Application of scaling to mouse spontaneous movement: Path curvature varies with speed and linear distance features isochrony.

To conserve sequential behavior in relation to the topographic challenges of space, it is proposed that humans and nonhuman animals can organize behavior using different scaling principles. To deal with increases in linear distance, isochrony suggest that there is a corresponding increase in speed, whereas to deal with changes in curvature, speed is adjusted according to a power function. The present study investigates whether these principles provide a framework for describing the organization of mouse behavior in a variety of standard experimental tasks. The structure of movement was examined in ambulation during open field exploration; manipulation in a string-pulling task, in which a string is advanced hand over hand to retrieve food; and rung-walking, in which the limbs successively step from rung to rung on a horizontal ladder. Both principles were found to be conserved in the organization of mouse behavior across scales of movement. These principles provide novel measures of the temporal and geometric features of movement in the mouse and insights into how the temporal and geometric features of movement are conserved within different species.

Cue polarization and representation in mouse home base behaviors.

The nature of the representation guiding spatial navigation has been investigated extensively; however, most of this work has used behavioral tasks that involved learning the location of food reward or an escape platform. In contrast, relatively few studies have focused on the spatial representation of a home base, a ubiquitous feature of open-field behavior, and its ability to be encoded relative to environmental cues. The current set of experiments investigated acquisition and retention of the location of home base establishment. In general, proximal cues anchored the position of the home base during acquisition sessions across all four experiments. Although mice established a home base during retention sessions, previous experience did not influence its position during retention sessions. These observations demonstrate that stimulus control of home base position depends on access to proximal cues. Further work is needed to determine the extent that home base establishment may provide a framework to encode goal-directed spatial behaviors.

Age-related changes in the organization of spontaneously occurring behaviors.

Age-related changes in spatial and temporal processing have been documented across a range of species. Rodent studies typically investigate differences in performance between adult and senescent animals; however, progressive loss of neurons in the hippocampus and cortex has been observed to occur as early as after adolescence. Therefore, the current study evaluated the effects of age in three- and ten-month-old female rats on the organization of movement in open field and food protection behaviors, two tasks that have previously dissociated hippocampal and cortical pathology. Age-related differences were observed in general measures of locomotion, spatial orientation, and attentional processing. The results of the current study are consistent with age-related changes in the processing of spatial information and motivation that occur earlier in life than previously anticipated. These observations establish a foundation for future studies evaluating interventions that influence these age-related differences in performance.

Differential organization of open field behavior in mice following acute or chronic simulated GCR exposure.

Astronauts undertaking deep space travel will receive chronic exposure to the mixed spectrum of particles that comprise Galactic Cosmic Radiation (GCR). Exposure to the different charged particles of varied fluence and energy that characterize GCR may impact neural systems that support performance on mission critical tasks. Indeed, growing evidence derived from years of terrestrial-based simulations of the space radiation environment using rodents has indicated that a variety of exposure scenarios can result in significant and long-lasting decrements to CNS functionality. Many of the behavioral tasks used to quantify radiation effects on the CNS depend on neural systems that support maintaining spatial orientation and organization of rodent open field behavior. The current study examined the effects of acute or chronic exposure to simulated GCR on the organization of open field behavior under conditions with varied access to environmental cues in male and female C57BL/6 J mice. In general, groups exhibited similar organization of open field behavior under dark and light conditions. Two exceptions were noted: the acute exposure group exhibited significantly slower and more circuitous homeward progressions relative to the chronic group under light conditions. These results demonstrate the potential of open field behavior organization to discriminate between the effects of select GCR exposure paradigms.

Potential emerging chemical risks in the food chain associated with substances registered under REACH.

A screening procedure for the identification of potential emerging chemical risks in the food and feed chain developed in a previous EFSA-sponsored pilot study was applied to 15021 substances registered under the REACH Regulation at the time of evaluation. Eligible substances were selected from this dataset by excluding (a) intermediates handled under strictly controlled conditions, (b) substances lacking crucial input data and (c) compounds considered to be outside the applicability domain of the models used. Selection of eligible substances resulted in a considerable reduction to 2336 substances. These substances were assessed and scored for environmental release (tonnage and use information from REACH registration dossiers), biodegradation (predictions from BIOWIN models 3, 5 and 6 evaluated in a battery approach), bioaccumulation in food/feed (ACC-HUMANsteady modelling) and chronic human health hazards (classification according to the CLP Regulation for carcinogenicity, mutagenicity, reproductive toxicity and repeated dose toxicity as well as IARC classification for carcinogenicity). Prioritisation based on the scores assigned and additional data curation steps identified 212 substances that are considered potential emerging risks in the food chain. Overall, 53% of these substances were prioritised due to chronic hazards identified in REACH registrations dossiers only (i.e. hazards not identified in classifications from other sources). Bioaccumulation in food and feed predicted on the basis of ACC-HUMANsteady modelling identified many substances that are not considered bioaccumulative in aquatic or terrestrial organisms based on screening criteria of the relevant ECHA guidance documents. Furthermore, 52% of the priority substances have not yet been assessed for their presence in food/feed by EU regulatory agencies. This finding and illustrative examples suggest that the screening procedure identified substances that have the potential to be emerging chemical risks in the food chain. Future research should investigate whether they actually represent emerging chemical risks as defined in EFSA's mandate.

