Are environmental regulations keeping up with innovation? A case study of the nanotechnology industry.

Manufactured nanomaterials entered the marketplace of consumer goods in the mid-1990s. With the exception of pending reporting requirements in Canada, no new regulatory requirements have been imposed on the manufacture or use of nanomaterials or their commercial products, although in the past three years governments, industry, and nongovernmental organizations have questioned the need for new regulatory approaches. The debate hinges on whether current scientific information is sufficient for making risk-based decisions, if nanomaterial effects differ from macroscale products, and how much knowledge about potential risk governments should require before products are brought to market. The debate over when and how to regulate manufactured nanomaterials opens the door for a renewed discussion on regulatory environmental policy and suggests that the public may be demanding increased precaution and assurances from government. How government, in concert with industry and the open market, responds will set the bar for future regulations of emerging technologies.

Federal environmental legislation in the U.S. for protection of wildlife and regulation of environmental contaminants.

The U.S. has a long history of legislation to protect wildlife, beginning with the Lacey Act of 1900. There are now over 170 Federal laws that regulate environmental activities which may affect wildlife. Two important laws are the Pittman-Robertson Act enacted in 1937 that authorizes a tax for wildlife management and the Fish and Wildlife Coordination Act passed in 1958 whose primary purpose is conservation of fish and wildlife, both of which continue to provide significant funding for wildlife management. Modern environmental regulations began by passage of the National Environmental Policy Act in 1969, followed by the Clean Water Act, Superfund, and other laws to regulate pesticides and toxics and clean up contaminated sites. International conventions regulate sale, use and disposal of toxics and ocean dumping. These laws and conventions should protect wildlife from unintended consequences of global industrialization.

Scientific integrity issues in Environmental Toxicology and Chemistry: Improving research reproducibility, credibility, and transparency.

High-profile reports of detrimental scientific practices leading to retractions in the scientific literature contribute to lack of trust in scientific experts. Although the bulk of these have been in the literature of other disciplines, environmental toxicology and chemistry are not free from problems. While we believe that egregious misconduct such as fraud, fabrication of data, or plagiarism is rare, scientific integrity is much broader than the absence of misconduct. We are more concerned with more commonly encountered and nuanced issues such as poor reliability and bias. We review a range of topics including conflicts of interests, competing interests, some particularly challenging situations, reproducibility, bias, and other attributes of ecotoxicological studies that enhance or detract from scientific credibility. Our vision of scientific integrity encourages a self-correcting culture that promotes scientific rigor, relevant reproducible research, transparency in competing interests, methods and results, and education. Integr Environ Assess Manag 2019;00:000-000. © 2019 SETAC.

Toward Sustainable Environmental Quality: Priority Research Questions for North America.

Anticipating, identifying, and prioritizing strategic needs represent essential activities by research organizations. Decided benefits emerge when these pursuits engage globally important environment and health goals, including the United Nations Sustainable Development Goals. To this end, horizon scanning efforts can facilitate identification of specific research needs to address grand challenges. We report and discuss 40 priority research questions following engagement of scientists and engineers in North America. These timely questions identify the importance of stimulating innovation and developing new methods, tools, and concepts in environmental chemistry and toxicology to improve assessment and management of chemical contaminants and other diverse environmental stressors. Grand challenges to achieving sustainable management of the environment are becoming increasingly complex and structured by global megatrends, which collectively challenge existing sustainable environmental quality efforts. Transdisciplinary, systems-based approaches will be required to define and avoid adverse biological effects across temporal and spatial gradients. Similarly, coordinated research activities among organizations within and among countries are necessary to address the priority research needs reported here. Acquiring answers to these 40 research questions will not be trivial, but doing so promises to advance sustainable environmental quality in the 21st century. Environ Toxicol Chem 2019;38:1606-1624. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Use of multiple lines of evidence to provide a realistic toxic substances control act ecological risk evaluation based on monitoring data: D4 case study.

