Assessing the Ecological Risks of Per- and Polyfluoroalkyl Substances: Current State-of-the Science and a Proposed Path Forward.

Per- and poly-fluoroalkyl substances (PFAS) encompass a large, heterogenous group of chemicals of potential concern to human health and the environment. Based on information for a few relatively well-understood PFAS such as perfluorooctane sulfonate and perfluorooctanoate, there is ample basis to suspect that at least a subset can be considered persistent, bioaccumulative, and/or toxic. However, data suitable for determining risks in either prospective or retrospective assessments are lacking for the majority of PFAS. In August 2019, the Society of Environmental Toxicology and Chemistry sponsored a workshop that focused on the state-of-the-science supporting risk assessment of PFAS. The present review summarizes discussions concerning the ecotoxicology and ecological risks of PFAS. First, we summarize currently available information relevant to problem formulation/prioritization, exposure, and hazard/effects of PFAS in the context of regulatory and ecological risk assessment activities from around the world. We then describe critical gaps and uncertainties relative to ecological risk assessments for PFAS and propose approaches to address these needs. Recommendations include the development of more comprehensive monitoring programs to support exposure assessment, an emphasis on research to support the formulation of predictive models for bioaccumulation, and the development of in silico, in vitro, and in vivo methods to efficiently assess biological effects for potentially sensitive species/endpoints. Addressing needs associated with assessing the ecological risk of PFAS will require cross-disciplinary approaches that employ both conventional and new methods in an integrated, resource-effective manner. Environ Toxicol Chem 2021;40:564-605. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

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.

Considerations of Environmentally Relevant Test Conditions for Improved Evaluation of Ecological Hazards of Engineered Nanomaterials.

Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects. Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant concentrations-where observing outcomes is difficult-versus higher ENM doses, where responses are observable. What exposure conditions are typically used in assessing ENM hazards to populations? What conditions are used to test ecosystem-scale hazards? What is known regarding actual ENMs in the environment, via measurements or modeling simulations? How should exposure conditions, ENM transformation, dose, and body burden be used in interpreting biological and computational findings for assessing risks? These questions were addressed in the context of this critical review. As a result, three main recommendations emerged. First, researchers should improve ecotoxicology of ENMs by choosing test end points, duration, and study conditions-including ENM test concentrations-that align with realistic exposure scenarios. Second, testing should proceed via tiers with iterative feedback that informs experiments at other levels of biological organization. Finally, environmental realism in ENM hazard assessments should involve greater coordination among ENM quantitative analysts, exposure modelers, and ecotoxicologists, across government, industry, and academia.

Aquatic hazard, bioaccumulation and screening risk assessment for ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate.

The fluoropolymer manufacturing industry is moving to alternative polymerization processing aid technologies with more favorable toxicological and environmental profiles as part of a commitment to curtail the use of long-chain perfluoroalkyl acids (PFAAs). To facilitate the environmental product stewardship assessment and premanufacture notification (PMN) process for a candidate replacement chemical, we conducted acute and chronic aquatic toxicity tests to evaluate the toxicity of ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (C6HF11O3.H3N) or the acid form of the substance to the cladoceran, Daphnia magna, the green alga, Pseudokirchneriella subcapitata, and a number of freshwater fish species including the rainbow trout, Oncorhynchus mykiss, In addition, testing with the common carp, Cyprinus carpio, was conducted to determine the bioconcentration potential of the acid form of the compound. Based on the relevant criteria in current regulatory frameworks, the results of the aquatic toxicity and bioconcentration studies indicate the substance is of low concern for aquatic hazard and bioconcentration in aquatic organisms. Evaluation of environmental monitoring data in conjunction with the predicted no effect concentration (PNEC) based on the available data suggest low risk to aquatic organisms.

Aquatic hazard, bioaccumulation and screening risk assessment for 6:2 fluorotelomer sulfonate.

This study assessed the aquatic toxicity and bioaccumulation potential of 6:2 fluorotelomer sulfonate (6:2 FTSA). Acute and chronic aquatic hazard endpoints indicate 6:2 FTSA is not classified for aquatic hazard according to GHS or European CLP legislation. The aqueous bioconcentration factors for 6:2 FTSA were <40 and the dietary assimilation efficiency, growth corrected half-life and dietary biomagnification factor (BMF) were 0.435, 23.1d and 0.295, respectively. These data indicate that 6:2 FTSA is not bioaccumulative in aquatic organisms. Comparison of PNECs with the reported surface water concentrations (non-spill situations) suggests low risk to aquatic organisms from 6:2 FTSA. Future studies are needed to elucidate the biotic and abiotic fate of commercial AFFF surfactants in the environment.

