Abstract
There is much contradiction between different experimental studies on beryllium (Be) toxicity. The majority of studies focus on occupational pathologies, caused by the exposure to Be dust. However, Be pollution may affect wide population groups through other exposure routes. The discrepancies between experimental studies may be attributed to the lack of adequate Be toxicity model since conventional administration routes are hampered by high acidity and low solubility of Be compounds. This study was aimed to develop a novel way to implement Be toxicity avoiding side effects, related to high acidity or low solubility of Be salts. Intraperitoneal injection of Be–glycine composition (containing BeSO4, glycine, purified water, pH adjusted to 5.5 with NaOH) was tested in the dose range 238–7622 µmol Be kg−1 (body weight, b/w) in full-grown Wistar male rats. The model provided reliable uptake of Be from the peritoneum into general circulation for at least 48 h. LD50 was found to be 687 µmol Be kg−1 (b/w). The established LD50 value differed from previous data on gastrointestinal, intramuscular or intravenous administration of Be compounds. The liver was found to act as a primary elimination route for Be and related to the highest Be content in the animal. However, it had no signs of morphological damage, which was observed only in the testes (deterioration of germinal epithelium). At the same time, the lungs, stated as a primary target tissue for Be in the models of chronic beryllium disease, did not show strong Be accumulation nor morphological changes. Survived animals showed behavioral changes, including increased motor activity and aggressive reactions in some cases, and complete spasticity in other. The obtained data show the applicability of the established modeling protocol and testified for the independence of chronic beryllium disease on Be2+ ion toxicity per se.
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The study was partially supported by the Russian Science Foundation, Grant no. 18-73-00055.
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All procedures of the study involving animals were approved by the Local Bioethics Committee of the Institute of Toxicology of Federal Medico-Biological Agency (Protocol no. 3/17, dated 25.04.2017); handling and manipulations of the animals were conducted in accordance with the ethical regulations in order to reduce the suffering.
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Drobyshev, E., Kybarskaya, L., Dagaev, S. et al. New insight in beryllium toxicity excluding exposure to beryllium-containing dust: accumulation patterns, target organs, and elimination. Arch Toxicol 93, 859–869 (2019). https://doi.org/10.1007/s00204-019-02432-7
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DOI: https://doi.org/10.1007/s00204-019-02432-7