Improved prediction of PFAS partitioning with PPLFERs and QSPRs.

Per- and polyfluoroalkyl substances (PFAS) are chemicals of high concern and are undergoing hazard and risk assessment worldwide. Reliable physicochemical property (PCP) data are fundamental to assessments. However, experimental PCP data for PFAS are limited and property prediction tools such as quantitative structure-property relationships (QSPRs) therefore have poor predictive power for PFAS.

A framework for understanding the bioconcentration of surfactants in fish.

Surfactants are a class of chemicals released in large quantities to water, and therefore bioconcentration in fish is an important component of their safety assessment. Their structural diversity, which encompasses nonionic, anionic, cationic and zwitterionic molecules with a broad range of lipophilicity, makes their evaluation challenging. A strong influence of environmental pH adds a further layer of complexity to their bioconcentration assessment.

An amended - extrapolation model that accounts for first pass clearance effects on chemical bioaccumulation in fish.

Measured rates of intrinsic clearance for fish may be extrapolated to the whole animal as a means of estimating a whole-body biotransformation rate constant (; d). This estimate of can then be used as an input to existing bioaccumulation prediction models. Most - extrapolationbioaccumulation (IVIVE/B) modeling efforts to date have focused on predicting the chemical bioconcentration in fish (aqueous only exposure), with less attention paid to dietary exposures.

Developing an internal threshold of toxicological concern (iTTC).

Background: Threshold of Toxicological Concern (TTC) approaches are used for chemical safety assessment and risk-based priority setting for data poor chemicals. TTCs are derived from in vivo No Observed Effect Level (NOEL) datasets involving an external administered dose from a single exposure route, e.g.

Dynamic Mass Balance Modeling for Chemical Distribution Over Time in Systems With Repeated Dosing.

As toxicologists and risk assessors move away from animal testing and more toward using models and biological modeling, it is necessary to produce tools to quantify the chemical distribution within the environment prior to extrapolating concentrations to human equivalent doses. Although models predicting chemical distribution have been developed, very little has been done for repeated dosing scenarios, which are common in prolonged experiments where the medium needs to be refreshed. Failure to account for repeated dosing may lead to inaccurate estimations of exposure and introduce bias into subsequent to extrapolations.

Predicting the Accumulation of Ionizable Pharmaceuticals and Personal Care Products in Aquatic and Terrestrial Organisms.

The extent to which chemicals bioaccumulate in aquatic and terrestrial organisms represents a fundamental consideration for chemicals management efforts intended to protect public health and the environment from pollution and waste. Many chemicals, including most pharmaceuticals and personal care products (PPCPs), are ionizable across environmentally relevant pH gradients, which can affect their fate in aquatic and terrestrial systems. Existing mathematical models describe the accumulation of neutral organic chemicals and weak acids and bases in both fish and plants.

Bioconcentration of 10 Anionic Surfactants in Rainbow Trout Explained by Data on Partitioning and S9 Clearance.

Bioconcentration factors (BCFs) in rainbow trout were measured for 10 anionic surfactants with a range of alkyl chain lengths and different polar head groups. The BCFs ranged from 0.04 L kg ww (for CSO) to 1370 L kg ww (CSO).

Graphical tools for the planning and interpretation of polyurethane foam based passive air sampling campaigns.

Due to low cost and easy handling during sampling and extraction, passive air samplers (PASs) using polyurethane foam (PUF) as a sorbent have become the most commonly deployed PASs for semi-volatile organic compounds (SVOCs). However, depending on the scenario, PUF-PAS may not always be operating in the linear uptake phase, which implies the need to consider how temperature, wind speed, deployment length and chemical properties interact to determine the amount of a target chemical taken up and the fraction of a depuration compound (DC) being lost during deployment. Guidance is, therefore, necessary to quantitatively interpret curvi-linear uptake in the PUF-PAS and avoid selection of DCs unsuited to the deployment conditions.