TFA from HFO-1234yf: accumulation and aquatic risk in terminal water bodies.

A next-generation mobile automobile air-conditioning (MAC) refrigerant, HFO-1234yf (CF(3) CF = CH(2)), is being developed with improved environmental characteristics. In the atmosphere, it ultimately forms trifluoroacetic acid (TFA(A); CF(3)COOH), which is subsequently scavenged by precipitation and deposited on land and water as trifluoroacetate (TFA; CF(3)COO(-)). Trifluoroacetate is environmentally stable and has the potential to accumulate in terminal water bodies, that is, aquatic systems receiving inflow but with little or no outflow and with high rates of evaporation. Previous studies have estimated the emission rates of HFO-1234yf and have modeled the deposition concentrations and rates of TFA across North America. The present study uses multimedia modeling and geographic information system (GIS)-based modeling to assess the potential concentrations of TFA in terminal water bodies over extended periods. After 10 years of emissions, predicted concentrations of TFA in terminal water bodies across North America are estimated to range between current background levels (i.e., 0.01-0.22 µg/L) and 1 to 6 µg/L. After 50 years of continuous emissions, aquatic concentrations of 1 to 15 µg/L are predicted, with extreme concentrations of up to 50 to 200 µg/L in settings such as the Sonoran Desert along the California/Arizona (USA) border. Based on the relative insensitivity of aquatic organisms to TFA, predicted concentrations of TFA in terminal water bodies are not expected to impair aquatic systems, even considering potential emissions over extended periods.

Comparative acute freshwater hazard assessment and preliminary PNEC development for eight fluorinated acids.

Short-term 48, 72 and 96-h aquatic toxicity tests were conducted to evaluate the acute toxicity of eight fluorinated acids to the cladoceran, Daphnia magna, the green alga, Pseudokirchneriella subcapitata, and the rainbow trout, Oncorhynchus mykiss or the fathead minnow, Pimephales promelas. The eight fluorinated acids studied were tridecafluorohexyl ethanoic acid (6:2 FTCA), heptadecafluorooctyl ethanoic acid (8:2 FTCA), 2H-dodecafluoro-2-octenoic acid (6:2 FTUCA), 2H-hexadecafluoro-2-decenoic acid (8:2 FTUCA), 2H,2H,3H,3H-undecafluoro octanoic acid (5:3 acid), 2H,2H,3H,3H-pentadecafluoro decanoic acid (7:3 acid), n-perfluoropentanoic acid (PFPeA) and n-perfluorodecanoic acid (PFDA). The results of the acute toxicity tests conducted during this study suggest that the polyfluorinated acids, 8:2 FTCA, 8:2 FTUCA, 6:2 FTCA, 6:2 FTUCA, 7:3 acid and 5:3 acid, and the perfluorinated acids PFPeA and PFDA, are generally of low to medium concern based on evaluation of their acute freshwater toxicity (EC/LC50s typically between 1 and >100 mg L(-1)) using the USEPA TSCA aquatic toxicity evaluation paradigm. For the polyfluorinated acids, aquatic toxicity generally decreased as the number of fluorinated carbons decreased and as the overall carbon chain length decreased from 12 to 8. Acute aquatic toxicity of the 5 and 10 carbon perfluorocarboxylic acids (EC/LC50s between 10.6 and >100 mg L(-1)) was greater or similar to that of the 6-9 carbon perfluorocarboxylic acids (EC/LC50s>96.5 mg L(-1)). This study also provides the first report of the acute aquatic toxicity of the 5:3 acid (EC/LC50s of 22.5 to >103 mg L(-1)) which demonstrated less aquatic toxicity than the 7:3 acid (EC/LC50s of 0.4-32 mg L(-1)). The cladoceran, D. magna and the green alga, P. subcapitata had generally similar EC50 values for a given substance while fish were typically equally or less sensitive with the exception that PFPeA was most toxic to fish. Predicted no-effect concentrations (PNECs) were estimated using approaches consistent with REACH guidance and when compared with available environmental concentrations, these PNECs suggest that the fluorinated acids tested pose little risk for aquatic organisms.

