Acute health effects of desktop 3D printing (fused deposition modeling) using acrylonitrile butadiene styrene and polylactic acid materials: An experimental exposure study in human volunteers.

3D printers are increasingly run at home. Nanoparticle emissions from those printers have been reported, which raises the question whether adverse health effects from ultrafine particles (UFP) can be elicited by 3D printers. We exposed 26 healthy adults in a single-blinded, randomized, cross-over design to emissions of a desktop 3D printer using fused deposition modeling (FDM) for 1 hour (high UFP-emitting acrylonitrile butadiene styrene [ABS] vs low-emitting polylactic acid [PLA]). Before and after exposures, cytokines (IL-1ß, IL-6, TNF-α, INF-γ) and ECP in nasal secretions, exhaled nitric oxide (FeNO), urinary 8-isoprostaglandin F2α (8-iso PGF2α ), and self-reported symptoms were assessed. The exposures had no significant differential effect on 8-iso PGF2α and nasal biomarkers. However, there was a difference (P < .05) in the time course of FeNO, with higher levels after ABS exposure. Moreover, indisposition and odor nuisance were increased for ABS exposure. These data suggest that 1 hour of exposure to 3D printer emissions had no acute effect on inflammatory markers in nasal secretions and urine. The slight relative increase in FeNO after ABS printing compared to PLA might be due to eosinophilic inflammation from inhaled UFP particles. This possibility should be investigated in further studies using additional biomarkers and longer observation periods.

Respiratory allergies among veterinarians: two cross-sectional surveys from 2006 to 2012.

PURPOSE: Animal-related allergy is known to be an occupational hazard among veterinarians; however, there is a lack of data showing to which extent these are affected. We aimed at describing the prevalence of respiratory allergies in this population. METHODS: In two repeated cross-sectional surveys in 2006 and 2012 in Bavaria, we examined the prevalence of wheezing, asthma and allergic rhinitis by questionnaires. We additionally performed multiple regression analysis to identify associated factors. RESULTS: Overall participation rate was above 60%, leading to sample sizes of 512 in 2006 and 596 in 2012, respectively. Prevalences of allergic symptoms ranged from 5.1 to 5.6% for asthma, 17.0 to 20.2% for rhinitis, and 11.4 to 14.3% for wheezing, as well as 7.2 to 11.3% for wheezing without having a cold. The percentage of women in this occupation grew between the first and second survey. There were gender differences in both surveys concerning age and practice type (p < 0.0001). Women had a lower mean age (42.1 vs. 53.0 years in 2012) and worked much more often exclusively with small animals (50.2 vs. 15.9% in 2012). There was a borderline significantly higher prevalence for allergic rhinitis in women than in men in 2012 (20.1 vs. 13.7, p = 0.052). Having allergic rhinitis was clearly associated with wheezing, wheezing without cold and asthma. CONCLUSIONS: In a repeated cross-sectional survey at an interval of 6 years among veterinarians, we found a relatively stable overall prevalence of wheeze, wheeze without having a cold, asthma and allergic rhinitis.

Health effects of laser printer emissions: a controlled exposure study.

Ultrafine particles emitted from laser printers are suspected to elicit adverse health effects. We performed 75-minute exposures to emissions of laser printing devices (LPDs) in a standardized, randomized, cross-over manner in 23 healthy subjects, 14 mild, stable asthmatics, and 15 persons reporting symptoms associated with LPD emissions. Low-level exposures (LLE) ranged at the particle background (3000 cm-3 ) and high-level exposures (HLE) at 100 000 cm-3 . Examinations before and after exposures included spirometry, body plethysmography, transfer factors for CO and NO (TLCO, TLNO), bronchial and alveolar NO, cytokines in serum and nasal secretions (IL-1ß, IL-5, IL-6, IL-8, GM-CSF, IFNγ, TNFα), serum ECP, and IgE. Across all participants, no statistically significant changes occurred for lung mechanics and NO. There was a decrease in volume-related TLNO that was more pronounced in HLE, but the difference to LLE was not significant. ECP and IgE increased in the same way after exposures. Nasal IL-6 showed a higher increase after LLE. There was no coherent pattern regarding the responses in the participant subgroups or single sets of variables. In conclusion, the experimental acute responses to short but very high-level LPD exposures were small and did not indicate clinically relevant effects compared to low particle number concentrations.

