Evaluation of models to estimate the bioaccumulation of organic chemicals in earthworms.

Modelling approaches to estimate the bioaccumulation of organic chemicals by earthworms are important for improving the realism in risk assessment of chemicals. However, the applicability of existing models is uncertain, partly due to the lack of independent datasets to test them. This study therefore conducted a comprehensive literature review on existing empirical and kinetic models that estimate the bioaccumulation of organic chemicals in earthworms and gathered two independent datasets from published literature to evaluate the predictive performance of these models. The Belfroid et al. (1995a) model is the best-performing empirical model, with 91.2% of earthworm body residue simulations within an order of magnitude of observation. However, this model is limited to the more hydrophobic pesticides and to the earthworm species Eisenia fetida or Eisenia andrei. The kinetic model proposed by Jager et al. (2003b) which out-performs that of Armitage and Gobas (2007), predicted uptake of PCB 153 in the earthworm E. andrei to within a factor of 10. However, the applicability of Jager et al.'s model to other organic compounds and other earthworm species is unknown due to the limited evaluation dataset. The model needs to be parameterised for different chemical, soil, and species types prior to use, which restricts its applicability to risk assessment on a broad scale. Both the empirical and kinetic models leave room for improvement in their ability to reliably predict bioaccumulation in earthworms. Whether they are fit for purpose in environmental risk assessment needs careful consideration on a case by case basis.

Earthworm lipid content and size help account for differences in pesticide bioconcentration between species.

The uptake and elimination kinetics of pesticides from soil to earthworms are important in characterising the risk of pesticides to soil organisms and the risk from secondary poisoning. However, the understanding of the relative importance of chemical, soil, and species differences in determining pesticide bioconcentration into earthworms is limited. Furthermore, there is insufficient independent data in the literature to fully evaluate existing predictive bioconcentration models. We conducted kinetic uptake and elimination experiments for three contrasting earthworm species (Lumbricus terrestris, Aporrectodea caliginosa, Eisenia fetida) in five soils using a mixture of five pesticides (log Kow 1.69 - 6.63). Bioconcentration increased with pesticide hydrophobicity and decreased with soil organic matter. Bioconcentration factors were comparable between earthworm species for hydrophilic pesticides due to the similar water content of earthworm species. Inter-species variations in bioconcentration of hydrophobic pesticides were primarily accounted for by earthworm lipid content and specific surface area (SSA). Existing bioconcentration models either failed to perform well across earthworm species and for more hydrophilic compounds (log Kow < 2) or were not parameterised for a wide range of compounds and earthworm species. Refined models should incorporate earthworm properties (lipid content and SSA) to account for inter-species differences in pesticide uptake from soil.

Effects of soil redistribution by tillage on subsequent transport of pesticide to subsurface drains.

BACKGROUND: Tillage operations will change the distribution in soil for any pesticide residues still present from earlier applications. This redistributive effect of tillage has been neglected in the study of pesticide leaching behavior. This study reviews the literature to characterize this redistributive effect for different tillage operations and uses a pesticide leaching model to investigate the impact of redistribution on pesticide transport to subsurface drains which is a significant input route to surface water bodies. RESULTS: Inversion ploughing moves the majority of any residues of pesticide present at or near the soil surface into the bottom two-thirds of the plough layer, whereas non-inversion ploughing has only a limited redistributive effect. Incorporating this redistributive effect into model simulations resulted in large changes (typically 5-10-fold difference) in both the maximum concentration and total mass of pesticide transported to drains over the winter following cultivation. More intense cultivation decreased subsequent leaching for relatively mobile compounds (Koc ≤1000 mL g-1 ), but increased it for strongly sorbed pesticides (Koc ≥2000 mL g-1 ). CONCLUSION: The redistributive effect of soil tillage on pesticide residues can have a large effect on subsequent transport to subsurface drains. This effect has been neglected in the literature. Field research is required to validate the model simulations presented here, and consideration should be given as to whether the effect needs to be included within risk assessment procedures. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Development of a Highly Differentiated Human Primary Proximal Tubule MPS Model (aProximate MPS Flow).

