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PURPOSE OF REVIEW: Experimental and epidemiological evidence suggests that cholesterol may play a promotional role in prostate cancer development and progression. This review seeks to provide an overview of established links between cholesterol and prostate cancer, with an emphasis on very recent scientific contributions supporting a role of cholesterol in prostate cancer etiology. RECENT FINDINGS: Elevated cholesterol levels in prostate cancer cells have been found to result from aberrant regulation of cholesterol metabolism. Recent studies have identified Akt/protein kinase B and sterol response element binding proteins as major players regulating cholesterol biosynthesis and feedback regulation. It has also become apparent that prostate cancer cells process critical cell survival cues via specialized membrane microdomains that are dependent on cholesterol for signal transduction. These findings converge to support a scenario in which abnormal cholesterol metabolism influences signal transduction events at the membrane in a manner that promotes tumor cell growth, inhibits apoptotic signals and potentially stimulates other malignant cellular behaviors. SUMMARY: Recent experimental evidence has invigorated the discussion of a role for cholesterol in prostate cancer. The identification of cholesterol as a critical component in signal transduction events in prostate cancer cells has not only provided new mechanistic insights but also opened up new avenues for chemotherapeutic intervention. [ABSTRACT FROM AUTHOR]

The residues of neonicotinoid insecticides in honey have raised global concern for their adverse effects on non-target organisms. However, information on the presence of neonicotinoids in raw honey in China is limited. Our study investigated the distribution profiles of neonicotinoids in raw honey samples collected from apiaries in plain and mountainous areas surrounding Beijing City. At least one of four neonicotinoids, imidacloprid, thiamethoxam, acetamiprid, or clothianidin, was found in 46.9% of samples. Neonicotinoids in multi-floral honey in plain areas exhibited higher concentrations and prevalence than in uni-floral honey collected from mountainous areas. These results indicated that neonicotinoid residues in honey were linked to the agricultural ecosystems influenced by geographies, particularly the intensity of agriculture and nectariferous plant types. The dietary risks to adult and children health from neonicotinoid exposure were deemed de minimis, while risks to honeybees at the maximum concentration level require much attention through refined, higher-tier assessments and possible mitigation measures for the use of these products., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The protection of Earth's stratospheric ozone (O 3 ) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O 3 . The United Nations Environment Programme's Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O 3 , future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge., (© 2024. The Author(s).)

This Assessment Update by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) considers the interactive effects of solar UV radiation, global warming, and other weathering factors on plastics. The Assessment illustrates the significance of solar UV radiation in decreasing the durability of plastic materials, degradation of plastic debris, formation of micro- and nanoplastic particles and accompanying leaching of potential toxic compounds. Micro- and nanoplastics have been found in all ecosystems, the atmosphere, and in humans. While the potential biological risks are not yet well-established, the widespread and increasing occurrence of plastic pollution is reason for continuing research and monitoring. Plastic debris persists after its intended life in soils, water bodies and the atmosphere as well as in living organisms. To counteract accumulation of plastics in the environment, the lifetime of novel plastics or plastic alternatives should better match the functional life of products, with eventual breakdown releasing harmless substances to the environment., (© 2024. The Author(s).)

Ultraviolet (UV) radiation drives the net production of tropospheric ozone (O 3 ) and a large fraction of particulate matter (PM) including sulfate, nitrate, and secondary organic aerosols. Ground-level O 3 and PM are detrimental to human health, leading to several million premature deaths per year globally, and have adverse effects on plants and the yields of crops. The Montreal Protocol has prevented large increases in UV radiation that would have had major impacts on air quality. Future scenarios in which stratospheric O 3 returns to 1980 values or even exceeds them (the so-called super-recovery) will tend to ameliorate urban ground-level O 3 slightly but worsen it in rural areas. Furthermore, recovery of stratospheric O 3 is expected to increase the amount of O 3 transported into the troposphere by meteorological processes that are sensitive to climate change. UV radiation also generates hydroxyl radicals (OH) that control the amounts of many environmentally important chemicals in the atmosphere including some greenhouse gases, e.g., methane (CH 4 ), and some short-lived ozone-depleting substances (ODSs). Recent modeling studies have shown that the increases in UV radiation associated with the depletion of stratospheric ozone over 1980-2020 have contributed a small increase (~ 3%) to the globally averaged concentrations of OH. Replacements for ODSs include chemicals that react with OH radicals, hence preventing the transport of these chemicals to the stratosphere. Some of these chemicals, e.g., hydrofluorocarbons that are currently being phased out, and hydrofluoroolefins now used increasingly, decompose into products whose fate in the environment warrants further investigation. One such product, trifluoroacetic acid (TFA), has no obvious pathway of degradation and might accumulate in some water bodies, but is unlikely to cause adverse effects out to 2100., (© 2023. The Author(s).)

The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth's surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1-67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change., (© 2022. The Author(s).)