Cisplatin and oxaliplatin surface contamination in intensive care units (ICUs) and hospital wards during attendance of HIPEC patients.

PURPOSE: The aim of this pilot study was to evaluate surface contamination by platinum drugs in the environment of patients in ICUs and wards treated by hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: The monitoring included 12 HIPEC treatments from four hospitals during the following 3 days after perfusion. A total of 33 urine and 33 drainage fluids from HIPEC patients and 160 wipe samples from several surfaces (urine/drainage bags, floors, gloves) were taken during the study period. RESULTS: In urine, the highest platinum concentrations were measured on the first day after perfusion. Median platinum concentrations were 1260 ng/ml for patients after cisplatin perfusion and 11,000 ng/ml for oxaliplatin treatment. Concentrations decreased until day three to 413 ng/ml cisplatin and 529 ng/ml oxaliplatin, respectively. In drainage liquids, platinum concentrations were generally lower. Platinum concentrations from surfaces of bags and floors ranged from 0.01 to 439 pg/cm(2) (median: urine bag 2.77 pg/cm(2), drainage bag 0.22 pg/cm(2), floor left 0.14 pg/cm(2), floor right 0.24 pg/cm(2)), with the highest contamination found on the outer surface of the urine bags. Samples from nurses' protective gloves ranged between 0.03 and 12 pg/cm(2) (median: 0.2 pg/cm(2)). CONCLUSIONS: High platinum-drug concentrations in urine and drainage liquids are the main source of contamination. Therefore, safe handling of these liquids is the best way to avoid cross-contamination on surfaces in wards and ICUs. Our results show that it is possible to take care of HIPEC patients without high contaminations during the first 3 days.

Low surface contamination by cis/oxaliplatin during hyperthermic intraperitoneal chemotherapy (HIPEC).

AIM: The aim of this study was to evaluate contamination by platinum drugs in the operating room during hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Environmental sampling of 151 wipe samples from surfaces on the HIPEC devices and operating room floors was performed for platinum in six German hospitals during 19 HIPEC procedures. Additionally, 45 wipe samples from surgeons' and perfusionists' protective gloves were analyzed. RESULTS: Platinum concentrations from the HIPEC devices and operating room floors ranged from 0.07 to 110,000 pg/cm(2) (Median: 1.5 pg/cm(2)) with high contamination on the regulation knob and reservoir after HIPEC procedure, particularly when injecting the cytostatic drug into the reservoir via syringe. Samples from perfusionists' and surgeons' protective gloves ranged between 0.01 and 729 ng/pair. CONCLUSIONS: Although sporadically high platinum concentrations on surfaces on the HIPEC device and operating room floor were detected, our study revealed that low surface loads are definitely possible and can be documented by wipe samples. Important factors for achieving low surface contamination are the use of infusion bags instead of syringes for injection of the cytostatic solution, careful cleaning of the device after HIPEC and wearing of two pairs of gloves.

Effects of particulate matter on cytokine production in vitro: a comparative analysis of published studies.

In recent years evidence has accumulated indicating that airborne particles cause adverse health effects. To understand the underlying mechanisms, a multitude of in vitro studies have been performed focusing on inflammatory responses, especially cytokine production. However, the diversity of studies renders it difficult to determine which results are consistent and which exposures most effective. The present review thus aimed to perform a comparative analysis of the available data. Forty-nine studies dealing with in vitro effects of particles on cytokine production in bronchial epithelial or related cells and monocytes/macrophages were included. Twenty-eight studies investigated epithelial cells and could be categorized according to specific combinations of exposure level and time, and 27 dealt with monocytes/macrophages. Eight studies provided further data using non-compatible exposure modes. The most common finding was that particles significantly induced cytokine production in both epithelial cells and monocytes/macrophages at concentrations of 50-100 microg/mL and exposure times of 9-24 h. The effects did not appear to be significantly different between cell or particle types. There were virtually no effects reported below 10 microg/mL, but these levels were used in only a few studies. Thus, the available data demonstrate that cytokine measurements are sensitive enough to assess cell activation after particle exposure in vitro, yielding relatively consistent results across cell types. However, since the majority of data refers to high particle load compared to in vivo conditions, future studies should consider more sensitive assays, multivariate panels describing the cell's regulatory state, interactions between cell types, and second-line outcome measures that are close to clinically observed effects.

