An integrated optical modulator operating at cryogenic temperatures.

Photonic integrated circuits (PICs) operating at cryogenic temperatures are fundamental building blocks required to achieve scalable quantum computing and cryogenic computing technologies1,2. Silicon PICs have matured for room-temperature applications, but their cryogenic performance is limited by the absence of efficient low-temperature electro-optic modulation. Here we demonstrate electro-optic switching and modulation from room temperature down to 4 K by using the Pockels effect in integrated barium titanate (BaTiO3) devices3. We investigate the temperature dependence of the nonlinear optical properties of BaTiO3, showing an effective Pockels coefficient of 200 pm V-1 at 4 K. The fabricated devices show an electro-optic bandwidth of 30 GHz, ultralow-power tuning that is 109 times more efficient than thermal tuning, and high-speed data modulation at 20 Gbps. Our results demonstrate a missing component for cryogenic PICs, removing major roadblocks for the realization of cryogenic-compatible systems in the field of quantum computing, supercomputing and sensing, and for interfacing those systems with instrumentation at room temperature.

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food.

The European Commission asked EFSA to update its 2011 risk assessment on polybrominated diphenyl ethers (PBDEs) in food, focusing on 10 congeners: BDE-28, -47, -49, -99, -100, -138, -153, -154, -183 and ­209. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour and reproductive/developmental effects are the critical effects in rodent studies. For four congeners (BDE-47, -99, -153, -209) the Panel derived Reference Points, i.e. benchmark doses and corresponding lower 95% confidence limits (BMDLs), for endpoint-specific benchmark responses. Since repeated exposure to PBDEs results in accumulation of these chemicals in the body, the Panel estimated the body burden at the BMDL in rodents, and the chronic intake that would lead to the same body burden in humans. For the remaining six congeners no studies were available to identify Reference Points. The Panel concluded that there is scientific basis for inclusion of all 10 congeners in a common assessment group and performed a combined risk assessment. The Panel concluded that the combined margin of exposure (MOET) approach was the most appropriate risk metric and applied a tiered approach to the risk characterisation. Over 84,000 analytical results for the 10 congeners in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary Lower Bound exposure to PBDEs were meat and meat products and fish and seafood. Taking into account the uncertainties affecting the assessment, the Panel concluded that it is likely that current dietary exposure to PBDEs in the European population raises a health concern.

Quantifying experts' uncertainty about the future cost of exotic diseases.

Since the foot-and-mouth disease outbreak of 2001 in the United Kingdom, there has been debate about the sharing, between government and industry, both the costs of livestock disease outbreaks and responsibility for the decisions that give rise to them. As part of a consultation into the formation of a new body to manage livestock diseases, government veterinarians and economists produced estimates of the average annual costs for a number of exotic infectious diseases. In this article, we demonstrate how the government experts were helped to quantify their uncertainties about the cost estimates using formal expert elicitation techniques. This has enabled the decisionmakers to have a greater appreciation of government experts' uncertainty in this policy area.

Retrospective cumulative dietary risk assessment of craniofacial alterations by residues of pesticides.

EFSA established cumulative assessment groups and conducted retrospective cumulative risk assessments for two types of craniofacial alterations (alterations due to abnormal skeletal development, head soft tissue alterations and brain neural tube defects) for 14 European populations of women in childbearing age. Cumulative acute exposure calculations were performed by probabilistic modelling using monitoring data collected by Member States in 2017, 2018 and 2019. A rigorous uncertainty analysis was performed using expert knowledge elicitation. Considering all sources of uncertainty, their dependencies and differences between populations, it was concluded with varying degrees of certainty that the MOET resulting from cumulative exposure is above 100 for the two types of craniofacial alterations. The threshold for regulatory consideration established by risk managers is therefore not exceeded. Considering the severity of the effects under consideration, it was also assessed whether the MOET is above 500. This was the case with varying levels of certainty for the head soft tissue alterations and brain neural tube defects. However, for the alterations due to abnormal skeletal development, it was found about as likely as not that the MOET is above 500 in most populations. For two populations, it was even found more likely that the MOET is below 500. These results were discussed in the light of the conservatism of the methodological approach.

