CLS-logo.png Whether you’re developing innovative consumer products, ground-breaking agrochemicals or advanced cosmetic products, investigating the effect of novel chemicals on health and the environment is a critical part of the development pathway. Eliminating toxic substances and understanding the effects of chemicals on people and planet is made easy with the latest predictive and mechanistic assays. 

  • Channel investment into innovations that will meet stricter regulatory standards. 
  • Advance future-proofed products that will see sustained market success. 

When it comes to innovation, it’s the small details that make a big difference. 

The challenge

Regulatory bodies such as the OECD are introducing stricter standards around toxicology studies and are enforcing precise methods and techniques. But identifying whether a compound has toxic potential is hard, impacts can be unpredictable and downstream consequences hard to track. 

To understand what a toxicity assay readout means for your product you need a thorough understanding of the full mechanism of action and an appreciation of cross-species sensitivity. Testing for safety against the full toxicity spectrum is now critical for regulatory sign-off. 

By safety screening thoroughly and early, developers see more products emerge from their development pipeline with long marketable life.

The solution 

Companies across the world are already using our novel predictive and mechanistic assay services to: 

  • Provide data for updates to reregistration dossiers in line with updated regulatory requirements.
  • Create detailed comparative data on toxicological risk across species.
  • Screen candidate compounds and invest only in those compounds that will pass regulatory approval and deliver future-proofed sales. 
  • Develop products that are best for people and the planet.

We operate to the highest quality standards supported by our in-house program management and quality teams. We are a GLP-certified laboratory and can deliver both GLP and non-GLP studies, completing predictive, exploratory and discovery toxicology through: 

Endocrine toxicology

Endocrine disruptors are hitting the headlines again with links to reduced fertility and developmental and growth issues in humans and animals.

Our tailored, mechanistic investigations accurately evaluate the potential of a compound to disrupt endocrine signaling and include OECD Tier 2 endocrine disruption and bespoke thyroid assays. 

OECD Tier 2 assays

Androgen receptor assay (OECD Test Number 458)

We use our AR-EcoScreen™ cell line, stably transfected with the AR-responsive luciferase reporter gene, to identify both activators and inhibitors of AR-dependent transcription. 

Estrogen receptor assay (OECD Test Number 455)

The VM7Luc4E2 cell line, expressing estrogen receptors α and ß, is stably transfected with an ER-responsive luciferase reporter gene. The resulting assay can be performed in agonist and antagonist mode to identify chemicals that activate or inhibit ER-dependent transcription. 

Steroidogenesis assay (OECD Test Number 456)

This in vitro test system uses the human H295R adenocarcinoma line to investigate a compound’s effect on steroid hormone biosynthesis, specifically 17ß-estradiol and testosterone. 

Aromatase inhibition (OPPS.890.1200)

Human recombinant CYP19 microsomes are used to establish the risk of a compound activating the production of aromatase which, in turn, leads to the conversion of androgens to estrogens. 

Bespoke thyroid hormone modulation assays

Regulatory concern is rising around compounds that might disrupt thyroid hormone signals, especially considering the link to neurological development in juveniles. Our bespoke thyroid assays measure trigger points for thyroid hormone disruption, from the regulators to the cotransporters. With cross-species models, we evaluate species sensitivity to evaluate human relevance. 

Our assays include: 

  • Sodium /iodide symporter (NIS) assay 
    A spectrophotometer method to measure the uptake of iodide into rat follicular cells. This sensitive assay measures a chemical’s effects on the first step of thyroid hormone synthesis

  • Deiodinase (DIO) assay
    This robust panel of sensitive assays evaluates inhibition of all three master regulators (DIO 1,2 and 3) of thyroid hormone signaling. Available in rat, dog and human models

  • Thyroperoxidase (TPO) assay
    This assay evaluates the effect of compounds on early-stage oxidation and incorporation of iodide to produce thyroglobulin. Available in rat, dog, pig and human models

  • Thyroid hormone receptor assay
    For a full activation evaluation

  • Cross-species comparative induction of UDP-glucuronosyltransferase (UGT) expression

Non-genotoxic carcinogenicity evaluations

By evaluating toxicological processes across species and conducting detailed pathway studies, we accurately determine a compound’s risk to humans. 

As experts in liver toxicology, we have a range of hepatocyte assays to assess the known differences in toxicity risk between rodents and humans, as well as the human relevance of rodent liver carcinogenicity readouts. We interrogate the association with nuclear hormone receptor CAR/PXR or PPARα-specific pathways, including the species differences in downstream secondary toxicity in thyroid and testes.

Our human relevance carcinogenicity capabilities include:

  • Evaluating data to create a robust hypothesis
  • Designing and running studies to confirm the mechanism of action in rodent hepatocytes (in vivo and in vitro)
  • Performing human relevance studies in vitro with primary human hepatocytes, including secondary toxicity evaluation
  • Specifying the nuclear receptors involved
  • Cross-species liver metabolism studies
  • Analyzing and interpreting results

Immuno-safety

New molecular entities can induce broad inflammatory responses and adverse reactions – characterized as cytokine release syndrome. Using the most effective protocols for each test substance, we detect release profiles on a full cytokine panel. 

With world-class immunology expertise, our biology team design a bespoke plan of work to evaluate the immuno-safety of your product. 

Visit our immunology service pages to find out more.

Neurotoxicology

This new area of safety testing accesses the latest in pluripotent stem cell and primary CNS cell-based assay platforms. It is now recognized that the impact of thyroid hormone modulation on neurodevelopment is an important consideration for future products.  

Our neuroscience team offers a range of assays and bespoke endpoints to evaluate the impact of your product on neurodevelopment. 

Visit our neuroscience service pages to find out more. 

If it’s toxic, we’ll find it

Contact our expert team and find out how can we help you eliminate development-stopping toxic substances from your product pipeline.