Neurobehavioural Toxicology and Chemosensation is a toxicological research group representing the more applied branch of toxicology at the IfADo. The three health risks neurotoxicity, sensory irritation and odor annoyance are important endpoints in regulatory toxicology. For almost 40 % of the chemicals in the working environment OELs are set to avoid sensory irritation (Brueninget al., 2014) while the prevention of neurotoxic effects is the critical endpoint for about 20 % of the workplace chemicals (e.g. see US TLVs: ACGIH, 2014).
This high relevance is caused by the high susceptibility of the nervous system to the adverse effects of xenobiotics. Parts of the peripheral nervous system are directly ex-posed to airborne chemicals that enter the body via inhalation. Especially the upper compartments of the respiratory tract (RT) but also the mucus membranes of the eyes are innervated by cranial nerves and various receptors serve as sentinels protecting the human body from inhalable health hazards like irritants (Shusterman, 2003). Different defense mechanisms like lacrimation, cough, or sneezing are elicited in response to the stimulation of these receptors reducing local deposition as well as penetration into deeper compartments of the respiratory tract. The peripheral neuronal structures are highly intertwined with the human immune system and several responses of peripheral receptors are modulated by immune signals (Chiu et al., 2012). This biological intersection provides an important link to the ‘Department of Immunology’ at the IfADo.
Anatomically, the central nervous system is located in a more protected region but due to its high metabolic requirements and the enormous blood supply (Belanger et al., 2011) various xenobiotics can enter the brain from the blood stream. Here, neurons and glia cells provide various unique biological targets (e.g. neurotransmitter receptors) and neurotoxic chemicals can perturb their functionality with far-reaching consequences via numerous mechanisms. Another inherent feature of the nervous system, its activity-dependent plasticity also increases its susceptibility for toxic compounds. Any up- or downregulation of neurophysiological processes related to these stimulus-driven changes (e.g. inhibition of neurotransmitter receptors and voltage-gated ion channels by pesticides) can result in persistent damages to the functionality and also the structure of the brain. Type I and II pyrethroids (e. g. permethrin and deltamethrin) are known to modify the opening and closing of sodium channels that might the biochemical basis for changes in EEG pattern and subsequent changes in activity-dependent neuronal plasticity (Freeborn et al., 2015). Like in other areas of neuroscience behavioral methods (e.g. cognitive performance in neuropsychological tests) are suitable surrogate markers for these functional and structural changes in the CNS in humans and laboratory animals. Here our toxicological approaches, like the search for dose-response relationships, are strongly liked to paradigms from the neuroscience and ergonomic groups.
Based on these different types of interactions between workplace chemicals and the nervous system our research is divided into two areas: Neurotoxicology and chemosensation. Within these areas we pursue our three aims by combining various in vivo and in vitro methods and approaches. Table 1 gives an overview about the four research fields of the group also emphasizing different exposure durations.