Towards a consensus view on understanding nanomaterials hazards and managing exposure

The aim of this article is to present an overview of salient issues of exposure, characterisation and hazard assessment of nanomaterials as they emerged from the consensus-building of experts undertaken within the four year European Commission coordination project NanoImpactNet. The approach adopted is to consolidate and condense the findings and problem-identification in such a way as to identify knowledge-gaps and generate a set of interim recommendations of use to industry, regulators, research bodies and funders. The categories of recommendation arising from the consensual view address: significant gaps in vital factual knowledge of exposure, characterisation and hazards; the development, dissemination and standardisation of appropriate laboratory protocols; address a wide range of technical issues in establishing an adequate risk assessment platform; the more efficient and coordinated gathering of basic data; greater inter-organisational cooperation; regulatory harmonization; the wider use of the life-cycle approaches; and the wider involvement of all stakeholders in the discussion and solution-finding efforts for nanosafety.

Prospective randomized study of two cryopreservation policies avoiding embryo selection: the pronucleate stage leads to a higher cumulative delivery rate than the early cleavage stage.

OBJECTIVE: To compare the cumulative live birth rates obtained after cryopreservation of either pronucleate (PN) zygotes or early-cleavage (EC) embryos. DESIGN: Prospective randomized study. SETTING: University hospital. PATIENT(S): Three hundred eighty-two patients, involved in an IVF/ICSI program from January 1993 to December 1995, who had their supernumerary embryos cryopreserved either at the PN (group I) or EC (group II) stage. For 89 patients, cryopreservation of EC embryos was canceled because of poor embryo development (group III). Frozen-thawed embryo transfers performed up to December 1998 were considered. MAIN OUTCOME MEASURE(S): Age, oocytes, zygotes, cryopreserved and transferred embryos, damage after thawing, cumulative embryo scores, implantation, and cumulative live birth rates. RESULT(S): The clinical pregnancy and live birth rates were similar in all groups after fresh embryo transfers. Significantly higher implantation (10.5% vs. 5.9%) and pregnancy rates (19.5% vs. 10.9%; P< or = .02 per transfer after cryopreserved embryo transfers were obtained in group I versus group II, leading to higher cumulative pregnancy (55.5% vs. 38.6%; P < or = .002 and live birth rates (46.9% vs. 27.7%; P< or = .0001.Conclusion(s): The transfer of a maximum of three unselected embryos and freezing of all supernumerary PN zygotes can be safely done with significantly higher cumulative pregnancy chances than cryopreserving at a later EC stage.

Residual effects of successive exposure of soybean Bradyrhizobium strains to aluminium on solid defined medium

The aim of these studies was to investigate whether residual toxic effects of exposing soybean root nodule bacteria to Al in a solid defined media (SDM) alter tolerance to Al, survival, sensitivity to antibiotics, N2 fixation effectiveness and genetic diversity of Bradyrhizobium strains. After being exposed four times to Al, strains showed variation in Al tolerance but there was no evidence of change in their original Al tolerance, sensitivity to the antibiotics or genetic diversity. Exposure of Bradyrhizobium strains to SDM plus Al did not alter biological N2 fixation effectiveness of five strains. Strain SEMIA 587 showed a reduction in its N2 fixation effectiveness but it seems that it was just a superficial toxic effect because one single passage through the plant eliminated this effect. Residual Al did not cause increases in Al tolerance and reductions in the survival and N2 fixation effectiveness of Bradyrhizobium strains USDA 143, SEMIA 586, SEMIA 5019, SEMIA 5039 and SEMIA 5073. It also did not alter the resistance to antibiotics of strains USDA 143, SEMIA 5039 and SEMIA 5073, and the genetic diversity of the strains SEMIA 587 and SEMIA 5019.

Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration.

BACKGROUND: Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear. Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infarction in a large, prospective observational cohort of HIV-infected patients. METHODS: We used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33 347 patients enrolled in the D:A:D study. We adjusted for cardiovascular risk factors that are unlikely to be affected by antiretroviral therapy, cohort, calendar year, and use of other antiretrovirals. FINDINGS: Over 157,912 person-years, 517 patients had a myocardial infarction. We found no associations between the rate of myocardial infarction and cumulative or recent use of zidovudine, stavudine, or lamivudine. By contrast, recent-but not cumulative-use of abacavir or didanosine was associated with an increased rate of myocardial infarction (compared with those with no recent use of the drugs, relative rate 1.90, 95% CI 1.47-2.45 [p=0.0001] with abacavir and 1.49, 1.14-1.95 [p=0.003] with didanosine); rates were not significantly increased in those who stopped these drugs more than 6 months previously compared with those who had never received these drugs. After adjustment for predicted 10-year risk of coronary heart disease, recent use of both didanosine and abacavir remained associated with increased rates of myocardial infarction (1.49, 1.14-1.95 [p=0.004] with didanosine; 1.89, 1.47-2.45 [p=0.0001] with abacavir). INTERPRETATION: There exists an increased risk of myocardial infarction in patients exposed to abacavir and didanosine within the preceding 6 months. The excess risk does not seem to be explained by underlying established cardiovascular risk factors and was not present beyond 6 months after drug cessation.

