High-throughput migration modelling for estimating exposure to chemicals in food packaging in screening and prioritization tools.

Specialty software and simplified models are often used to estimate migration of potentially toxic chemicals from packaging into food. Current models, however, are not suitable for emerging applications in decision-support tools, e.g. in Life Cycle Assessment and risk-based screening and prioritization, which require rapid computation of accurate estimates for diverse scenarios. To fulfil this need, we develop an accurate and rapid (high-throughput) model that estimates the fraction of organic chemicals migrating from polymeric packaging materials into foods. Several hundred step-wise simulations optimised the model coefficients to cover a range of user-defined scenarios (e.g. temperature). The developed model, operationalised in a spreadsheet for future dissemination, nearly instantaneously estimates chemical migration, and has improved performance over commonly used model simplifications. When using measured diffusion coefficients the model accurately predicted (R2 = 0.9, standard error (Se) = 0.5) hundreds of empirical data points for various scenarios. Diffusion coefficient modelling, which determines the speed of chemical transfer from package to food, was a major contributor to uncertainty and dramatically decreased model performance (R2 = 0.4, Se = 1). In all, this study provides a rapid migration modelling approach to estimate exposure to chemicals in food packaging for emerging screening and prioritization approaches.

Stochastic modeling of near-field exposure to parabens in personal care products.

Exposure assessment is a key step in determining risks to chemicals in consumer goods, including personal care products (PCPs). Exposure models can be used to estimate exposures to chemicals in the absence of biomonitoring data and as tools in chemical risk prioritization and screening. We apply a PCP exposure model based on the product intake fraction (PiF), which is defined as the fraction of chemical in a product that is taken in by the exposed population, to estimate chemical intake based on physicochemical properties and PCP usage characteristics. The PiF can be used to estimate route and pathway-specific exposures during both the use and disposal stages of a product. As a case study, we stochastically quantified population level exposures to parabens in PCPs, and compared estimates with biomarker values. We estimated exposure based on the usage of PCPs in the female US population, taking into account population variability, product usage characteristics, paraben occurrence in PCPs and the PiF. Intakes were converted to urine levels and compared with National Health and Nutrition Examination Survey (NHANES) biomonitoring data. Results suggest that for parabens, chemical exposure during product use is substantially larger than environmentally mediated exposure after product disposal. Modeled urine concentrations reflect well the NHANES variation of three orders of magnitude across parabens for the 50th, 75th, 90th, and 95th percentiles and were generally in good agreement with measurements, when taking uncertainty into account. This study presents an approach to estimate multi-pathway exposure to chemicals in PCPs and can be used as a tool within exposure-based screening of chemicals as well in higher tier exposure estimates.

High-throughput exposure modeling to support prioritization of chemicals in personal care products.

We demonstrate the application of a high-throughput modeling framework to estimate exposure to chemicals used in personal care products (PCPs). As a basis for estimating exposure, we use the product intake fraction (PiF), defined as the mass of chemical taken by an individual or population per mass of a given chemical used in a product. We calculated use- and disposal- stage PiFs for 518 chemicals for five PCP archetypes. Across all product archetypes the use- and disposal- stage PiFs ranged from 10(-5) to 1 and 0 to 10(-3), respectively. There is a distinction between the use-stage PiF for leave-on and wash-off products which had median PiFs of 0.5 and 0.02 across the 518 chemicals, respectively. The PiF is a function of product characteristics and physico-chemical properties and is maximized when skin permeability is high and volatility is low such that there is no competition between skin and air losses from the applied product. PCP chemical contents (i.e. concentrations) were available for 325 chemicals and were combined with PCP usage characteristics and PiF yielding intakes summed across a demonstrative set of products ranging from 10(-8)-30 mg/kg/d, with a median of 0.1 mg/kg/d. The highest intakes were associated with body lotion. Bioactive doses derived from high-throughput in vitro toxicity data were combined with the estimated PiFs to demonstrate an approach to estimate bioactive equivalent chemical content and to screen chemicals for risk.

Coupled near-field and far-field exposure assessment framework for chemicals in consumer products.

Humans can be exposed to chemicals in consumer products through product use and environmental emissions over the product life cycle. Exposure pathways are often complex, where chemicals can transfer directly from products to humans during use or exchange between various indoor and outdoor compartments until sub-fractions reach humans. To consistently evaluate exposure pathways along product life cycles, a flexible mass balance-based assessment framework is presented structuring multimedia chemical transfers in a matrix of direct inter-compartmental transfer fractions. By matrix inversion, we quantify cumulative multimedia transfer fractions and exposure pathway-specific product intake fractions defined as chemical mass taken in by humans per unit mass of chemical in a product. Combining product intake fractions with chemical mass in the product yields intake estimates for use in life cycle impact assessment and chemical alternatives assessment, or daily intake doses for use in risk-based assessment and high-throughput screening. Two illustrative examples of chemicals used in personal care products and flooring materials demonstrate how this matrix-based framework offers a consistent and efficient way to rapidly compare exposure pathways for adult and child users and for the general population. This framework constitutes a user-friendly approach to develop, compare and interpret multiple human exposure scenarios in a coupled system of near-field ('user' environment), far-field and human intake compartments, and helps understand the contribution of individual pathways to overall human exposure in various product application contexts to inform decisions in different science-policy fields for which exposure quantification is relevant.