Atrazine is a triazine herbicide used predominantly on corn, sorghum, and sugarcane in the US. Its use potentially overlaps with the ranges of listed (threatened and endangered) species. In response to registration review in the context of the Endangered Species Act, we evaluated potential direct and indirect impacts of atrazine on listed species and designated critical habitats. Atrazine has been widely studied, extensive environmental monitoring and toxicity data sets are available, and the spatial and temporal uses on major crops are well characterized. Ranges of listed species are less well-defined, resulting in overly conservative designations of "May Effect". Preferences for habitat and food sources serve to limit exposure among many listed animal species and animals are relatively insensitive. Atrazine does not bioaccumulate, further diminishing exposures among consumers and predators. Because of incomplete exposure pathways, many species can be eliminated from consideration for direct effects. It is toxic to plants, but even sensitive plants tolerate episodic exposures, such as those occurring in flowing waters. Empirical data from long-term monitoring programs and realistic field data on off-target deposition of drift indicate that many other listed species can be removed from consideration because exposures are below conservative toxicity thresholds for direct and indirect effects. Combined with recent mitigation actions by the registrant, this review serves to refine and focus forthcoming listed species assessment efforts for atrazine. Abbreviations: a.i. = Active ingredient (of a pesticide product). AEMP = Atrazine Ecological Monitoring Program. AIMS = Avian Incident Monitoring SystemArach. = Arachnid (spiders and mites). AUC = Area Under the Curve. BE = Biological Evaluation (of potential effects on listed species). BO = Biological Opinion (conclusion of the consultation between USEPA and the Services with respect to potential effects in listed species). CASM = Comprehensive Aquatic System Model. CDL = Crop Data LayerCN = field Curve Number. CRP = Conservation Reserve Program (lands). CTA = Conditioned Taste Avoidance. DAC = Diaminochlorotriazine (a metabolite of atrazine, also known by the acronym DACT). DER = Data Evaluation Record. EC25 = Concentration causing a specified effect in 25% of the tested organisms. EC50 = Concentration causing a specified effect in 50% of the tested organisms. EC50 RGR = Concentration causing a 50% reduction in relative growth rate. ECOS = Environmental Conservation Online System. EDD = Estimated Daily Dose. EEC = Expected Environmental Concentration. EFED = Environmental Fate and Effects Division (of the USEPA). EFSA = European Food Safety Agency. EIIS = Ecological Incident Information System. ERA = Environmental Risk Assessment. ESA = Endangered Species Act. ESU = Evolutionarily Significant UnitsFAR = Field Application RateFIFRA = Federal Insecticide, Fungicide, and Rodenticide Act. FOIA = Freedom of Information Act (request). GSD = Genus Sensitivity Distribution. HC5 = Hazardous Concentration for ≤ 5% of species. HUC = Hydrologic Unit Code. IBM = Individual-Based Model. IDS = Incident Data System. K OC = Partition coefficient between water and organic matter in soil or sediment. K OW = Octanol-Water partition coefficient. LC50 = Concentration lethal to 50% of the tested organisms. LC-MS-MS = Liquid Chromatograph with Tandem Mass Spectrometry. LD50 = Dose lethal to 50% of the tested organisms. LAA = Likely to Adversely Affect. LOAEC = Lowest-Observed-Adverse-Effect Concentration. LOC = Level of Concern. MA = May Affect. MATC = Maximum Acceptable Toxicant Concentration. NAS = National Academy of Sciences. NCWQR = National Center of Water Quality Research. NE = No Effect. NLAA = Not Likely to Adversely Affect. NMFS = National Marine Fisheries Service. NOAA = National Oceanic and Atmospheric Administration. NOAEC = No-Observed-Adverse-Effect Concentration. NOAEL = No-Observed-Adverse-Effect Dose-Level. OECD = Organization of Economic Cooperation and Development. PNSP = Pesticide National Synthesis Project. PQ = Plastoquinone. PRZM = Pesticide Root Zone Model. PWC = Pesticide in Water Calculator. QWoE = Quantitative Weight of Evidence. RGR = Relative growth rate (of plants). RQ = Risk Quotient. RUD = Residue Unit Doses. SAP = Science Advisory Panel (of the USEPA). SGR = Specific Growth Rate. SI = Supplemental Information. SSD = Species Sensitivity Distribution. SURLAG = Surface Runoff Lag Coefficient. SWAT = Soil & Water Assessment Tool. SWCC = Surface Water Concentration Calculator. UDL = Use Data Layer (for pesticides). USDA = United States Department of Agriculture. USEPA = United States Environmental Protection Agency. USFWS = United States Fish and Wildlife Service. USGS = United States Geological Survey. WARP = Watershed Regressions for Pesticides.

The chemical and biological properties of glyphosate are key to understanding its fate in the environment and potential risks to non-target organisms. Glyphosate is polar and water soluble and therefore does not bioaccumulate, biomagnify, or accumulate to high levels in the environment. It sorbs strongly to particles in soil and sediments and this reduces bioavailability so that exposures to non-target organisms in the environment are acute and decrease with half-lives in the order of hours to a few days. The target site for glyphosate is not known to be expressed in animals, which reduces the probability of toxicity and small risks. Technical glyphosate (acid or salts) is of low to moderate toxicity; however, when mixed with some formulants such as polyoxyethylene amines (POEAs), toxicity to aquatic animals increases about 15-fold on average. However, glyphosate and the formulants have different fates in the environment and they do not necessarily co-occur. Therefore, toxicity tests on formulated products in scenarios where they would not be used are unrealistic and of limited use for assessment of risk. Concentrations of glyphosate in surface water are generally low with minimal risk to aquatic organisms, including plants. Toxicity and risks to non-target terrestrial organisms other than plants treated directly are low and risks to terrestrial invertebrates and microbial processes in soil are very small. Formulations containing POEAs are not labeled for use over water but, because POEA rapidly partitions into sediment, risks to aquatic organisms from accidental over-sprays are reduced in shallow water bodies. We conclude that use of formulations of glyphosate under good agricultural practices presents a de minimis risk of direct and indirect adverse effects in non-target organisms., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive assessment (Photochemical and Photobiological Sciences, 2019, 18, 595-828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality; human health; terrestrial and aquatic ecosystems; biogeochemical cycles; and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.

Glyphosate is one of the most widely used herbicides in the world, but it has also been the focus of discussion and restrictions in several countries since it was declared 'probably carcinogenic to humans (Group 2A)' by the International Agency for Research on Cancer in 2015. Since that time, several regulatory agencies have reviewed the public literature and guideline studies submitted for regulatory purposes and have concluded that it is not a carcinogen, and revised acceptable daily intakes (ADIs) and the reference dose (RfD) have been published. Also, restrictions on use have been lifted in many locations. Risk assessment for any pesticide requires knowledge of exposure in humans and the environment, and this paper is an update on a previous review in 2016 and includes papers published after 2016. These exposure data for air, water, bystanders, the general public, domesticated animals, pets, and applicators were combined and compared to the revised exposure criteria published by regulatory agencies. In all cases, measured and estimated systemic exposures to glyphosate in humans and animals were less than the ADIs and the RfD. Based on this large dataset, these exposures represent a de minimis risk. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