Development of a novel scoring system for identifying emerging chemical risks in the food chain.

The European Food Safety Authority (EFSA) is responsible for risk assessment of all aspects of food safety, including the establishment of procedures aimed at the identification of emerging risks to food safety. Here, a scoring system was developed for identifying chemicals registered under the European REACH Regulation that could be of potential concern in the food chain using the following parameters: (i) environmental release based on maximum aggregated tonnages and environmental release categories; (ii) biodegradation in the environment; (iii) bioaccumulation and in vivo and in vitro toxicity. The screening approach was tested on 100 data-rich chemicals registered under the REACH Regulation at aggregated volumes of at least 1000 tonnes per annum. The results show that substance-specific data generated under the REACH Regulation can be used to identify potential emerging risks in the food chain. After application of the screening procedure, priority chemicals can be identified as potentially emerging risk chemicals through the integration of exposure, environmental fate and toxicity. The default approach is to generate a single total score for each substance using a predefined weighting scenario. However, it is also possible to use a pivot table approach to combine the individual scores in different ways that reflect user-defined priorities, which enables a very flexible, iterative definition of screening criteria. Possible applications of the approaches are discussed using illustrative examples. Either approach can then be followed by in-depth evaluation of priority substances to ensure the identification of substances that present a real emerging chemical risk in the food chain.

Consumer exposure modelling under REACH: Assessing the defaults.

Consumer exposure to chemicals from products and articles is rarely monitored. Since an assessment of consumer exposure has become particularly important under the European REACH Regulation, dedicated modelling approaches with exposure assessment tools are applied. The results of these tools are critically dependent on the default input values embedded in the tools. These inputs were therefore compiled for three lower tier tools (ECETOC TRA (version 3.0), EGRET and REACT)) and benchmarked against a higher tier tool (ConsExpo (version 4.1)). Mostly, conservative input values are used in the lower tier tools. Some cases were identified where the lower tier tools used less conservative values than ConsExpo. However, these deviations only rarely resulted in less conservative exposure estimates compared to ConsExpo, when tested in reference scenarios. This finding is mainly due to the conservatism of (a) the default value for the thickness of the product layer (with complete release of the substance) used for the prediction of dermal exposure and (b) the complete release assumed for volatile substances (i.e. substances with a vapour pressure ⩾10Pa) for inhalation exposure estimates. The examples demonstrate that care must be taken when changing critical defaults in order to retain conservative estimates of consumer exposure to chemicals.

The impact of REACH on classification for human health hazards.

The REACH Regulation represents a major piece of chemical legislation in the EU and requires manufacturers and importers of chemicals to assess the safety of their substances. The classification of substances for their hazards is one of the crucial elements in this process. We analysed the effect of REACH on classification for human health endpoints by comparing information from REACH registration dossiers with legally binding, harmonised classifications. The analysis included 142 chemicals produced at very high tonnages in the EU, the majority of which have already been assessed in the past. Of 20 substances lacking a harmonised classification, 12 chemicals were classified in REACH registration dossiers. More importantly, 37 substances with harmonised classifications for human health endpoints had stricter classifications in registration dossiers and 29 of these were classified for at least one additional endpoint not covered by the harmonised classification. Substance-specific analyses suggest that one third of these additional endpoints emerged from experimental studies performed to fulfil information requirements under REACH, while two thirds resulted from a new assessment of pre-REACH studies. We conclude that REACH leads to an improved hazard characterisation even for substances with a potentially good data basis.

Allometric principles for interspecies extrapolation in toxicological risk assessment--empirical investigations.

Four types of data (toxicokinetic data of pharmaceuticals from six species including humans, LD(50) values from eight animal species, long-term NOAEL values of pesticides from mice, rats, and dogs, and toxicity data on anti-neoplastic agents from six species including humans) were used for interspecies comparisons. Species differences with regard to kinetic parameters and toxicity were evaluated and the concordance with predictions by allometric scaling according to caloric demand (allometric exponent 0.75) or to body weight (allometric exponent 1) was checked. For LD(50) values, agreement was poor for both allometric concepts. Recently reported concordance of LD(50) species differences with body weight scaling could be traced back to biased data selection. The other three datasets are clearly in agreement with the allometric scaling according to caloric demand. Caloric demand scaling is thus proposed as a generic interspecies extrapolation method in the absence of substance-specific data. Moreover, the evaluated data make it possible to describe uncertainty associated with the process of interspecies extrapolation by allometric rules.

Uptake of nitroaromatic compounds in plants : Implications for risk assessment of ammunition sites.

The uptake of nitroaromatic compounds by plants from the soil was studied at an ammunition site. After the development of analytical methods for 2,4,6-trinitrotoluene, aminodinitrotoluenes and dinitrotoluenes in plant material, we could show that these substances accumulated in the roots of plants and are found to a lesser extent inleaves and stems. We observed only moderate differences between various plant species. It is likely that a metabolic transformation in plants leads to the formation of dinitrotoluenes which are considered to be potent carcinogens. Results from soils with a wide range of explosive concentrations show a good correlation between the plant and soil concentrations. The relative accumulation in plant material is higher at lower soil concentrations. At low soil concentrations of about 1 mg trinitrotoluene/kg soil, an accumulation factor of about 0.5 can be derived. These data are an important input for the risk assessment of ammunition sites.