D4 (octamethylcyclotetrasiloxane) is a high-production-volume cyclic volatile methyl siloxane with a wide range of industrial and consumer applications. This study conducted a robust ecological risk evaluation for D4 using exposure data collected under a nation-wide environmental monitoring program facilitated under the Toxic Substances Control Act (TSCA). This ecological risk evaluation was conducted consistent with the principles outlined in the U.S. Environmental Protection Agency's (EPA's) Guidance to Assist Interested Persons in Developing and Submitting Draft Risk Evaluations under TSCA (U.S. EPA 2017a). The evaluation examined multiple lines of evidence (LoEs) to determine the potential risks from D4 to aquatic receptors in rivers and streams in the United States from municipal wastewater treatment plant (WWTP) discharges and discharges from manufacturing, processing, and/or formulating (MPF) facilities after onsite wastewater treatment. The LoEs consisted of comparing D4 concentrations measured in water and sediment to toxicity thresholds derived from laboratory studies; comparing D4 concentrations measured in biota tissue to critical target lipid body burdens (CTLBBs); comparing fugacity-based chemical activities between toxicity thresholds and measured environmental concentrations; and assessing benthic macroinvertebrate community structure and habitat suitability. The approach taken moves beyond a standard deterministic hazard quotient approach to incorporate more advanced methods for risk prediction, using distributions rather than conservative point estimates of exposure to obtain a realistic view of the probability of harm, consistent with EPA's stated intent to "strive to utilize probabilistic approaches for exposure assessments included in a risk evaluation" (U.S. EPA 2017b). The risk evaluation concluded there is negligible risk to water column and sediment receptors from D4 discharged from MPF facilities after onsite wastewater treatment or from municipal WWTPs that may treat a mix of industrial and consumer wastewater.

Association between a shelter-neuter-return program and cat health at a large municipal animal shelter.

OBJECTIVE To determine effects of a shelter-neuter-return (SNR) program on cat admissions and health at a large municipal animal shelter in Northern California. DESIGN Retrospective cohort study. ANIMALS 117,383 cats for which data were recorded in the San Jose Animal Care Center database between January 1, 2006, and December 31, 2013. PROCEDURES Shelter records were analyzed for trends in cat demographic data, shelter intake and outcome types, and prevalence of upper respiratory infection (URI) over the 8-year period and before and after initiation of an SNR program on March 8, 2010. RESULTS Number of cats admitted to the shelter each year decreased significantly over 8 years; beginning in 2010, duration of stay decreased. Proportion of cats euthanized decreased from 66.6% (28,976/43,517) in the pre-SNR period to 34.9% (11,999/34,380) in the post-SNR period, whereas prevalence of URI increased from 5.5% to 6.8%, and median duration of shelter stay decreased from 6 to 5 days for cats < 4 months of age and from 8 to 6 days for older cats. With implementation of the SNR program and a new treatment policy for cats with URI, more cats received treatment with less medication, yielding cost savings. CONCLUSIONS AND CLINICAL RELEVANCE Initiation of the SNR program was associated with a decreased number of cats admitted to the shelter and a lower proportion euthanized. With increased resources to care for cats with URI and changes in the URI treatment protocol, fewer cats were euthanized for URI and more cats were treated at lower cost and with a briefer shelter stay.

Review of laboratory-based terrestrial bioaccumulation assessment approaches for organic chemicals: Current status and future possibilities.

In the last decade, interest has been renewed in approaches for the assessment of the bioaccumulation potential of chemicals, principally driven by the need to evaluate large numbers of chemicals as part of new chemical legislation, while reducing vertebrate test organism use called for in animal welfare legislation. This renewed interest has inspired research activities and advances in bioaccumulation science for neutral organic chemicals in aquatic environments. In January 2013, ILSI Health and Environmental Sciences Institute convened experts to identify the state of the science and existing shortcomings in terrestrial bioaccumulation assessment of neutral organic chemicals. Potential modifications to existing laboratory methods were identified, including areas in which new laboratory approaches or test methods could be developed to address terrestrial bioaccumulation. The utility of "non-ecotoxicity" data (e.g., mammalian laboratory data) was also discussed. The highlights of the workshop discussions are presented along with potential modifications in laboratory approaches and new test guidelines that could be used for assessing the bioaccumulation of chemicals in terrestrial organisms.

Examination of rare earth element concentration patterns in freshwater fish tissues.

