A retrospective analysis of honey bee (Apis mellifera) pesticide toxicity data.

Current USEPA ecological risk assessments for pesticide registration include a determination of potential risks to bees. Toxicity data are submitted to support these assessments and the USEPA maintains a large database containing acute and chronic toxicity data on adult and larval honey bees (Apis mellifera), which USEPA considers a surrogate for Apis and non-Apis bees. We compared these toxicity data to explore possible trends. This analysis indicated a significant correlation between acute contact and oral median lethal dose (LD50) values for adult honey bees (ρ = 0.74, p <0.0001). Using default EPA modeling assumptions, where exposure for an individual bee is roughly 12x lower through contact than through ingestion, the analysis indicates that the oral LD50 is similarly if not more protective of the contact LD50 for the majority of pesticides and modes of action evaluated. The analysis also provided evidence that compounds with a lower acute toxicity for adults through contact and oral exposure pathways may still be acutely toxic for larvae. The acute toxicity of herbicides and fungicides was higher for larvae relative to oral and contact toxicity for adult honey bees for the same compounds and the no observed adverse effect level (NOAEL) from chronic toxicity studies were lower for larvae relative to adults, indicating increased sensitivity of larvae. When comparing 8-day LD50 values between single dose larval acute studies to those derived from repeat dose 22-day larval chronic toxicity studies, the LD50 values derived from chronic studies were significantly lower than those from acute toxicity tests (Z = -37, p = 0.03).

Coupling toxicokinetic-toxicodynamic and population models for assessing aquatic ecological risks to time-varying pesticide exposures.

Population modeling evaluations of pesticide exposure time series were compared with aspects of a currently used risk assessment process. The US Environmental Protection Agency's Office of Pesticide Programs models daily aquatic 30-yr pesticide exposure distributions in its risk assessments, but does not routinely make full use of the information in such time series. We used mysid shrimp Americamysis bahia toxicity and demographic data to demonstrate the value of a toxicokinetic-toxicodynamic model coupled with a series of matrix population models in risk assessment refinements. This species is a small epibenthic marine crustacean routinely used in regulatory toxicity tests. We demonstrate how the model coupling can refine current risk assessments using only existing standard regulatory toxicity test results. Several exposure scenarios (each with the same initial risk characterization as determined by a more traditional organism-based approach) were created within which population modeling documented risks different from those of assessments based on the traditional approach. We also present different acute and chronic toxicity data scenarios by which toxicokinetic-toxicodynamic coupled with population modeling can distinguish responses that traditional risk evaluations are not designed to detect. Our results reinforce the benefits of this type of modeling in risk evaluations, especially related to time-varying exposure concentrations. Environ Toxicol Chem 2018;37:2633-2644. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Selenium toxicity to survival and reproduction of Collembola and Enchytraeids in a sandy loam soil.

We investigated the toxicity of selenium (Se) to the soil invertebrates Folsomia candida (Collembola) and Enchytraeus crypticus (potworm). Studies were designed to generate ecotoxicological benchmarks for developing ecological soil screening levels (Eco-SSLs) for risk assessments of contaminated soils. For the present studies, we selected Sassafras sandy loam, an aerobic upland soil with soil characteristics (low levels of clay and organic matter, soil pH adjusted from 5.2 to 7.1) that support high relative bioavailability of the anionic Se species that is typically found in aerobic soil. The Se was amended into soil as sodium selenate, subjected to weathering and aging using 21 d of alternating cycles of air-drying/rehydration to 60% of the water-holding capacity of the Sassafras sandy loam soil, under ambient greenhouse conditions. Effective concentrations at 20 and 50% (EC20 and EC50) levels for production of juveniles (reproduction) were 4.7 and 10.9 mg of Se/kg of soil (dry mass basis), respectively, for Collembola, and 4.4 and 6.2 mg/kg, respectively, for the potworms. The data enabled the derivation of toxicity benchmarks, contributing to the development of a soil invertebrate-based Eco-SSL of 4.1 mg/kg for Se. Environ Toxicol Chem 2018;37:846-853. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Weight of evidence evaluation of a network of adverse outcome pathways linking activation of the nicotinic acetylcholine receptor in honey bees to colony death.