Bioaccumulation data from laboratory and field studies: are they comparable?

Once they are released into the environment, a number of chemicals are known to bioaccumulate in organisms, sometimes to concentrations that may threaten the individual or their predators. However, use of physical or chemical properties or results from laboratory bioaccumulation tests to predict concentrations sometimes found in wild organisms remains a challenge. How well laboratory studies and field measurements agree or disagree, and the cause of any discrepancies, is a subject of great interest and discussion from both a scientific and a regulatory perspective. A workshop sponsored by the ILSI Health and Environmental Sciences Institute, US Environmental Protection Agency, and the Society of Environmental Toxicology and Chemistry assembled scientists from academia, industry, and government to compare and contrast laboratory and field bioaccumulation data. The results of this workshop are summarized in a series of 5 articles published in this issue of Integrated Environmental Assessment and Management. The articles describe: 1) a weight-of-evidence approach that uses fugacity ratios to bring field measurements into the assessment of biomagnification potential for legacy chemicals; 2) a detailed comparison between laboratory and field data for the most commonly measured bioaccumulation endpoint, the biota-sediment accumulation factor; 3) a study that identifies and quantifies the differences between laboratory and field metrics of bioaccumulation for aquatic and terrestrial organisms; and 4) 2 reports on trophic magnification factors: the 1st addresses how trophic magnification factors are determined and interpreted and the 2nd describes how they could be used in regulatory assessments. Collectively, these articles present the workshop participants' current understanding and assessment of bioaccumulation science and make a number of recommendations on how to improve the collection and interpretation of bioaccumulation data.

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

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

Comparing laboratory and field measured bioaccumulation endpoints.

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

Predicting chemical impacts on vertebrate endocrine systems.

Animals have evolved diverse protective mechanisms for responding to toxic chemicals of both natural and anthropogenic origin. From a governmental regulatory perspective, these protective responses complicate efforts to establish acceptable levels of chemical exposure. To explore this issue, we considered vertebrate endocrine systems as potential targets for environmental contaminants. Using the hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-gonad (HPG), and hypothalamic-pituitary-adrenal (HPA) axes as case examples, we identified features of these systems that allow them to accommodate and recover from chemical insults. In doing so, a distinction was made between effects on adults and those on developing organisms. This distinction was required because endocrine system disruption in early life stages may alter development of organs and organ systems, resulting in permanent changes in phenotypic expression later in life. Risk assessments of chemicals that impact highly regulated systems must consider the dynamics of these systems in relation to complex environmental exposures. A largely unanswered question is whether successful accommodation to a toxic insult exerts a fitness cost on individual animals, resulting in adverse consequences for populations. Mechanistically based mathematical models of endocrine systems provide a means for better understanding accommodation and recovery. In the short term, these models can be used to design experiments and interpret study findings. Over the long term, a set of validated models could be used to extrapolate limited in vitro and in vivo testing data to a broader range of untested chemicals, species, and exposure scenarios. With appropriate modification, Tier 2 assays developed in support of the U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program could be used to assess the potential for accommodation and recovery and inform the development of mechanistically based models.

Monitoring the tidal Delaware River for ambient toxicity.

This study assessed ambient waters in an urbanized area of the Delaware River, to determine whether river water samples exhibited chronic lethal or sublethal toxicity when measured in laboratory experiments. Toxicity was assessed at 16 fixed stations in the main-stem river and 29 stations in tributaries of the tidal Delaware River with salinities from 0 to 15 parts per 1000 (ppt) using Pimephales promelas, Americamysis bahia, Menidia beryllina, and Ceriodaphnia dubia in 7-d tests; Pseudokirchneriella subcapitata in a 96-h test; and Hyalella azteca in a 10-d water-only test. The toxicity tests measured organism survival, growth, and reproduction. Results from testing water samples collected in 4 different y indicated that the samples from sites tested in the main-stem of the Delaware River and from the majority of its tributaries did not produce chronic toxicity. The surveys identified tributaries that warrant further assessment for toxicity.

Development of a preliminary relative risk model for evaluating regional ecological conditions in the Delaware River Estuary, USA.

