National characterization of pesticide runoff and erosion potential to put USEPA standard ecological scenarios in context for pyrethroids.

Decision-making for pesticide registration by the US Environmental Protection Agency (USEPA) relies upon crop-specific scenarios in a tiered framework. These standard modeling scenarios are stated to represent "…sites expected to produce runoff greater than would be expected at 90% of the sites for a given crop/use." This study developed a novel approach to compare the pesticide runoff + erosion (SumRE ) mass flux potential of a hydrophobic chemical using 36 of these ecological regulatory scenarios with national-scale distributions of modeled SumRE from over 750 000 USA-wide agricultural catchments to provide real-world context for the simulated transport predictions used for regulatory decision-making. For the standard scenarios and national scale modeling, "edge of field" SumRE mass flux was estimated using regulatory guidance for a hypothetical pyrethroid. The national-scale simulations were developed using publicly available soil, hydrography, and crop occurrence /regional timings databases. Relevant soil and crop combinations identified by spatial overlay along with weather data were used in a regulatory model to generate daily SumRE estimates, which were assigned to the catchments. The resulting average annual total SumRE mass fluxes were ranked to produce distributions to compare with the standard regulatory scenario outputs. These comparisons showed that SumRE flux from 25 of the 36 USEPA ecological regulatory crop-specific scenarios modeled ranked above the 99th percentile of pyrethroid runoff + erosion vulnerability from any catchment growing that crop; SumRE flux from six scenarios was more severe than any catchment. For 12 USEPA regulatory scenarios, the resulting eroded sediment corresponds to highly erodible land (HEL), which the US Department of Agriculture mandates should not be cropped without substantial additional erosion prevention controls for sustainability. Since the pesticide regulatory framework already incorporates many acknowledged assumptions to ensure it conservatively meets protection goals, these HEL observations suggest that the standard scenarios overestimate potential aquatic exposure and that the regulatory process is more protective than intended. Integr Environ Assess Manag 2023;19:175-190. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Impact of Wind Speed and Direction and Key Meteorological Parameters on Potential Pesticide Drift Mass Loadings from Sequential Aerial Applications.

Pesticide spray drift is potentially a significant source of exposure to off-target, adjacent aquatic habitats. To estimate the magnitude of pesticide drift from aerial or ground applications, regulatory agencies in North America, Europe, and elsewhere rely on spray drift models to predict spray drift deposition for risk assessments. Refined assessments should ultimately depend on best-available data for exposure modeling. However, when developing lower tier "screening" assessments designed to indicate whether further refinement is needed, regulators often make conservative assumptions with a resulting increased level of uncertainty in estimating environmental exposure or risk. In the United States, it is generally accepted that, to ensure conservative regulatory assessments, it is reasonable to assume that the wind speed might be 4.47 m/s (10 miles per hour [mph]), the relative humidity and temperature are highly conducive to drift, and the wind is blowing directly toward a receiving water for any given single spray event in a season. However, what is the probability these conditions will all co-occur for each of 4 sequential spray events spaced a week apart (common practice for insecticides)? The refined approach in the present study investigates this question using hourly meteorological data sets for 5 United States Environmental Protection Agency (USEPA) standard crop scenarios to understand how real-world data can reduce unnecessary uncertainty for sequential applications. The impact of wind speeds, temperatures, relative humidity, and wind direction at different times of day on annual drift loadings has been examined using a stepwise process for comparison with corresponding regulatory default loading estimates. The impacts on drift estimates were significant; interestingly, the time of day of the applications impacted variability more than did the selected crop scenario. When all these real-world factors were considered, estimated 30-y total drift loads ranged from 2% to 5% greater than the default estimate (2 of 30 cases due to high afternoon wind speeds) to 51% to 86% reductions (25 of 30 cases) with an overall average reduction of 63%. Integr Environ Assess Manag 2020;16:197-210. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Comparison of empirical and mechanistic equations for vegetative filter strip pesticide mitigation in long-term environmental exposure assessments.

