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ATHON: Assessing the toxicity and hazard of non-dioxin-like PCBs present in food

Principle investigator: Elsa C. Antunes Fernandes, Ph.D.
Project leader: R.H.S. Westerink, Ph.D. and M.B.M. van Duursen, Ph.D
Project description:
The aim of this project is to study the neurotoxic and endocrine disruptive effect of non-dioxin-like PCBs (NDL-PCBs). Therefore, the effects NDL-PCBs on pre- and postsynaptic aspects of neurotransmission, steroidogenesis, steroid metabolism, androgen receptor expression, and enzymes activities in vitro will be investigated.
The effects of NDL-PCBs on the function of the human GABAA expressed in Xenopus oocytes will be assed by measuring the effects on GABA-evoked Cl- currents. Amperometry and calcium-imaging techniques will be used to study which congeners (or metabolites) affect intracellular calcium homeostasis and basal or evoked neurotransmitter release in neuroendocrine PC12 cells. Several cell lines will be used to study effects of several PCBs congeners and their hydroxyl- and methylsulfonyl-metabolites on steroidogenesis and steroid metabolism. Special attention will be given to androgen receptor expression, aromatase and COMT activity.
PCBs are prevalent contaminants in fatty food of animal origin, such as meat, certain fish and dairy products. The present PCB exposure of general population in several countries is in the same range as the exposure level at which subtle neurotoxic effects have been observed in infants following perinatal exposure. Unlike dioxin-like PCBs (DL-PCBs) congeners, there is little insufficient information on the mechanisms of action of NDL-PCBs congeners and their relevance and presence in food to perform a health risk assessment. Because NDL-PCBs congeners constitute a large part of PCB congeners found in food and human tissues, it is of major importance to understand the toxicology of NDL-PCBs.
Recent publications:
- Langeveld, W.T., Meijer, M., Westerink, R.H.S. (2012) Differential effects of 20 non-dioxin-like PCBs on basal and depolarisation-evoked intracellular calcium levels in PC12 cells. Toxicological Sciences 126, 487-496.
- Stenberg, M., Hamers, T., Machala, M., Fonnum, F., Stenius, U., Lauy, A.A., van Duursen, M.B., Westerink, R.H.S., Antunes Fernandes, E.C., Andersson, P.L. (2011). Multivariate toxicity profiles and QSAR modeling of non-dioxin-like PCBs - An investigation of in vitro screening data from ultra-pure congeners. Chemosphere 85, 1423-1429.
- Hendriks, H.S., Antunes Fernandes, E.C., Bergman, Å, van den Berg, M., Westerink, R.H.S. (2010). PCB-47, PBDE-47 and 6-OH-PBDE-47 differentially modulate human GABAA and a4b2 nicotinic acetylcholine receptors. Toxicological Sciences 118, 635-642.
- Antunes Fernandes, E.C., Hendriks, H.S., van Kleef, R.G.D.M., van den Berg, M., Westerink R.H.S. (2010) Potentiation of the human GABAA receptor as a novel mode of action of lower-chlorinated non-dioxin-like PCBs. Environmental Science & Technology; 448, 2864-2869.
- Antunes Fernandes, E.C., Hendriks, H.S. van Kleef, R.G.D.M., Reniers, A., Andersson, P.L., van den Berg, M., Westerink, R.H.S. (2010). Activation and potentiation of human GABAA receptors by non-dioxin-like-PCBs depends on chlorination pattern. Toxicological Sciences 118, 183-190.