Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System

Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (<100 nm) of TiO2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2

The diversity of neuronal phenotypes in rodent and human autonomic ganglia

Selective sympathetic and parasympathetic pathways that act on target organs represent the terminal actors in the neurobiology of homeostasis and often become compromised during a range of neurodegenerative and traumatic disorders. Here, we delineate several neurotransmitter and neuromodulator phenotypes found in diverse parasympathetic and sympathetic ganglia in humans and rodent species. The comparative approach reveals evolutionarily conserved and non-conserved phenotypic marker constellations. A developmental analysis examining the acquisition of selected neurotransmitter properties has provided a detailed, but still incomplete, understanding of the origins of a set of noradrenergic and cholinergic sympathetic neuron populations, found in the cervical and trunk region. A corresponding analysis examining cholinergic and nitrergic parasympathetic neurons in the head, and a range of pelvic neuron populations, with noradrenergic, cholinergic, nitrergic, and mixed transmitter phenotypes, remains open. Of particular interest are the molecular mechanisms and nuclear processes that are responsible for the correlated expression of the various genes required to achieve the noradrenergic phenotype, the segregation of cholinergic locus gene expression, and the regulation of genes that are necessary to generate a nitrergic phenotype. Unraveling the neuron population-specific expression of adhesion molecules, which are involved in axonal outgrowth, pathway selection, and synaptic organization, will advance the study of target-selective autonomic pathway generation