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In Vivo And Ex Vivo Toxicology

Integrated studies to support mechanistic toxicology and regulatory decision-making

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In Vivo and Ex Vivo Toxicology

How can integrated in vivo and ex vivo toxicology help us make confident regulatory and safety decisions?

When screening data raises questions, it’s not the lack of data but understanding what it means.

By integrating in vivo studies with mechanistic ex vivo endpoints, you can link molecular changes to whole-organism outcomes, clarify mode-of-action (MoA) and build robust weight-of-evidence (WoE) for regulatory and internal decision-making.

Our expertise in liver and thyroid biology ensures your findings are scientifically sound and regulator-ready under frameworks including REACH, ECHA, EFSA, FDA, and EMA frameworks.

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Toxicology studies

In vivo toxicology: Targeted, hypothesis-driven design

We design in vivo toxicology studies to answer your specific mechanistic or regulatory questions. Our studies are typically hypothesis-driven and aligned with:

  • Mechanistic follow-up of in vitro findings
  • Clarification of liver or thyroid-related effects
  • Development MoA and adverse outcome pathways (AOP) narratives
  • Regulatory interpretation and decision-making

Where appropriate, studies can be designed to support GLP-compliant data generation, giving you data that is not only scientifically meaningful but also suitable for regulatory submission.

Ex vivo toxicology: Mechanistic depth beyond apical endpoints

Apical endpoints alone rarely provide enough context to support confident decisions. By adding ex vivo mechanistic endpoints, you gain insight into why effects occur, not just that they occur.

These endpoints provide molecular, biochemical, and histological insight that strengthens interpretation of systemic findings.

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What insights can targeted gene expression analysis (mRNA) provide?

Targeted gene expression analysis (mRNA) enables detailed understanding of transcriptional changes linked to key biological pathways.

  • Nuclear receptor (NR) activation.
  • Xenobiotic metabolism.
  • Liver and thyroid hormone homeostasis.
  • Adaptive versus adverse responses.

This data provides critical mechanistic context to support mode of action (MoA) development, adverse outcome pathway (AOP) mapping, and regulatory interpretation.

How is liver enzyme activity assessed?

Phase I and Phase II liver enzyme activity is measured using robust, validated methods including LC-MS/MS and fluorescence-based readouts.

Phase I enzyme activity includes:

  • Total CYP (P450) content
  • PROD, BROD, EROD
  • Benzyloxyquinoline (BQ)
  • Lauric acid hydroxylation (LAH)
  • Pentoxyresorufin O-dealkylation (PCOA)

Phase II enzyme activity includes:

  • T4 glucuronidation (T4-UGT)
  • Bilirubin glucuronidation (Bil-GT)
  • Nitrophenol glucuronidation (NP-UGT)

These assays provide functional confirmation of enzyme induction observed at the transcriptional level and are critical for interpreting liver-mediated endocrine and thyroid effects, supporting defensible regulatory conclusions.

How do you assess hepatocyte proliferation?

Hepatocyte proliferation is assessed to determine whether observed liver changes reflect adaptive responses or adverse pathology.

  • BrdU incorporation.
  • Ki67 immunostaining.

When integrated with gene expression, enzyme activity, and histopathology, these endpoints provide strong support for MoA-based and weight-of-evidence driven conclusions.

What clinical chemistry parameters are evaluated?

Standard and mechanism-relevant clinical chemistry parameters are assessed to support interpretation of liver injury and systemic effects.

  • ALT
  • AST
  • ALP

These endpoints provide essential context for integrating histological and molecular findings.

How are thyroid hormone endpoints measured?

Circulating thyroid hormones are measured using LC-MS/MS-based readouts to support thyroid-related MoA and endocrine disruption assessments.

  • T3
  • T4
  • TSH

Integration with ex vivo liver assays and in vitro thyroid mechanistic data enhances confidence in regulatory interpretations.

How do you assess steatosis and fibrosis?

Beyond routine histopathology, targeted assessments are applied to evaluate chronic or progressive liver effects.

These endpoints support interpretation of long-term liver changes and strengthen regulatory narratives around adversity.

What histopathology techniques are used?

Comprehensive tissue evaluation is complemented by advanced imaging and molecular localization techniques.

These approaches enable precise molecular localisation in liver and thyroid tissues, supporting mechanistic interpretation and translational relevance.

Can ex vivo endpoints be tailored to specific study needs?

Ex vivo endpoints can be tailored to align with specific program requirements and regulatory expectations.

  • Selection of molecular or biochemical markers.
  • Integration with in vitro hepatocyte MoA data.
  • Alignment with evolving regulatory frameworks.

This ensures data generation is fit-for-purpose, scientifically robust, and fully defensible.

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Make confident decisions with integrated in vivo and ex vivo toxicology

By combining targeted in vivo studies with deep ex vivo mechanistic analysis, you are able to obtain:

  • A clear linkage between molecular events and apical outcomes.
  • Stronger MoA and AOP narratives.
  • Reduced uncertainty in regulatory interpretation.
  • Data that integrates seamlessly with in vitro hepatocyte and endocrine mechanistic studies.

This integrated strategy supports confident decision-making for pharmaceuticals, agrochemicals, industrial chemicals, and specialty products.

Explore related capabilities

  • Hepatocyte and liver mode-of-action assays.
  • Endocrine and thyroid disruption assays.

Integrate these findings with our Hepatocyte and Liver MoA assays and Endocrine and Thyroid Disruption assays to strengthen MoA, AOP, and regulatory submissions.

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ADMET, DMPK and Toxicology

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