Cumulative dietary risk assessment of chronic acetylcholinesterase inhibition by residues of pesticides.

A retrospective cumulative risk assessment of dietary exposure to pesticide residues was conducted for chronic inhibition of acetylcholinesterase. The pesticides considered in this assessment were identified and characterised in a previous scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the nervous system. The exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2016, 2017 and 2018, and individual food consumption data from 10 populations of consumers from different countries and from different age groups. Exposure estimates were obtained by means of a two-dimensional probabilistic model, which was implemented in SAS ® software. The characterisation of cumulative risk was supported by an uncertainty analysis based on expert knowledge elicitation. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides contributing to the chronic inhibition of acetylcholinesterase does not exceed the threshold for regulatory consideration established by risk managers.

Cumulative dietary risk characterisation of pesticides that have acute effects on the nervous system.

A retrospective acute cumulative risk assessment of dietary exposure to pesticide residues, supported by an uncertainty analysis based on expert knowledge elicitation, was conducted for two effects on the nervous system: brain and/or erythrocyte acetylcholinesterase inhibition, and functional alterations of the motor division. The pesticides considered in this assessment were identified and characterised in the scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the nervous system. Cumulative exposure assessments were conducted through probabilistic modelling by EFSA and the Dutch National Institute for Public Health and the Environment (RIVM) using two different software tools and reported separately. These exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2014, 2015 and 2016 and individual consumption data from 10 populations of consumers from different countries and different age groups. This report completes the characterisation of cumulative risk, taking account of the available data and the uncertainties involved. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides that have the acute effects on the nervous system mentioned above does not exceed the threshold for regulatory consideration established by risk managers.

Cumulative dietary risk characterisation of pesticides that have chronic effects on the thyroid.

A retrospective chronic cumulative risk assessment of dietary exposure to pesticide residues, supported by an uncertainty analysis based on expert knowledge elicitation, was conducted for two effects on the thyroid, hypothyroidism and parafollicular cell (C-cell) hypertrophy, hyperplasia and neoplasia. The pesticides considered in this assessment were identified and characterised in the scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the thyroid. Cumulative exposure assessments were conducted through probabilistic modelling by EFSA and the Dutch National Institute for Public Health and the Environment (RIVM) using two different software tools and reported separately. These exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2014, 2015 and 2016 and individual consumption data from 10 populations of consumers from different countries and different age groups. This report completes the characterisation of cumulative risk, taking account of the available data and the uncertainties involved. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides that have the chronic effects on the thyroid mentioned above does not exceed the threshold for regulatory consideration established by risk managers.

A retain and refine approach to cumulative risk assessment.

Mixtures of substances to which humans are exposed may lead to cumulative exposure and health effects. To study their effects, it is first necessary to identify a cumulative assessment group (CAG) of substances for risk assessment or hazard testing. Excluding substances from consideration before there is sufficient evidence may underestimate the risk. Conversely, including everything and treating the inevitable uncertainties using conservative assumptions is inefficient and may overestimate the risk, with an unknown level of protection. An efficient, transparent strategy is described to retain a large group, quantifying the uncertainty of group membership and other uncertainties. Iterative refinement of the CAG then focuses on adding information for the substances with high probability of contributing significantly to the risk. Probabilities can be estimated using expert opinion or derived from data on substance properties. An example is presented with 100 pesticides, in which the retain step identified a single substance to target refinement. Using an updated hazard characterisation for this substance reduced the mean exposure estimate from 0.43 to 0.28 µg kg-bw-1 day-1 and reduced the 99.99th percentile exposure from 24.9 to 5.1 µg kg-bw-1 day-1. Other retained substances contributed little to the risk estimates, even after accounting for uncertainty.

On the application of loss functions in determining assessment factors for ecological risk.