Recent advances in mechanistic modeling of vegetated filter strips (VFS) have made it possible to incorporate VFS mitigation into environmental exposure assessments (EEAs). However, outside of fixed efficiency approaches, there are no widely adopted and standardized procedures for incorporating VFS quantitative mitigation into long-term, higher-tier EEAs. A source of hesitation involves the use of empirical equations for predicting pesticide trapping by the VFS. A recent study evaluated existing empirical equations and a mechanistic mass-balance approach using the most extensive field database available of VFS pesticide efficiency from single-event storms. That study concluded that an updated empirical equation (Sabbagh equation) and a mechanistic mass-balance approach performed reasonably well. The objective of this research was to study the effect of upscaling the VFS trapping equations from single events into long-term EEAs. The U.S. EPA Pesticide in Water Calculator (PWC) model linked with the Vegetative Filter Strip MODeling system (VFSMOD) long-term EEA modeling framework (30 yr) was updated to incorporate the alternative trapping equations and tested VFS mitigation results under contrasting agroecological settings with varying erosion/sediment transport conditions. Differences in both acute and chronic 90th percentile estimated environmental exposure concentrations (EECs) were relatively small when comparing predictions using the four pesticide trapping equations. A global sensitivity analysis (GSA) also indicated that selection of a specific trapping equation for predicting EECs was less important than other important input factors such as the VFS length and pesticide properties. However, in terms of the percent reductions in EECs, the choice of pesticide trapping equation was as important as the VFS length. This research builds upon the conclusion of previous single-event studies that the mechanistic mass-balance and refit Sabbagh empirical equation were both valid for EEAs. The mass balance approach represents a reasonable option for regulatory agencies that prefer mechanistic approaches.

Effect of vegetative filter strip pesticide residue degradation assumptions for environmental exposure assessments.

Understanding and simulating the fate and transport of pesticides from a field to adjacent receiving water bodies is critical for estimating long-term environmental exposure concentrations (EECs) in regulatory higher-tier environmental exposure assessments (EEA). The potential of field mitigation practices like vegetative filter strips (VFS) to reduce pesticide pollution is receiving increasing attention. Previous research has proposed a modeling framework that links the US Environmental Protection Agency's (US-EPA) PRZM/EXAMS higher-tier EEA with a process-based VFS model (VFSMOD). This framework was updated to consider degradation and carryover of pesticide residue trapped in the VFS. However, there is disagreement on pesticide degradation assumptions among different regional EEA regulations (i.e. US or European Union), and in particular on how temperature and soil moisture dynamics may affect EECs. This research updated the VFS modeling framework to consider four degradation assumptions and determine if VFS residues and/or EECs differed with each assumption. Two model pesticides (mobile-labile and immobile-persistent) were evaluated for three distinct agroecological scenarios (continental row-crop agriculture, wet maritime agriculture, and dry Mediterranean intensive horticulture) with receiving water bodies and VFS lengths from 0 to 9m. The degradation assumption was important in long-term assessments to predict VFS pesticide residues (statistically different at p<0.01). However, due to the relatively small contribution of residues on the total pesticide mass moving through the VFS, degradation assumptions had a negligible impact on EECs. This indicates that, while important differences exist between EU or US EEAs, the choice of pesticide degradation assumption is not a main source of these differences.

Ecology-based evaluation of groundwater ecosystems under intensive agriculture: A combination of community analysis and sentinel exposure.

Ecological criteria are needed for a comprehensive evaluation of groundwater ecosystem health by including biological components with the physical and chemical properties that are already required by European directives. Two methodological approaches to assess the ecological status of groundwater ecosystems were combined in two alluvial plains (the Ariège and Hers Rivers, southwestern France) varying in agriculture intensity (from grassland to crop rotation including maize and sunflower, and to maize monoculture). In the first approach, the composition of invertebrate assemblages (only obligate-groundwater crustaceans, i.e. stygobionts) sampled in 28 wells differing in their land use contexts was analysed. Abundance, species richness, and assemblage composition significantly changed with agricultural land use or urbanization around the wells. In the second approach, we tested an in situ exposure of sentinel organisms to quantify their response to the environmental pressures. The epigean and native amphipod species Gammarus cf. orinos was used as the sentinel species. Amphipods (30 individuals in each of 10 wells) were exposed for one week to the in situ conditions at two seasons with contrasted concentrations of pollutants. The Ecophysiological Index (EPI) synthetizing the survival rates and energetic storage decreased in wells with low oxygen and high nitrate concentrations, but only during the highest contamination period. Atrazine-related compounds negatively impacted sentinel health whatever the season. The combination of these two approaches may have major applications for orientating groundwater ecosystem management.

Does mechanistic modeling of filter strip pesticide mass balance and degradation processes affect environmental exposure assessments?