Risk factors of sunburns from occupational sun exposure in outdoor workers

Question: Outdoor workers can be exposed to intense ultraviolet (UV) solar radiation likely to results to sunburns. As sunburn is an important risk factor for skin cancer, in particular melanoma, we investigated the causes of occupational sunburns (OS) in French outdoor workers. Methods: A population-based survey was conducted in May-June 2012 through computer-assisted telephonic interviews in population 25 to 69 years of age. History of sunburn from occupational exposure within the year preceding interview was collected. We analysed the risk of OS in multivariate logistic regression. Results: Out of 1442 individuals who declared having an occupational exposure to solar UV radiation, 403 (27.9%) reported a sunburn from occupational exposure in the year preceding the interview. Sunburns were more frequent in women (30% vs. 26.4% in men although not significant p = 0.14), in younger workers (p = 0.0099), in sensitive phototype (40% in phototype I/II vs. 23% in phototype III/IV, p < 0.001) and in workers taking lunch outdoor (p = 0.0355). Some occupations were more associated with OS (more than 30%): health occupations, managing, research/engineering, construction workers and culture/art/social sciences workers. In multivariate analysis, risk factors for OS are phototype (I vs. IV, OR = 4.30 95% CI [2.65-6.98]), sunburn during leisure time (OR = 3.46 95% CI [2.62-4.59]), seasonality of exposure (seasonal vs. constant exposure OR = 1.36 95% CI [1.02-1.81] and annual UVA exposure (OR for 10J/m² daily average increment 1.08 95% CI [1.02-1.14]). In multivariate analysis the type of occupation was not associated with increased OS. Conclusion: Sunburns from occupation was also observed in non sensitive population, phototype IV, which shows that outdoor workers are potentially exposed to intense UV radiations. This study suggests that prevention should target UV sensitive outdoor workers as well as those cumulating intense UV exposure.

Solid-phase microextraction as short-term sampling technique for BTEX occupational exposure

Solid phase microextraction (SPME) has been widely used for many years in various applications, such as environmental and water samples, food and fragrance analysis, or biological fluids. The aim of this study was to suggest the SPME method as an alternative to conventional techniques used in the evaluation of worker exposure to benzene, toluene, ethylbenzene, and xylene (BTEX). Polymethylsiloxane-carboxen (PDMS/CAR) showed as the most effective stationary phase material for sorbing BTEX among other materials (polyacrylate, PDMS, PDMS/divinylbenzene, Carbowax/divinylbenzene). Various experimental conditions were studied to apply SPME to BTEX quantitation in field situations. The uptake rate of the selected fiber (75 μm PDMS/CAR) was determined for each analyte at various concentrations, relative humidities, and airflow velocities from static (calm air) to dynamic (>200 cm/s) conditions. The SPME method also was compared with the National Institute of Occupational Safety and Health method 1501. Unlike the latter, the SPME approach fulfills the new requirement for the threshold limit value-short term exposure limit (TLV-STEL) of 2.5 ppm for benzene (8 mg/m3).

Vancomycin exposure from active calcium sulfate bone filler

Objective: Bone cements and substitutes are commonly used in surgery to deliver antibiotics locally. The objective of this study was to assess the systemic absorption and disposition of vancomycin in patients treated with active calcium sulfate bone filler and to predict systemic concentrations under various conditions. Method: 277 blood samples were taken from 42 patients receiving vancomycin in bone cement during surgery. Blood samples were collected from 3h to 10 days after implantation. Vancomycin was measured by immunoenzymatic assay. Population pharmacokinetic (PK) analysis was performed using NONMEM to assess average estimates and variability of PK parameters. Based on the final model, simulations with various doses and renal function levels were performed. Results: The patients were 64 ± 20 years old, their body weight was 81 ± 22 kg and Cockcroft-Gault creatinine clearance (CLcr) 98 ± 55 mL/min. Vancomycin doses ranged from 200 mg to 6000 mg and implantation sites were hip (n=16), tibia (10) or others (16). Concentration profiles remained low and consistent with absorption rate-limited first-order release, while showing prominent variability. Mean clearance (CL) was 3.87 L/h (CV 35%), absorption rate constant (ka) 0.004 h-1 (66%) and volume of distribution (V) 9.5 L. Simulations with up to 8000 mg vancomycin implant showed systemic concentrations exceeding 20 mg/L for 3.5 days in 43% of the patients with CLcr 15 mL/min, whereas 7% of the patients with normal renal function had a concentration above 20 mg/L for 1.1 days. Subtherapeutic concentrations (0.4-4 mg/L) were predicted during a median of 22 days in patients with normal renal function and 4000 mg vancomycin implant, with limited influence of dose or renal function. Conclusion: Vancomycin-laden calcium sulfate implant does not raise toxicity concern. Selection of resistant bacteria, such as Enterococcus and Staphylococcus species, might however be a concern, as simulations show persistent subtherapeutic systemic concentrations during 3 to 4 weeks in these patients.

