This review paper reports the consensus of a technical workshop hosted by the European network, NanoImpactNet (NIN). The workshop aimed to review the collective experience of working at the bench with manufactured nanomaterials (MNMs), and to recommend modifications to existing experimental methods and OECD protocols. Current procedures for cleaning glassware are appropriate for most MNMs, although interference with electrodes may occur. Maintaining exposure is more difficult with MNMs compared to conventional chemicals. A metal salt control is recommended for experiments with metallic MNMs that may release free metal ions. Dispersing agents should be avoided, but if they must be used, then natural or synthetic dispersing agents are possible, and dispersion controls essential. Time constraints and technology gaps indicate that full characterisation of test media during ecotoxicity tests is currently not practical. Details of electron microscopy, dark-field microscopy, a range of spectroscopic methods (EDX, XRD, XANES, EXAFS), light scattering techniques (DLS, SLS) and chromatography are discussed. The development of user-friendly software to predict particle behaviour in test media according to DLVO theory is in progress, and simple optical methods are available to estimate the settling behaviour of suspensions during experiments. However, for soil matrices such simple approaches may not be applicable. Alternatively, a Critical Body Residue approach may be taken in which body concentrations in organisms are related to effects, and toxicity thresholds derived. For microbial assays, the cell wall is a formidable barrier to MNMs and end points that rely on the test substance penetrating the cell may be insensitive. Instead assays based on the cell envelope should be developed for MNMs. In algal growth tests, the abiotic factors that promote particle aggregation in the media (e.g. ionic strength) are also important in providing nutrients, and manipulation of the media to control the dispersion may also inhibit growth. Controls to quantify shading effects, and precise details of lighting regimes, shaking or mixing should be reported in algal tests. Photosynthesis may be more sensitive than traditional growth end points for algae and plants. Tests with invertebrates should consider non-chemical toxicity from particle adherence to the organisms. The use of semi-static exposure methods with fish can reduce the logistical issues of waste water disposal and facilitate aspects of animal husbandry relevant to MMNs. There are concerns that the existing bioaccumulation tests are conceptually flawed for MNMs and that new test(s) are required. In vitro testing strategies, as exemplified by genotoxicity assays, can be modified for MNMs, but the risk of false negatives in some assays is highlighted. In conclusion, most protocols will require some modifications and recommendations are made to aid the researcher at the bench.

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The NERC and CEH trademarks and logos ('the Trademarks') are registered trademarks of NERC in the UK and other countries, and may not be used without the prior written consent of the Trademark owner. ARs in the U.S. in 1997, 3 (ii) a market analysis suggesting that U. ADVERSE OUTCOME PATHWAY FOR ANTICOAGULANT RODENTICIDES 60An AOP is a conceptual framework portraying existing knowledge as a logical sequence of 61 processes linking a direct molecular initiating event to an adverse effect across multiple levels of 62 biological organization, which is relevant in risk assessment. [17][18][19] In an ecological context, warfarin resistance is at Y139; common mutations include substitutions of S, C, and F, for Y. 119Other common mutations that afford warfarin resistance are indicated in yellow. 9 FGARs (warfarin, chlorophacinone) exceeded levels of concern for non-target birds and 296 mammals. Consumption of SGAR-exposed prey also exceeded levels of concern for predatory 297 birds and mammals. While consumption of FGAR-exposed prey posed a hazard for non-target 298 mammals, levels of concern were rarely exceeded for birds. 4 In some use scenarios (e.g., 299Rozol® for control of prairie dogs, Cynomys ludovicianus), label requirements even state that 300 applicators must make multiple follow-up visits after application to remove dead or dying target 301 species to mitigate hazard to non-target scavengers and predators. 86 UNSOLVED ISSUES 380There are significant unknowns related to exposure and effects to predatory wildlife associated 381 with use of ARs. Among these are basic and applied data needs to supplement risk assessments. 382Some of these data are best derived from controlled exposure trials using captive animals, while 383 other information can only be generated from field observations and hypothesis-driven eco-384 epidemiological studies, and even a combination of these activities. Exposure pathways can be complex, with non-target predators encountering a combination 396 of ARs. Notably, tissues analyzed from mortality incidents document exposure to multiple 397 SGARs to varying degrees, 12,51,52,56,62,63,65,68,71,100 and occasionally even combinations of FGARs 398 and SGARs. 51,56 That suggests that some predators may reside and forage opportunistically at the 399 interface of urban/suburban/rural and agricultural settings. For example, rats and non-target 400 small mammals (but not house mice) exposed to SGARs while indoors may move outdoors from 419In contrast to the aforementioned terrestrial exposure pathway, there is now evidence that 420 warfarin, at nanogram per liter quantities, is detectable in some wastewater effluents. 120 Its 421 source is presumed to be of human origin. However, based on both its low concentration and log 422 K ow (2.37), it is highly unlikely that this is a significant source of exposure for predatory wildlife. hemorrhagic syndrome in chickens, and warfarin sensitivity and resistance in rats, has been 436 studied in great detail, 125 vitamin K status has not been e...

A schematic summary of the most important transformation processes a NM may undergo during environmental transport, and the parameters of highest importance for inclusion in models of NM environmental fate and uptake.

In the regulatory context, bioaccumulation assessment is often hampered by substantial data uncertainty as well as by the poorly understood differences often observed between results from laboratory and field bioaccumulation studies. Bioaccumulation is a complex, multifaceted process, which calls for accurate error analysis. Yet, attempts to quantify and compare propagation of error in bioaccumulation metrics across species and chemicals are rare. Here, we quantitatively assessed the combined influence of physicochemical, physiological, ecological, and environmental parameters known to affect bioaccumulation for 4 species and 2 chemicals, to assess whether uncertainty in these factors can explain the observed differences among laboratory and field studies. The organisms evaluated in simulations including mayfly larvae, deposit-feeding polychaetes, yellow perch, and little owl represented a range of ecological conditions and biotransformation capacity. The chemicals, pyrene and the polychlorinated biphenyl congener PCB-153, represented medium and highly hydrophobic chemicals with different susceptibilities to biotransformation. An existing state of the art probabilistic bioaccumulation model was improved by accounting for bioavailability and absorption efficiency limitations, due to the presence of black carbon in sediment, and was used for probabilistic modeling of variability and propagation of error. Results showed that at lower trophic levels (mayfly and polychaete), variability in bioaccumulation was mainly driven by sediment exposure, sediment composition and chemical partitioning to sediment components, which was in turn dominated by the influence of black carbon. At higher trophic levels (yellow perch and the little owl), food web structure (i.e., diet composition and abundance) and chemical concentration in the diet became more important particularly for the most persistent compound, PCB-153. These results suggest that variation in bioaccumulation assessment is reduced most by improved identification of food sources as well as by accounting for the chemical bioavailability in food components. Improvements in the accuracy of aqueous exposure appear to be less relevant when applied to moderate to highly hydrophobic compounds, because this route contributes only marginally to total uptake. The determination of chemical bioavailability and the increase in understanding and qualifying the role of sediment components (black carbon, labile organic matter, and the like) on chemical absorption efficiencies has been identified as a key next steps.