Ongoing honey bee (Apis mellifera) colony losses are of significant international concern because of the essential role these insects play in pollinating crops. Both chemical and non-chemical stressors have been implicated as possible contributors to colony failure; however, the potential role(s) of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptors (nAChRs) in the central nervous system to eliminate pest insects. However, mounting evidence indicates that neonicotinoids also may adversely affect beneficial pollinators, such as the honey bee, via impairments on learning and memory, and ultimately foraging success. The specific mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. The objective of this review was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between activation of the physiological target site, the nAChR, and colony level consequences. Potential for exposure was not a consideration in AOP development and therefore this effort should not be considered a risk assessment. Nonetheless, development of the AOPs described herein has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect normal colony functions, causing colony instability and subsequent bee population failure. A putative AOP network was developed, laying the foundation for further insights as to the role of combined chemical and non-chemical stressors in impacting bee populations. Insights gained from the AOP network assembly, which more realistically represents multi-stressor impacts on honey bee colonies, are promising toward understanding common sensitive nodes in key biological pathways and identifying where mitigation strategies may be focused to reduce colony losses.

Review of existing terrestrial bioaccumulation models and terrestrial bioaccumulation modeling needs for organic chemicals.

Protocols for terrestrial bioaccumulation assessments are far less-developed than for aquatic systems. This article reviews modeling approaches that can be used to assess the terrestrial bioaccumulation potential of commercial organic chemicals. Models exist for plant, invertebrate, mammal, and avian species and for entire terrestrial food webs, including some that consider spatial factors. Limitations and gaps in terrestrial bioaccumulation modeling include the lack of QSARs for biotransformation and dietary assimilation efficiencies for terrestrial species; the lack of models and QSARs for important terrestrial species such as insects, amphibians and reptiles; the lack of standardized testing protocols for plants with limited development of plant models; and the limited chemical domain of existing bioaccumulation models and QSARs (e.g., primarily applicable to nonionic organic chemicals). There is an urgent need for high-quality field data sets for validating models and assessing their performance. There is a need to improve coordination among laboratory, field, and modeling efforts on bioaccumulative substances in order to improve the state of the science for challenging substances.

Comparing laboratory- and field-measured biota-sediment accumulation factors.

Standardized laboratory protocols for measuring the accumulation of chemicals from sediments are used in assessing new and existing chemicals, evaluating navigational dredging materials, and establishing site-specific biota-sediment accumulation factors (BSAFs) for contaminated sediment sites. The BSAFs resulting from the testing protocols provide insight into the behavior and risks associated with individual chemicals. In addition to laboratory measurement, BSAFs can also be calculated from field data, including samples from studies using in situ exposure chambers and caging studies. The objective of this report is to compare and evaluate paired laboratory and field measurement of BSAFs and to evaluate the extent of their agreement. The peer-reviewed literature was searched for studies that conducted laboratory and field measurements of chemical bioaccumulation using the same or taxonomically related organisms. In addition, numerous Superfund and contaminated sediment site study reports were examined for relevant data. A limited number of studies were identified with paired laboratory and field measurements of BSAFs. BSAF comparisons were made between field-collected oligochaetes and the laboratory test organism Lumbriculus variegatus and field-collected bivalves and the laboratory test organisms Macoma nasuta and Corbicula fluminea. Our analysis suggests that laboratory BSAFs for the oligochaete L. variegatus are typically within a factor of 2 of the BSAFs for field-collected oligochaetes. Bivalve study results also suggest that laboratory BSAFs can provide reasonable estimates of field BSAF values if certain precautions are taken, such as ensuring that steady-state values are compared and that extrapolation among bivalve species is conducted with caution.

Comparing laboratory and field measured bioaccumulation endpoints.

An approach for comparing laboratory and field measures of bioaccumulation is presented to facilitate the interpretation of different sources of bioaccumulation data. Differences in numerical scales and units are eliminated by converting the data to dimensionless fugacity (or concentration-normalized) ratios. The approach expresses bioaccumulation metrics in terms of the equilibrium status of the chemical, with respect to a reference phase. When the fugacity ratios of the bioaccumulation metrics are plotted, the degree of variability within and across metrics is easily visualized for a given chemical because their numerical scales are the same for all endpoints. Fugacity ratios greater than 1 indicate an increase in chemical thermodynamic activity in organisms with respect to a reference phase (e.g., biomagnification). Fugacity ratios less than 1 indicate a decrease in chemical thermodynamic activity in organisms with respect to a reference phase (e.g., biodilution). This method provides a holistic, weight-of-evidence approach for assessing the biomagnification potential of individual chemicals because bioconcentration factors, bioaccumulation factors, biota-sediment accumulation factors, biomagnification factors, biota-suspended solids accumulation factors, and trophic magnification factors can be included in the evaluation. The approach is illustrated using a total 2393 measured data points from 171 reports, for 15 nonionic organic chemicals that were selected based on data availability, a range of physicochemical partitioning properties, and biotransformation rates. Laboratory and field fugacity ratios derived from the various bioaccumulation metrics were generally consistent in categorizing substances with respect to either an increased or decreased thermodynamic status in biota, i.e., biomagnification or biodilution, respectively. The proposed comparative bioaccumulation endpoint assessment method could therefore be considered for decision making in a chemicals management context.