Effective environmental management and restoration of urbanized systems such as the Delaware River Estuary requires a holistic understanding of the relative importance of various stressor-related impacts throughout the watershed, both historical and ongoing. To that end, it is important to involve as many stakeholders as possible in the management process and to develop a system for sharing of scientific data and information, as well as effective technical tools for evaluating and disseminating the data needed to make management decisions. In this study, we describe a preliminary assessment that was undertaken to evaluate the relative risks for the variety of stressors currently operating within the Delaware Estuary using a relative risk model (RRM) framework. This model was constructed using existing data and information on the ecological conditions and stressors in the main-stem Delaware River below the head of tide at Trenton, New Jersey, USA. A large database was developed with pertinent data from a variety of library, scientific, and regulatory sources. Data were compiled, reviewed, and characterized before development of the Estuary-specific RRM. Our primary goals and objectives in developing this preliminary RRM for the Estuary were to 1) determine if the RRM framework can be adapted to a large complex estuarine system such as the Delaware River, 2) identify the issues associated with adapting the model framework to the various management issues and regional areas/habitats of the River, 3) help identify data needs and potential refinements that might be needed to more specifically quantify relative stressor risks in various areas and habitats of the Estuary to better inform future management goals/actions by Stakeholders. The key conclusions of our preliminary assessment are 1) a diverse suite of stressors is likely affecting the ecological conditions of the Delaware Estuary, 2) chemical (toxicants/contaminants) and physical (sedimentation, habitat loss) stressors were found to be on par with regards to their ranking, and 3) the RRM, in its current form, made it difficult to effectively balance the inequality in the sizes of the study subareas considered in the assessment. Management objectives and related research activities should focus on collecting the necessary data and information to further refine the RRM and assess the relative impacts of these stressors at various scales in the Estuary. By having such a framework and tool available, we believe that stakeholders within the Delaware River watershed will be able to make more informed and risk-based management decisions regarding restoration options for the Estuary.

Xenobiotic intrinsic clearance in freshly isolated hepatocytes from rainbow trout (Oncorhynchus mykiss): determination of trout hepatocellularity, optimization of cell concentrations and comparison of serum and serum-free incubations.

Metabolism plays an important role in bioaccumulation of xenobiotics in fish. In vitro determination of xenobiotic intrinsic clearance (CLint) in trout hepatocytes and subsequent extrapolation to in vivo hepatic clearance (CLH) using the "well-stirred" liver model greatly improved our current practice of bioaccumulation assessment [Han, X., Nabb, D.L., Mingoia, R.T., Yang, C.H., 2007. Determination of xenobiotic intrinsic clearance in freshly isolated hepatocytes from rainbow trout (Oncorhynchus mykiss) and rat and its application in bioaccumulation assessment. Environ. Sci. Technol. 41, 3269-3276]. In an effort to further optimize this approach, we experimentally obtained the value of trout hepatocellularity (HT), a key scaling factor in the "well-stirred" liver model. HT was determined to be (540+/-12)x10(6)cells/g liver for male trout. We also investigated the potential effect of different cell concentrations on the determination of CL(int) values of molinate, 4,4-bis(dimethylamino)benzophenone, 4-nonylphenol, 2,4-di-tert-butylphenol, and benzo(a)pyrene. Linear relationships were established between clearance rates and cell concentrations at 1x10(6), 2x10(6), 5x10(6), and 10x10(6)cells/mL. This suggests that under our experimental conditions, CLint determination was independent of hepatocyte concentrations. In order to better understand the "in vitro binding" effect in in vitro-to-in vivo scaling, we obtained CLint values for the above-mentioned compounds in trout hepatocytes that were suspended in trout serum. Incubations in serum, in general, resulted relatively larger prediction of CLH values. Our findings suggest that in bioaccumulation assessment, the traditional medium incubation method offers a conservative estimate on fish metabolism of xenobiotics and the serum incubation approach could be used for certain classes of compounds that are of challenge for in silico prediction of their plasma and in vitro binding properties.

Acute and chronic aquatic toxicity of ammonium perfluorooctanoate (APFO) to freshwater organisms.