Vegetative filter strips (VFS) are a widely adopted practice for limiting pesticide transport from adjacent fields to receiving waterbodies. The efficacy of VFS depends on site-specific input factors. To elucidate the complex and non-linear relationships among these factors requires a process-based modeling framework. Previous research proposed linking existing higher-tier environmental exposure models with a well-tested VFS model (VFSMOD). However, the framework assumed pesticide mass stored in the VFS was not available for transport in subsequent storm events. A new pesticide mass balance component was developed to estimate surface pesticide residue trapped in the VFS and its degradation between consecutive runoff events. The influence and necessity of the updated framework on acute and chronic estimated environmental concentrations (EECs) and percent reductions in EECs were investigated across three, 30-year U.S. EPA scenarios: Illinois corn, California tomato, and Oregon wheat. The updated framework with degradation predicted higher EECs than the existing framework without degradation for scenarios with greater sediment transport, longer VFS lengths, and highly sorbing and persistent pesticides. Global sensitivity analysis (GSA) assessed the relative importance of mass balance and degradation processes in the context of other input factors like VFS length (VL), organic-carbon sorption coefficient (Koc), and soil and water half-lives. Considering VFS pesticide residue and degradation was not important if single, large runoff events controlled transport, as is typical for higher percentiles considered in exposure assessments. Degradation processes become more important when considering percent reductions in acute or chronic EECs, especially under scenarios with lower pesticide losses.

fMRI investigation of the effect of local and systemic lidocaine on noxious electrical stimulation-induced activation in spinal cord.

Spinal cord fMRI offers an excellent opportunity to quantify nociception using neuronal activation induced by painful stimuli. Measurement of the magnitude of stimulation-induced activation, and its suppression with analgesics can provide objective measures of pain and efficacy of analgesics. This study investigates the feasibility of using spinal cord fMRI in anesthetized rats as a pain assay to test the analgesic effect of locally and systemically administered lidocaine. Blood volume (BV)-weighted fMRI signal acquired after intravenous injection of ultrasmall superparamagnetic iron oxide (USPIO) particles was used as an indirect readout of the neuronal activity. Transcutaneous noxious electrical stimulation was used as the pain model. BV-weighted fMRI signal could be robustly quantified on a run-by-run basis, opening the possibility of measuring pharmacodynamics (PD) of the analgesics with a temporal resolution of approximately 2 min. Local administration of lidocaine was shown to ablate all stimulation-induced fMRI signals by the total blockage of peripheral nerve transmission, while the analgesic effect of systemically administered lidocaine was robustly detected after intravenous infusion of approximately 3mg/kg, which is similar to clinical dosage for human. This study establishes spinal cord fMRI as a viable assay for analgesics. With respect to the mode of action of lidocaine, this study suggests that systemic lidocaine, which is clinically used for the treatment of neuropathic pain, and believed to only block the peripheral nerve transmission of abnormal neural activity (ectopic discharge) originating from the damaged peripheral nerves, also blocks the peripheral nerve transmission of normal neural activity induced by transcutaneous noxious electrical stimulation.

The voltage-gated sodium channel Nav1.9 is required for inflammation-based urinary bladder dysfunction.

Tetrodotoxin (TTX)-resistant sodium channels are found in small diameter primary sensory neurons and are thought to be important in the maintenance of inflammatory pain. Here we examined bladder urodynamics of Nav1.9 voltage-gated sodium channel knock out (KO) mice, and the contribution of Nav1.9 to the development of inflammation-based bladder dysfunction. Basal urodynamics were not different between wildtype (WT) mice and those lacking Nav1.9. Peripheral nerve recordings from pelvic afferents in Nav1.9 KO mice revealed a lack of sensitization to intravesicularly applied prostaglandin E2 (PGE2). Consistent with this, cyclophosphamide treatment in vivo, which is associated with an enhancement of PGE2 production, evoked a reduction in bladder capacity of WT, but not Nav1.9 KO mice. We conclude that the Nav1.9 sodium channel provides an important link between inflammatory processes and changes in urodynamic properties that occur during urinary bladder inflammation.

Many vaginal microbicide trial participants acknowledged they had misreported sensitive sexual behavior in face-to-face interviews.