The tissue residue approach for toxicity assessment: findings and critical reviews from a Society of Environmental Toxicology and Chemistry Pellston Workshop.

Over the past few years, the "critical body residue" approach for assessing toxicity based on bioaccumulated chemicals has evolved into a more expansive consideration of tissue residues as the dose metric when defining dose-response relationships, evaluating mixtures, developing protective guidelines, and conducting risk assessments. Hence, scientists refer to "tissue residue approach for toxicity assessment" or "tissue residue-effects approach" (TRA) when addressing ecotoxicology issues pertaining to tissue (or internal) concentrations. This introduction provides an overview of a SETAC Pellston Workshop held in 2007 to review the state of the science for using tissue residues as the dose metric in environmental toxicology. The key findings of the workshop are presented, along with recommendations for research to enhance understanding of toxic responses within and between species, and to advance the use of the TRA in assessment and management of chemicals in the environment.

Application of the tissue residue approach in ecological risk assessment.

The objective of this work is to present a critical review of the application of the tissue residue approach (TRA) in ecological risk and/or impact assessment (ERA) of chemical stressors and environmental criteria development. A secondary goal is to develop a framework for integrating the TRA into ecological assessments along with traditional, exposure concentration-based assessment approaches. Although widely recognized for its toxicological appeal, the utility of the TRA in specific applications will depend on numerous factors, such as chemical properties, exposure characteristics, assessment type, availability of tissue residue-response data, and ability to quantify chemical exposure. Therefore, the decision to use the TRA should include an evaluation of the relative strengths, limitations, and uncertainties among exposure and residue-based methods for characterizing toxicological effects. Furthermore, rather than supplanting exposure concentration-based toxicity assessments, the TRA can be highly effective for evaluating and reducing uncertainty when used in a complementary manner (e.g., when evaluating multiple lines of evidence in field studies). To address limitations with the available tissue residue-response data, approaches for extrapolating residue-based toxicity data across species, tissues, and exposure durations are discussed. Some of these approaches rely on predicted residue-response relationships or toxicological models that have an implicit residue-response basis (e.g., biotic ligand model). Because risk to an organism is a function of both its exposure potential and inherent sensitivity (i.e., on a residue basis), bioaccumulation models will be required not only for translating tissue residue criteria into corresponding water and sediment criteria, but also for defining the most vulnerable species in an assemblage (i.e., highly exposed and highly sensitive species). Application of the TRA in ecological assessments and criteria development are summarized for bioaccumulative organic chemicals, TBT, and in situ bioassays using bivalve molluscs.

A physiologically based toxicokinetic model for methylmercury in female American kestrels.

A physiologically based toxicokinetic (PBTK) model was developed to describe the uptake, distribution, and elimination of methylmercury (CH(3)Hg) in female American kestrels. The model consists of six tissue compartments corresponding to the brain, liver, kidney, gut, red blood cells, and remaining carcass. Additional compartments describe the elimination of CH(3)Hg to eggs and growing feathers. Dietary uptake of CH(3)Hg was modeled as a diffusion-limited process, and the distribution of CH(3)Hg among compartments was assumed to be mediated by the flow of blood plasma. To the extent possible, model parameters were developed using information from American kestrels. Additional parameters were based on measured values for closely related species and allometric relationships for birds. The model was calibrated using data from dietary dosing studies with American kestrels. Good agreement between model simulations and measured CH(3)Hg concentrations in blood and tissues during the loading phase of these studies was obtained by fitting model parameters that control dietary uptake of CH(3)Hg and possible hepatic demethylation. Modeled results tended to underestimate the observed effect of egg production on circulating levels of CH(3)Hg. In general, however, simulations were consistent with observed patterns of CH(3)Hg uptake and elimination in birds, including the dominant role of feather molt. This model could be used to extrapolate CH(3)Hg kinetics from American kestrels to other bird species by appropriate reassignment of parameter values. Alternatively, when combined with a bioenergetics-based description, the model could be used to simulate CH(3)Hg kinetics in a long-term environmental exposure.

Framework for metals risk assessment.