Particle exposure scenarios for research and production activities involving nanomaterials

Nanomaterials with structures in the nanoscale (1 to 100 nm) often have chemical, physical and bioactive characteristics different from those of larger entities of the same material. This is interesting for industry but raises questions about the health of exposed people. However, little is known so far about the exposure of workers to inhalable airborne nanomaterials. We investigated several activities in research laboratories and industry to learn about relevant exposure scenarios. Work process analyses were combined with measurements of airborne particle mass concentrations and number−size distributions. Background levels in research settings were mostly low, while in industrial production, levels were sometimes elevated, especially in halls near busy roads or in the presence of diesel fork lifts without particle filters. Peak levels were found in an industrial setting dealing with powders (up to 80,000 particles/cm³ and up to 15 mg/m³). Mostly low concentrations were found for activities involving liquid applications. However, centrifugation and lyophilization of nanoparticle containing solutions resulted in very high particle number concentrations (up to 300,000 particles/cm³), whereas no increases were seen for the same activities conducted with nanoparticle−free liquids. No significant increases of particle concentrations were found for processes involving nanoparticles bound to surfaces. Also no increases were observed in laboratories that were visualizing properties and structures of small amounts of nanomaterials. Conclusion: When studying exposure scenarios for airborne nanomaterials, the focus should not only be on processes involving nano−powders, but also on processes involving intensively treated nanoparticle−containing liquids. Acknowledgement: We thank Chantal Imhof, MSc and Guillaume Ferraris, MSc for their contributions.

Contribution of fine particulate matter sources to indoor exposure in bars, restaurants, and cafes

This study investigated the contribution of sources and establishment characteristics, on the exposure to fine particulate matter (PM(2.5)) in the non-smoking sections of bars, cafes, and restaurants in central Zurich. PM(2.5)-exposure was determined with a nephelometer. A random sample of hospitality establishments was investigated on all weekdays, from morning until midnight. Each visit lasted 30 min. Numbers of smokers and other sources, such as candles and cooking processes, were recorded, as were seats, open windows, and open doors. Ambient air pollution data were obtained from public authorities. Data were analysed using robust MM regression. Over 14 warm, sunny days, 102 establishments were measured. Average establishment PM(2.5) concentrations were 64.7 microg/m(3) (s.d. = 73.2 microg/m(3), 30-min maximum 452.2 microg/m(3)). PM(2.5) was significantly associated with the number of smokers, percentage of seats occupied by smokers, and outdoor PM. Each smoker increased PM(2.5) on average by 15 microg/m(3). No associations were found with other sources, open doors or open windows. Bars had more smoking guests and showed significantly higher concentrations than restaurants and cafes. Smokers were the most important PM(2.5)-source in hospitality establishments, while outdoor PM defined the baseline. Concentrations are expected to be even higher during colder, unpleasant times of the year. PRACTICAL IMPLICATIONS: Smokers and ambient air pollution are the most important sources of fine airborne particulate matter (PM(2.5)) in the non-smoking sections of bars, restaurants, and cafes. Other sources do not significantly contribute to PM(2.5)-levels, while opening doors and windows is not an efficient means of removing pollutants. First, this demonstrates the impact that even a few smokers can have in affecting particle levels. Second, it implies that creating non-smoking sections, and using natural ventilation, is not sufficient to bring PM(2.5) to levels that imply no harm for employees and non-smoking clients. [Authors]

Comparison of hospital-wide and unit-specific cumulative antibiograms in hospital- and community-acquired infection.

BACKGROUND: Empirical antibacterial therapy in hospitals is usually guided by local epidemiologic features reflected by institutional cumulative antibiograms. We investigated additional information inferred by aggregating cumulative antibiograms by type of unit or according to the place of acquisition (i.e. community vs. hospital) of the bacteria. MATERIALS AND METHODS: Antimicrobial susceptibility rates of selected pathogens were collected over a 4-year period in an university-affiliated hospital. Hospital-wide antibiograms were compared with those selected by type of unit and sampling time (<48 or >48 h after hospital admission). RESULTS: Strains isolated >48 h after admission were less susceptible than those presumably arising from the community (<48 h). The comparison of units revealed significant differences among strains isolated >48 h after admission. When compared to hospital-wide antibiograms, susceptibility rates were lower in the ICU and surgical units for Escherichia coli to amoxicillin-clavulanate, enterococci to penicillin, and Pseudomonas aeruginosa to anti-pseudomonal beta-lactams, and in medical units for Staphylococcus aureus to oxacillin. In contrast, few differences were observed among strains isolated within 48 h of admission. CONCLUSIONS: Hospital-wide antibiograms reflect the susceptibility pattern for a specific unit with respect to community-acquired, but not to hospital-acquired strains. Antibiograms adjusted to these parameters may be useful in guiding the choice of empirical antibacterial therapy.