OBJECTIVE: We investigated whether participants in a phase II randomized clinical trial of a candidate vaginal microbicide ever intentionally misled interviewers. STUDY DESIGN AND SETTING: We used audio computer-assisted self-interviews (ACASI) to ask the South African women (n=132) participating in the trial about the accuracy of self-reported data collected during face-to-face interviews. The trial protocol recommended that women use their assigned gel (active microbicide or placebo) with condoms during each vaginal sex act. RESULTS: Nearly four-fifths of participants (n=104, 79%) reported that they had misinformed trial interviewers at least once. Motivations included politeness (n=45, 34% of ACASI participants) to avoid criticism or seek praise (n=32, 24%), and embarrassment (n=24, 18%). Participants acknowledged misreporting eligibility characteristics to enroll (11%) and, during follow-up, exaggerating their enthusiasm for the study gel (13%), applicator (13%), and the effect of the gel on sexual pleasure (13%). In general, women who were untruthful had actually used the gel with condoms less and used the gel alone more than they had reported during the trial. Women overwhelmingly found the computer survey easy. CONCLUSION: Researchers cannot assume that participants always tell the truth about sensitive behaviors in face-to-face interviews. ACASI was efficient and acceptable in this population.

Habitat variation influences movement rates and population structure of an intertidal fish.

Understanding how variation in habitat characteristics influences the demography and behavior of organisms is of primary interest in ecological research. I studied how patterns of distribution, abundance, mortality and movement of the fluffy sculpin, Oligocottus snyderi, are related to variation in habitat characteristics within and between sites. The recruitment levels of O. snyderi are very similar at two different intertidal sites, yet post-recruitment processes modify the original recruitment signal at only one of the two sites. The two sites differ significantly in only one measured aspect of their tidepool habitat-the amount of cover provided by surfgrass or algae. Both recruits and adults of O. snyderi exhibit positive associations with the amount of tidepool cover, particularly the presence of surfgrass. A mark-recapture study determined that these differences in the habitat characteristics between the two sites are associated with differences in post-recruitment movement rates. In fact, the absence of a correlation at one site between O. snyderi recruit and adult abundances, which would typically be considered evidence for significant post-recruitment mortality, appears to be driven by strong within-site post-recruitment movement. Furthermore, although post-recruitment mortality rates do not vary significantly across the two sites, variation in post-recruitment mortality is weakly related to within-site variation in tidepool characteristics at one site. The results of this study suggest that post-settlement intertidal fishes continue to sample their surrounding environment as they mature and will redistribute themselves according to within-site spatial variation in habitat characteristics-a behavioral process that may obscure estimates of post-settlement mortality.

Discovery of a novel class of benzazepinone Na(v)1.7 blockers: potential treatments for neuropathic pain.

A series of benzodiazepines and benzazepinones were synthesized and evaluated as potential sodium channel blockers in a functional, membrane potential-based assay. One member of the benzazepinone series, compound 47, displayed potent, state-dependent block of hNa(v)1.7, and was orally efficacious in a rat model of neuropathic pain.

Expression and localization of the Nav1.9 sodium channel in enteric neurons and in trigeminal sensory endings: implication for intestinal reflex function and orofacial pain.

The Nav1.9 sodium channel is expressed in nociceptive DRG neurons where it contributes to spontaneous pain behavior after peripheral inflammation. Here, we used a newly developed antibody to investigate the distribution of Nav1.9 in rat and mouse trigeminal ganglion (TG) nerve endings and in enteric nervous system (ENS). In TGs, Nav1.9 was expressed in the soma of small- and medium-sized, peripherin-positive neurons. Nav1.9 was present along trigeminal afferent fibers and at terminals in lip skin and dental pulp. In the ENS, Nav1.9 was detected within the soma and proximal axons of sensory, Dogiel type II, myenteric and submucosal neurons. Immunological data were correlated with the detection of persistent TTX-resistant Na(+) currents sharing similar properties in DRG, TG and myenteric neurons. Collectively, our data support a potential role of Nav1.9 in the transmission of trigeminal pain and the regulation of intestinal reflexes. Nav1.9 might therefore constitute a molecular target for therapeutic treatments of orofacial pain and gastrointestinal syndromes.

Relationship between the firing frequency of injured peripheral neurons and inhibition of firing by sodium channel blockers.