This assessment, by the United Nations Environment Programme (UNEP) Environmental Effects Assessment Panel (EEAP), one of three Panels informing the Parties to the Montreal Protocol, provides an update, since our previous extensive assessment (Photochem. Photobiol. Sci., 2019, 18, 595-828), of recent findings of current and projected interactive environmental effects of ultraviolet (UV) radiation, stratospheric ozone, and climate change. These effects include those on human health, air quality, terrestrial and aquatic ecosystems, biogeochemical cycles, and materials used in construction and other services. The present update evaluates further evidence of the consequences of human activity on climate change that are altering the exposure of organisms and ecosystems to UV radiation. This in turn reveals the interactive effects of many climate change factors with UV radiation that have implications for the atmosphere, feedbacks, contaminant fate and transport, organismal responses, and many outdoor materials including plastics, wood, and fabrics. The universal ratification of the Montreal Protocol, signed by 197 countries, has led to the regulation and phase-out of chemicals that deplete the stratospheric ozone layer. Although this treaty has had unprecedented success in protecting the ozone layer, and hence all life on Earth from damaging UV radiation, it is also making a substantial contribution to reducing climate warming because many of the chemicals under this treaty are greenhouse gases.

Quantitative weight of evidence (QWoE) provides a framework and process for evaluating different toxicological studies based on quality and relevance of the results. This framework allows for data from these studies to be combined in separate lines of evidence to address causality, and relevance to environmental risks. In 2014, such a QWoE that examined the body of available company reports and peer reviewed literature regarding the effects of the herbicide atrazine on fish, amphibians, and reptiles was published. Since that time, new studies have been conducted and/or published. One of the advantages of the QWoE framework is that additional information can be added as it becomes available. Thus, these new studies were evaluated in the same manner as previously and the new data incorporated into the existing QWoE. As before, the new updated QWoE was based on the same process of objective scoring of individual studies with respect to the quality of the methods and the relevance of individual responses to the apical endpoints of survival, growth, development, and reproduction. These new data did not identify new responses or indicate any relevant effects of atrazine. The new updated QWoE analysis concluded that atrazine does not adversely affect fish, amphibians, and reptiles, at environmentally relevant concentrations (<100 µg atrazine/L), which is consistent with the previous conclusions. These new studies and data are discussed in this paper and the accompanying supplement information provides detailed and transparent information to support these conclusions.

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., (© 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.)

Background: Statins have demonstrated protection against aggressive/late-stage and/or lethal prostate cancer (PC), but prior studies are limited by small populations, short follow-up and unequal health-care access. Research has not demonstrated that non-statin lipid-lowering medications (NSLLMs) provide a similar benefit, which would support a cholesterol-based mechanism. We sought to rigorously test the hypothesis that cholesterol-lowering drugs affect PC incidence and severity., Methods: A retrospective cohort study was conducted by abstracting prescription and health service records for 249,986 Saskatchewan men aged ≥40 years between January 1, 1990 and December 31, 2014 and comparing first-time statin and NSLLM users with age-matched non-users and glaucoma medication (GM) users for PC incidence, metastases at diagnosis and PC mortality using Cox proportional hazards regression., Results: In comparing statin users to non-users, a weak association was detected with increased PC incidence (hazard ratio [HR] 1.07, 95% confidence interval [CI]: 1.02-1.12) that disappeared when compared with GM users. Substantial protective associations were observed between statin use and metastatic PC and PC mortality (HRs 0.69, 95% CI: 0.61-0.79 and 0.73, 95% CI: 0.66-0.81, respectively), which were stronger when compared with GM use (HRs 0.52, 95% CI: 0.40-0.68 and 0.51, 95% CI: 0.41-0.63, respectively). Similar associations were found for NSLLM versus GM for metastatic PC (HR 0.57, 95% CI: 0.41-0.79) and PC mortality (HR 0.66, 95% CI: 0.51-0.85)., Conclusions: Our analyses provide one of the more comprehensive findings to date that statins may reduce risk of metastatic PC and PC mortality, and the first to demonstrate that NSLLM have similar effects, supporting a cholesterol-based mechanism., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The composition of the air we breathe is determined by emissions, weather, and photochemical transformations induced by solar UV radiation. Photochemical reactions of many emitted chemical compounds can generate important (secondary) pollutants including ground-level ozone (O 3 ) and some particulate matter, known to be detrimental to human health and ecosystems. Poor air quality is the major environmental cause of premature deaths globally, and even a small decrease in air quality can translate into a large increase in the number of deaths. In many regions of the globe, changes in emissions of pollutants have caused significant changes in air quality. Short-term variability in the weather as well as long-term climatic trends can affect ground-level pollution through several mechanisms. These include large-scale changes in the transport of O 3 from the stratosphere to the troposphere, winds, clouds, and patterns of precipitation. Long-term trends in UV radiation, particularly related to the depletion and recovery of stratospheric ozone, are also expected to result in changes in air quality as well as the self-cleaning capacity of the global atmosphere. The increased use of substitutes for ozone-depleting substances, in response to the Montreal Protocol, does not currently pose a significant risk to the environment. This includes both the direct emissions of substitutes during use and their atmospheric degradation products (e.g. trifluoroacetic acid, TFA).

