Monique Chalansonnet

Biopersistence and translocation to extrapulmonary organs of titanium dioxide nanoparticles after subacute inhalation exposure to aerosol in adult and elderly rats.

The increasing industrial use of nanoparticles (NPs) has raised concerns about their impact on human health. Since aging and exposure to environmental factors are linked to the risk for developing pathologies, we address the question of TiO2 NPs toxicokinetics in the context of a realistic occupational exposure. We report the biodistribution of titanium in healthy young adults (12-13-week-old) and in elderly rats (19-month-old) exposed to 10mg/m3 of a TiO2 nanostructured aerosol 6h/day, 5days/week for 4 weeks. We measured Ti content in major organs using inductively coupled plasma mass spectrometry immediately and up to 180days after the end of exposure. Large amounts of titanium were initially found in lung which were slowly cleared during the post-exposure period. From day 28, a small increase of Ti was found in the spleen and liver of exposed young adult rats. Such an increase was however never found in their blood, kidneys or brain. In the elderly group, translocation to extra-pulmonary organs was significant at day 90. Ti recovered from the spleen and liver of exposed elderly rats was higher than in exposed young adults. These data suggest that TiO2 NPs may translocate from the lung to extra-pulmonary organs where they could possibly promote systemic health effects.

Mineralization of TiO2 nanoparticles for the determination of titanium in rat tissues

In order to draw appropriate conclusions about the possible adverse biological effects of titanium dioxide nanoparticles (TiO2—NPs), the so-called “dose?effect” relationship must be explored. This requires proper quantification of titanium in complex matrices such as animal organs for future toxicological studies. This study presents the method development for mineralizing TiO2—NPs for analysis of biological tissues. We compared the recovery and quantification limits of the four most commonly used mineralization methods for metal oxides. Microwave-assisted dissolution in an HNO3–HF mixture followed by H2O2 treatment produced the best results for a TiO2—NPs suspension, with 96 ± 8% recovery and a limit of quantification as low as 0.9 µg/L. This method was then used for the determination of titanium levels in tissue samples taken from rats. However, our tests revealed that even this method is not sensitive enough for quantifying titanium levels in single olfactory bulbs or hippocampus in control animals.

Continuous exposure to low-frequency noise and carbon disulfide: combined effects on hearing

HIGHLIGHTSCarbon disulfide temporarily potentiates the effects of low‐frequency noise on cochlear function.Low‐frequency noise provokes hearing loss in a frequency range wider than expected.No evidence of cochlear toxicity due to carbon disulfide. ABSTRACT Carbon disulfide (CS2) is used in industry; it has been shown to have neurotoxic effects, causing central and distal axonopathies.However, it is not considered cochleotoxic as it does not affect hair cells in the organ of Corti, and the only auditory effects reported in the literature were confined to the low‐frequency region. No reports on the effects of combined exposure to low‐frequency noise and CS2 have been published to date. This article focuses on the effects on rat hearing of combined exposure to noise with increasing concentrations of CS2 (0, 63,250, and 500 ppm, 6 h per day, 5 days per week, for 4 weeks). The noise used was a low‐frequency noise ranging from 0.5 to 2 kHz at an intensity of 106 dB SPL. Auditory function was tested using distortion product oto‐acoustic emissions, which mainly reflects the cochlear performances. Exposure to noise alone caused an auditory deficit in a frequency area ranging from 3.6 to 6 kHz. The damaged area was approximately one octave (6 kHz) above the highest frequency of the exposure noise (2.8 kHz); it was a little wider than expected based on the noise spectrum.Consequently, since maximum hearing sensitivity is located around 8 kHz in rats, low‐frequency noise exposure can affect the cochlear regions detecting mid‐range frequencies. Co‐exposure to CS2 (250‐ppm and over) and noise increased the extent of the damaged frequency window since a significant auditory deficit was measured at 9.6 kHz in these conditions.Moreover, the significance at 9.6 kHz increased with the solvent concentrations. Histological data showed that neither hair cells nor ganglion cells were damaged by CS2. This discrepancy between functional and histological data is discussed. Like most aromatic solvents, carbon disulfide should be considered as a key parameter in hearing conservation régulations.

Study of potential transfer of aluminum to the brain via the olfactory pathway

Many employees in the aluminum industry are exposed to a range of aluminum compounds by inhalation, and the presence of ultrafine particles in the workplace has become a concern to occupational health professionals. Some metal salts and metal oxides have been shown to enter the brain through the olfactory route, bypassing the blood-brain barrier, but few studies have examined whether aluminum compounds also use this pathway. In this context, we sought to determine whether aluminum was found in rat olfactory bulbs and whether its transfer depended on physicochemical characteristics such as solubility and granulometry. Aluminum salts (chloride and fluoride) and various nanometric aluminum oxides (13nm, 20nm and 40-50nm) were administered to rats by intranasal instillation through one nostril (10μg Al/30μL for 10days). Olfactory bulbs (ipsilateral and contralateral relative to instilled nostril) were harvested and the aluminum content was determined by graphite furnace atomic absorption spectrometry after tissue mineralization. Some transfer of aluminum salts to the central nervous system via the olfactory route was observed, with the more soluble aluminum chloride being transferred at higher levels than aluminum fluoride. No cerebral translocation of any of the aluminas studied was detected.

Combined exposure to carbon disulfide and low-frequency noise reversibly affects vestibular function

HIGHLIGHTSCo‐exposure to low‐frequency noise and CS2 temporarily perturbs vestibular function.CS2 alone causes a reversible decrease of PRN saccade number.Low‐frequency noise alone has no effect on PRN parameters.No evidence of CS2‐induced peripheral vestibulotoxicity was found.CS2 may trigger reversible central neurochemical effects that impair the VOR. ABSTRACT Chronic occupational exposure to carbon disulfide (CS2) has debilitating motor and sensory effects in humans, which can increase the risk of falls. Although no mention of vestibulotoxic effects is contained in the literature, epidemiological and experimental data suggest that CS2 could cause low‐frequency hearing loss when associated with noise exposure. Low‐frequency noise might also perturb the peripheral balance receptor through an as‐yet unclear mechanism. Here, we studied how exposure to a low‐frequency noise combined with 250‐ppm CS2 affected balance in rats. Vestibular function was tested based on post‐rotary nystagmus recorded by a video‐oculography system. These measurements were completed by behavioral tests and analysis of the cerebellum to measure expression levels for gene expression associated with neurotoxicity. Assays were performed prior to and following a 4‐week exposure, and again after a 4‐week recovery period. Functional measurements were completed by histological analyses of the peripheral organs.Nystagmus was unaltered by exposure to noise alone, while CS2 alone caused a moderate 19% decrease of the saccade number. In contrast, coexposure to 250‐ppm CS2 and low‐frequency noise decreased both saccade number and duration by 33% and 34%, respectively. After four weeks, recovery was only partial but measures were not significantly different from pre‐exposure values. Real‐time quantitative polymerase chain reaction (RT‐qPCR) analysis of cerebellar tissue revealed a slight but significant modification in expression levels for two genes linked to neurotoxicity in CS2‐exposed animals. However, neither histopathological changes to the peripheral receptor nor behavioral differences were observed. Based on all these results, we propose that the effects of CS2 were due to reversible neurochemical disturbance of the efferent pathways managing post‐rotatory nystagmus. Because the nervous structures involving the vestibular function appear particularly sensitive to CS2, post‐rotary nystagmus could be used as an early, non‐invasive measurement to diagnose CS2 intoxication as part of an occupational conservation program.