BDS has generated a panel of CALUX® cell lines that respond to chemically-induced alterations of key cellular pathways (see Product section for details). Exposure of the respective cells to the chemicals class of interest results in the production of luciferase and the emission of light. This signal predicts the type and magnitude of the biological effect that can be expected from exposure to the chemical or chemical mixture. We employ these methods in the discovery of compounds and compound mixtures with beneficial health effects, like functional foods, and drug candidates. When, however, these pathways are overstimulated or repressed, effects of chemicals may become adverse, which forms the basis of our effect-based safety assessment. CALUX assays are used to quantitatively assess hazard profiles of chemicals and complex mixtures. In addition, assays have been developed for targeted analysis of groups of chemicals addressing the same biological effect, such as dioxins and PFASs. Analyses carried out in our service department are strictly confidential and are performed under ISO17025 and GMP+ certified conditions. BDS offers its technologies and services world-wide through a network of laboratories and agents.
A wide range of assays is used by BDS to assess hazard profiles of chemicals and complex mixtures. Their application is in safety assessment and quality control of food, chemicals, cosmetics and pharmaceuticals, bio-based materials, water and the environment, for bioactivity profiling of clinical samples and functional foods, and any other application requiring straight forward animal-free safety assessment. These measurements are relevant to predict toxic effects like genotoxicity/carcinogenicity, endocrine disruption, reproductive toxicity, and interferences with lipid metabolism/obesogens.
Our p53 CALUX assay detects compounds that are genotoxic by causing damage to the DNA. This assay can optionally be performed in combination with microsomal S9 fractions to detect compounds that require metabolic conversion to be active. In addition, our assay panel includes a wide range of assays involved in proliferation and differentiation steps that are relevant for non-genotoxic carcinogens, including several nuclear receptor- and dioxin-receptor pathway assays.
Endocrine disruption has been recognized as a priority endpoint in safety evaluation of chemicals and consumer products. Endocrine disrupting compounds (EDCs) are being classified as substances of very high concern and regulations to restrict their use are being installed world-wide. EDC effects are hard to predict and are best tested using in vitro bioassays. To avoid animal studies BDS has developed a range of assays that allow screening and safety assessment of chemicals and consumer products in a rapid and cost-effective way.
Reproductive toxicity
Reproductive toxicity, including developmental toxicity involves a large variety of possible mechanisms and endpoints. Precise predictions of these effects is challenging, also when using the golden standard cost-, animal- and labour intensive animal tests. Concordance between these regulatory animal tests in different species is known to be around 60% only, not very far away from flipping a coin. Therefore, alternatives are urgently needed. Remarkably, when evaluated in a battery of state-of-the art relevant in vitro tests, the CALUX high throughput battery performed equally well as the entire battery, clearly demonstrating its applicability in this important area.
This CALUX panel contains assays that can measure the activity of all three members of the peroxisome proliferator activated receptors (PPARs). These are linked to beneficial health effects, but when aberrantly stimulated may also lead to adverse effects. In particular, concerns have been raised that some environmental compounds act as so-called obesogens by targeting PPARs. This opens another application area of the PPAR assays, and tests installed to further validate when possible adverse effects are found.
In addition to the exemplified effect-based assays and their applications, we have a wide range of specific CALUX assays for other major mechanistic pathways, including chemical stress-induced protective- and detoxification pathways. These are involved in a wide range of classical toxicological endpoints as assessed in animal studies, like acute toxicity and sensitisation. When overstimulated, effects will become adverse, corresponding to the so-called adverse outcome pathways (AOPs). An overview of the bioassays that are currently available is presented here. Please enquire for your specific effect class of interest.
The CALUX reporter gene assays address very specific effects pathways, facilitating measurement and interpretation of results. The pathways included are central in regulating cell functioning and are interesting targets for drugs and nutraceuticals. This includes ones that are relevant for obesity and metabolic syndrome (e.g. PPARs, dioxin- and steroid receptors), endocrine functioning (pathways e.g. related to sex steroid receptors), (anti)inflammatory and immune modulatory pathways (e.g. glucocorticoid receptors, NFkappaB signalling, sex steroid receptors and dioxin receptor), cancer (p21, p53 pathway, stress- and cytotoxicity pathways, angiogenesis, retinoid receptors, steroid receptors), and antioxidants/chemoprevention (nrf-2, retinoids), and others. With this high throughput screening (HTS) panel activities of interest can be rapidly identified in natural and environmental samples and in compound libraries for screening potential drug candidates. Additional testing to validate these hits can be carried out in more physiological models. Furthermore, an assessment of stability and the effect of metabolic conversions can be made. In combination with data on traditional use of the starting material, promising leads for improved formulations or new drug candidates can be identified.