Multi-pathway exposure modeling of chemicals in cosmetics with application to shampoo.

We present a novel multi-pathway, mass balance based, fate and exposure model compatible with life cycle and high-throughput screening assessments of chemicals in cosmetic products. The exposures through product use as well as post-use emissions and environmental media were quantified based on the chemical mass originally applied via a product, multiplied by the product intake fractions (PiF, the fraction of a chemical in a product that is taken in by exposed persons) to yield intake rates. The average PiFs for the evaluated chemicals in shampoo ranged from 3×10(-4) up to 0.3 for rapidly absorbed ingredients. Average intake rates ranged between nano- and micrograms per kilogram bodyweight per day; the order of chemical prioritization was strongly affected by the ingredient concentration in shampoo. Dermal intake and inhalation (for 20% of the evaluated chemicals) during use dominated exposure, while the skin permeation coefficient dominated the estimated uncertainties. The fraction of chemical taken in by a shampoo user often exceeded, by orders of magnitude, the aggregated fraction taken in by the population through post-use environmental emissions. Chemicals with relatively high octanol-water partitioning and/or volatility, and low molecular weight tended to have higher use stage exposure. Chemicals with low intakes during use (<1%) and subsequent high post-use emissions, however, may yield comparable intake for a member of the general population. The presented PiF based framework offers a novel and critical advancement for life cycle assessments and high-throughput exposure screening of chemicals in cosmetic products demonstrating the importance of consistent consideration of near- and far-field multi-pathway exposures.

Defining Product Intake Fraction to Quantify and Compare Exposure to Consumer Products.

There is a growing consciousness that exposure studies need to better cover near-field exposure associated with products use. To consistently and quantitatively compare human exposure to chemicals in consumer products, we introduce the concept of product intake fraction, as the fraction of a chemical within a product that is eventually taken in by the human population. This metric enables consistent comparison of exposures during consumer product use for different product-chemical combinations, exposure duration, exposure routes and pathways and for other life cycle stages. We present example applications of the product intake fraction concept, for two chemicals in two personal care products and two chemicals encapsulated in two articles, showing how intakes of these chemicals can primarily occur during product use. We demonstrate the utility of the product intake fraction and its application modalities within life cycle assessment and risk assessment contexts. The product intake fraction helps to provide a clear interface between the life cycle inventory and impact assessment phases, to identify best suited sentinel products and to calculate overall exposure to chemicals in consumer products, or back-calculate maximum allowable concentrations of substances inside products.

Exploring consumer exposure pathways and patterns of use for chemicals in the environment.

Humans are exposed to thousands of chemicals in the workplace, home, and via air, water, food, and soil. A major challenge in estimating chemical exposures is to understand which chemicals are present in these media and microenvironments. Here we describe the Chemical/Product Categories Database (CPCat), a new, publically available (http://actor.epa.gov/cpcat) database of information on chemicals mapped to "use categories" describing the usage or function of the chemical. CPCat was created by combining multiple and diverse sources of data on consumer- and industrial-process based chemical uses from regulatory agencies, manufacturers, and retailers in various countries. The database uses a controlled vocabulary of 833 terms and a novel nomenclature to capture and streamline descriptors of chemical use for 43,596 chemicals from the various sources. Examples of potential applications of CPCat are provided, including identifying chemicals to which children may be exposed and to support prioritization of chemicals for toxicity screening. CPCat is expected to be a valuable resource for regulators, risk assessors, and exposure scientists to identify potential sources of human exposures and exposure pathways, particularly for use in high-throughput chemical exposure assessment.

Effect of redox conditions on pharmaceutical loss during biological wastewater treatment using sequencing batch reactors.

We lack a clear understanding of how wastewater treatment plant (WWTP) process parameters, such as redox environment, impact pharmaceutical fate. WWTPs increasingly install more advanced aeration control systems to save energy and achieve better nutrient removal performance. The impact of redox condition, and specifically the use of microaerobic (low dissolved oxygen) treatment, is poorly understood. In this study, the fate of a mixture of pharmaceuticals and several of their transformation products present in the primary effluent of a local WWTP was assessed in sequencing batch reactors operated under different redox conditions: fully aerobic, anoxic/aerobic, and microaerobic (DO concentration ≈0.3mg/L). Among the pharmaceuticals that were tracked during this study (atenolol, trimethoprim, sulfamethoxazole, desvenlafaxine, venlafaxine, and phenytoin), overall loss varied between them and between redox environments. Losses of atenolol and trimethoprim were highest in the aerobic reactor; sulfamethoxazole loss was highest in the microaerobic reactors; and phenytoin was recalcitrant in all reactors. Transformation products of sulfamethoxazole and desvenlafaxine resulted in the reformation of their parent compounds during treatment. The results suggest that transformation products must be accounted for when assessing removal efficiencies and that redox environment influences the degree of pharmaceutical loss.