The kidney proximal tubule (PT) mediates renal drug elimination in vivo and is a major site of drug-induced toxicity. To reliably assess drug efficacy, it is crucial to construct a model in which PT functions are replicated. Current animal studies have proven poorly predictive of human outcome. To address this, we developed a physiologically relevant micro-physiological system (MPS) model of the human PT, the aProximate MPS Flow platform (Patent No: G001336.GB). In this model, primary human PT cells (hPTCs) are subjected to fluidic media flow and a shear stress of 0.01-0.2 Pa. We observe that these cells replicate the polarity of hPTCs and exhibit a higher expression of all the key transporters of SLC22A6 (OAT1), SLC22A8 (OAT3), SLC22A2 (OCT2), SLC47A1 (MATE1), SLC22A12 (URAT1), SLC2A9 (GLUT9), ABCB1 (MDR1), ABCC2 (MRP2), LRP2 (megalin), CUBN (cubilin), compared with cells grown under static conditions. Immunofluorescence microscopy confirmed an increase in OAT1, OAT3, and cilia protein expression. Increased sensitivity to nephrotoxic protein cisplatin was observed; creatinine and FITC-albumin uptake was significantly increased under fluidic shear stress conditions. Taken together, these data suggest that growing human PT cells under media flow significantly improves the phenotype and function of hPTC monolayers and has benefits to the utility and near-physiology of the model.

c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis.

Fibrosis is a common pathological feature of chronic disease. Deletion of the NF-κB subunit c-Rel limits fibrosis in multiple organs, although the mechanistic nature of this protection is unresolved. Using cell-specific gene-targeting manipulations in mice undergoing liver damage, we elucidate a critical role for c-Rel in controlling metabolic changes required for inflammatory and fibrogenic activities of hepatocytes and macrophages and identify Pfkfb3 as the key downstream metabolic mediator of this response. Independent deletions of Rel in hepatocytes or macrophages suppressed liver fibrosis induced by carbon tetrachloride, while combined deletion had an additive anti-fibrogenic effect. In transforming growth factor-ß1-induced hepatocytes, c-Rel regulates expression of a pro-fibrogenic secretome comprising inflammatory molecules and connective tissue growth factor, the latter promoting collagen secretion from HMs. Macrophages lacking c-Rel fail to polarize to M1 or M2 states, explaining reduced fibrosis in RelΔLysM mice. Pharmacological inhibition of c-Rel attenuated multi-organ fibrosis in both murine and human fibrosis. In conclusion, activation of c-Rel/Pfkfb3 in damaged tissue instigates a paracrine signalling network among epithelial, myeloid and mesenchymal cells to stimulate fibrogenesis. Targeting the c-Rel-Pfkfb3 axis has potential for therapeutic applications in fibrotic disease.

A knowledge-based approach to designing control strategies for agricultural pests.

Chemical control of insect pests remains vital to agricultural productivity, but limited mechanistic understanding of the interactions between crop, pest and chemical control agent have restricted our capacity to respond to challenges such as the emergence of resistance and demands for tighter environmental regulation. Formulating effective control strategies that integrate chemical and non-chemical management for soil-dwelling pests is particularly problematic owing to the complexity of the soil-root-pest system and the variability that occurs between sites and between seasons. Here, we present a new concept, termed COMPASS, that integrates ecological knowledge on pest development and behaviour together with crop physiology and mechanistic understanding of chemical distribution and toxic action within the rhizosphere. The concept is tested using a two-dimensional systems model (COMPASS-Rootworm) that simulates root damage in maize from the corn rootworm Diabrotica spp. We evaluate COMPASS-Rootworm using 119 field trials that investigated the efficacy of insecticidal products and placement strategies at four sites in the USA over a period of ten years. Simulated root damage is consistent with measurements for 109 field trials. Moreover, we disentangle factors influencing root damage and pest control, including pest pressure, weather, insecticide distribution, and temporality between the emergence of crop roots and pests. The model can inform integrated pest management, optimize pest control strategies to reduce environmental burdens from pesticides, and improve the efficiency of insecticide development.