Rare earth elements (REEs or lanthanides) were measured in ten freshwater fish species from a reservoir in Washington State (United States). The REE distribution patterns were examined within fillet and whole body tissues for three size classes. Total concentrations (ΣREE) ranged from 0.014 to 3.0 mg kg(-1) (dry weight) and averaged 0.243 mg kg(-1) (dry weight). Tissue concentration patterns indicated that REEs accumulated to a greater extent in organs, viscera, and bone compared to muscle (fillet) tissues. Benthic feeding species (exposed to sediments) exhibited greater concentrations of REEs than pelagic omnivorous or piscivorous fish species. Decreasing REE concentrations were found with increasing age, total length or weight for largescale and longnose suckers, smallmouth bass, and walleye. Concentration patterns in this system were consistent with natural conditions without anthropogenic sources of REEs. These data provide additional reference information with regard to the fate and transport of REEs in freshwater fish tissues in a large aquatic system.

Fugacity and activity analysis of the bioaccumulation and environmental risks of decamethylcyclopentasiloxane (D5).

As part of an initiative to evaluate commercial chemicals for their effects on human and environmental health, Canada recently evaluated decamethylcyclopentasiloxane (D5; CAS no. 541-02-06), a high-volume production chemical used in many personal care products. The evaluation illustrated the challenges encountered in environmental risk assessments and the need for the development of better tools to increase the weight of evidence in environmental risk assessments. The present study presents a new risk analysis method that applies thermodynamic principles of fugacity and activity to express the results of field monitoring and laboratory bioaccumulation and toxicity studies in a comprehensive risk analysis that can support risk assessments. Fugacity and activity ratios of D5 derived from bioaccumulation measures indicate that D5 does not biomagnify in food webs, likely because of biotransformation. The fugacity and activity analysis further demonstrates that reported no-observed-effect concentrations of D5 normally cannot occur in the environment. Observed fugacities and activities in the environment are, without exception, far below those corresponding with no observed effects, in many cases by several orders of magnitude. This analysis supports the conclusion of the Canadian Board of Review and the Minister of the Environment that D5 does not pose a danger to the environment. The present study further illustrates some of the limitations of a persistence-bioaccumulation-toxicity-type criteria-based risk assessment approach and discusses the merits of the fugacity and activity approach to increase the weight of evidence and consistency in environmental risk assessments of commercial chemicals.

Characterization of ecological risks from environmental releases of decamethylcyclopentasiloxane (D5).

Decamethylcyclopentasiloxane (D5) is used in personal care products and industrial applications. The authors summarize the risks to the environment from D5 based on multiple lines of evidence and conclude that it presents negligible risk. Laboratory and field studies show that D5 is not toxic to aquatic organisms or benthic invertebrates up to its solubility limit in water or porewater or its sorptive capacity in sediment. Comparison of lipid-normalized internal concentrations with measured concentrations in benthos indicates that field-collected organisms do not achieve toxic levels of D5 in their tissues, suggesting negligible risk. Exposure to D5 resulted in a slight reduction of root biomass in barley at test concentrations 2 orders of magnitude greater than measured D5 levels in biosolids-amended soils and more than twice as high as the maximum calculated sorptive capacity of the soil. No effects were observed in soil invertebrates exposed to similar concentrations, indicating that D5 poses a de minimis risk to the terrestrial environment. High rates of metabolism and elimination of D5 compared with uptake rates from food results in biodilution in the food web rather than biomagnification, culminating in de minimis risk to higher trophic level organisms via the food chain. A fugacity approach substantiates all conclusions that were made on a concentration basis.

Sources of variability in plant toxicity testing.

Published literature is investigated regarding the response of plants to various substances to determine the sensitivity of agricultural plants versus other species, the similarity of effects seen at different taxonomic levels, sensitivity of plants growing outdoors versus in a greenhouse, and the sensitivity of different measurement endpoints. We find that agricultural species are not consistently more or less sensitive to the herbicides tested than non-crop species. Genus and family taxonomic groupings may show similar responses among species, but this similarity quickly decreases as the comparison progress between orders and classes. Results from field and greenhouse studies are less in agreement between studies than data from the other topics. Shoot length will be affected at concentrations lower than for other vegetative endpoints for most species tested for inorganic substances, but for organic substances root and shoot mass were more sensitive. Overall, there is no one species or endpoint that is consistently the most sensitive for all species or all chemicals in all soils, and differences in bioavailability among compounds may confound comparison of test results. Therefore, species sensitivity distributions, adjusted for bioavailability when possible, should be considered in order to better evaluate effects to non-target terrestrial plants.

