New Approach Methodologies (NAMs)

Advances in New Approach Methodologies (NAMs) are transforming approaches to chemical safety, offering cost-effective, scientifically robust alternatives to traditional animal testing. At Blue Frog Scientific, we specialise in in silico profiling and designing and monitoring in vitro/ex vivo testing, helping clients reduce reliance on animal studies while meeting regulatory requirements under REACH, biocides, plant protection products, human and veterinary medicines, and other industry frameworks.

NAMs are not only essential for regulatory compliance but also play a key role in early-stage product development, helping to identify candidate molecules, assess safety profiles, and streamline research and development (R&D) pipelines.

NAMs Regulatory Strategy

As regulatory agencies worldwide increase their focus on NAMs, our expert team ensures that alternative testing approaches are implemented effectively, scientifically validated, and fully compliant with evolving regulatory standards:

• NAMs Integration in Regulatory Dossiers – Ensuring that regulatory acceptance of any alternative testing methods identified for a substance is appropriately assessed and potential risks of their use are quantified and contextualised
• Advocacy for NAMs Acceptance – Supporting clients in responding to regulatory challenges against the use of NAMs, ensuring proportional and science-based evaluation of alternative methods
• Read-Across Feasibility – A screening level assessment of the feasibility of using read-across to fulfil endpoints for a chemical substance

In silico Profiling & Computational Modelling

Computational modelling is a powerful tool for predicting the intrinsic properties of substances, supporting both regulatory submissions and early-stage chemical screening. Our in silico profiling services provide comprehensive assessments of physicochemical, environmental, and toxicological properties, supporting:

• Identification of Candidate Molecules – Screening new substances for desirable safety and efficacy profiles during R&D
• Read-Across & Category Formation – Profiling source and target molecules for read-across justifications in regulatory submissions
• Data Gap Analysis & Testing Strategy Development – Supporting cost-effective study planning by identifying alternative data sources and indicative endpoint conclusions
• Regulatory Endpoint Predictions – Generating key data points for regulatory dossiers, either as standalone studies or as part of a weight-of-evidence (WoE) approach
• Expert Justification Reports – Preparing scientific rationales to accompany computational predictions in regulatory submissions (QMRF/QPRF documentation)

In silico Skin Sensitisation Assessment

We also offer an in silico skin sensitisation assessment service, to satisfy the integrated testing strategy requirements in accordance with the REACH Regulation. The assessment is a precursor to in vitro and in vivo skin sensitisation testing to identify pre-haptens and pro-haptens and estimation of physicochemical properties (e.g., octanol-water partition coefficient, log Kow) if needed, the results of which dictate the approach that must be taken to conclude on the skin sensitisation endpoint.

In Vitro & Ex Vivo Testing – Advanced NAMs for Product Development & Compliance

In vitro and ex vivo methods provide human-relevant, mechanistic insights into chemical safety and biological interactions, allowing companies to refine their product development pipelines while safeguarding regulatory compliance.  These studies are also useful for building adverse outcome pathways during hazard assessment.  

Here are some of the common mechanistic in vitro assays we can incorporate into strategies for investigating hazardous properties:

• Genotoxicity & Mutagenicity:
  • Ames Test (OECD 471) – Detects mutagenic potential in bacteria
  • Micronucleus Assay (OECD 487) – Evaluates chromosomal damage and clastogenicity
  • Comet Assay (OECD 489) – Assesses DNA strand breaks in mammalian cells
  • HPRT & TK Gene Mutation Assays (OECD 476) – Identifies gene mutations in mammalian cells
• Skin & Eye Irritation/Corrosion:
  • Reconstructed Human Epidermis (RhE) Models (OECD 431, 439) – Assess skin irritation and corrosion
  • BCOP (OECD 437) & ICE (OECD 438) – Evaluate eye irritation and damage using ex vivo models
• Skin Sensitisation (Defined Approaches for REACH & BPR):
  • Direct Peptide Reactivity Assay (DPRA, OECD 442C) – Measures covalent binding to proteins (Key Event 1 in AOP)
  • KeratinoSens™ (OECD 442D) – Evaluates Nrf2-ARE pathway activation in keratinocytes (Key Event 2)
  • h-CLAT (OECD 442E) – Assesses dendritic cell activation (Key Event 3)
  • U-SENS™, IL-8 Luc Assay – Additional dendritic cell activation assays for hazard identification
• Endocrine Disruption:
  • Estrogen Receptor (ER) & Androgen Receptor (AR) Transactivation Assays (OECD 455, 458) – Evaluate hormone receptor binding and activation
  • Aromatase Inhibition Assay (OECD 456) – Measures steroidogenesis disruption
  • Thyroid Disruption Assays  – e.g. NIS and TPO assay, to assess effects on thyroid hormone synthesis, transport, and metabolism
• Developmental & Reproductive Toxicity (DART):
  • Mouse Embryonic Stem Cell Test (mEST) – Evaluates early embryotoxicity
  • Zebrafish Embryotoxicity Test (ZFET, OECD 236) – Screens for developmental defects
  • H295R Steroidogenesis Assay (OECD 456) – Assesses hormone biosynthesis disruption
• Neurotoxicity & Developmental Neurotoxicity (DNT):
  • Neurite Outgrowth Assays – Assess neurodevelopmental disruption
  • Microelectrode Array (MEA) Technology – Measures neural activity changes due to toxicants
  • Astrocyte & Oligodendrocyte Differentiation Assays – Evaluate effects on glial cell development
• Metabolism & Biotransformation:
  • Hepatocyte-Based Assays – Assess hepatic metabolism and CYP450 enzyme induction/inhibition
  • Caco-2 Permeability Assay – Predicts intestinal absorption and bioavailability
  • OECD 319A/B (In Vitro Biotransformation in Fish & Mammals) – Evaluates xenobiotic metabolism for environmental risk assessment

At Blue Frog Scientific, we design and implement scientifically robust, regulatory-compliant strategies to utilise new approach methodologies (NAMs) in support of chemical, biocide, and plant protection product registrations. Our highly qualified team, with backgrounds in regulatory agencies, industry, and research, ensures that your use of alternative methods will meet the highest regulatory standards.

Contact us today to discuss how we can support your application of new approach methodologies.