Objective: To investigate the use of 5α-reductase inhibitors (5ARIs) and α-blockers among men with benign prostatic hyperplasia (BPH) in relation to prostate cancer (PCa) incidence, severity and mortality., Patients and Methods: A retrospective 20-year cohort study in men residing in Saskatchewan, aged 40-89 years, with a BPH-coded medical claim between 1995 and 2014, was conducted. Cox proportional hazards regression was used to compare incidence of PCa diagnosis, metastatic PCa, Gleason score 8-10 PCa, and PCa mortality among 5ARI users (n = 4 571), α-blocker users (n = 7 764) and non-users (n = 11 677)., Results: In comparison with both non-users and α-blocker users, 5ARI users had a ~40% lower risk of a PCa diagnosis (11.0% and 11.4% vs 5.8%, respectively), and α-blocker users had an 11% lower risk of a PCa diagnosis compared with non-users. Overall, the incidence of metastatic PCa and PCa mortality was not significantly different among 5ARI or α-blocker users compared with non-users (adjusted hazard ratios [HR] of metastatic PCa: 1.12 and 1.13, respectively, and PCa mortality: 1.11 and 1.18, respectively, P > 0.05 for both drugs), but both 5ARI and a-blocker users had ~30% higher risk of Gleason score 8-10 cancer, adjusted HR 1.37, 95% confidence interval [CI] 1.03-1.82, P = 0.03, and adjusted HR 1.28, 95% CI 1.03-1.59, P = 0.02, respectively compared with non-users., Conclusion: The use of 5ARIs was associated with lower risk of PCa diagnosis, regardless of comparison group. Risk of high grade PCa was higher among both 5ARI users and α-blocker users compared with non-users; however, this did not translate into higher risk of PCa mortality., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Background: Some, but not all, epidemiologic evidence supports a role for cholesterol, the precursor for steroid hormone synthesis, in prostate cancer. Using a PTEN-null transgenic mouse model of prostate cancer, we tested the effect of modifying serum cholesterol levels on prostate tumor development and growth. We hypothesized that serum cholesterol reduction would lower tumor androgens and slow prostate cancer growth., Methods: PTEN loxP/loxP -Cre + mice consuming ad libitum high fat, high cholesterol diets (40% fat, 1.25% cholesterol) were randomized after weaning to receive the cholesterol uptake inhibitor, ezetimibe (30 mg/kg/day), or no intervention, and sacrificed at 2, 3, or 4 months of age. Serum cholesterol and testosterone were measured by ELISA and intraprostatic androgens by mass spectrometry. Prostate histology was graded, and proliferation and apoptosis in tumor epithelium and stroma was assessed by Ki67 and TUNEL, respectively., Results: Ezetimibe-treated mice had lower serum cholesterol at 4 months (p = 0.031). Serum cholesterol was positively correlated with prostate weight (p = 0.033) and tumor epithelial proliferation (p = 0.069), and negatively correlated with tumor epithelial apoptosis (p = 0.004). Serum cholesterol was unrelated to body weight (p = 0.195). Tumor stromal cell proliferation was reduced in the ezetimibe group (p = 0.010). Increased serum cholesterol at 4 months was associated with elevated intraprostatic DHEA, testosterone, and androstenedione (p = 0.043, p = 0.074, p = 0.031, respectively). However, cholesterol reduction did not significantly affect adenocarcinoma development at 2, 3, or 4 months of age (0, 78, and 100% in ezetimibe-treated vs. 0, 80, and 100% in mice not receiving ezetimibe)., Conclusions: Though serum cholesterol reduction did not significantly affect the rate of adenocarcinoma development in the PTEN-null transgenic mouse model of prostate cancer, it lowered intraprostatic androgens and slowed tumor growth. These findings support a role for serum cholesterol in promoting prostate cancer growth, potentially via enhanced tumor androgen signaling, and may provide new insight into cholesterol-lowering interventions for prostate cancer treatment.

The trophodynamics of halogenated flame retardants (HFRs) including polybrominated diphenyl ethers (PBDEs) and alternative HFRs were investigated in the terrestrial, vegetation-caribou-wolf food chain in the Bathurst Region of northern Canada. The greatest concentrations in vegetation (geometric mean of lichens, moss, grasses, willow, and mushrooms) were of the order 2,4,6-tribromophenyl allyl ether (TBP-AE) (10 ng g -1 lw) > BDE47 (5.5 ng g -1 lw) > BDE99 (3.9 ng g -1 lw) > BDE100 (0.82 ng g -1 lw) > 1,2,3,4,5-pentabromobenzene (PBBz) (0.72 ng g -1 lw). Bioconcentration among types of vegetation was consistent, though it was typically greatest in rootless vegetation (lichens, moss). Biomagnification was limited in mammals; only BDE197, BDE206-208 and ∑PBDE biomagnified to caribou from vegetation [biomagnification factors (BMFs) = 2.0-5.1]. Wolves biomagnified BDE28/33, BDE153, BDE154, BDE206, BDE207, and ∑PBDE significantly from caribou (BMFs = 2.9-17) but neither mammal biomagnified any alternative HFRs. Only concentrations of BDE28/33, BDE198, nonaBDEs, and ∑PBDE increased with trophic level, though the magnitude of biomagnification was low relative to legacy, recalcitrant organochlorine contaminants [trophic magnification factors (TMFs) = 1.3-1.8]. Despite bioaccumulation in vegetation and mammals, the contaminants investigated here exhibited limited biomagnification potential and remained at low parts per billion concentrations in wolves.

The Environmental Effects Assessment Panel (EEAP) is one of three Panels of experts that inform the Parties to the Montreal Protocol. The EEAP focuses on the effects of UV radiation on human health, terrestrial and aquatic ecosystems, air quality, and materials, as well as on the interactive effects of UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously held. Because of the Montreal Protocol, there are now indications of the beginnings of a recovery of stratospheric ozone, although the time required to reach levels like those before the 1960s is still uncertain, particularly as the effects of stratospheric ozone on climate change and vice versa, are not yet fully understood. Some regions will likely receive enhanced levels of UV radiation, while other areas will likely experience a reduction in UV radiation as ozone- and climate-driven changes affect the amounts of UV radiation reaching the Earth's surface. Like the other Panels, the EEAP produces detailed Quadrennial Reports every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Update Reports of recent and relevant scientific findings. The most recent of these was for 2016 (Photochem. Photobiol. Sci., 2017, 16, 107-145). The present 2017 Update Report assesses some of the highlights and new insights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. A full 2018 Quadrennial Assessment, will be made available in 2018/2019.