Analysis of field and laboratory data to derive selenium toxicity thresholds for birds.

In this paper, we critically evaluate the statistical approaches and datasets previously used to derive chronic egg selenium thresholds for mallard ducks (laboratory data) and black-necked stilts (field data). These effect concentration thresholds of 3%, 10% (EC10), or 20% have been used by regulatory agencies to set avian protection criteria and site remediation goals, thus the need for careful assessment of the data. The present review indicates that the stilt field dataset used to establish a frequently cited chronic avian egg selenium threshold of 6 mg/kg dry weight lacks statistical robustness (r2 = 0.19-0.28 based on generalized linear models), suggesting that stilt embryo sensitivity to selenium is highly variable or that factors other than selenium are principally responsible for the increase in effects observed at the lower range of this dataset. Hockey stick regressions used with the stilt field dataset improve the statistical relationship (r2 = 0.90-0.97) but result in considerably higher egg selenium thresholds (EC10 = 21-31 mg/kg dry wt). Laboratory-derived (for mallards) and field-derived (for stilts) teratogenicity EC10 values are quite similar (16-24 mg/kg dry wt). Laboratory data regarding mallard egg inviability and duckling mortality data provide the most sensitive and statistically robust chronic threshold (EC10) with logit, probit, and hockey stick regressions fitted to laboratory data, resulting in mean egg selenium EC10 values of 12 to 15 mg/kg dry weight (r2 = 0.75-0.90).

Acute toxicity of lead, steel, and an iron-tungsten-nickel shot to mallard ducks (Anas platyrhynchos).

Twenty mallards (Anas platyrhynchos) of both sexes were dosed by oral gavage with Heavi-Shot (H-S; Environ-Metal, Inc., Sweet Home, Oregon, USA) pellets, 20 with steel shot, and 10 with lead (Pb) pellets, all of equal size. All pellets were fired from a shotgun into an absorbent material, retrieved, and weighed prior to introduction into the ducks. Birds were fed whole kernel corn and grit and observed for signs of toxicity for 30 days following dosing. Hevi-Shot pellets lost an average of 6.2% of their mass and steel shot pellets lost 57% of their mass in the birds' gizzards. Almost all (90%) of the Pb shot dosed birds died before the end of the study, while no mortality was observed in the steel or H-S dosed groups. Even though total food consumption differed between the H-S and steel shot groups, mean bird weight change was not different. There were no significant morphologic or histopathologic abnormalities of the liver and kidney in the H-S and steel shot groups. Results indicated that mallards dosed orally with eight No. 4 H-S pellets were not adversely affected over a 30-day period, and that H-S provides another environmentally safe nontoxic shot for use in waterfowl hunting.

Next steps in the development of ecological soil clean-up values for metals.

This special series in Integrated Environmental Assessment Management presents the results from 6 workgroups that were formed at the workshop on Ecological Soil Levels-Next Steps in the Development of Metal Clean-Up Values (17-21 September 2012, Sundance, Utah). This introductory article presents an overview of the issues assessors face when conducting risk assessments for metals in soils, key US Environmental Protection Agency (USEPA) documents on metals risk assessment, and discusses the importance of leveraging from recent major terrestrial research projects, primarily to address Registration, Evaluation, Authorization and Restriction of Chemical Substances (REACH) requirements in Europe, that have significantly advanced our understanding of the behavior and toxicity of metals in soils. These projects developed large data sets that are useful for the risk assessment of metals in soil environments. The workshop attendees met to work toward developing a process for establishing ecological soil clean-up values (Eco-SCVs). The goal of the workshop was to progress from ecological soil screening values (Eco-SSLs) to final clean-up values by providing regulators with the methods and processes to incorporate bioavailability, normalize toxicity thresholds, address food-web issues, and incorporate background concentrations. The REACH data sets were used by workshop participants as case studies in the development of the ecological standards for soils. The workshop attendees discussed scientific advancements in bioavailability, soil biota and wildlife case studies, soil processes, and food-chain modeling. In addition, one of the workgroups discussed the processes needed to frame the topics to gain regulatory acceptance as a directive or guidance by Canada, the USEPA, or the United States.