Recent concerns have been raised concerning the widespread distribution of perfluorinated compounds in environmental matrices and biota. The compounds of interest include ammonium perfluorooctanoate (APFO, the ammonium salt of perfluorooctanoic acid, PFOA). APFO is used primarily as a processing aid in the production of fluoropolymers and fluoroelastomers. The environmental presence of perfluorooctanoate (PFO(-), the anion of APFO) and its entry into the environment as APFO make quality aquatic toxicity data necessary to assess the aquatic hazard and risk of APFO. We conducted acute and chronic freshwater aquatic toxicity studies with algae, Pseudokirchneriella subcapitata, the water flea, Daphnia magna, and embryo-larval rainbow trout, Oncorhynchus mykiss, using OECD test guidelines and a single, well-characterized sample of APFO. Acute 48-96 h LC/EC(50) values were greater than 400mg/l APFO and the lowest chronic NOEC was 12.5mg/l for inhibition of the growth rate and biomass of the freshwater alga. Un-ionized ammonia was calculated to be a potential significant contributor to the observed toxicity of APFO. Based on environmental concentrations of PFO(-) from various aquatic ecosystems, the PNEC value from this study, and unionized ammonia contributions to observed toxicity, APFO demonstrates little or no risk for acute or chronic toxicity to freshwater and marine aquatic organisms at relevant environmental concentrations.

Are PFCAs bioaccumulative? A critical review and comparison with regulatory criteria and persistent lipophilic compounds.

Perfluorinated acids, including perfluorinated carboxylates (PFCAs), and perfluorinated sulfonates (PFASs), are environmentally persistent and have been detected in a variety of wildlife across the globe. The most commonly detected PFAS, perfluorooctane sulfonate (PFOS), has been classified as a persistent and bioaccumulative substance. Similarities in chemical structure and environmental behavior of PFOS and the PFCAs that have been detected in wildlife have generated concerns about the bioaccumulation potential of PFCAs. Differences between partitioning behavior of perfluorinated acids and persistent lipophilic compounds complicate the understanding of PFCA bioaccumulation and the subsequent classification of the bioaccumulation potential of PFCAs according to existing regulatory criteria. Based on available research on the bioaccumulation of perfluorinated acids, five key points are highlighted in this review: (1) bioconcentration and bioaccumulation of perfluorinated acids are directly related to the length of each compound's fluorinated carbon chain; (2) PFASs are more bioaccumulative than PFCAs of the same fluorinated carbon chain length; (3) PFCAs with seven fluorinated carbons or less (perfluorooctanoate (PFO) and shorter PFCAs) are not considered bioaccumulative according to the range of promulgated bioaccumulation,"B", regulatory criteria of 1000-5000 L/kg; (4) PFCAs with seven fluorinated carbons or less have low biomagnification potential in food webs, and (5) more research is necessary to fully characterize the bioaccumulation potential of PFCAs with longer fluorinated carbon chains (>7 fluorinated carbons), as PFCAs with longer fluorinated carbon chains may exhibit partitioning behavior similar to or greater than PFOS. The bioaccumulation potential of perfluorinated acids with seven fluorinated carbons or less appears to be several orders of magnitude lower than "legacy" persistent lipophilic compounds classified as bioaccumulative. Thus, although many PFCAs are environmentally persistent and can be present at detectable concentrations in wildlife, it is clear that PFCAs with seven fluorinated carbons or less (including PFO) are not bioaccumulative according to regulatory criteria.

Polyfluorinated chemicals in a spatially and temporally integrated food web in the Western Arctic.

This study reports on an investigation of the presence of polyfluorinated chemicals in a spatially and temporally integrated set of biological samples representing an Arctic food web. Zooplankton, Arctic cod, and seal tissues from the western Canadian Arctic were analyzed for perfluoroalkyl sulfonates [PFAS], perfluorocarboxylates [PFCAs], and other polyfluorinated acids. Perfluorooctane sulfonate [PFOS] was found in all samples [0.20-34 ng/g] and in the highest concentrations. PFCAs from nine to 12 carbons were quantified in most of the samples [0.28-6.9 ng/g]. PFCAs with carbon chain lengths of eight or less were not detected. Likewise, 8-2 fluorotelomer acid [8-2 FTA] and 8-2 fluorotelomer unsaturated acid [8-2 FTUA], products of fluorotelomer environmental transformation, were not detected. 2H,2H,3H,3H, heptadecafluoro decanoic acid [7-3 Acid], an additional metabolite from fluorotelomer biological transformation, was detected only in seal liver tissue [0.5-2.5 ng/g]. The ratios of branched to linear PFOS isomers in fish and seal tissue were not similar and did not match that of technical PFOS as manufactured. No branched PFCA isomers were detected in any samples. It is concluded that differing pharmacokinetics complicate the use of branched to linear ratios of PFCAs in attributing their presence to a specific manufacturing process. A statistical analysis of the data revealed significant correlations between PFOS and the PFCAs detected as well as among the PFCAs themselves. The 7-3 Acid was not correlated with either PFCAs or PFAS, which suggests that it may have a different exposure pathway.