Background: Epidemiologic data suggest cholesterol-lowering drugs may prevent the progression of prostate cancer, but not the incidence of the disease. However, the association of combination therapy in cholesterol reduction on prostate or any cancer is unclear. In this study, we compared the effects of the cholesterol lowering drugs simvastatin and ezetimibe alone or in combination on the growth of LAPC-4 prostate cancer in vivo xenografts., Methods: Proliferation assays were conducted by MTS solution and assessed by Student's t-test. 90 male nude mice were placed on a high-cholesterol Western-diet for 7 days then injected subcutaneously with 1 × 10 5 LAPC-4 cells. Two weeks post-injection, mice were randomized to control, 11 mg/kg/day simvastatin, 30 mg/kg ezetimibe, or the combination and sacrificed 42 days post-randomization. We used a generalized linear model with the predictor variables of treatment, time, and treatment by time (i.e., interaction term) with tumor volume as the outcome variable. Total serum and tumor cholesterol were measured. Tumoral RNA was extracted and cDNA synthesized from 1 ug of total RNA for quantitative real-time PCR., Results: Simvastatin directly reduced in vitro prostate cell proliferation in a dose-dependent, cell line-specific manner, but ezetimibe had no effect. In vivo, low continuous dosing of ezetimibe, delivered by food, or simvastatin, delivered via an osmotic pump had no effect on tumor growth compared to control mice. In contrast, dual treatment of simvastatin and ezetimibe accelerated tumor growth. Ezetimibe significantly lowered serum cholesterol by 15%, while simvastatin had no effect. Ezetimibe treatment resulted in higher tumor cholesterol. A sixfold induction of low density lipoprotein receptor mRNA was observed in ezetimibe and the combination with simvastatin versus control tumors., Conclusions: Systemic cholesterol lowering by ezetimibe did not slow tumor growth, nor did the cholesterol independent effects of simvastatin and the combined treatment increased tumor growth. Despite lower serum cholesterol, tumors from ezetimibe treated mice had higher levels of cholesterol. This study suggests that induction of low density lipoprotein receptor is a possible mechanism of resistance that prostate tumors use to counteract the therapeutic effects of lowering serum cholesterol. Prostate 77:446-457, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

A series of toxicity tests with MON 0818, a commercial surfactant mixture of polyoxyethylene tallow amines, were performed: 1) in the presence of sediment for benthic invertebrates and fish: 2) to examine the recovery capacity of Daphnia magna and 4 primary producers after a pulsed (24-h) exposure; and 3) to examine the potential effect of increased water temperature on toxicity of MON 0818 to 2 cold-water fishes. In the presence of sediment, no acute (24-h) mortality was observed for 3 of the 5 species up to 10 mg L -1 . The median effective concentrations for the other 2 species were significantly greater than for water only tests. The EC50 at 15 °C for Salvelinus alpinus was statistically lower than that at 10 °C. Latent effects of a 24-h exposure (1 mg L -1 ) were observed for Rhabdocelis subcapitata and Chlorella vulgaris, as indicated by delayed growth during recovery phase; however, both cultures were able to recover, as indicated by a lack of changes in maximum absolute growth rates. No significant effects of a 24-h exposure to MON 0818 were observed for Oophila sp. (1.5 mg L -1 ) or Lemna minor (100 mg L -1 ). Latent mortality after a 24-h exposure to 5 mg L -1 was observed during the recovery phase for D. magna; however, reproduction endpoints on surviving individuals were not altered. The results indicate that quick dissipation of MON 0818 in the presence of sediment can reduce the effects on exposed organisms, and that full recovery from 24-h exposures to concentrations of MON 0818 equal to, or greater than, those expected in the environment is possible. Environ Toxicol Chem 2017;36:512-521. © 2016 SETAC., (© 2016 SETAC.)

The sensitivity of 15 aquatic species, including primary producers, benthic invertebrates, cladocerans, mollusks, and fish, to MON 0818, a commercial surfactant mixture of polyoxyethylene tallow amines, was evaluated in standard acute (48-96-h) laboratory tests. In addition, the potential for chronic toxicity (8 d) was evaluated with Ceriodaphnia dubia. Exposure concentrations were confirmed. No significant effects on any endpoint were observed in the chronic test. A tier-1 hazard assessment was conducted by comparing species sensitivity distributions based on the generated data, as well as literature data, with 4 exposure scenarios. This assessment showed moderate levels of hazard (43.1% of the species exposed at or above median effective concentration levels), for a chosen worst-case scenario-unintentional direct over-spray of a 15-cm-deep body of water with the maximum label application rate for the studied formulations (Roundup Original, Vision Forestry Herbicide; 12 L formulation ha -1 , equivalent to 4.27 kg acid equivalent [a.e.] ha -1 ). The hazard decreased to impairment of 20.9% of species under the maximum application rate for more typical uses (6 L formulation ha -1 , 2.14 kg a.e. ha -1 ), and down to 6.9% for a more frequently employed application rate (2.5 L formulation ha -1 , 0.89 kg a.e. ha -1 ). Finally, the percentage (3.8%) was less than the hazardous concentration for 5% of the species based on concentrations of MON 0818 calculated from maximum measured concentrations of glyphosate in the environment. Environ Toxicol Chem 2017;36:501-511. © 2016 SETAC., (© 2016 SETAC.)

The surfactant mixture MON 0818 is an adjuvant in various commercial formulations of the herbicide glyphosate. Initial studies have shown that MON 0818 is more toxic to aquatic animals than the active ingredient. However, few studies have examined the effect of exposure to MON 0818 on species of mollusks, and no studies have examined the effect on gastropods. The present study investigated the effect of acute exposure (96 h) of MON 0818 to the eggs, juveniles, and adults of the file ramshorn snail (Planorbella pilsbryi). Concentrations of MON 0818 up to 9.9 mg/L did not have a significant effect on the viability of eggs (p > 0.05). Juvenile snails (50% lethal concentration [LC50] = 4.0 mg/L) were more sensitive than adult snails (LC50 = 4.9-9.1 mg/L). Oviposition was inhibited by exposure to MON 0818 (median effective concentration [EC50] = 0.4-2.0 mg/L). However, oviposition resumed when snails were removed to clean water, even after 96-h exposure to up to 4.9 mg/L of MON 0818. Exposure to a concentration ≥2.7 mg/L caused visible damage to the tentacles of adult snails, which could potentially impact chemoreception. A deterministic hazard assessment indicated that environmentally relevant concentrations of MON 0818 could pose a hazard to the deposition of eggs. However, because of the relatively short half-life of MON 0818 in aquatic systems and the ability of snails to resume oviposition following the dissipation of MON 0818, environmentally relevant concentrations of MON 0818 likely pose a de minimis risk to populations of ramshorn snails. Environ Toxicol Chem 2017;36:522-531. © 2016 SETAC., (© 2016 SETAC.)