Heart rate variability, hemostatic and acute inflammatory blood parameters in healthy adults after short-term exposure to welding fume.

The present study aimed to investigate, whether short-term experimental exposure to high levels of welding fumes would be capable of exerting acute effects in healthy subjects. Specifically, we assessed cardiovascular function in terms of heart rate variability (HRV) as well as the concentrations of inflammatory mediators and hemostatic proteins in blood as outcome measures. Twenty subjects without a history of airway and cardiovascular diseases were exposed to either control air or welding fume for 1 h on 2 separate days under standardized conditions. The median concentration of the alveolar particle fraction during welding was 3.5 mg/m(3 )(quartiles: 1.4-6.3 mg/m(3); range 1.0-25.3 mg/m(3)). Five hours later a panel of clinical assessments was performed, including HRV measurement and drawing of blood samples. There were no changes in symptom ratings or lung function after welding fume exposure. Exposures did also not differ regarding effects on time- and frequency-domain parameters of HRV. Similarly, blood leukocyte numbers, cell differentials and the blood levels of fibrinogen, C-reactive protein, antithrombin III, factor VIII, von Willebrand factor, ristocetin cofactor, sICAM-1, tumor necrosis factor alpha, interleukin 6, interleukin 8 and epithelial neutrophil activating peptide 78 were not altered by welding fume inhalation. However, there was a significant fall in the level of endothelin-1 (P < 0.01). In conclusion, the data did not indicate effects of clinical significance of a short-term high-level exposure to welding fumes on HRV or a set of blood hemostatic and acute inflammatory parameters in healthy subjects. The small but statistically significant effect on endothelin levels demonstrated that measurable effects could be elicited even in these individuals. Overall, welding fumes are not likely to exert acute cardiovascular effects in healthy individuals.

Urinary excretion of platinum in chemotherapy-treated long-term survivors of testicular cancer.

As the majority of patients with metastatic testicular cancer are cured by cisplatin-based chemotherapy and can expect an additional life span of around 50 years, late toxicity is of particular relevance. Urine and serum concentrations of platinum were determined by voltammetry in 37 patients at 5.3 to 16.8 years after cisplatin-based chemotherapy. Urinary excretion and serum levels of platinum were 100 to 1000 times higher in patients than in unexposed controls. There may be an association between platinum storage and endocrinologic and metabolic late sequelae, as well as a risk of second cancer. However, further research is necessary to clarify the biological relevance of long-term storage of platinum.

Biological monitoring of hospital pharmacy personnel occupationally exposed to cytostatic drugs: urinary excretion and cytogenetics studies.

For evaluation of the risk borne by hospital pharmacy personnel exposed to antineoplastic agents, the incorporation of cyclophosphamide, ifosfamide, and platinum-containing drugs was quantified by the determination of urinary concentrations. In addition, the induction of micronuclei (MN) and sister-chromatid-exchange (SCE) rates in peripheral blood lymphocytes were studied for correlation with the urinary excretion of cytostatic drugs. Cyclophosphamide and ifosfamide were determined in 24-h urine samples using gas chromatography with electron capture (detection limit 2.5 micrograms/l). Voltammetric analysis enabled the determination of platinum concentrations of 4 ng/l. Heparinized blood (20 ml) was drawn and lymphocytes were cultured for MN and SCE studies. In all, 13 hospital pharmacists and pharmacy technicians regularly involved in the preparation of cytostatic drugs participated in this investigation (7 persons represent a follow-up group). All subjects applied standard safety precautions, including the use of a vertical laminar air-flow hood, protective gowns, and latex gloves. On the day of urine sampling an average of 4,870 mg cyclophosphamide, 5,580 mg ifosfamide, and 504 mg platinum-containing drugs were handled. The excretion of 5 and 9 micrograms cyclophosphamide/l urine was measured in two samples, respectively. An elevated level of urinary platinum was found in one pharmacist (22.3 ng/g creatinine) in comparison with a nonexposed control group. Mean frequencies of MN and SCE did not differ significantly between the drug exposed group and control group. The employees who had incorporated chemotherapeutic agents were part of the follow-up group and, thus, particularly cautious and sensitive to a possible hazard. The results emphasize the necessity of improving personal protection of hospital pharmacy personnel occupationally exposed to cytostatic drugs and support the importance of biological monitoring. In an ongoing project in our department the sources of contamination are being investigated parallel to biological monitoring so as to determine critical situations and improve personal protection.

