Safety Assessments via NAM

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NAMs are transforming toxicology and safety assessment by providing human-relevant models for predicting compound toxicity, skin sensitization, endocrine disruption, and mixture toxicology. This section explores how regulatory agencies and industries are adopting these methods to improve chemical risk assessment and reduce reliance on animal testing.

Endocrine Disruption Assessment

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The Tox21 estrogen receptor pathway battery identified compounds interfering with human hormones using robotic screening results. The EPA accepted this computational model as an alternative to rodent assays, validating the use of robotically derived data. This provides a recognized non-animal alternative for hazard identification regarding endocrine disruptors.
Toxic Alerts of Endocrine Disruption Revealed by Explainable Artificial Intelligence
Tox21: Chemical testing in the 21st century
Use of New Approach Methodologies

Skin Sensitization Hazard & Potency Prediction

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The OECD TG 497 guideline combined multiple NAMs, such as peptide reactivity and keratinocyte activation assays, to classify skin sensitization. The performance was validated as equal to or better than mouse assays, even for chemicals not previously tested in animals. This established a regulatory framework for animal-free safety testing of skin sensitizers.
Skin Sensitisation Case Study: Comparison of Defined Approaches including OECD 497 Guidance
Advancing Skin Sensitization Potency Categorization Using U-SENS™ in OECD TG 497
Standardisation and international adoption of defined approaches for skin sensitisation
Evaluating the ability of defined approaches to predict the human skin sensitisation potential of chemicals previously untested in new approach methodologies
Case Study on the Use of Integrated Approaches for Testing and Assessment for skin sensitisation

BER for PFAS Risk Assessment

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Regulators used in vitro assays to calculate human equivalent doses and derive a Bioactivity-Exposure Ratio (BER) for emerging PFAS compounds. The BER served as a validated protective surrogate in the absence of traditional animal data. This enabled risk-based prioritization of chemicals based on biological perturbation likelihood.
S13-02 NAMs to investigate chemical-induced immunotoxicity: the cases of PFAS and BPA analogs
Use of new approach methods (NAMs) in risk assessment
Sensitivity Analysis of the Inputs for Bioactivity-Exposure Ratio Calculations in a NAM-Based Systemic Safety Toolbox

Mixture Toxicology via NAMs

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NAM-based defined approaches were extended to complex mixtures such as pesticide formulations to assess their collective toxicity. Panels of in chemico and in vitro assays demonstrated they could accurately identify and rank sensitization potential. This impact advanced the understanding of combined exposure effects without resorting to animal testing.
iPSC derived cardiomyocytes for cardiac toxicity assessment
Case Study on the Use of Integrated Approaches for Testing and Assessment for skin sensitisation of Diethanolamine
Chemical testing using new approach methodologies

Reconstructed Human Skin Models

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Reconstructed human skin models have been validated by the OECD as replacements for the Draize rabbit skin irritation test. These models are now standard in the EU and increasingly adopted globally for testing cosmetics and chemicals. Their use eliminates animal testing for skin irritation and corrosion endpoints in multiple jurisdictions.
In Vitro Skin Models as Non-Animal Methods for Dermal Drug Development and Safety Assessment
Artificial Skin Models for Animal-Free Testing

Corneal and Eye Irritation Models

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Validated alternatives to the Draize rabbit eye test, such as EpiOcular and SkinEthic HCE, assess the eye irritation potential of chemicals and consumer products. These human-relevant models provide accurate safety assessments for a wide range of industrial applications. They offer a validated non-animal alternative that is both more ethical and biologically relevant.
Tissue Engineered Mini-Cornea Model for Eye Irritation Test
Corneal epithelium models for safety assessment in drug development: Present and future directions