The ILSI Health and Environmental Sciences Institute (HESI) has developed a framework to support a transition in the way in which information for chemical risk assessment is obtained and used (RISK21). The approach is based on detailed problem formulation, where exposure drives the data acquisition process in order to enable informed decision-making on human health safety as soon as sufficient evidence is available. Information is evaluated in a transparent and consistent way with the aim of optimizing available resources. In the context of risk assessment, cumulative risk assessment (CRA) poses additional problems and questions that can be addressed using the RISK21 approach. The focus in CRA to date has generally been on chemicals that have common mechanisms of action. Recently, concern has also been expressed about chemicals acting on multiple pathways that lead to a common health outcome, and non-chemical other conditions (non-chemical stressors) that can lead to or modify a common outcome. Acknowledging that CRAs, as described above, are more conceptually, methodologically and computationally complex than traditional single-stressor risk assessments, RISK21 further developed the framework for implementation of workable processes and procedures for conducting assessments of combined effects from exposure to multiple chemicals and non-chemical stressors. As part of the problem formulation process, this evidence-based framework allows the identification of the circumstances in which it is appropriate to conduct a CRA for a group of compounds. A tiered approach is then proposed, where additional chemical stressors and/or non-chemical modulating factors (ModFs) are considered sequentially. Criteria are provided to facilitate the decision on whether or not to include ModFs in the formal quantitative assessment, with the intention to help focus the use of available resources to have the greatest potential to protect public health.

A quantitative weight of evidence (QWoE) methodology was developed and used to assess many higher-tier studies on the effects of three neonicotinoid insecticides: clothianidin (CTD), imidacloprid (IMI), and thiamethoxam (TMX) on honeybees. A general problem formulation, a conceptual model for exposures of honeybees, and an analysis plan were developed. A QWoE methodology was used to characterize the quality of the available studies from the literature and unpublished reports of studies conducted by or for the registrants. These higher-tier studies focused on the exposures of honeybees to neonicotinoids via several matrices as measured in the field as well as the effects in experimentally controlled field studies. Reports provided by Bayer Crop Protection and Syngenta Crop Protection and papers from the open literature were assessed in detail, using predefined criteria for quality and relevance to develop scores (on a relative scale of 0-4) to separate the higher-quality from lower-quality studies and those relevant from less-relevant results. The scores from the QWoEs were summarized graphically to illustrate the overall quality of the studies and their relevance. Through mean and standard errors, this method provided graphical and numerical indications of the quality and relevance of the responses observed in the studies and the uncertainty associated with these two metrics. All analyses were conducted transparently and the derivations of the scores were fully documented. The results of these analyses are presented in three companion papers and the QWoE analyses for each insecticide are presented in detailed supplemental information (SI) in these papers.

A quantitative weight of evidence (QWoE) methodology was used to assess several higher-tier studies on the effects of thiamethoxam (TMX) on honeybees. Assessment endpoints were population size and viability of commercially managed honeybee colonies and quantity of hive products. A higher-tier field toxicology study indicated a no-observed-adverse effect concentration (NOAEC) of 29.5 µg TMX/kg syrup, equivalent to an oral no-observed-adverse-effect-dose (NOAED) of 8.6 ng/bee/day for all responses measured. For exposures via deposition of dust, a conservative no-observed-adverse-effect-rate at the level of the colony was 0.1 g TMX/ha. There was minimal risk to honeybees from exposure to TMX via nectar and pollen from its use as a seed-treatment. For exposures via dust and dust/seed applications, there were no concentrations above the risk values for TMX in nectar and pollen. Although some risks were identified for potential exposures via guttation fluid, this route of exposure is incomplete; no apparent adverse effects were observed in field studies. For exposures via dust/seed and dust/foliar applications, few adverse effects were observed. Considering all lines of evidence, the quality of the studies included in this analysis was variable. However, the results of the studies were consistent and point to the same conclusion. The overall weight of evidence based on many studies indicates that TMX has no adverse effects on viability or survival of the colony. Thus, the overall conclusion is that the treatment of seeds with thiamethoxam, as currently used in good agricultural practices, does not present a significant risk to honeybees at the level of the colony.

This paper is a postscript to the four companion papers in this issue of the Journal (Solomon and Stephenson 2017a , 2017b ; Stephenson and Solomon 2017a , 2017b ). The first paper in the series described the conceptual model and the methods of the QWoE process. The other three papers described the application of the QWoE process to studies on imidacloprid (IMI), clothianidin (CTD), and thiamethoxam (TMX). This postscript was written to summarize the utility of the methods used in the quantitative weight of evidence (QWoE), the overall relevance of the results, and the environmental implications of the findings. Hopefully, this will be helpful to others who wish to conduct QWoEs and use these methods in assessment of risks.

A quantitative weight of evidence (QWoE) methodology was used to assess higher tier studies on the effects of clothianidin (CTD) on honeybees. Assessment endpoints were population size and viability of commercially managed bees and quantity of hive products. A colony-level no-observed-adverse effect concentration (NOAEC) of 25 µg CTD/kg syrup, equivalent to an oral no-observed-adverse effect-dose (NOAED) of 7.3 ng/bee/d for all responses measured. Based on a NOAEC of 19.7 µg/kg pollen, the NOAED for honeybee larvae was 2.4 ng/bee larva/d. For exposures via dust, a no-observed-adverse effect rate of 4 g CTD/ha was used to assess relevance of exposures via deposition of dust. The overall weight of evidence suggested that there is minimal risk to honeybees from exposure to CTD from its use as a seed treatment. For exposures via dust, dust/seed and dust/foliar applications, there were no exposures greater than the NOAED for CTD in nectar and pollen, indicating a de minimis risk to honeybees when the route of exposure was via uptake in plants. Analysis of effect studies in the field indicated a consistent lack of relevant effects, regardless of the way CTD was applied. For exposures via dust, there were no adverse effects because of these applications and there were no exposures greater than the NOAED for CTD in nectar and pollen. The overall weight of evidence based on many studies indicated no adverse effects on colony viability or survival of the colony. Thus, the overall conclusion is that clothianidin, as currently used in good agricultural practices, does not present a significant risk to honeybees at the level of the colony.