EPA recognized that metals present unique risk assessment issues, and saw the need to develop a framework document that puts forth key scientific principles for metals risk assessments to help ensure consistency in metals assessments across EPA programs and regional offices. This framework, called the "Framework for Metals Risk Assessment," is a science-based document that describes basic principles that address the special attributes and behaviors of metals and metal compounds to be considered when assessing their human health and ecological risks. The Risk Assessment Forum oversaw the development of this document, including input from stakeholders and experts throughout the Agency, and obtained through several expert workshops, followed by peer review by the EPA Science Advisory Board (SAB). The Framework for Metals Risk Assessment document is intended to serve as a guide for all EPA programs and regional offices to supplement or update the policies, practices and guidance they currently use in their respective metals assessments. This framework document is not a prescriptive guide on how any particular type of assessment should be conducted within an EPA program office. Rather, it outlines key metal principles and describes how they should be considered in conducting human health and ecological risk assessments to advance our understanding of metals impact and foster consistency across EPA programs and regions. Although the audience for the framework is primarily intended to be Agency risk assessors, it also will communicate principles and recommendations for metals risk assessment to stakeholders and the public. This framework will be used in conjunction with guidance developed by the programs and regions for site-specific risk assessment, criteria derivation, ranking or categorization and other similar Agency activities related to metals. The Framework for Metals Risk Assessment document is intended to serve as a guide for all EPA programs and regional offices to supplement or update the policies, practices and guidance they currently use in their respective metals assessments. EPA assessments can vary in level of detail from simple, screening analyses to complex, definitive assessments. More complex scientific tools and metal specific methods should be applied as the complexity of the hazard assessment or risk assessment increases.

Evaluation of two methods for prediction of bioaccumulation factors.

Two methods for deriving bioaccumulation factors (BAFs) used by the U.S. Environmental Protection Agency in development of water quality criteria were evaluated using polychlorinated biphenyl (PCB) data from the Hudson River and Green Bay ecosystems. One method predicts BAF(L)fd values (BAFs based upon concentrations of freely dissolved chemical in ambient water and in the lipid fraction of tissue) using field-measured biota-sediment accumulation factors (BSAFs): greater than 90% of the predicted BAF(L)fd values were within a factor of 5 of their measured values for both ecosystems. The second method predicts BAF(L)fd values as the chemical's 1-octanol/water partition coefficient (Kow) times a food chain multiplier: greater than 90% of the predicted BAF(L)fd values were within a factor of 5 of their measured values for the Green Bay ecosystem and for three of the six sampling locations on the Hudson River. Poorer predictive ability with the Kow method for the other three sampling locations was believed to be due to the existence of environmental conditions not representative of the longer term ecosystem conditions assumed for the method. BAF(L)fd and BAF(T)t values (BAFs based upon concentrations of total chemical in ambient water and in wet tissue) were compared. The within ecosystem and across ecosystems comparisons demonstrated a 2-5-fold decrease in variability (expressed as ratios of coefficients of variation, percentile ranges, and confidence ranges) for predicted BAF(L)fd values in comparison to BAF(T)t values.

Development of aquatic life criteria for selenium: a regulatory perspective on critical issues and research needs.

The US is currently in the process of revising its freshwater, chronic aquatic life criterion for selenium. The fundamental issues being addressed include which environmental compartment(s) support the most reliable expression of the criterion, which form(s) of selenium should be measured in the medium (media) of choice, and which site-specific water quality (or other factors) should be linked to the expression of the criterion. Literature reviews and a recent workshop were conducted to assess the state of the science on various issues related to water-, tissue- and sediment-based criteria for selenium. Evaluation of many of these issues is ongoing. In terms of water column criteria issues, data limitations will likely restrict the expression of a criterion to operationally defined forms (e.g. total recoverable, dissolved). The specific identity of organoselenium in natural systems is lacking and may not be appropriately represented by free seleno-amino acids (e.g. selenomethionine). The available data do not appear to support quantitative relationships between chronic toxicity and water quality characteristics. In terms of a tissue-based criterion, reproductive tissue (ovary, egg) has been recommended as the tissue of choice, but practical concerns and data availability require consideration of other tissues (e.g. whole-body). Organoselenium (bound to peptides or proteins) is thought to be the form of greatest toxicological importance in fish, however, direct measurements of organoselenium compounds in tissues are very limited. Route of exposure (food vs. water uptake) may prove important for establishing diagnostic tissue residues for selenium based on laboratory data. Data on toxicological aspects of selenium in sediments appear sparse, particularly in relation to different sedimentary forms. Reliable assessments of bioaccumulation will likely be critical for making site-specific modifications to chronic selenium criteria, however, many technical issues for assessing bioaccumulation remain. The need for improved analytical methods for directly speciating organoselenium in various environmental media underpins many of the current data gaps. Improving analytical methodologies to enable affordable and reliable measurement of organoselenium compounds holds significant promise for advancing selenium ecotoxicological research.