Using 21st Century Science to Improve Risk-Related Evaluations (2017) / Chapter Skim
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2 Advances in Exposure Science
2 Advances in Exposure Science
Pages 18-50
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From page 18... ...
Figure 2-1 illustrates the series of events in this chapter, the use of the frameworks will enable from introduction of a stressor into the environment and the development of infrastructure to support exposureits movement through the environment via specific path- data acquisition, collection, organization, and access and ways to the receptor and the triggering of a biological to improve the accuracy, completeness, efficiency, and response of potential regulatory concern. The figure pro- transparency of exposure assessment and modeling.
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The application of remote-sensing technologies technologies that measure basic health data, such as heart with ground-based monitoring will continue to improve and respiratory rates and activity level. Information on human exposure assessment.
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Specifically, the seminal near-field chemical exposures of humans, for quantify- model developed for simulating chemical transport in an ing relationships between external and internal exposures indoor environment (Bennett and Furtaw 2004) has been and between in vivo and in vitro exposures, and for high- revised to include exposure pathways for which external throughput exposure estimation that has been used alone human exposures (intake fractions)
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pathways for aggregate human exposure assessments are Because of the extensive measurement-data gaps, the also being developed and applied (Isaacs et al. 2014; Shin recent advances in computational tools for exposure sciet al.
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. Chemical-specific Chemical Exposure Assessment adducts of the carcinogens butadiene, formaldehyde, and acetaldehyde have emerged recently as metrics of expo Important advances in two complementary ap- sure to these extremely short-lived chemicals (Swenberg proaches for characterizing human exposure -- targeted et al.
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The findings highlight the importance of using highly sensitive analytical instrumentation to characterize human exposure. Source: Rappaport et al.
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. Increased focus on categorizcontrast with metabolomic approaches that quantify ex- ing chemicals in consumer products and on assembling posure to specific metabolites of endogenous and exoge- exposure data for use in exposure assessment is one imnous chemicals, proteomic and transcriptomic approaches mediate outcome of the recent studies.
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tween test systems and human-exposure scenarios. In particular, the rapidly expanding use of high-throughput Physiologically Based Pharmacokinetic Models and in vitro cell and cell-free systems to characterize the bio Models for Translating Exposure Between Systems activity of chemicals and materials, such as nanomateri als, has led to a need to translate in vitro exposure data Physiologically based pharmacokinetic (PBPK)
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Chemical concentrations in an in vitro test system can change as a function of the chemical properties, the test system, and time. Measured and estimated dissolved and cell concentrations can be orders of magnitude different from assumed (nominal)
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of drugs tations of the systems to predict chemical kinetics and and environmental chemicals. Variations in ADME prointernal exposures will become important.
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Important considerations Continued success in using the new tools described for the application of exposure data in decision-making here for measuring and calculating biochemical and phys- are the quality of the data and the context in which the iological determinants of internal exposure will improve data will be used; data quality can be determined by exposure assessment and ultimately will support the suc- evaluating accuracy, integrity, suitability, transparency, cessful integration of in vitro, computational, and in vivo and concordance of multiple lines of data or evidence approaches into risk assessment.
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From page 29... ...
. be used to make initial decisions to set priorities among Guidance for evaluating exposure data and expostressors for improved exposure assessment, toxicity as- sure assessments developed by WHO and EPA and pubsessment, or epidemiological assessment.
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The greatest confidence occurs when there is concordance between multiple exposure-estimation approaches or between multiple exposure measures, especially when divergent exposure metrics are considered. The confidence that is required for exposure data and assessments should be determined by data-acquision costs and the decision context; the highest levels of confidence are not required for many decision contexts.