A quantitative weight of evidence (QWoE) methodology was used to assess higher-tier studies on the effects of imidacloprid (IMI) on honeybees. Assessment endpoints were population size and viability of commercially managed bees and quantity of hive products. A colony-level no-observed-adverse effect concentration (NOAEC) of 25 µg IMI/kg syrup, equivalent to an oral no-observed-adverse-effect-dose of 7.3 ng/bee/d for all responses, was measured. The overall weight of evidence indicates that there is minimal risk to honeybees from exposure to IMI from its use as a seed treatment. Exposures via dusts from currently used seed coatings present a de minimis risk to honeybees when the route of exposure is via uptake in plants that are a source of pollen or nectar for honeybees. There were few higher-tier observational (ecoepidemiological) studies conducted with IMI. Considering all lines of evidence, the quality of the studies included in this analysis was variable, but the results of the studies were consistent and point to the same conclusion - that IMI had no adverse effects on viability of the honeybee colony. Thus, the overall conclusion is that IMI, as currently used as a seed treatment and with good agricultural practices, does not present a significant risk to honeybees at the level of the colony.

Pendimethalin (PND, CAS registry number 40487-42-1) is a dinitroaniline herbicide that selectively controls broad-leaf and grassy weeds in a variety of crops and in noncrop areas. It has been on the market for about 30 yr and is currently under review for properties related to persistence (P), bioaccumulation (B), and toxicity (T) in the European Union (EU). A critical review of these properties as well as potential for long-range transport (LRT) was conducted. Pendimethalin has a geometric mean (GM) half-life of 76-98 d in agriculturally relevant soils under aerobic conditions in the lab. The anaerobic half-life was 12 d. The GM for field half-lives was 72 d. The GM half-life for sediment-water tests in the lab was 20 d and that in field aquatic cosms ranged from 45 to 90 d. From these data PND is not persistent as defined in the Annex II of EC regulation 1107/2009. The GM bioconcentration factor for PND was 1878, less than the criterion value. This was consistent with lack of biomagnification or accumulation in aquatic and terrestrial food chains. The GM no-observed-effect concentration (NOEC) value for fish was 43 µg/L, and 11 µg/L for algae. These do not trigger the criterion value for toxicity. In air, the DT50 of PND was estimated to be 0.35 d, which is well below the criterion of 2 d for LRT under the United Nations Economic Commission for Europe (UNECE) Aarhus protocol. Modeling confirmed lack of LRT. Because of its volatility, PND may be transported over short distances in air and was found in samples in local and semiremote regions; however, these concentrations are not of toxicological concern. Unlike other current-use pesticides, PND has not been found in samples from remote regions since 2000 and there is no apparent evidence that this herbicide accumulates in food chains in the Arctic.

When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors. As part of the HESI Risk Assessment in the 21st Century (RISK21) Project, a framework for CRA was developed in which problem formulation plays a critical role. The focus of this effort is primarily on a chemical CRA (i.e., two or more chemicals) with subsequent consideration of non-chemical stressors, defined as "modulating factors" (ModFs). Problem formulation is a systematic approach that identifies all factors critical to a specific risk assessment and considers the purpose of the assessment, scope and depth of the necessary analysis, analytical approach, available resources and outcomes, and overall risk management goal. There are numerous considerations that are specific to multiple stressors, and proper problem formulation can help to focus a CRA to the key factors in order to optimize resources. As part of the problem formulation, conceptual models for exposures and responses can be developed that address these factors, such as temporal relationships between stressors and consideration of the appropriate ModFs.

The acute toxicity of herbicides to algae is commonly assessed under conditions (e.g., light intensity, water temperature, concentration of nutrients, pH) prescribed by standard test protocols. However, the observed toxicity may vary with changes in one or more of these parameters. This study examined variation in toxicity of the herbicide atrazine to a representative green algal species Raphidocelis subcapitata (formerly Pseudokirchneriella subcapitata) with changes in light intensity, water temperature, concentrations of nutrients or combinations of these three parameters. Conditions were chosen that could be representative of the intensive corn growing Midwestern region of the United States of America where atrazine is used extensively. Varying light intensity (4-58µmol/m(2)s) resulted in no observable trend in 96-h EC50 values for growth rate. EC50 values for PSII yield generally increased with decreasing light intensity but not significantly in all cases. The 96-h EC50 values for growth rate decreased with decreases in temperature (20-5°C) from standard conditions (25°C), but EC50 values for PSII yield at lower temperatures were not significantly different from standard conditions. Finally, there was no clear trend in 96-h EC50 values for both endpoints with increases in nitrogen (4.1-20mg/L) and phosphorus (0.24-1.2mg/L). The 96-h EC50 values for both endpoints under combinations of conditions mimicking aquatic systems in the Midwestern U.S. were not significantly different from EC50 values generated under standard test conditions. This combination of decreased light intensity and temperature and increased nutrients relative to standard conditions does not appear to significantly affect the observed toxicity of atrazine to R. subcapitata. For atrazine specifically, and for perhaps other herbicides, this means current laboratory protocols are useful for extrapolating to effects on algae under realistic environmental conditions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The recent classification of glyphosate as a probable human carcinogen by the International Agency for Research on Cancer (IARC) was arrived at without a detailed assessment of exposure. Glyphosate is widely used as an herbicide, which might result in exposures of the general public and applicators. Exposures were estimated from information in the open literature and unpublished reports provided by Monsanto Company. Based on the maximum measured concentration in air, an exposure dose of 1.04 × 10  -   6  mg/kg body mass (b.m.)/d was estimated. Assuming consumption of surface water without treatment, the 90th centile measured concentration would result in a consumed dose of 2.25 × 10  -   5  mg/kg b.m./d. Estimates by the Food and Agriculture Organization of the United Nations (FAO) of consumed doses in food provided a median exposure of 0.005 mg/kg b.m./d (range 0.002-0.013). Based on tolerance levels, the conservative estimate by the US Environmental Protection Agency (US EPA) for exposure of the general population via food and water was 0.088 mg/kg b.m./d (range 0.058-0.23). For applicators, 90th centiles for systemic exposures based on biomonitoring and dosimetry (normalized for penetration through the skin) were 0.0014 and 0.021 mg/kg b.m./d, respectively. All of these exposures are less than the reference dose and the acceptable daily intakes proposed by several regulatory agencies, thus supporting a conclusion that even for these highly exposed populations the exposures were within regulatory limits.

