Using 21st Century Science to Improve Risk-Related Evaluations (2017) / Chapter Skim
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5 A New Direction for Risk Assessment and Applications of 21st Century Science
5 A New Direction for Risk Assessment and Applications of 21st Century Science
Pages 92-107
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From page 92... ...
tion for risk assessment with its focus on discerning toxreport Risk Assessment in the Federal Government: Man- icity pathways, which were defined as "cellular response aging the Process (NRC 1983) defined risk assessment pathways that, when sufficiently perturbed in an intact as "the use of the factual base to define the health effects animal, are expected to result in adverse health effects." of exposure of individuals or populations to hazardous Since publication of that report, the understanding of materials and situations." The report noted that risk as- biological processes underlying disease has increased sessment had four components -- hazard identification, dramatically and has provided an opportunity to underexposure assessment, dose–response assessment, and stand the biological basis of how different environmental risk characterization -- and that risk assessments contain stressors can affect the same pathway, each potentially some or all of them.
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From page 93... ...
Alternatively, societal factors could per- exposure data arising from the technological advances in exposure science will provide much needed and increas ingly rich information. For example, comprehensive ex posure assessments that use targeted and nontargeted analyses of environmental and biomonitoring samples or that use computational exposure methods will help to identify chemical mixtures to which people are exposed.
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From page 94... ...
Abbreviations: CSI, cholesterol synthesis-inhibiting; DHCR7, 7-dehydrocholesterol reductase; R, retinol; RA, retinoic acid; shh, sonic hedgehog.
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From page 95... ...
. Those methods have been Some categories of chemicals that are intended to automated and allow for rapid identification of chemicals have biological activity, such as drugs and pesticides, are that have specific chemical features that have been idenroutinely subjected to a suite of toxicity tests as required tified as potentially problematic, such as reactive funcby law.
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From page 96... ...
Comparisons of Chemical assessments encompass a broad array of analogues with the chemical of interest are based on the analyses, from Integrated Risk Information System as- premise that the chemical of interest and its analogues sessments that include hazard and dose–response assess- are metabolized to common or biologically similar mements to ones that also incorporate exposure assessments tabolites or that they are sufficiently similar in structure to to produce risk characterizations. Moreover, chemical have the same or similar biological activity (for example, assessments performed by the federal agencies cover they activate receptors similarly)
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From page 97... ...
. Testing for similar biological activity can be chemical, and the hypotheses could be tested virtually in Probability Range for Effect Levels Probability Range for Exposures Exposure data Toxicity data streams streams Measured: In Silico: Predicted: QSAR, SAR, Direct (e.g., In Vitro Multimedia or Read blood)
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From page 98... ...
This approach will require some knowledge of the key events that connect the initial interaction of an exog- Cumulative risk assessment could benefit from the enous chemical with its molecular target and the ultimate mechanistic data that are being generated. It is well unadverse outcome.
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From page 99... ...
applied in support of cumulative risk assessment will also The advances described in Chapters 2–4 can address support multifactorial risk evaluations discussed further each element involved in site-specific assessments. Tarin Chapter 7.
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Although sites and chemical releases often involve chemicals on the high-throughput or high-content models still require which few toxicity data are available. In the case of waste validation, the read-across approach could be applied imsites, EPA assigns provisional reference values for a num- mediately.
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2006) in which the biological activity of a of hazard data was conducted on the dispersants that were single chemical entity is compared with the fingerprint used to treat the crude oil released during the Deepwater of other chemicals in a large dataset, and it is assumed Horizon disaster (Judson et al.
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From page 102... ...
Green-chemistry de Finally, new methods in exposure science, -omics sign is another case in which the use of modern in vitro technologies, and epidemiology provide another approach toxicology methods could have great utility by providing to generate hypotheses about the role of chemicals and guidance on which molecular features are associated with chemical mixtures in specific disease states and to gather greater or less toxicity and by identifying chemicals that information about potential risks associated with specific do not affect biological pathways that are known to be sites. Information generated on chemical mechanisms, relevant for toxicity (Voutchkova et al.
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that could not initially be assigned to distinct chemicals. Some features were later identified by using analytical standards that were selected on the basis of probable matches to chemical structures in EPA's Distributed Structure-Searchable Toxicity database.
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From page 104... ...
• Identifying chemicals present. The committee considers a large historically contaminated site with land and surface water near a major population center and describes how targeted and nontargeted analyses of chemi cals can be used at the site.
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2011. Toxicity testing in the 21 evaluate the potential for toxicity present a challenge in century: Defining new risk assessment approaches based synthesizing information in a way that supports decision- on perturbation of intracellular toxicity pathways.
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2016. Nominations to tests for endocrine and other biological activity.
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:1840-1861. cal screening and prioritization using exposure models and in vitro bioactivity assays.
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