A weight of evidence approach for bioaccumulation assessment.

Bioaccumulation assessments conducted by regulatory agencies worldwide use a variety of methods, types of data, metrics, and categorization criteria. Lines of evidence (LoE) for bioaccumulation assessment can include bioaccumulation metrics such as in vivo bioconcentration factor (BCF) and biomagnification factor (BMF) data measured from standardized laboratory experiments, and field (monitoring) data such as BMFs, bioaccumulation factors (BAFs), and trophic magnification factors (TMFs). In silico predictions from mass-balance models and quantitative structure-activity relationships (QSARs) and a combination of in vitro biotransformation rates and in vitro-in vivo extrapolation (IVIVE) models can also be used.

Development and Evaluation of a Holistic and Mechanistic Modeling Framework for Chemical Emissions, Fate, Exposure, and Risk.

Background: Large numbers of chemicals require evaluation to determine if their production and use pose potential risks to ecological and human health. For most chemicals, the inadequacy and uncertainty of chemical-specific data severely limit the application of exposure- and risk-based methods for screening-level assessments, priority setting, and effective management.

Objective: We developed and evaluated a holistic, mechanistic modeling framework for ecological and human health assessments to support the safe and sustainable production, use, and disposal of organic chemicals.

Update and Evaluation of a High-Throughput In Vitro Mass Balance Distribution Model: IV-MBM EQP v2.0.

This study demonstrates the utility of an updated mass balance model for predicting the distribution of organic chemicals in in vitro test systems (IV-MBM EQP v2.0) and evaluates its performance with empirical data. The IV-MBM EQP v2.

Screening the baseline fish bioconcentration factor of various types of surfactants using phospholipid binding data.

Fish bioconcentration factors (BCFs) are commonly used in chemical hazard and risk assessment. For neutral organic chemicals BCFs are positively correlated with the octanol-water partition ratio (), but is not a reliable parameter for surfactants. Membrane lipid-water distribution ratios () can be accurately measured for all kinds of surfactants, using phospholipid-based sorbents.

Biotransformation Potential of Cationic Surfactants in Fish Assessed with Rainbow Trout Liver S9 Fractions.

Biotransformation may substantially reduce the extent to which organic environmental contaminants accumulate in fish. Presently, however, relatively little is known regarding the biotransformation of ionized chemicals, including cationic surfactants, in aquatic organisms. To address this deficiency, a rainbow trout liver S9 substrate depletion assay (RT-S9) was used to measure in vitro intrinsic clearance rates (CL ; ml min g liver ) for 22 cationic surfactants that differ with respect to alkyl chain length and degree of methylation on the charged nitrogen atom.

Bioconcentration of Several Series of Cationic Surfactants in Rainbow Trout.

Cationic surfactants have a strong affinity to sorb to phospholipid membranes and thus possess an inherent potential to bioaccumulate, but there are few measurements of bioconcentration in fish. We measured the bioconcentration of 10 alkylamines plus two quaternary ammonium compounds in juvenile rainbow trout at pH 7.6, and repeated the measurements at pH 6.

Development and intercomparison of single and multicompartment physiologically-based toxicokinetic models: Implications for model selection and tiered modeling frameworks.

This study describes the development and intercomparison of generic physiologically-based toxicokinetic (PBTK) models for humans comprised of internally consistent one-compartment (1Co-) and multi-compartment (MCo-) implementations (G-PBTK). The G-PBTK models were parameterized for an adult male (70 kg) using common physiological parameters and in vitro biotransformation rate estimates and subsequently evaluated using independent concentration versus time data (n = 6) and total elimination half-lives (n = 15) for diverse organic chemicals. The model performance is acceptable considering the inherent uncertainty in the biotransformation rate data and the absence of model calibration.

Acritical review and weight of evidence approach for assessing the bioaccumulation of phenanthrene in aquatic environments.

