Toxicology | Regulatory Insight

For years, read-across, a scientific approach that uses data from similar substances to predict the properties of another chemical, has been viewed as a useful alternative when traditional toxicity data were unavailable. Regulators and industry often treated it as a supplementary approach – a way to fill data gaps while avoiding unnecessary testing.

That perception is changing.

Recent developments across Europe and elsewhere internationally suggest that read-across is increasingly becoming a foundational component of modern chemical safety assessment. Regulatory agencies, industry organizations, and scientific experts are investing significant effort into developing frameworks, guidance documents, and New Approach Methodologies (NAMs) that improve confidence in read-across predictions and support broader adoption.

At the 2026 International Cooperation on Cosmetics Regulation (ICCR/ICCS) Symposium, discussions repeatedly highlighted the growing role of integrated evidence approaches, exposure-based decision making, and NAM-supported read-across strategies. The conversation was no longer centered on whether read-across can be used, but rather on how to use it effectively and transparently.

What Is Read-Across?

Read-across is a scientific approach that predicts the properties of one substance using data from another substance or group of substances that are sufficiently similar. The underlying principle is straightforward: chemicals that are structurally, biologically, and toxicologically similar are expected to behave similarly.

Traditionally, similarity assessments focused heavily on chemical structure. However, experience has shown that structural similarity alone is often insufficient. Small differences in metabolism, toxicokinetics, or biological activity can lead to substantially different toxicological outcomes.

As a result, modern read-across frameworks increasingly require evidence demonstrating similarity across multiple domains, including:

• Chemical structure
• Physicochemical properties
• Metabolism
• Toxicokinetics
• Biological activity
• Mechanistic pathways
• Toxicological endpoints

The question is no longer simply “Do these chemicals look alike?” but rather “Do these chemicals behave alike in biologically meaningful ways?”

Why Read-Across Is Gaining Momentum

Several factors are driving increased reliance on read-across.

1. Regulatory Demand for Efficient Data Generation

Around the world, regulatory agencies are searching for ways to evaluate larger numbers of chemicals more efficiently while reducing unnecessary animal testing and maintaining confidence in safety decisions.

Europe has arguably led the way in formalizing read-across through the REACH regulation and the European Chemicals Agency’s (ECHA) Read-Across Assessment Framework (RAAF). More recently, the European Commission’s roadmap toward phasing out animal testing has reinforced the importance of integrated approaches that combine existing data, read-across, exposure science, and NAMs.

In the United States, the regulatory landscape has evolved differently. While there is no direct equivalent to REACH’s formal read-across framework, agencies including the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA) have invested heavily in computational toxicology, integrated approaches to testing and assessment (IATA), physiologically based pharmacokinetic (PBPK) modeling, and NAM development. These efforts increasingly rely on many of the same scientific principles that underpin robust read-across.

Health Canada, OECD, and international scientific collaborations have similarly developed case studies, guidance, and reviews demonstrating how read-across, when supported by appropriate mechanistic, toxicokinetic, and exposure data, can provide scientifically defensible evidence for chemical safety assessments.

Although regulatory implementation differs across jurisdictions, the direction is consistent: decisions are increasingly being informed by integrated evidence rather than any single study or test.

2. Expansion of New Approach Methodologies (NAMs)

Perhaps the most significant change is the growing availability of NAMs. Historically, one of the greatest challenges facing read-across was demonstrating that source and target chemicals were truly similar from a biological perspective.

Today, NAMs can provide evidence supporting:

• Shared biological activity
• Common molecular initiating events
• Similar metabolic pathways
• Comparable toxicokinetics
• Consistent potency relationships
• Relevant exposure metrics

Rather than relying solely on structural similarity, scientists can now generate targeted data that directly evaluate the read-across hypothesis.

3. Increased Focus on Mechanistic Understanding

Modern toxicology is increasingly focused on understanding why chemicals cause effects rather than simply documenting whether effects occur. This shift aligns naturally with read-across. When scientists understand a chemical’s mode of action, adverse outcome pathway (AOP), metabolism, and exposure characteristics, they can often make more informed predictions than would be possible using apical animal study results alone.

The Role of NAMs in Strengthening Read-Across

One of the most important conclusions emerging from recent scientific efforts is that NAMs are strengthening read-across approaches. A 2021 workshop involving regulators, industry, academia, the European Chemicals Agency (ECHA), the European Food and Safety Authority (EFSA), the Organisation for Economic Co-operation and Development (OECD), Health Canada, and the U.S. Environmental Protection Agency (EPA) concluded that NAMs can significantly improve confidence in read-across by helping define category boundaries, characterize similarities and differences among chemicals, and reduce uncertainty associated with predictions.

Importantly, participants emphasized that successful read-across requires a fit-for-purpose strategy rather than a “more data is better” approach. Carefully selected NAMs that address key uncertainties are often more valuable than large volumes of unrelated data.

This represents an important shift in thinking. The goal is not to generate every possible piece of information. The goal is to generate the information needed to support a regulatory decision.

Exposure and Toxicokinetics Information Are Becoming Essential

One of the strongest themes emerging from both the ICCS Symposium and recent literature is the increasing importance of exposure and toxicokinetics data. Historically, read-across often focused primarily on hazard.

Today, regulators increasingly recognize that understanding absorption, distribution, metabolism, and excretion (ADME), internal dose, and bioavailability is critical for establishing whether chemicals truly behave similarly. Physiologically based pharmacokinetic (PBPK) modeling, in vitro to in vivo extrapolation (IVIVE), and exposure-based approaches are becoming key tools for supporting read-across decisions.

This creates a natural connection between toxicology, exposure science, and risk assessment.

What This Means for Industry

For U.S. companies, these developments are important even when products are marketed primarily in North America. Global supply chains, multinational product portfolios, and evolving international regulations increasingly require companies to understand how ingredients may be evaluated across multiple jurisdictions. Building read-across strategies early in product development can help support regulatory submissions, product stewardship decisions, and responses to customer or retailer requests while reducing the need for additional testing.

Organizations that proactively develop chemical categories, build robust similarity assessments, and integrate NAMs into decision-making processes may be better positioned to:

• Address regulatory data requirements
• Support product stewardship programs
• Prioritize testing resources
• Reduce development timelines
• Respond to evolving regulatory expectations

The companies that benefit most will likely be those that view read-across not as a last resort, but as part of a broader evidence-based safety assessment strategy.

Looking Ahead

The future of toxicology will not rely on a single method. Instead, regulatory decisions will increasingly be informed by integrated evidence streams that combine traditional animal toxicity assays, read-across, NAMs, exposure information, toxicokinetic modeling, and mechanistic understanding.

Read-across sits at the center of this transition. As regulatory frameworks continue to evolve and NAM capabilities expand, the question facing many organizations will no longer be whether read-across can be used. The more important question will be whether they are prepared to use it effectively.

A recurring theme at the 2026 ICCS Symposium was that the scientific community is moving beyond asking whether NAMs and read-across are feasible. Instead, discussions focused on implementation: how to build confidence, establish best practices, and integrate multiple lines of evidence into regulatory decision-making. For industry, this signals that developing expertise in read-across is becoming less about preparing for the future and more about preparing for today’s regulatory expectations.

At RHP Risk Management, we continue to monitor developments in NAMs, exposure science, toxicology, and regulatory risk assessment to help clients navigate this rapidly changing landscape and develop scientifically defensible approaches to chemical safety evaluation.

To discuss a read-across, NAM, or chemical safety assessment question, contact RHP Risk Management or call (866) 481-8188.