High prevalence of the neonicotinoid clothianidin in liver and plasma samples collected from gamebirds during autumn sowing.

Since neonicotinoid insecticides were introduced to the agricultural market, evidence of the negative impacts of these systemic compounds on non-target species has accumulated. Birds are one of the largest groups of species to inhabit farmland, but the extent of neonicotinoid exposure in avian communities is poorly understood and very little is known about how any exposure may affect wild birds. Here, free-living gamebirds were used as a model group to measure the extent of avian exposure to the neonicotinoid clothianidin via seed treatment. During a typical sowing period of winter cereals treated with clothianidin, blood and liver samples were collected simultaneously from individual hunted gamebird carcasses, both pre- (n = 18) and post-sowing (n = 57) and were analysed for clothianidin via LC/MS-MS. Body weight, fat score and faecal parasite load were also quantified in the birds to ascertain whether any of these health parameters were associated with clothianidin exposure under field conditions. Clothianidin was detected in 6% of individuals sampled pre-sowing and 89% of individuals sampled post-sowing. The frequency of clothianidin detection in plasma samples and the concentration of clothianidin in liver and plasma samples decreased significantly between the first week and 2-4 weeks post-sowing. Faecal parasite load was positively associated with concentrations of clothianidin in the liver (but not plasma) of partridge species, but there was no association between clothianidin concentration and fat score or body weight, for either sample type. This study provides clear evidence that treated seed is a source of pesticide exposure for gamebirds following autumn sowing. These findings have implications for gamebirds worldwide where seed treatments are in use, and will aid the design of any future avian biomonitoring studies for agrochemical compounds.

From seeds to plasma: Confirmed exposure of multiple farmland bird species to clothianidin during sowing of winter cereals.

Neonicotinoids are the largest group of systemic insecticides worldwide and are most commonly applied as agricultural seed treatments. However, little is known about the extent to which farmland birds are exposed to these compounds during standard agricultural practices. This study uses winter cereal, treated with the neonicotinoid clothianidin, as a test system to examine patterns of exposure in farmland birds during a typical sowing period. The availability of neonicotinoid-treated seed was recorded post-sowing at 39 fields (25 farms), and camera traps were used to monitor seed consumption by wild birds in situ. The concentration of clothianidin in treated seeds and crop seedlings was measured via liquid chromatography-tandem mass spectrometry, and avian blood samples were collected from 11 species of farmland bird from a further six capture sites to quantify the prevalence and level of clothianidin exposure associated with seed treatments. Neonicotinoid-treated seeds were found on the soil surface at all but one of the fields surveyed at an average density of 2.8 seeds/m2. The concentration of clothianidin in seeds varied around the target application rate, whilst crop seedlings contained on average 5.9% of the clothianidin measured in seeds. Exposure was confirmed in 32% of bird species observed in treated fields and 50% of individual birds post-sowing; the median concentration recorded in positive samples was 12 ng/mL. Results here provide clear evidence that a variety of farmland birds are subject to neonicotinoid exposure following normal agricultural sowing of neonicotinoid-treated cereal seed. Furthermore, the widespread availability of seeds at the soil surface was identified as a primary source of exposure. Overall, these data are likely to have global implications for bird species and current agricultural policies where neonicotinoids are in use, and may be pertinent to any future risk assessments for systemic insecticide seed treatments.

Comparison of technical and systems-based approaches to managing pesticide contamination in surface water catchments.

Diffuse pollution of surface waters by herbicides remains a problem despite 25 years of research into mitigation approaches. This study adopts the grassweed herbicide propyzamide as a focus to compare the efficacy of technical, field-scale, interventions with systems-based cropping solutions in a 900 ha headwater catchment on heavy clay soils. Catchment monitoring was combined with modelling of land management options using SWAT, and semi-structured discussions with farmers. Vegetated buffers are the main mitigation in the catchment at present, and these are estimated to be halving propyzamide concentrations in the headwater stream. Increasing vegetated buffers to 20 m width around all water courses would be the most effective technical intervention. Collaboration between farmers to ensure differentiated application timings would be ineffective without precise forecasting to avoid application soon before storm events. Downstream pesticide limits could only be met by restricting the area of land treated with propyzamide, requiring a switch away from oilseed rape cultivation. This restriction was not acceptable to farmers who noted the lack of enablers for coordination between landowners and the need for pesticide targets that are specific to headwater catchments.