The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non-Hodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans.

The distribution of current-use pesticides (CUPs) in seawater and their trophodynamics were investigated in 3 Canadian Arctic marine food chains. The greatest ranges of dissolved-phase concentrations in seawater for each CUP were endosulfan sulfate (less than method detection limit (MDL) to 19 pg L(-1) ) > dacthal (0.76-15 pg L(-1) ) > chlorpyrifos (less than MDL to 8.1 pg L(-1) ) > pentachloronitrobenzene (less than MDL to 2.6 pg L(-1) ) > α-endosulfan (0.20-2.3 pg L(-1) ). Bioaccumulation factors (BAFs, water-respiring organisms) were greatest in plankton, including chlorothalonil (log BAF = 7.4 ± 7.1 L kg(-1) , mean ± standard error), chlorpyrifos (log BAF = 6.9 ± 6.7 L kg(-1) ), and α-endosulfan (log BAF = 6.5 ± 6.0 L kg(-1) ). The largest biomagnification factors (BMFs) were found for dacthal in the capelin:plankton trophic relationship (BMF = 13 ± 5.0) at Cumberland Sound (Nunvavut), and for β-endosulfan (BMF = 16 ± 4.9) and α-endosulfan (BMF = 9.3 ± 2.8) in the polar bear-ringed seal relationship at Barrow and Rae Strait (NU), respectively. Concentrations of endosulfan sulfate exhibited trophic magnification (increasing concentrations with increasing trophic level) in the poikilothermic portion of the food web (trophic magnification factor = 1.4), but all of the CUPs underwent trophic dilution in the marine mammal food web, despite some trophic level-specific biomagnification. Together, these observations are most likely indicative of metabolism of these CUPs in mammals. Environ Toxicol Chem 2016;35:1695-1707. © 2016 SETAC., (© 2016 SETAC.)

Technology and scientific advancements are accelerating changes in society at a pace that is challenging the abilities of government regulatory agencies and legal courts to understand the benefits and costs of these changes to humans, wildlife, and their environments. The social, economic, and political facets of concern, such as the potential effects of chemicals, complicate the preparation of regulatory standards and practices intended to safeguard the public. Court judges and attorneys and, in some cases, lay juries are tasked with interpreting the data and implications underlying these new advancements, often without the technical background necessary to understand complex subjects and subsequently make informed decisions. Here, we describe the scientific-quasi-judicial process adopted in Canada under the Canadian Environmental Protection Act, 1999, which could serve as a model for resolving conflicts between regulatory agencies and the regulated community. An example and process and lessons learned from the first Board of Review, which was for decamethylcyclopentasiloxane (D5; CAS# 541-02-06), are provided. Notable among these lessons are: 1) the need to apply state-of-the-science insights into the regulatory process, 2) to encourage agencies to continuously review and update their assessment processes, criteria, and models, and 3) provide these processes in guidance documents that are transparent and available to all stakeholders and generally foster closer cooperation between regulators, the academic community, industry, and nongovernment organizations (NGOs). Integr Environ Assess Manag 2016;12:572-579. © 2015 SETAC., (© 2015 SETAC.)

Trifluoroacetic acid (TFA) is a breakdown product of several hydrochlorofluorocarbons (HCFC), regulated under the Montreal Protocol (MP), and hydrofluorocarbons (HFC) used mainly as refrigerants. Trifluoroacetic acid is (1) produced naturally and synthetically, (2) used in the chemical industry, and (3) a potential environmental breakdown product of a large number (>1 million) chemicals, including pharmaceuticals, pesticides, and polymers. The contribution of these chemicals to global amounts of TFA is uncertain, in contrast to that from HCFC and HFC regulated under the MP. TFA salts are stable in the environment and accumulate in terminal sinks such as playas, salt lakes, and oceans, where the only process for loss of water is evaporation. Total contribution to existing amounts of TFA in the oceans as a result of the continued use of HCFCs, HFCs, and hydrofluoroolefines (HFOs) up to 2050 is estimated to be a small fraction (<7.5%) of the approximately 0.2 μg acid equivalents/L estimated to be present at the start of the millennium. As an acid or as a salt TFA is low to moderately toxic to a range of organisms. Based on current projections of future use of HCFCs and HFCs, the amount of TFA formed in the troposphere from substances regulated under the MP is too small to be a risk to the health of humans and environment. However, the formation of TFA derived from degradation of HCFC and HFC warrants continued attention, in part because of a long environmental lifetime and due many other potential but highly uncertain sources.

Cyclic volatile methyl siloxanes (cVMSs) are highly volatile and have an unusual combination of physicochemical properties, which are unlike those of halocarbon-based chemicals used to establish criteria for identification of persistent organic pollutants (POPs) that undergo long-range transport (LRT). A transparent quantitative weight of evidence (QWoE) evaluation was conducted to characterize their properties. Measurements of concentrations of cVMSs in the environment are challenging, but currently, concentrations measured in robust studies are all less than thresholds of toxicity. The cVMSs are moderately persistent in air with half-lives ≤11 d (greater than the criterion of 2 d) but these compounds partition into the atmosphere, the final sink. The cVMSs are rapidly degraded in dry soils, partition from wet soils into the atmosphere, and are not classifiable as persistent in soils. Persistence in water and sediment is variable, but the greatest concentrations in the environment are observed in sediments. Based upon the measurements that have been made in the environment, cVMSs should not be classified as persistent. Studies in food webs support a conclusion that the cVMSs do not biomagnify, a conclusion that is consistent with results of toxicokinetic studies. Concentrations in air in remote locations are small and deposition has not been detected. Taken together, evidence indicates that traditional measures of persistence and biomagnification used for legacy POP are not suitable for cVMS. Refined approaches used here suggest that cVMSs are not classifiable as persistent, bioaccumulative, or toxic. Further, these chemicals do not undergo LRT in the sense of legacy POPs.