Assessment factors have been proposed as a means to extrapolate from data on the concentrations hazardous to a small sample of species to the concentration hazardous to p% of the species in a given community (HCp). Aldenberg and Jaworska [2000. Uncertainty of the hazardous concentration and fraction affected for normal species sensitivity distributions. Ecotoxicol. Environ. Saf. 46, 1-18] proposed estimators that prescribed universal assessment factors which made use of distributional assumptions associated with species sensitivity distributions. In this paper we maintain those assumptions but introduce loss functions which punish over- and under-estimation. Furthermore, the final loss function is parameterised such that conservatism can be asymmetrically and non-linearly controlled which enables one to better represent the reality of risk assessment scenarios. We describe the loss functions and derive Bayes rules for each. We demonstrate the method by producing a table of universal factors that are independent of the substance being assessed and which can be combined with the toxicity data in order to estimate the HC5. Finally, through an example we illustrate the potential strength of the newly proposed estimators which rationally accounts for the costs of under- and over-estimation to choose an estimator; as opposed to arbitrarily choosing a one-sided lower confidence limit.

Bayesian modeling of measurement errors and pesticide concentration in dietary risk assessments.

We propose new models for dealing with various sources of variability and uncertainty that influence risk assessments for dietary exposure. The uncertain or random variables involved can interact in complex ways, and the focus is on methodology for integrating their effects and on assessing the relative importance of including different uncertainty model components in the calculation of dietary exposures to contaminants, such as pesticide residues. The combined effect is reflected in the final inferences about the population of residues and subsequent exposure assessments. In particular, we show how measurement uncertainty can have a significant impact on results and discuss novel statistical options for modeling this uncertainty. The effect of measurement error is often ignored, perhaps due to the laboratory process conforming to the relevant international standards, for example, or is treated in an ad hoc way. These issues are common to many dietary risk analysis problems, and the methods could be applied to any food and chemical of interest. An example is presented using data on carbendazim in apples and consumption surveys of toddlers.

Establishment of cumulative assessment groups of pesticides for their effects on the nervous system.

Cumulative assessment groups of pesticides have been established for five effects on the nervous system: brain and/or erythrocyte acetylcholinesterase inhibition, functional alterations of the motor, sensory and autonomic divisions, and histological neuropathological changes in neural tissue. Sources of uncertainties resulting from the methodological approach and from the limitations in available data and scientific knowledge have been identified and considered. This report supports the publication of a scientific report on cumulative risk assessment to pesticides affecting the nervous system, in which all uncertainties identified for either the exposure assessment or the establishment of the cumulative assessment groups are incorporated into a consolidated risk characterisation.

Establishment of cumulative assessment groups of pesticides for their effects on the thyroid.

Cumulative assessment groups of pesticides have been established for two specific effects on the thyroid: firstly hypothyroidism, and secondly parafollicular cell (C-cell) hypertrophy, hyperplasia and neoplasia. Sources of uncertainties resulting from the methodological approach and from the limitations in available data and scientific knowledge have been identified and considered. This report supports the publication of a scientific report on cumulative risk assessment to pesticides affecting the thyroid, in which all uncertainties identified for either the exposure assessment or the establishment of the cumulative assessment groups are incorporated into a consolidated risk characterisation.

Assessing the risk to U.K. children from carbendazim residues in apple products.

We present a detailed study into the effects that uncertainty and variability have on the levels of dietary exposure of young children to carbendazim in a range of apple products, including raw apples, apple juice and processed apple foods. It is estimated that exposure is greater than the provisional EU acute reference dose of 0.02 mg/kg-bw/day on 0.29% of person days, although there is large uncertainty in the true number. The contribution from apple juice consumption appears to be significant. The issues presented are common to many dietary risk analysis problems, and the methods could be applied to any food group and chemical of interest.

Evaluating European Food Safety Authority Protection Goals for Honeybees (Apis mellifera): What Do They Mean for Pollination?