Using long-term datasets to assess the impacts of dietary exposure to neonicotinoids on farmland bird populations in England.

Over the last 20 years, a new group of systemic insecticides-the neonicotinoids-has gained prominence in arable systems, and their application globally has risen year on year. Previous modelling studies using long-term data have suggested that neonicotinoid application has had a detrimental impact on bird populations, but these studies were either limited to a single species or neglected to analyse specific exposure pathways in conjunction with observed population trends. Using bird abundance data, neonicotinoid usage records and cropping data for England at a 5x5 km resolution, generalised linear mixed models were used to test for spatio-temporal associations between neonicotinoid use and changes in the populations of 22 farmland bird species between 1994 and 2014, and to determine whether any associations were explained by dietary preferences. We assigned farmland bird species to three categories of dietary exposure to neonicotinoids based on literature data for species diets and neonicotinoid residues present in dietary items. Significant estimates of neonicotinoid-related population change were obtained for 13 of the 22 species (9 positive effects, 4 negative effects). Model estimates for individual species were not collectively explained by dietary risk categories, so dietary exposure to neonicotinoids via ingestion of treated seeds and seedlings could not be confirmed as a causal factor in farmland bird declines. Although it is not possible to infer any generic effect of dietary exposure to neonicotinoids on farmland bird populations, our analysis identifies three species with significant negative estimates that may warrant further research (house sparrow Passer domesticus, skylark Alauda arvensis and red-legged partridge Alectoris rufa). We conclude that there was either no consistent effect of dietary exposure to neonicotinoids on farmland bird populations in England, or that any over-arching effect was not detectable using our study design. The potential for indirect effects of insecticide use on bird populations via reduced food availability was not considered here and should be a focus for future research.

Response of the popliteal artery to treadmill exercise and stress positioning in patients with and without exertional lower extremity symptoms.

OBJECTIVE: Functionally limiting exertional lower extremity pain and neurologic symptoms are commonly encountered in military and civilian settings. Exertional muscle compression of the popliteal artery (PA) and tibial nerve in the proximal calf (the "popliteal outlet") can be associated with these symptoms but is rarely investigated as a cause. Exertional ankle-brachial index (EABI) and dynamic PA ultrasound imaging may be suitable to screen for this syndrome of "functional" popliteal entrapment, but neither has been rigorously studied. Our objective was to characterize the response of the PA to lower extremity exertion and dynamic ankle positioning in symptomatic and asymptomatic limbs. METHODS: Limbs characterized as symptomatic (n = 29) or asymptomatic (n = 61) had duplex ultrasound PA diameter and peak systolic velocity measurements with the ankle neutral and maximally plantar flexed. EABIs were obtained at rest and 1 minute and 5 minutes after walking (5 minutes, 3 mph, 10-degree incline) and running (5 minutes, 6 mph, 0-degree incline). Significance was set at P ≤ .05. Data are expressed as mean ± standard error of the mean. RESULTS: Plantar flexion resulted in PA occlusion and changes in diameter and peak systolic velocity in symptomatic (three occluded, -2.4 ± 0.34 mm, +49 cm/s) and asymptomatic (six occluded, -1.6 ± 0.21 mm, +65 cm/s) limbs. The difference in percentage change was significant between groups only for diameter change. EABIs in both groups were similar at rest, decreased with running and walking at 1 minute, and were not fully recovered by 5 minutes. Symptomatic limbs had a greater decrease in ABI than did asymptomatic limbs with both running and walking. The decrease was greatest at 1 minute after running and significantly more pronounced in symptomatic (-0.18) than in asymptomatic (-0.02) limbs. CONCLUSIONS: EABI decrease at 1 minute after running and PA diameter decrease with dynamic ankle plantar flexion are significantly greater in limbs with than without exertional lower extremity symptoms. These noninvasive measurements may be valuable in the workup of such symptoms. PA and tibial nerve compression at the popliteal outlet may be a more frequent cause of functionally limiting exertional lower extremity pain and neurologic symptoms than previously recognized.