Guidance for evaluating in vivo fish bioaccumulation data.

Currently, the laboratory-derived fish bioconcentration factor (BCF) serves as one of the primary data sources used to assess the potential for a chemical to bioaccumulate. Consequently, fish BCF values serve a central role in decision making and provide the basis for development of quantitative structure-property relationships (QSPRs) used to predict the bioaccumulation potential of untested compounds. However, practical guidance for critically reviewing experimental BCF studies is limited. This lack of transparent guidance hinders improvement in predictive models and can lead to uninformed chemical management decisions. To address this concern, a multiple-stakeholder workshop of experts from government, industry, and academia was convened by the International Life Sciences Institute Health and Environmental Sciences Institute to examine the data availability and quality issues associated with in vivo fish bioconcentration and bioaccumulation data. This paper provides guidance for evaluating key aspects of study design and conduct that must be considered when judging the reliability and adequacy of reported laboratory bioaccumulation data. Key criteria identified for judging study reliability include 1) clear specification of test substance and fish species investigated, 2) analysis of test substance in both fish tissue and exposure medium, 3) no significant adverse effects on exposed test fish, and 4) a reported test BCF that reflects steady-state conditions with unambiguous units. This guidance is then applied to 2 data-rich chemicals (anthracene and 2,3,7,8-tetrachlorodibenzo-p-dioxin) to illustrate the critical need for applying a systematic data quality assessment process. Use of these guidelines will foster development of more accurate QSPR models, improve the performance and reporting of future laboratory studies, and strengthen the technical basis for bioaccumulation assessment in chemicals management.

Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management.

The development of a risk management system for nanoscale or ultrafine particle-types requires a base set of hazard data. Assessing risk is a function of hazard and exposure data. Previously, we have suggested "parallel tracks" as a strategy for conducting nanoparticle research. On the one hand, mechanistic studies on "representative" nanoparticles could be supported by governmental agencies. Alternatively, with regard to commercial nanoparticles, the environmental, health and safety (EHS) framework would include a minimum base set of toxicity studies which should be supported by the companies that are developing nano-based products. The minimum base set could include the following criteria: substantial particle characterization, pulmonary toxicity studies, acute dermal toxicity and sensitization studies, acute oral and ocular toxicity studies, along with screening type genotoxicity, and aquatic toxicity studies. We report here the toxicity results of a base set of hazard tests on a set of newly developed, well-characterized, ultrafine TiO(2) (uf-TiO(2)) particle-types. In vivo pulmonary toxicity studies in rats demonstrated low inflammatory potential and lung tissue toxicity. Acute dermal irritation studies in rabbits and local lymph node assay results in mice indicated that uf-TiO(2) was not a skin irritant or dermal sensitizer. Acute oral toxicity studies demonstrated very low toxicity and uf-TiO(2) produced short-term and reversible ocular conjunctival redness in rabbits. Genotoxicity tests demonstrated that uf-TiO(2) was negative in both the bacterial reverse mutation test and in an in vitro mammalian chromosome aberration test with Chinese hamster ovary cells. The results of aquatic toxicity screening studies demonstrated that uf-TiO(2) exhibited low concern for aquatic hazard in unaerated, 48h, static acute tests using the water flea, Daphnia magna; exhibited low concern for aquatic hazard in unaerated, 96h, static acute tests using the rainbow trout, Oncorhynchus mykiss; and exhibited medium concern in a 72h acute test using the green algae Pseudokirchneriella subcapitata. To summarize the findings, the results of most of the studies demonstrated low hazard potential in mammals or aquatic species following acute exposures to the ultrafine TiO(2) particle-types tested in this program.