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From page 31... ...
and tox BOX 2-3 High-Value Applications for Exposure Sciences • Aligning exposures between test systems and humans • Improving exposure assessment for epidemiological studies • Exposure-based screening and priority-setting • Identifying new chemical exposures for toxicity testing • Predicting exposure to support registration and use of new chemicals • Identifying, evaluating, and mitigating sources of exposure • Assessing cumulative exposure and exposure to mixtures
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Protein Binding Protein Binding Aerosol Properties Protein Binding Protein Binding Protein Binding Degradation Degradation Particle Properties Degradation Loss Loss Deposition Loss Absorption Absorption Metabolism Uptake Metabolism Distribution Distribution Partitioning Solubility Partitioning Metabolism Metabolism Uptake Agglomeration Uptake Elimination Elimination Particle Size Particle Size Particle Density Particle Density Agglomeration Agglomeration Solubility Solubility Absorption Distribution Metabolism Elimination Total or Free Liquid Concentration Free Serum Concentration Deposited Particles Deposited Particles Consistent Exposure Metrics For Aligning Exposure-Response Across Systems FIGURE 2-6 Alignment of exposures across experimental toxicity-testing systems can be achieved by understanding, measuring, and applying this information on the processes that control the time course of concentrations and delivery of chemicals and particles to target cells in each system. Common target-cell exposure metrics could be total or free concentrations, peak concentrations, or area under the concentration–time curve.
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or inferring causation. External-exposure measures have been and will continue to be sufficient, and in some cas- Exposure-Based Screening and Priority-Setting es superior to internal-exposure measures, for example, where portal-of-entry effects are involved or large pop- Several exposure-based priority-setting approaches ulation-scale exposure assessments are necessary and that benefit from the emerging exposure-science tools and internal-exposure assessments are impractical.
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. Cumulative exposures to following certain requirements, "exposure-based waiv- chemicals in specific classes might move some chemicals ing" for toxicity testing or "exposure-based adaptation of up in priority -- an outcome of improved exposure data.
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From page 35... ...
and computational exposure-science tools described in Human-exposure data on a much larger suite of this chapter can support high-throughput screening-level chemicals than is now available would provide important exposure assessment and exposure-based priority-setting new data for guiding selection of chemicals and exposure for later toxicity testing. Exposure models can be ap- concentrations for hazard testing and mechanistic toxiplied to screen large numbers of chemicals in commerce cology.
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. The committee that prepared the report recomproach for identifying and setting priorities among chemi- mended an increased emphasis on comparative exposure cals for additional exposure assessment, hazard testing, assessment and stated that inherent hazard should be the and risk assessment that complements the current hazard- focus only in cases where the exposure routes and conoriented paradigm.
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, stability (degradation sors -- for example, cell-phone–based sulfur oxide and and metabolism half-lives) , and proposed use scenarios nitrogen oxide sensors -- use native GIS systems to colcan be used to set parameter values for exposure models lect real-time exposure data, which can be used to identhat are used to predict concentrations in environmental tify locations with high exposures and the source locamedia and humans, over life spans, and on local and na- tions that contribute to the exposures.
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Incrementally increasing the number posure data streams and the potential for high-throughput of chemicals included in monitoring programs can help in toxicity screening, there are opportunities to address the evaluating and refining exposure models and in developuncertainty related to potential effects of mixture expo- ing new approaches to integrate exposure data and consures better. Measurements obtained from human tissue stitutes an initial and pragmatic path.
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From page 39... ...
The methods interdisciplinary communication in the development and should be used to quantify human exposures to chemiapplication of exposure information. cal mixtures (parent chemicals and metabolites)
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2009. Development that focus on integrating measurements and models for of a method for personal, spatiotemporal exposure assessimproved quantitative exposure assessment.
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Ein- als for air pollution exposure assessments: Model evalua stein, R.E. Jacob, J
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2011. Introduction to Examination Survey and human exposure to environmen- benchmark dose methods and US EPA's benchmark dose tal chemicals.
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2012. The exposure data Environ.
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Tran- useful in vitro toxicity data with measured free concentra sue, Y.M.
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2010. Physiologically based pharmacokiKolanczyk, R.C., P
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Physiologically based pharmacokinetic model use in the 21st Century: A Vision and a Strategy. Washington, in risk assessment-why being published is not enough.
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Environ. Health a physiologically based pharmacokinetic model for estra- Perspect.
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2014. Attrib- dosimetry: Interpreting trihalomethanes biomonitoring uting population-scale human exposure to various source data using physiologically based pharmacokinetic model categories: Merging exposure models and biomonitoring ing.
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2016. Modeling human exposure van Donkelaar, A., R.V.
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Evaluation of simple in vitro to in vivo extrapola Characterizing and Applying Human Exposure Models. tion approaches for environmental compounds.
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