Assessment of occupational exposure to pesticide mixtures with endocrine-disrupting activity.

Occupational exposure to pesticide mixtures comprising active substance(s) and/or co-formulant(s) with known/possible endocrine-disrupting activity was assessed using long-term activity records for 50 professional operators representing arable and orchard cropping systems in Greece, Lithuania, and the UK. Exposure was estimated using the harmonised Agricultural Operator Exposure Model, and risk was quantified as a point of departure index (PODI) using the lowest no observed (adverse) effect level. Use of substances with known/possible endocrine activity was common, with 43 of the 50 operators applying at least one such active substance on more than 50% of spray days; at maximum, one UK operator sprayed five such active substances and 10 such co-formulants in a single day. At 95th percentile, total exposure was largest in the UK orchard system (0.041 × 10-2 mg kg bw-1 day-1) whereas risk was largest in the Greek cropping systems (PODI 0.053 × 10-1). All five cropping systems had instances indicating potential for risk when expressed at a daily resolution (maximum PODI 1.2-10.7). Toxicological data are sparse for co-formulants, so combined risk from complex mixtures of active substances and co-formulants may be larger in reality.

Small Water Bodies in Great Britain and Ireland: Ecosystem function, human-generated degradation, and options for restorative action.

Small, 1st and 2nd-order, headwater streams and ponds play essential roles in providing natural flood control, trapping sediments and contaminants, retaining nutrients, and maintaining biological diversity, which extend into downstream reaches, lakes and estuaries. However, the large geographic extent and high connectivity of these small water bodies with the surrounding terrestrial ecosystem makes them particularly vulnerable to growing land-use pressures and environmental change. The greatest pressure on the physical processes in these waters has been their extension and modification for agricultural and forestry drainage, resulting in highly modified discharge and temperature regimes that have implications for flood and drought control further downstream. The extensive length of the small stream network exposes rivers to a wide range of inputs, including nutrients, pesticides, heavy metals, sediment and emerging contaminants. Small water bodies have also been affected by invasions of non-native species, which along with the physical and chemical pressures, have affected most groups of organisms with consequent implications for the wider biodiversity within the catchment. Reducing the impacts and restoring the natural ecosystem function of these water bodies requires a three-tiered approach based on: restoration of channel hydromorphological dynamics; restoration and management of the riparian zone; and management of activities in the wider catchment that have both point-source and diffuse impacts. Such activities are expensive and so emphasis must be placed on integrated programmes that provide multiple benefits. Practical options need to be promoted through legislative regulation, financial incentives, markets for resource services and voluntary codes and actions.

The Importance of Incorporating OCT2 Plasma Membrane Expression and Membrane Potential in IVIVE of Metformin Renal Secretory Clearance.

Transporter expression, determined by quantitative proteomics, together with PBPK models is a promising approach for in vitro-to-in vivo extrapolation (IVIVE) of transporter-mediated drug clearance. OCT2-expressing HEK293 and MDCKII cells were used to predict in vivo renal secretory clearance (CLr,sec) of metformin. [14C]-Metformin uptake clearance in OCT2-expressing cells was determined and scaled to in vivo CLr,sec by using OCT2 expression in the cells versus the human kidney cortex. Through quantitative targeted proteomics, the total expression of OCT2 in HEK293, MDCKII cells, and human kidney cortex was 369.4 ± 26.8, 19 ± 1.1, and 7.6 ± 3.8 pmol/mg cellular protein, respectively. The expression of OCT2 in the plasma membrane of HEK293 and MDCKII cells, measured using an optimized biotinylation method followed by quantitative proteomics, was 30.2% and 51.6%, respectively. After correcting for percent of OCT2 expressed in the plasma membrane and the resting membrane potential (millivolts) difference between the OCT2-expressing cells and the renal epithelial cells, the predicted CLr,sec of metformin was 250.7 ml/min, a value within the range of the observed CLr,sec of metformin. These data demonstrate the promise of using quantitative proteomics for IVIVE of transporter-mediated drug clearance and highlight the importance of quantifying plasma membrane expression of transporters and utilizing cells that mimic the in vivo mechanism(s) of transport of drugs.