UNLABELLED: Animal models of neuropathic pain in which a peripheral nerve is damaged result in spontaneous activity in primary afferents that can be inhibited by intravenous administration of sodium channel blockers. Many of these compounds exhibit use-dependent block of sodium current, leading to the prediction that they should more readily inhibit neurons that fire at higher frequencies. This prediction was tested in 2 rat models of nerve injury, L5 spinal nerve section and sciatic nerve section. Sciatic nerve section produced average firing frequencies that were higher than spinal nerve section and often manifested as high-frequency bursting. Inhibition of firing by intravenous sodium channel blockers was longer lasting in this model. Within each model, higher frequency of firing did not translate into more effective block. In the spinal nerve section model, there was a robust inverse correlation between frequency and inhibition. Within the sciatic section model, only neurons that fired in rhythmic bursts were inhibited, and again, those firing at lower mean frequencies were more effectively inhibited. These results indicate that the efficacy of sodium channel blockers depends on the nature of the injury and the pattern of the resulting activity rather than simply the frequency of action potentials generated. PERSPECTIVE: This study examines the ability of frequency-dependent sodium channel blockers to inhibit spontaneous firing of injured peripheral nerves in vivo. It outlines the conditions under which inhibition is more and less effective and will provide insight into conditions under which sodium channel blockers are likely to be therapeutically useful.

Glial cell-line-derived neurotrophic factor expression in skin alters the mechanical sensitivity of cutaneous nociceptors.

Neurons classified as nociceptors are dependent on nerve growth factor (NGF) during embryonic development, but a large subpopulation lose this dependence during embryonic and postnatal times and become responsive to the transforming growth factor beta family member, glial cell line-derived growth factor (GDNF). To elucidate the functional properties of GDNF-dependent nociceptors and distinguish them from nociceptors that retain NGF dependence, the cellular and physiologic properties of sensory neurons of wild-type and transgenic mice that overexpress GDNF in the skin (GDNF-OE) were analyzed using a skin, nerve, dorsal root ganglion, and spinal cord preparation, immunolabeling, and reverse transcriptase-PCR assays. Although an increase in peripheral conduction velocity of C-fibers in GDNF-OE mice was measured, other electrophysiological properties, including resting membrane potential and somal action potentials, were unchanged. We also show that isolectin B4 (IB4)-positive neurons, many of which are responsive to GDNF, exhibited significantly lower thresholds to mechanical stimulation relative to wild-type neurons. However, no change was observed in heat thresholds for the same population of cells. The increase in mechanical sensitivity was found to correlate with significant increases in acid-sensing ion channels 2A and 2B and transient receptor potential channel A1, which are thought to contribute to detection of mechanical stimuli. These data indicate that enhanced expression of GDNF in the skin can change mechanical sensitivity of IB4-positive nociceptive afferents and that this may occur through enhanced expression of specific types of channel proteins.

Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior.

The transmission of pain signals after injury or inflammation depends in part on increased excitability of primary sensory neurons. Nociceptive neurons express multiple subtypes of voltage-gated sodium channels (NaV1s), each of which possesses unique features that may influence primary afferent excitability. Here, we examined the contribution of NaV1.9 to nociceptive signaling by studying the electrophysiological and behavioral phenotypes of mice with a disruption of the SCN11A gene, which encodes NaV1.9. Our results confirm that NaV1.9 underlies the persistent tetrodotoxin-resistant current in small-diameter dorsal root ganglion neurons but suggest that this current contributes little to mechanical thermal responsiveness in the absence of injury or to mechanical hypersensitivity after nerve injury or inflammation. However, the expression of NaV1.9 contributes to the persistent thermal hypersensitivity and spontaneous pain behavior after peripheral inflammation. These results suggest that inflammatory mediators modify the function of NaV1.9 to maintain inflammation-induced hyperalgesia.

Most Comfortable Listening Level and Speech Attenuation by Hearing Protectors.

Hearing protectors attenuate both the background noise and the useful sounds embedded in noise such as the sounds of speech and warning signals. An effective hearing protector is one that attenuates background noise while leaving sufficient energy of speech and warning signals to reach the ear of the worker. At present, however, there are no established criteria for assessing effective change in speech-to-noise ratio caused by hearing protection devices (HPDs). One such criterion could be a change in most comfortable (listening) level (MCL) for speech caused by the presence of HPDs. In this study the HPD-related shift in MCL for speech presented in quiet was measured and compared with two measures of noise attenuation: Noise Reduction Rating (NRR) and high-medium-low (H-M-L). The results indicate that the MCL shift may be a sensitive measure of speech attenuation by HPDs, which together with the appropriate H-M-L may describe technical properties of HPDs.