Risks of neonicotinoid insecticides to honeybees.

The European honeybee, Apis mellifera, is an important pollinator of agricultural crops. Since 2006, when unexpectedly high colony losses were first reported, articles have proliferated in the popular press suggesting a range of possible causes and raising alarm over the general decline of bees. Suggested causes include pesticides, genetically modified crops, habitat fragmentation, and introduced diseases and parasites. Scientists have concluded that multiple factors in various combinations-including mites, fungi, viruses, and pesticides, as well as other factors such as reduction in forage, poor nutrition, and queen failure-are the most probable cause of elevated colony loss rates. Investigators and regulators continue to focus on the possible role that insecticides, particularly the neonicotinoids, may play in honeybee health. Neonicotinoid insecticides are insect neurotoxicants with desirable features such as broad-spectrum activity, low application rates, low mammalian toxicity, upward systemic movement in plants, and versatile application methods. Their distribution throughout the plant, including pollen, nectar, and guttation fluids, poses particular concern for exposure to pollinators. The authors describe how neonicotinoids interact with the nervous system of honeybees and affect individual honeybees in laboratory situations. Because honeybees are social insects, colony effects in semifield and field studies are discussed. The authors conclude with a review of current and proposed guidance in the United States and Europe for assessing the risks of pesticides to honeybees.

Furthering the derivation of predictive wildlife toxicity reference values for use in soil cleanup decisions.

The development of media-specific ecological values for risk assessment includes the derivation of acceptable levels of exposure for terrestrial wildlife (e.g., birds, mammals, reptiles, and amphibians). Although the derivation and subsequent application of these values can be used for screening purposes, there is a need to identify toxicological effects thresholds specifically for making remedial decisions at individual contaminated sites. A workshop was held in the fall of 2012 to evaluate existing methods and recent scientific developments for refining ecological soil screening levels (Eco-SSLs) and improving the derivation of site-specific ecological soil clean-up values for metals (Eco-SCVs). This included a focused session on the development and derivation of toxicity reference values (TRVs) for terrestrial wildlife. Topics that were examined included: methods for toxicological endpoint selection, techniques for dose-response assessment, approaches for cross-species extrapolation, and tools to incorporate environmental factors (e.g., metal bioavailability and chemistry) into a reference value. The workgroup also made recommendations to risk assessors and regulators on how to incorporate site-specific wildlife life history and toxicity information into the derivation of TRVs to be used in the further development of soil cleanup levels.

A Causal Analysis of Observed Declines in Managed Honey Bees (Apis mellifera).

The European honey bee (Apis mellifera) is a highly valuable, semi-free-ranging managed agricultural species. While the number of managed hives has been increasing, declines in overwinter survival, and the onset of colony collapse disorder in 2006, precipitated a large amount of research on bees' health in an effort to isolate the causative factors. A workshop was convened during which bee experts were introduced to a formal causal analysis approach to compare 39 candidate causes against specified criteria to evaluate their relationship to the reduced overwinter survivability observed since 2006 of commercial bees used in the California almond industry. Candidate causes were categorized as probable, possible, or unlikely; several candidate causes were categorized as indeterminate due to lack of information. Due to time limitations, a full causal analysis was not completed at the workshop. In this article, examples are provided to illustrate the process and provide preliminary findings, using three candidate causes. Varroa mites plus viruses were judged to be a "probable cause" of the reduced survival, while nutrient deficiency was judged to be a "possible cause." Neonicotinoid pesticides were judged to be "unlikely" as the sole cause of this reduced survival, although they could possibly be a contributing factor.

Sensitivity of ecological soil-screening levels for metals to exposure model parameterization and toxicity reference values.

