Time-dependent toxicity of neonicotinoids and other toxicants: Implications for a new approach to risk assessment

A fundamental goal of toxicology is to determine safe levels of exposure to potentially poisonous substances for humans and the environment. Traditionally, safe levels of a chemical have been derived from the non-observable effect level (NOEL) estimated in laboratory toxicity bioassays with organisms which are representative of certain taxa. There are fundamental problems with the validity of this approach, both conceptual and statistical in nature. Firstly, the outdated NOEL concept is being replaced by the no-effect concentration (NEC) level, which assumes that toxic chemicals do not have any effect on a population of organisms at very low concentrations. Recent developments in ecotoxicology, however, suggest that some toxicants can produce effects at any concentration level provided their exposure time is sufficiently long. Consequently, risk assessment of these chemicals, which includes neonicotinoid insecticides, some carcinogenic substances and certain metallic compounds, may require entirely new approaches. Secondly, the traditional approach to toxicity testing is to consider dose or concentration-effect relationships at arbitrarily fixed exposure durations which are supposed to reflect âacuteâ or âchronicâ time scales. This approach measures the proportion of all exposed individuals responding by the end of those fixed exposure times. However, the endpoint values obtained this way cannot be linked to make predictions for the wide range of exposures encountered by humans or in the environment, thus leading to serious underestimates of actual risk. In order to overcome this handicap, an increasing number of researchers are using a variant of the traditional toxicity testing protocol which includes time to event (TTE) methods. This TTE approach measures the times to respond for all individuals, and provides information on the acquired doses as well as the exposure times needed for a toxic compound to produce any level of effect on the organisms tested. Consequently, extrapolations and predictions of toxic effects for any combination of concentration and time are now made possible. Examples are shown to demonstrate that this approach is superior to current toxicological testing procedures, and has important implications for risk assessment of chemicals, particularly when the chemical has delayed toxic effects in a time-dependent manner

Phosphoinositide-binding interface proteins involved in shaping cell membranes

The mechanism by which cell and cell membrane shapes are created has long been a subject of great interest. Among the phosphoinositide-binding proteins, a group of proteins that can change the shape of membranes, in addition to the phosphoinositide-binding ability, has been found. These proteins, which contain membrane-deforming domains such as the BAR, EFC/F-BAR, and the IMD/I-BAR domains, led to inward-invaginated tubes or outward protrusions of the membrane, resulting in a variety of membrane shapes. Furthermore, these proteins not only bind to phosphoinositide, but also to the N-WASP/WAVE complex and the actin polymerization machinery, which generates a driving force to shape the membranes

Global Intermittency and Collapsing Turbulence in the Stratified Planetary Boundary Layer

Direct numerical simulation of the turbulent Ekman layer over a smooth wall is used to investigate bulk properties of a planetary boundary layer under stable stratification. Our simplified configuration depends on two non-dimensional parameters: a Richardson number characterizing the stratification and a Reynolds number characterizing the turbulence scale separation. This simplified configuration is sufficient to reproduce global intermittency, a turbulence collapse, and the decoupling of the surface from the outer region of the boundary layer. Global intermittency appears even in the absence of local perturbations at the surface; the only requirement is that large-scale structures several times wider than the boundary-layer height have enough space to develop. Analysis of the mean velocity, turbulence kinetic energy, and external intermittency is used to investigate the large-scale structures and corresponding differences between stably stratified Ekman flow and channel flow. Both configurations show a similar transition to the turbulence collapse, overshoot of turbulence kinetic energy, and spectral properties. Differences in the outer region resulting from the rotation of the system lead, however, to the generation of enstrophy in the non-turbulent patches of the Ekman flow. The coefficient of the stability correction function from Monin-Obukhov similarity theory is estimated as (Formula presented.) in agreement with atmospheric observations, theoretical considerations, and results from stably stratified channel flows. Our results demonstrate the applicability of this set-up to atmospheric problems despite the intermediate Reynolds number achieved in our simulations. © 2014 The Author(s)

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous WIA in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little, while not much new information has been gathered on soil organisms. The impact on marine coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal classneonicotinoids and fipronil. , withContinued large scale – mostly prophylactic – use of these persistent organochlorine pesticides has the potential to greatly decreasecompletely eliminate populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates, and their deleterious impacts on growth, reproduction and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015)

Turbulence in Rivers

The study of turbulence has always been a challenge for scientists working on geophysical flows. Turbulent flows are common in nature and have an important role in geophysical disciplines such as river morphology, landscape modeling, atmospheric dynamics and ocean currents. At present, new measurement and observation techniques suitable for fieldwork can be combined with laboratory and theoretical work to advance the understanding of river processes. Nevertheless, despite more than a century of attempts to correctly formalize turbulent flows, much still remains to be done by researchers and engineers working in hydraulics and fluid mechanics. In this contribution we introduce a general framework for the analysis of river turbulence. We revisit some findings and theoretical frameworks and provide a critical analysis of where the study of turbulence is important and how to include detailed information of this in the analysis of fluvial processes. We also provide a perspective of some general aspects that are essential for researchers/ practitioners addressing the subject for the first time. Furthermore, we show some results of interest to scientists and engineers working on river flows

The molecular basis of simple relationships between exposure concentration and toxic effects with time.

Understanding the toxicity of chemicals to organisms requires considering the molecular mechanisms involved as well as the relationships between exposure concentration and toxic effects with time. Our current knowledge about such relationships is mainly explained from a toxicodynamic and toxicokinetic perspective. This paper re-introduces an old approach that takes into account the biochemical mode of action and their resulting biological effects over time of exposure. Empirical evidence demonstrates that the Druckrey-Küpfmüller toxicity model, which was validated for chemical carcinogens in the early 1960s, is also applicable to a wide range of toxic compounds in ecotoxicology. According to this model, the character of a poison is primarily determined by the reversibility of critical receptor binding. Chemicals showing irreversible or slowly reversible binding to specific receptors will produce cumulative effects with time of exposure, and whenever the effects are also irreversible (e.g. death) they are reinforced over time; these chemicals have time-cumulative toxicity. Compounds having non-specific receptor binding, or involving slowly reversible binding to some receptors that do not contribute to toxicity, may also be time-dependent; however, their effects depend primarily on the exposure concentration, with time playing a minor role. Consequently, the mechanism of toxic action has important implications for risk assessment. Traditional risk approaches cannot predict the impacts of toxicants with time-cumulative toxicity in the environment. New assessment procedures are needed to evaluate the risk that the latter chemicals pose on humans and the environment. An example is shown to explain how the risk of time-dependent toxicants is underestimated when using current risk assessment protocols