In recent years there has been growing concern regarding the sudden and unexplained failure of honeybee (Apis mellifera) colonies. Several factors have been suggested, including pesticides. In an effort to regulate their impact, guidance published by the European Food Safety Authority (EFSA) has recommended that the magnitude of effects on exposed colonies should not exceed 7% reduction in colony size after 2 brood cycles. However, fears have been raised regarding the practicality of measuring such a loss in the field. It is also unclear how this protection goal relates to maintaining the ecosystem services provided by bees, which we argue should be a primary objective for regulators. Here, we evaluate what these protection goals mean in relation to ecosystems performance using a computational colony model that incorporates mechanisms to simulate both lethal and sublethal pesticide effects. To these simulations, we apply a testing regime similar to that commonly used in field trials to produce standard assessment metrics. By relating these measures to losses in forager activity, we aim to identify which could be used as effective indicators of reduced ecoservice and to quantify acceptable limits below which performance can be maintained. Our findings show that loss of colony size is the best indicator of reduced ecoservice. Metrics that focus on specific colony functions such as increased brood or forager mortality are ineffective indicators for all types of simulated pesticide effects. At the levels of colony loss recommended by EFSA, using our default parameterization, we predict a loss of ecosystems performance of 3% to 4%. However, based on an extensive sensitivity analysis, it is clear that this estimate is subject to substantial uncertainty with losses under alternative parameterizations of up to 14%. Nevertheless, our model provides a valuable framework for assessing protection goals, allowing regulators to test relevant impacts and quantify their magnitude. Integr Environ Assess Manag 2018;14:750-758. © 2018 Crown Copyright and SETAC.

Guidance on quantitative pest risk assessment.

This Guidance describes a two-phase approach for a fit-for-purpose method for the assessment of plant pest risk in the territory of the EU. Phase one consists of pest categorisation to determine whether the pest has the characteristics of a quarantine pest or those of a regulated non-quarantine pest for the area of the EU. Phase two consists of pest risk assessment, which may be requested by the risk managers following the pest categorisation results. This Guidance provides a template for pest categorisation and describes in detail the use of modelling and expert knowledge elicitation to conduct a pest risk assessment. The Guidance provides support and a framework for assessors to provide quantitative estimates, together with associated uncertainties, regarding the entry, establishment, spread and impact of plant pests in the EU. The Guidance allows the effectiveness of risk reducing options (RROs) to be quantitatively assessed as an integral part of the assessment framework. A list of RROs is provided. A two-tiered approach is proposed for the use of expert knowledge elicitation and modelling. Depending on data and resources available and the needs of risk managers, pest entry, establishment, spread and impact steps may be assessed directly, using weight of evidence and quantitative expert judgement (first tier), or they may be elaborated in substeps using quantitative models (second tier). An example of an application of the first tier approach is provided. Guidance is provided on how to derive models of appropriate complexity to conduct a second tier assessment. Each assessment is operationalised using Monte Carlo simulations that can compare scenarios for relevant factors, e.g. with or without RROs. This document provides guidance on how to compare scenarios to draw conclusions on the magnitude of pest risks and the effectiveness of RROs and on how to communicate assessment results.

Probabilistic risk assessment for snails, slugs, and endangered honeycreepers in diphacinone rodenticide baited areas on Hawaii, USA.

Three probabilistic models were developed for characterizing the risk of mortality and subacute coagulopathy to Poouli, an endangered nontarget avian species, in broadcast diphacinone-baited areas on Hawaii, USA. For single-day exposure, the risk of Poouli mortality approaches 0. For 5-d exposure, the mean probability of mortality increased to 3% for adult and 8% for juvenile Poouli populations. For Poouli that consume snails containing diphacinone residues for 14 d, the model predicted increased levels of coagulopathy for 0.42 and 11% of adult and juvenile Poouli populations, respectively. Worst-case deterministic risk characterizations predicted acceptable levels of risk for nonthreatened or endangered species such as northern bobwhite quail and mallards. Also, no acute toxicity was noted for snails and slugs that feed on diphacinone baits.

Probabilistic model for estimating field mortality of target and non-target bird populations when simultaneously exposed to avicide bait.

