based chemotherapy have been identified as reason for elevated urine concentrations. As fabrication of silicone involves platinum as catalyst, this study examines the potential release of platinum from silicone breast implants by quantifying urinary platinum concentration. METHODS AND RESULTS: Platinum release from three different types of silicone implants into saline solution was measured in a laboratory experiment. It showed a strong increase of platinum concentration during the first 30 min and high platinum concentrations even after 60 h. In the following field study urinary platinum concentrations were determined from 30 women with dental gold alloy restorations and 28 women without such dental inlays. Median platinum concentrations were 5.2 ng/l urine (21.2 ng/g creatinine) for the women with dental gold inlays and 6.0 ng/l urine (5.4 ng/g creatinine) for those without. Compared with the urinary platinum concentrations provided by the German Environmental Survey (GerES) for the general female population the urinary platinum levels of women with silicone implants of the presented study were significantly higher, both for the study groups with and without dental gold alloy inlays. CONCLUSIONS: Silicone breast implants must be considered as a new confounder and as a further contributor to elevated urinary platinum concentrations in human platinum background reference values of women.

High concentrations of cadmium, cerium and lanthanum in indoor air due to environmental tobacco smoke.

BACKGROUND: Environmental tobacco smoke (ETS) is one of the most important sources for indoor air pollution and a substantial threat to human health, but data on the concentrations of the trace metals cerium (Ce) and lanthanum (La) in context with ETS exposure are scarce. Therefore the aim of our study was to quantify Ce and La concentrations in indoor air with high ETS load. METHODS: In two subsequent investigations Ce, La and cadmium (Cd) in 3 smokers' (11 samples) and 7 non-smokers' (28 samples) households as well as in 28 hospitality venues in Southern Germany were analysed. Active sampling of indoor air was conducted continuously for seven days in every season in the smokers' and non-smokers' residences, and for 4h during the main visiting hours in the hospitality venues (restaurants, pubs, and discotheques). RESULTS: In terms of residences median levels of Cd were 0.1 ng/m(3) for non-smokers' and 0.8 ng/m(3) for smokers' households. Median concentrations of Ce were 0.4 ng/m(3) and 9.6 ng/m(3), and median concentrations of La were 0.2 ng/m(3) and 5.9 ng/m(3) for non-smokers' and for smokers' households, respectively. In the different types of hospitality venues median levels ranged from 2.6 to 9.7 ng/m(3) for Cd, from 18.5 to 50.0 ng/m(3) for Ce and from 10.6 to 23.0 ng/m(3) for La with highest median levels in discotheques. CONCLUSIONS: The high concentrations of Ce and La found in ETS enriched indoor air of smokers' households and hospitality venues are an important finding as Ce and La are associated with adverse health effects and data on this issue are scarce. Further research on their toxicological, human and public health consequences is urgently required.

Guidance values for surface monitoring of antineoplastic drugs in German pharmacies.

OBJECTIVES: Antineoplastic drugs are widely used in anticancer therapy due to their cytotoxic activity but many of them are classified as carcinogenic, mutagenic, or teratogenic to humans. In order to evaluate personal exposure, surface monitoring has been successfully applied for several years. In this study, we present a statistical description of our data set from 102 German pharmacies and propose 'threshold guidance values (TGVs)' to facilitate interpretation of monitoring results. METHODS: Our database included 1008 results for platinum (PT) and 1237 for 5-fluorouracil (FU) collected in 102 pharmacies in Germany. Wipe sampling on site was performed with one validated procedure. PT concentrations were measured by voltammetry and FU by gas chromatography/mass spectrometry. Data were stratified into 10 locations and statistically evaluated. RESULTS: Contamination was detected on all surfaces in the pharmacies with high levels on storage shelves and floors. The median values for the different locations ranged from 0.20 to 1.70 pg cm(-2) (mean: 0.57 pg cm(-2)) for PT and from 2.50 to 10.00 pg cm(-2) (mean: 5.34 pg cm(-2)) for FU. The mean 75th percentiles were 3.92 pg cm(-2) (PT) and 28.90 pg cm(-2) (FU). The TGV 1 value was set at the median value and results below demonstrate good working practices. Contaminations above the TGV 2, which was assigned at the 75th percentile, show a clear need for optimizing the handling procedures. CONCLUSIONS: The introduction of TGVs helps to reduce occupational exposure and allows pharmacy personnel to benchmark their own contamination levels. This provides a basis for improvement in occupational safety precautions and for regular contamination controls.