Cisplatin based chemotherapy in testicular cancer patients: long term platinum excretion and clinical effects.

Patients with advanced testicular cancer (TC) have a very good long-term prognosis owing to cisplatin-based polychemotherapy. Platinum is believed to be excreted at a rapid rate via urine within weeks after chemotherapy. As a new, highly sensitive method has become available detecting even natural background platinum levels in body fluids, this study was set up to analyze urinary and serum platinum levels in long-term survivors of testicular neoplasm after cisplatin based polychemotherapy and to correlate clinical data with urinary and serum platinum levels. Urinary platinum concentrations were measured in 64 healthy controls (C) and 22 male patients (TC) 150 to 3022 days after the last application of i.v. cisplatin using voltammetry after UV-photolysis. In the latter group (TC), serum platinum levels were measured as well. Clinical data were analysed as to long-term organ toxicity. Mean urinary platinum levels were 2700 times higher in the patient group (TC) than natural background noise (p < 0.0001). There was a decline of urinary and serum platinum levels over time, being significantly above normal even 8 years after cisplatin exposure. The only significant variables related to the urine platinum concentration were a) the interval between the last i.v. cisplatin application and time of study and b) the total dose given. Not significant were the number of chemotherapy cycles, pre-therapy renal disease, patient age, tumour resection before/after chemotherapy, site of pre/post therapy resection, clinical staging, histological subtypes or tumour markers. Post-therapy renal disease or peripheral nerve damage were not significantly associated with urinary platinum levels. Our data indicate that even 8 years after cisplatin based chemotherapy 500 times elevated urinary and serum platinum levels can be measured in testicular cancer patients. No organ toxicity related to long-term platinum excretion could be detected. This may be due to our small sample size.

Long-term platinum excretion in patients treated with cisplatin.

The purpose of this study was to determine long-term renal platinum excretion after chemotherapy with cisplatin. We examined urinary platinum concentrations in 23 men at 150-3022 days after anticancer treatment for testicular neoplasm. Spot urine samples were analyzed by voltammetry. This new, subtle method with a detection limit of 2 pg platinum allows determination of even the natural background level. Urinary platinum concentrations in our patients ranged between 0.74 and 77.24 micrograms/g creatinine, depending on the total delivered dose and follow-up period. Regression analysis of the data showed two phases of long-term renal platinum excretion, one occurring at between 150 and 900 days of follow-up and the other with an onset at 900 days after cisplatin administration (r1(2) = 0.82, r2(2) = 0.88). Two biological half-lives of 160 and 720 days were calculated. Our results show that urinary platinum concentrations determined at 8 years after cisplatin therapy are 40 times higher than the background level (up to 0.02 micrograms/g creatinine). Our findings on the long-term pharmacokinetics of this anticancer agent may facilitate further studies on sites of platinum storage in the human body as well as clinical studies on the late adverse effects of cisplatin.

Urinary platinum in hospital personnel occupationally exposed to platinum-containing antineoplastic drugs.

Urinary platinum levels of 21 nurses and hospital pharmacy personnel occupationally exposed to platinum containing antineoplastic drugs were determined in 24-h urine by voltammetric analysis after UV photolysis. All study participants applied standard safety measures, including a vertical laminar air-flow cabinet and latex gloves. The amount of platinum-containing drugs prepared for intravenous application ranged from 40-3260 mg/day. Urinary platinum was detected in 9 of 52 urine samples collected on days when platinum-containing drugs were mixed (limit of determination 4 ng/l). In comparison with a non-exposed control group, elevated urinary platinum levels were found in one pharmacist (35 ng/g creatinine) and one pharmacy technician (28 ng/g creatinine). The pharmacist's urinary platinum remained elevated after 2 days without occupational exposure to antineoplastic drugs. The urinary platinum level of the pharmacy technician dropped considerably after several weeks without handling cytostatic drugs. Voltammetric detection of urinary platinum is a highly sensitive method suitable for biological and environmental monitoring.