Ecological soil-screening levels (Eco-SSLs) were developed by the United States Environmental Protection Agency (USEPA) for the purposes of setting conservative soil screening values that can be used to eliminate the need for further ecological assessment for specific analytes at a given site. Ecological soil-screening levels for wildlife represent a simplified dietary exposure model solved in terms of soil concentrations to produce exposure equal to a no-observed-adverse-effect toxicity reference value (TRV). Sensitivity analyses were performed for 6 avian and mammalian model species, and 16 metals/metalloids for which Eco-SSLs have been developed. The relative influence of model parameters was expressed as the absolute value of the range of variation observed in the resulting soil concentration when exposure is equal to the TRV. Rank analysis of variance was used to identify parameters with greatest influence on model output. For both birds and mammals, soil ingestion displayed the broadest overall range (variability), although TRVs consistently had the greatest influence on calculated soil concentrations; bioavailability in food was consistently the least influential parameter, although an important site-specific variable. Relative importance of parameters differed by trophic group. Soil ingestion ranked 2nd for carnivores and herbivores, but was 4th for invertivores. Different patterns were exhibited, depending on which parameter, trophic group, and analyte combination was considered. The approach for TRV selection was also examined in detail, with Cu as the representative analyte. The underlying assumption that generic body-weight-normalized TRVs can be used to derive protective levels for any species is not supported by the data. Whereas the use of site-, species-, and analyte-specific exposure parameters is recommended to reduce variation in exposure estimates (soil protection level), improvement of TRVs is more problematic.

Efforts to standardize wildlife toxicity values remain unrealized.

Wildlife toxicity reference values (TRVs) are routinely used during screening level and baseline ecological risk assessments (ERAs). Risk assessment professionals often adopt TRVs from published sources to expedite risk analyses. The US Environmental Protection Agency (USEPA) developed ecological soil screening levels (Eco-SSLs) to provide a source of TRVs that would improve consistency among risk assessments. We conducted a survey and evaluated more than 50 publicly available, large-scale ERAs published in the last decade to evaluate if USEPA's goal of uniformity in the use of wildlife TRVs has been met. In addition, these ERAs were reviewed to understand current practices for wildlife TRV use and development within the risk assessment community. The use of no observed and lowest observed adverse effect levels culled from published compendia was common practice among the majority of ERAs reviewed. We found increasing use over time of TRVs established in the Eco-SSL documents; however, Eco-SSL TRV values were not used in the majority of recent ERAs and there continues to be wide variation in TRVs for commonly studied contaminants (e.g., metals, pesticides, PAHs, and PCBs). Variability in the toxicity values was driven by differences in the key studies selected, dose estimation methods, and use of uncertainty factors. These differences result in TRVs that span multiple orders of magnitude for many of the chemicals examined. This lack of consistency in TRV development leads to highly variable results in ecological risk assessments conducted throughout the United States.

Secondary poisoning risk assessment of terrestrial birds and mammals exposed to nickel.

The European Union's Existing Substances regulation (EEC 793/93) was developed to assess the ecological risks posed by chemical substances such as Ni and includes the assessment of secondary poisoning risks. The basic structure of this secondary poisoning risk assessment followed the Technical Guidance Document on Risk Assessment and thus included development of predicted exposure concentrations (PECs) and predicted no-effect concentrations (PNECs). A PEC to PNEC ratio greater than 1.0 is indicative of potential risk. The Technical Guidance Document on Risk Assessment provides a generic framework for assessing secondary poisoning risks and prescribes the following terrestrial food chain: soil → earthworm → worm-eating bird or mammal. This secondary poisoning evaluation was conducted at the regional level, and it was found that the generic approach resulted in widespread estimates of potential risk, even at ambient Ni soil concentrations. Accordingly, a tiered approach was used with increasing levels of refinement, including consideration of bioavailability, consideration of a variable diet, and development of dose-based PNEC values. Based on the refined approach, all PEC to PNEC ratios were less than 1.0, except for a ratio of 1.4 in a scenario focused on a regional clay soil, which was of natural origin. This regional-level secondary poisoning evaluation highlighted key risk assessment components that should be considered in future localized secondary poisoning assessments of Ni and other metals, including ingestion rate to body weight ratios for the test organisms used to derive PNECs versus the representative wildlife species evaluated, the appropriateness of high assessment factors for deriving PNECs for naturally occurring essential elements, representative dietary compositions, relative metal bioavailability between the dietary toxicity study and natural diets, and ground-truthing of the risk predictions versus background concentrations.