Elie Tourlonias

Incorporation and distribution of uranium in rats after a contamination on intact or wounded skin.

Uranium uptake can occur accidentally by inhalation, ingestion, injection, or absorption through intact or wounded skin. Intact or wounded skin routes of absorption of uranium have received little attention. The aims of our work were (1) to evaluate the influence of the type of wound contamination on the short term distribution and excretion of uranium in rats and (2) to generate data to assess the time available to treat contamination of intact or wounded skin before significant uptake of uranium occurs. Biokinetic data presented in the present paper are based on an in vivo rat model. This study shows that a significant uptake of a uranyl nitrate solution through intact skin can occur within the first 6 h of exposure. Absorption of a uranyl nitrate solution through excoriated skin is significant after only 30 min of exposure. After a 24-h exposure, uranium uptake through intact skin and excoriated skin represents about 0.4% and 38% of the initial deposit of uranium, respectively. Contaminated serious chemical skin burns induced by HNO3 or NaOH are paradoxically less important in terms of uranium uptake risk because 99% of the incorporated uranium remains trapped at the wound site and its incorporation is delayed for at least 6 h after the beginning of contamination. These results confirm that the biokinetics of a given physicochemical form of uranium incorporated after wound contamination depend largely on the physiological evolution of the considered wound. Each type of wound, with its corresponding biokinetics of a uranium species, is a particular case.

Inhalation of uranium nanoparticles: Respiratory tract deposition and translocation to secondary target organs in rats

Uranium nanoparticles (<100 nm) can be released into the atmosphere during industrial stages of the nuclear fuel cycle and during remediation and decommissioning of nuclear facilities. Explosions and fires in nuclear reactors and the use of ammunition containing depleted uranium can also produce such aerosols. The risk of accidental inhalation of uranium nanoparticles by nuclear workers, military personnel or civilian populations must therefore be taken into account. In order to address this issue, the absorption rate of inhaled uranium nanoparticles needs to be characterised experimentally. For this purpose, rats were exposed to an aerosol containing 10⁷ particles of uranium per cm³ (CMD=38 nm) for 1h in a nose-only inhalation exposure system. Uranium concentrations deposited in the respiratory tract, blood, brain, skeleton and kidneys were determined by ICP-MS. Twenty-seven percent of the inhaled mass of uranium nanoparticles was deposited in the respiratory tract. One-fifth of UO₂ nanoparticles were rapidly cleared from lung (T(½)=2.4 h) and translocated to extrathoracic organs. However, the majority of the particles were cleared slowly (T(½)=141.5 d). Future long-term experimental studies concerning uranium nanoparticles should focus on the potential lung toxicity of the large fraction of particles cleared slowly from the respiratory tract after inhalation exposure.

Role of the olfactory receptor neurons in the direct transport of inhaled uranium to the rat brain

Uranium presents numerous industrial and military uses and one of the most important risks of contamination is dust inhalation. In contrast to the other modes of contamination, the inhaled uranium has been proposed to enter the brain not only by the common route of all modes of exposure, the blood pathway, but also by a specific inhalation exposure route, the olfactory pathway. To test whether the inhaled uranium enter the brain directly from the nasal cavity, male Sprague-Dawley rats were exposed to both inhaled and intraperitoneally injected uranium using the (236)U and (233)U, respectively, as tracers. The results showed a specific frontal brain accumulation of the inhaled uranium which is not observed with the injected uranium. Furthermore, the inhaled uranium is higher than the injected uranium in the olfactory bulbs (OB) and tubercles, in the frontal cortex and in the hypothalamus. In contrast, the other cerebral areas (cortex, hippocampus, cerebellum and brain residue) did not show any preferential accumulation of inhaled or injected uranium. These results mean that inhaled uranium enters the brain via a direct transfer from the nasal turbinates to the OB in addition to the systemic pathway. The uranium transfer from the nasal turbinates to the OB is lower in animals showing a reduced level of olfactory receptor neurons (ORN) induced by an olfactory epithelium lesion prior to the uranium inhalation exposure. These results give prominence to a role of the ORN in the direct transfer of the uranium from the nasal cavity to the brain.

DISTRIBUTION OF 137Cs IN RAT TISSUES AFTER VARIOUS SCHEDULES OF CHRONIC INGESTION

The aim of this work was to compare the distribution of 137Cs in organisms after chronic ingestion following different schedules. Rats were contaminated through drinking water containing 6,500 Bq L−1 of 137Cs, starting either at birth, at weaning, or upon reaching adult age (13 wk). Animals were then sacrificed after different durations of ingestion. 137Cs content of organs and excreta were determined by &ggr; counting. A slight decrease in 137Cs elimination through urine was observed according to the age of animals. All organs tested showed similar 137Cs content, with the exception of striated muscles and the thyroid at certain ages, which showed the highest accumulation of 137Cs. The lowest 137Cs concentration was found in the blood, which acts as a transfer compartment after absorption in the intestine. Substructures of the central nervous system showed a homogeneous level of 137Cs accumulation, except for the olfactive bulbs. In these structures, an increased concentration of 137Cs was observed, suggesting a possible direct route of intake through the nasal epithelium. Overall, these results are in agreement with current models for the biokinetics of 137Cs. However, these results also suggest that the thyroid should be taken into account in future models of 137Cs biokinetics.

Influence on the mouse immune system of chronic ingestion of 137Cs

The aim of this work was to determine the possible occurrence of damage to the immune system during the course of chronic ingestion of (137)Cs. BALB/C mice were used, with (137)Cs intake via drinking water at a concentration of 20 kBq l(-1). Adults received (137)Cs before mating and offspring were sacrificed at various ages between birth and 20 weeks. Phenotypic analysis of circulating blood cells and thymocytes did not show any significant modification of immune cell populations in animals ingesting (137)Cs as compared with control animals, with the exception of a slight increase in Treg percentage at the age of 12 weeks. Functional tests, including proliferative response to mitogens such as phytohaemagglutinin, response to alloantigens in mixed lymphocyte reaction and immunoglobulin response to vaccine antigens such as tetanus toxin and keyhole limpet haemocyanin did not show any significant functional modification of the immune system in (137)Cs-ingesting animals as compared with control animals. Overall, our results suggest that chronic ingestion of a low concentration of (137)Cs in drinking water in the long term does not have any biologically relevant effect on the immune system.