A probabilistic model was developed to estimate target and non-target avian mortality associated with the application of the avicide CPTH (3-chloro-p-toluidine hydrochloride) to minimize sprouting rice damage in the southern USA. CPTH exposures for individual birds were predicted by random sampling from species-specific non-parametric distributions of bait seed consumption and CPTH residues detected on individual bait seeds. Mortality was predicted from the species-specific exposure versus mortality relationship. Individual variations in this response were captured in the model by Monte Carlo sampling from species-specific distributions of slopes and median toxicity values (LD50) for each bird. The model was used to simultaneously predict mortality (percentage of exposed population and number of birds killed/weight of consumed bait) for a target (blackbird) and non-target (mourning dove) species feeding on bait sites for up to five consecutive days.

New approaches to uncertainty analysis for use in aggregate and cumulative risk assessment of pesticides.

Risk assessments for human exposures to plant protection products (PPPs) have traditionally focussed on single routes of exposure and single compounds. Extensions to estimate aggregate (multi-source) and cumulative (multi-compound) exposure from PPPs present many new challenges and additional uncertainties that should be addressed as part of risk analysis and decision-making. A general approach is outlined for identifying and classifying the relevant uncertainties and variabilities. The implementation of uncertainty analysis within the MCRA software, developed as part of the EU-funded ACROPOLIS project to address some of these uncertainties, is demonstrated. An example is presented for dietary and non-dietary exposures to the triazole class of compounds. This demonstrates the chaining of models, linking variability and uncertainty generated from an external model for bystander exposure with variability and uncertainty in MCRA dietary exposure assessments. A new method is also presented for combining pesticide usage survey information with limited residue monitoring data, to address non-detect uncertainty. The results show that incorporating usage information reduces uncertainty in parameters of the residue distribution but that in this case quantifying uncertainty is not a priority, at least for UK grown crops. A general discussion of alternative approaches to treat uncertainty, either quantitatively or qualitatively, is included.

A European model and case studies for aggregate exposure assessment of pesticides.

Exposures to plant protection products (PPPs) are assessed using risk analysis methods to protect public health. Traditionally, single sources, such as food or individual occupational sources, have been addressed. In reality, individuals can be exposed simultaneously to multiple sources. Improved regulation therefore requires the development of new tools for estimating the population distribution of exposures aggregated within an individual. A new aggregate model is described, which allows individual users to include as much, or as little, information as is available or relevant for their particular scenario. Depending on the inputs provided by the user, the outputs can range from simple deterministic values through to probabilistic analyses including characterisations of variability and uncertainty. Exposures can be calculated for multiple compounds, routes and sources of exposure. The aggregate model links to the cumulative dietary exposure model developed in parallel and is implemented in the web-based software tool MCRA. Case studies are presented to illustrate the potential of this model, with inputs drawn from existing European data sources and models. These cover exposures to UK arable spray operators, Italian vineyard spray operators, Netherlands users of a consumer spray and UK bystanders/residents. The model could also be adapted to handle non-PPP compounds.

Application of uncertainty analysis in assessing dietary exposure.

Conventional approaches for assessing dietary exposure to contaminants and additives in food are deterministic, using point estimates for consumption and contamination. In reality, both consumption and contamination are variable. Furthermore our knowledge of them is uncertain, e.g. due to measurement uncertainty. Conventional approaches attempt to allow for this by using worst-case assumptions or safety factors, but these are often subjective and may result either in overestimation or underestimation of the true range of exposures. Probabilistic approaches take account of variability and uncertainty by using distributions rather than point estimates for consumption and contamination. The outputs are distributions for exposure, which provide a more complete and balanced description of risk for the decision-maker. These approaches also facilitate the use of sensitivity analysis to identify those factors that impact most on exposure, and to identify areas of uncertainty where additional data will improve exposure estimates. This paper reviews examples of the application of these methods to the assessment of dietary exposure to food contaminants, including dioxins in seafood, where it was found that the greatest uncertainties relate to toxicity rather than exposure. Further work required to implement probabilistic approaches for dietary exposure assessment is discussed.