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
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.
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.