Assessment of exposure of professional agricultural operators to pesticides.

This study investigates how field practices in handling and applying pesticides influence the long-term patterns of professional agricultural operators' exposure to pesticides. It presents the first use of a comprehensive pesticide application dataset collected on behalf of the European Food Safety Authority with 50 operators selected to cover arable and orchard cropping systems in Greece, Lithuania and the UK. Exposure was predicted based on the harmonised Agricultural Operator Exposure Model (AOEM) and compared with Acceptable Operator Exposure Levels (AOELs). The amount of pesticides handled by individual operators across a cropping season was largest in the UK arable and orchard systems (median 580 and 437kg active substance, respectively), intermediate for the arable systems in Greece and Lithuania (151 and 77kg, respectively), and smallest in the Greek orchard system (22kg). Overall, 30 of the 50 operators made at least one application within a day with predicted exposure greater than the AOEL. The rate of AOEL exceedance was greatest in the Greek cropping systems (8 orchard operators, 2.8-16% of total applications; 7 arable operators, 1.1-14% of total applications), and least for the Lithuanian arable system (2 operators, 2.9-4.5% of total applications). Instances in Greece when predicted exposure exceed the AOEL were strongly influenced by the widespread use of wettable powder formulations (>40% of the total pesticide active substance handled for 11 of the 20 Greek operators). In contrast, the total area of land treated with an active substance on a single day was more important in the UK and Lithuania (95th percentile observed value was 132 and 19haday-1 for UK arable and orchard systems, respectively). Study findings can be used to evaluate current assumptions in regulatory exposure calculations and to identify situations with potential risk that require further analysis including measurements of exposure to validate model estimations.

Assessment of acute toxicity tests and rhizotron experiments to characterize lethal and sublethal control of soil-based pests.

BACKGROUND: Characterizing lethal and sublethal control of soil-based pests with plant protection products is particularly challenging due to the complex and dynamic interplay of the system components. Here, we present two types of studies: acute toxcity experiments (homogenous exposure of individuals in soil) and rhizotron experiments (heterogeneous exposure of individuals in soil) to investigate their ability to strengthen our understanding of mechanisms driving the effectivness of the plant protection product. Experiments were conducted using larvae of the western corn rootworm Diabrotica virgifera LeConte and three pesticide active ingredients: clothianidin (neonicotinoid), chlorpyrifos (organophosphate) and tefluthrin (pyrethroid). RESULTS: The order of compound concentrations needed to invoke a specific effect intensity (EC50 values) within the acute toxicity tests was chlorpyrifos > tefluthrin > clothianidin. This order changed for the rhizotron experiments because application type, fate and transport of the compounds in the soil profile, and sublethal effects on larvae also influence their effectiveness in controlling larval feeding on corn roots. CONCLUSION: Beyond the pure measurement of efficacy through observing relative changes in plant injury to control plants, the tests generate mechanistic understanding for drivers of efficacy apart from acute toxicity. The experiments have the potential to enhance efficacy testing and product development, and might be useful tools for assessing resistance development in the future. © 2018 Society of Chemical Industry.

Prospective mixture risk assessment and management prioritizations for river catchments with diverse land uses.