Bioaccumulation (B) assessment is challenging because there are various B-metrics from laboratory and field studies, multiple criteria and thresholds for classifying bioaccumulative (B), very bioaccumulative (vB), and not bioaccumulative (nB) chemicals, as well as inherent variability and uncertainty in the data. These challenges can be met using a weight of evidence (WoE) approach. The Bioaccumulation Assessment Tool (BAT) provides a transparent WoE assessment framework that follows Organisation for Economic Co-operation and Development (OECD) principles for performing a WoE analysis.

PFAS Exposure Pathways for Humans and Wildlife: A Synthesis of Current Knowledge and Key Gaps in Understanding.

We synthesize current understanding of the magnitudes and methods for assessing human and wildlife exposures to poly- and perfluoroalkyl substances (PFAS). Most human exposure assessments have focused on 2 to 5 legacy PFAS, and wildlife assessments are typically limited to targeted PFAS (up to ~30 substances). However, shifts in chemical production are occurring rapidly, and targeted methods for detecting PFAS have not kept pace with these changes.

Tissue Distribution of Several Series of Cationic Surfactants in Rainbow Trout () Following Exposure via Water.

Bioaccumulation assessment is important for cationic surfactants in light of their use in a wide variety of consumer products and industrial processes. Because they sorb strongly to natural surfaces and to cell membranes, their bioaccumulation behavior is expected to differ from other classes of chemicals. Divided over two mixtures, we exposed rainbow trout to water containing 10 alkyl amines and 2 quaternary alkylammonium surfactants for 7 days, analyzed different fish tissues for surfactant residues, and calculated the tissues' contribution to fish body burden.

Application of an Iterative Fragment Selection (IFS) Method to Estimate Entropies of Fusion and Melting Points of Organic Chemicals.

The main objective of this study is to develop and evaluate novel Quantitative Structure-Property Relationships (QSPRs) for predicting entropy of fusion (ΔS ) and melting point (T ) of organic chemicals from chemical structure. The QSPRs are developed using the Iterative Fragment Selection (IFS) method that requires only 2D structural information from the user (SMILES codes) for property prediction. The QSPRs also provide information on the applicability domain for each calculation and uncertainty estimates for the predictions.

Model-based exploration of the variability in lake trout (Salvelinus namaycush) bioaccumulation factors: The influence of physiology and trophic relationships.

Because dietary consumption of fish is often a major vector of human exposure to persistent organic pollutants (POPs), much effort is directed toward a quantitative understanding of fish bioaccumulation using mechanistic models. However, many such models fail to explicitly consider how uptake and loss rate constants relate to fish physiology. We calculated the bioaccumulation factors (BAFs) of hypothetical POPs, with octanol-water partition coefficients ranging from 10 to 10 , in lake trout (Salvelinus namaycush) with a food-web bioaccumulation model that uses bioenergetics to ensure that physiological parameters applied to a species are internally consistent.

Development and Evaluation of a Combined Bioenergetics and Organic Chemical Mass-Balance Bioaccumulation Model for Fish.

This study describes the development and evaluation of a new bioenergetically balanced bioaccumulation (3B) model for organic chemicals in fish. The 3B model is developed from a large database of routine metabolic (oxygen consumption) rates composed of a range of species, body mass, and temperatures. The chemical uptake and elimination rates of the 3B model are compared against those from three existing bioaccumulation models.

A Model for Risk-Based Screening and Prioritization of Human Exposure to Chemicals from Near-Field Sources.

Exposure- and risk-based assessments for chemicals used indoors or applied to humans (i.e., in near-field environments) necessitate an aggregate exposure pathway framework that aligns chemical exposure information from use sources to internal dose and eventually to their potential for health effects.

Linking algal growth inhibition to chemical activity: Excess toxicity below 0.1% of saturation.

Chemical activity quantifies the energetic level of an organic compound relative to its pure liquid [0-1], and several studies have reported that baseline toxicity generally requires chemical activities of 0.01-0.1.