REGULATION & COMPLIANCE
UK, industrial chemicals are regulated under REACH, which follows a hazardbased approach, relying primarily on well-established in vivo test guidelines to determine a chemical’ s potential harm to human health or the environment.
In contrast, countries such as the US and Australia have adopted a risk-based approach, which focuses on evaluating the probability that the harmful outcome will happen and managing the risks associated with chemical use, employing control measures to ensure exposure remains below acceptable thresholds. This distinction influences the potential integration of NAMs, as risk-based frameworks may provide greater flexibility for incorporating alternative methods into safety assessments, while the CLP hazard classes are not well suited for non-animal methods that do not allow prediction of the adverse effects observed.
An alternative paradigm, advocated by several stakeholders, emphasises the extensive use of NAMs within a predictive, science-driven framework that is both exposure-led and risk-
High-throughput screening is one NAM
based. This approach has led to the emergence of the Next Generation Risk Assessment( NGRA), which integrates multiple lines of evidence to improve chemical safety assessments without relying on traditional animal testing. 10
NGRA employs a weight-of-evidence framework, combining diverse NAMs such as in vitro assays and computational models to determine safety thresholds. A key component of NGRA is the use of Points of Departure( PoD), reference values derived from in vitro assays that indicate the threshold at which a substance begins to cause a biological effect. Additionally, physiologically-based kinetic( PBK) modelling plays a crucial role by simulating how chemicals are absorbed, distributed, metabolised and excreted in the body.
A central concept in NGRA is the bioactivity exposure ratio( BER), which compares bioactivity levels( determined from in vitro PoD values) with real-world exposure levels. A high BER suggests a lower risk, whereas a low BER may indicate potential concern, guiding further steps in risk assessment. 11
Several case studies particularly in the cosmetics sector have demonstrated the feasibility of this approach, on the underlying premise that NAM-based NGRA safety assessments should protect individuals exposed to the chemical rather than predicting specific adverse effects that may occur only at excessively high doses. 12- 14
A major challenge in integrating NGRA into the REACH framework is the lack of robust monitoring and control over real-life exposure scenarios for industrial chemicals. Unlike consumer products, where exposure is often predictable, workplace and environmental exposures can be highly variable, influenced by factors such as compliance with safety regulations, process conditions and the effectiveness of risk management measures.
While risk management strategies are critical for minimising harm, they can never be as effective as eliminating hazards. This is particularly concerning when relying on risk management measures, which may lack enforceability and consistency across industries. Regulatory frameworks like REACH heavily rely on hazard identification to assess the potential risks of chemicals and then integrate a risk-based approach to prioritise the substances that pose the greatest threat to human health and the environment.
This raises a fundamental question: should regulatory approaches shift toward a full risk-based model, where some level of risk is tolerated, relying on exposure controls to prevent harm? Or should a precautionary stance be maintained, ensuring that protection is achieved primarily through the identification of hazard?
This choice is complex. It presents the challenge of balancing careful consideration of scientific advancements in exposure science and risk assessment against the practical challenges of ensuring consistent and reliable risk mitigation in real-world settings. Several roadmaps, strategic plans and frameworks are available for
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