Ecological risk assessment increasingly focuses on risks from chemical mixtures and multiple stressors because ecosystems are commonly exposed to a plethora of contaminants and nonchemical stressors. To simplify the task of assessing potential mixture effects, we explored 3 land use-related chemical emission scenarios. We applied a tiered methodology to judge the implications of the emissions of chemicals from agricultural practices, domestic discharges, and urban runoff in a quantitative model. The results showed land use-dependent mixture exposures, clearly discriminating downstream effects of land uses, with unique chemical "signatures" regarding composition, concentration, and temporal patterns. Associated risks were characterized in relation to the land-use scenarios. Comparisons to measured environmental concentrations and predicted impacts showed relatively good similarity. The results suggest that the land uses imply exceedances of regulatory protective environmental quality standards, varying over time in relation to rain events and associated flow and dilution variation. Higher-tier analyses using ecotoxicological effect criteria confirmed that species assemblages may be affected by exposures exceeding no-effect levels and that mixture exposure could be associated with predicted species loss under certain situations. The model outcomes can inform various types of prioritization to support risk management, including a ranking across land uses as a whole, a ranking on characteristics of exposure times and frequencies, and various rankings of the relative role of individual chemicals. Though all results are based on in silico assessments, the prospective land use-based approach applied in the present study yields useful insights for simplifying and assessing potential ecological risks of chemical mixtures and can therefore be useful for catchment-management decisions. Environ Toxicol Chem 2018;37:715-728. © 2017 The Authors. Environmental Toxicology Chemistry Published by Wiley Periodicals, Inc.

Prospective aquatic risk assessment for chemical mixtures in agricultural landscapes.

Environmental risk assessment of chemical mixtures is challenging because of the multitude of possible combinations that may occur. Aquatic risk from chemical mixtures in an agricultural landscape was evaluated prospectively in 2 exposure scenario case studies: at field scale for a program of 13 plant-protection products applied annually for 20 yr and at a watershed scale for a mixed land-use scenario over 30 yr with 12 plant-protection products and 2 veterinary pharmaceuticals used for beef cattle. Risk quotients were calculated from regulatory exposure models with typical real-world use patterns and regulatory acceptable concentrations for individual chemicals. The results could differentiate situations when there was concern associated with single chemicals from those when concern was associated with a mixture (based on concentration addition) with no single chemical triggering concern. Potential mixture risk was identified on 0.02 to 7.07% of the total days modeled, depending on the scenario, the taxa, and whether considering acute or chronic risk. Taxa at risk were influenced by receiving water body characteristics along with chemical use profiles and associated properties. The present study demonstrates that a scenario-based approach can be used to determine whether mixtures of chemicals pose risks over and above any identified using existing approaches for single chemicals, how often and to what magnitude, and ultimately which mixtures (and dominant chemicals) cause greatest concern. Environ Toxicol Chem 2018;37:674-689. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

How does exposure to pesticides vary in space and time for residents living near to treated orchards?

This study investigated changes over 25 years (1987-2012) in pesticide usage in orchards in England and Wales and associated changes to exposure and risk for resident pregnant women living 100 and 1000 m downwind of treated areas. A model was developed to estimate aggregated daily exposure to pesticides via inhaled vapour and indirect dermal contact with contaminated ground, whilst risk was expressed as a hazard quotient (HQ) based on estimated exposure and the no observed (adverse) effect level for reproductive and developmental effects. Results show the largest changes occurred between 1987 and 1996 with total pesticide usage reduced by ca. 25%, exposure per unit of pesticide applied slightly increased, and a reduction in risk per unit exposure by factors of 1.3 to 3. Thereafter, there were no consistent changes in use between 1996 and 2012, with an increase in number of applications to each crop balanced by a decrease in average application rate. Exposure per unit of pesticide applied decreased consistently over this period such that values in 2012 for this metric were 48-65% of those in 1987, and there were further smaller decreases in risk per unit exposure. All aggregated hazard quotients were two to three orders of magnitude smaller than one, despite the inherent simplifications of assuming co-occurrence of exposure to all pesticides and additivity of effects. Hazard quotients at 1000 m were 5 to 16 times smaller than those at 100 m. There were clear signals of the impact of regulatory intervention in improving the fate and hazard profiles of pesticides used in orchards in England and Wales over the period investigated.