Read-across is becoming an increasingly important part of human health risk assessment, particularly when direct toxicology data are limited. Its value depends on a transparent, scientifically justified assessment of whether data from one substance can appropriately inform another – and on carrying that uncertainty through the broader risk assessment.
CHICAGO, Oct. 7, 2026 /PRNewswire-PRWeb/ -- Human health risk assessment generally brings together four core elements: hazard identification, dose-response assessment, exposure assessment, and risk characterization. Read-across – a toxicological assessment approach that uses data from a structurally- or functionally-similar chemical to fill data gaps for another chemical – can strengthen that process by using information from sufficiently similar, better-studied substances to inform specific data gaps for a target chemical.
The approach is gaining visibility as regulators seek efficient ways to evaluate more chemicals while reducing reliance on new animal testing. In 2025, the European Food Safety Authority (EFSA) Scientific Committee adopted guidance for using read-across in food and feed chemical safety assessment. The European Chemicals Agency (ECHA) has a Framework to evaluate read-across justifications under REACH, and the European Commission's 2026 roadmap toward phasing out animal testing for chemical safety assessments identifies read-across among the approaches that can contribute to non-animal safety assessment. In the U.S., the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA) are increasingly reviewing and approving regulatory submissions that include NAMs in their submission packages.
This regulatory direction reflects an important change in emphasis. As RHP Risk Management noted in its recent perspective, "Read-Across Is No Longer Optional," regulators and industry have often used read-across as a supplementary approach to fill data gaps while avoiding unnecessary testing. Increasingly, however, read-across is being considered as part of broader evidence-integration strategies for chemical safety assessment.
That does not make read-across a shortcut. A defensible analysis requires a clear scientific rationale for analogue selection, consideration of both similarities and differences between substances, evaluation of relevant toxicokinetics and biological activity, and transparent treatment of uncertainty. Depending on the question, that work can draw on toxicology, epidemiology, exposure science, chemistry, industrial hygiene, and risk assessment.
What Is the Process for a Human Health Risk Assessment?
A human health risk assessment asks several related questions: Can the substance cause harm? At what dose or concentration? Who may be exposed, by what route, and at what exposure concentration? What do the hazard and exposure information mean when considered together (referred to as dose-response)? Read-across can inform several parts of that process, but its role differs by question and endpoint.
- Hazard identification: The assessment begins by evaluating whether a substance has the potential to cause adverse health effects. For a data-poor chemical, read-across may allow hazard information from one or more appropriate analogues to inform the target substance. The key is not simply whether two chemicals look alike structurally, but whether the available evidence supports similarity relevant to the health endpoint being assessed.
- Exposure assessment: Exposure assessment evaluates who is exposed, by what route, at what concentration or dose, how often, and for how long. Read-across is not a substitute for characterizing the actual exposure scenario. However, analogue information can sometimes help fill property or fate data gaps that influence exposure estimates, such as physicochemical behavior, degradation, or bioaccumulation. An analogue appropriate for one property or endpoint may not be appropriate for another.
- Dose-response assessment: The next step characterizes how the likelihood or severity of an effect changes with dose or concentration. In some circumstances, analogue data may help inform dose-response expectations or a point of departure (the specific dose or exposure concentration where a harmful biological effect first begins or is predicted to occur based on toxicological and epidemiologic studies) for a target substance. This requires particular care because differences in absorption, distribution, metabolism, elimination, potency, or mechanism can limit how directly quantitative information can be transferred.
- Risk characterization: Risk characterization integrates the hazard, exposure evidence, and dose-response and describes the resulting conclusions, uncertainties, and limitations. When read-across contributes to an upstream data element, the strength and uncertainty of that inference should remain visible in the final risk characterization rather than disappearing once a value or classification is carried forward.
The resulting risk characterization can then inform risk-management decisions, including product stewardship, additional testing, exposure controls, hazard communication, or other actions. The goal is not to force read-across into every assessment, but to use it where the scientific evidence supports the inference and to make clear where uncertainty remains.
How Is Read-Across Advancing Risk Assessment?
Read-across uses information from one or more source substances to predict properties or effects for a target substance when direct data are incomplete. It is most established as a data-gap-filling approach for hazard endpoints, but the same core principle – using relevant information from appropriate analogues – can also contribute to other parts of an assessment when scientifically justified.
The important shift is therefore not simply greater acceptance of read-across. It is the increasing expectation that the rationale be systematic, transparent, and biologically credible. Structural similarity is a starting point, not the conclusion. Assessors need to consider whether source and target substances share relevant physicochemical properties, toxicokinetics, metabolism, biological activity, and mechanisms, and whether any differences could change the inference for the endpoint or exposure route under consideration.
For example, two substances may be close structural analogues yet form different metabolites, weakening a toxicological read-across. Conversely, an analogue may be informative for one endpoint but not another, or useful for oral exposure but less appropriate for inhalation because volatility, deposition, or local effects differ. These are scientific judgments that benefit from toxicology and exposure expertise being integrated early rather than evaluated in isolation.
For organizations considering read-across, the practical question is not simply whether the method is accepted. It is whether the available evidence supports the specific inference needed for the decision at hand. A strong assessment defines that question first, selects and evaluates analogues against it, documents the basis for the inference, identifies uncertainty, and explains how the result can – and cannot – be used.
RHP Risk Management applies this science-first approach to chemical safety questions that require coordinated expertise across toxicology, epidemiology, exposure science, industrial hygiene, engineering, and risk assessment. The objective is decision-ready work in which the methods, assumptions, limitations, and conclusions are clear enough to support scientific, regulatory, and legal review.
About RHP Risk Management Inc.
RHP Risk Management Inc. combines industrial hygiene, exposure science, toxicology, epidemiology, engineering, and risk assessment as appropriate to each client's question. RHP uses science-driven, transparent, and reproducible methods and develops work intended to be scientifically, regulatorily, and legally defensible. The firm supports focused technical evaluations, ongoing programs, multi-site work, and matters requiring coordinated expertise across disciplines.
Media Contact
Shane Jones, RHP Risk Management, 1 (717) 928-0683, [email protected], https://rhprisk.com/
SOURCE RHP Risk Management
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