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MnFe 2 O 4 nanoparticles (NPs) are commonly produced in some occupational settings and may reach high concentration in activities such as arc-welding or ferroalloy metallurgy. Manganese is an essential cofactor in enzyme activities but it has been demonstrated that long-term exposure to excessive levels can lead to "manganism", a neurodegenerative disease resembling Parkinson features. Inhaled NPs deposit partially in pharynx and nasopharynx and may reach the central nervous system through the olfactory nerve, which is completely enveloped by the meningeal membranes throughout its course from the nasal cavity to the olfactory bulb or through the trigeminal nerves. This study investigated in vitro the transmeningeal absorption of 50 nm MnFe 2 O 4 NPs, using excised porcine meninges mounted on Franz diffusion cells. We tested two donor solutions: the first containing MnFe 2 O 4 NPs (2.0 g/L) and the second obtained by the ultrafiltration of the first one, in order to test only the NPs water soluble fraction. Each experiment was carried separately for 4 h. Results showed that no Mn flux permeation through the meninges occurred, since only trace of the metal was found in receivers solutions of cells exposed to MnFeNPs (5.5 ± 2.2 ng/cm 2 ), ultrafiltered solution (3.5 ± 1.5 ng/cm 2 ) and blank cells. (2.1 ± 0.6 ng/cm 2) (mean and SE). Differences did not reach the statistical significance. Our study shows - for the first time - that MnFe 2 O 4 NPs penetrate the meningeal membrane in a negligible amount, thus making unlikely the hypothesis of a transcellular and paracellular absorption through the olfactory nerve but not excluding the hypothesis of an active intraneuronal absorption., (Copyright © 2018. Published by Elsevier B.V.)

Silver nanoparticles (AgNPs) are used as a common ingredient in antiseptic sprays and mists; they can easily come into contact with the upper-airway mucosa. The intranasal pathway represents the only direct connection between the external environment and brain structures, which are generally considered to be well protected. Drugs absorption through this route has been widely studied, but toxicological knowledge is scant. The olfactory bundles are surrounded by meningeal sheets in their path from the nasal mucosa to the olfactory bulb. This study investigated the transmeningeal absorption of 19nm AgNPs, using excised porcine meninges mounted on Franz diffusion cells in vitro. Two donor solutions were used: one containing AgNPs (0.5gL(-1)), and another containing only the water-soluble silver species derived from the ultrafiltration of the first one. Each experiment was carried out separately for 2h. Results showed silver flux permeation through the meninges, with similar values in both experiments (0.78±0.71ngcm(-2)h(-1) and 0.73±0.43ngcm(-2)h(-1), for AgNPs and Ag ions respectively, mean and SD). This study demonstrates that the meningeal barrier is permeable to silver and silver ions, when it is exposed to this metal in nanoparticular form; this might lead to neurotoxic and neurodegenerative effects, as recently shown by other studies. Silver nanoparticles are used by workers and consumers, and potential penetration through meningeal membrane needs to be considered and prevented when it is possible an inhalation exposure., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Silver nanoparticles (AgNPs) can come in contact with human oral mucosa due to their wide use in food industry and hygiene devices. We evaluate transmucosal absorption of 19 nm AgNPs using excised porcine buccal mucosa applied on Franz diffusion cells. Two donor solutions were used: one containing AgNPs (0.5 g/L) and one derived from the ultrafiltration of the former and containing only Ag in its soluble form. Experiments were carried out separately for 4 h. Silver flux permeation was demonstrated through oral mucosa, showing similar values for AgNPs (6.8±4.5 ng cm(-2) h(-1)) and Ag ions (5.2±4.3 ng cm(-2) h(-1)). Our study demonstrates that silver can permeate the oromucosal barrier and that absorption is substantially due to Ag ions, since no permeation difference was found using the two solutions. Mucosal absorption has to be considered in further risk assessment studies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Salivary cortisol offers a novel approach to understand the relationship between psychosocial environment and health. This study examines the intra-individual relationships among indicators of the cortisol circadian rhythm and investigates the influence of determinants affecting the day-to-day variability of the cortisol measures. Over three weekdays, 87 healthy subjects (63 females and 24 males) collected saliva samples at seven time points to assess the cortisol awakening response (CAR), and to evaluate the post morning cortisol profile. The generalized estimating equations method was used to explore the relations between repeated cortisol measures and potential determinants (sociodemographic, health, and sampling factors) influencing salivary cortisol levels. Younger age, being smoker, and sampling on a working day were associated with higher at awakening and total cortisol excretion in the morning period. Higher overall cortisol excretion and cortisol increase in the first hour of the day were found for adherents to sampling procedure. Higher educational level was found associated with greater total cortisol excretion in the morning and post morning period, while a flatter diurnal slope was found in smokers. Results are consistent with the knowledge that the circadian cortisol rhythm is differentially determined by situational factors and that results obtained in the early morning hour are of crucial importance corroborating the evidence that the CAR is a highly state-dependent phenomenon. These data indicate that many confounding factors need to be controlled when using salivary cortisol as biomarker of the mind-health interrelationship., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)