Adverse immune responses induced by xenobiotic compounds
Chemial exposure och humans
We are continuously exposed to various chemicals in cosmetics, food, and household products and the prevalence of hypersensitivity is increasing. Thus, to limit adverse health effects, candidate chemical compounds need to be investigated in a variety of toxicity tests before they can be processed into different products. The current paradigm shift in toxicity testing relies on the power of modern molecular biology to evaluate changes in signaling pathways using relevant human cells rather than relying on high dose animal studies.
The concept of pathways-based approaches to risk assessment by the description of ‘Adverse Outcome Pathways’ (AOPs) need to be fueled by high quality biological research and translated into practical tools. In vitro tests based on human cells can provide both and are clearly in line with the EU policy on refinement, reduction and replacement of animal experiments (the 3Rs principles). The applicant’s group was during 2006-2011 involved in the EU 6FP consortium ‘Novel Testing Strategies for In vitro Assessment of Allergens – Sens-it-iv’.
GARD in vitro assay
One milestone of this project was the in-house development of the predictive RNA biomarker-based in vitro assay GARD. We are continuing the development and fine-tuning of 2D and 3D in vitro cell-based assays and are currently involved in projects focused on cellular and molecular mechanisms related to human immunotoxicity induced by herbicides, rubber chemicals and food additives. We are currently investigating the process of autophagy in response to xenobiotic exposure, which is an important self-eating degradation mechanism for dendritic cell function. We are further interested in development of assay systems for complex, real-life, products and studies of so-called cocktail effects, were mixes of chemicals can aggravate each other’s’ toxic effects.