Pharmacokinetics and toxicity evaluation following oral exposure to bisphenol F.

Bisphenol F is a substitute material for bisphenol A and is widely used in household products as a raw material for polycarbonate resin, epoxy resin, and plastic reinforcement. It is known to be mainly used in food containers, thermal paper for receipts, and coatings for water pipes. In some countries, bisphenol F has been detected in drinking water and human urine samples. However, due to the lack of safety evaluation data on bisphenol F, it is difficult to establish appropriate guidelines for the proper use of the substance, and social anxiety is increasing accordingly. This study investigated the use, exposure route, and distribution flow of bisphenol F, a household chemical. To determine the no-observed-adverse-effect level (NOAEL) and target organ of bisphenol F after exposure, a single-dose oral toxicity, dose-range finding (28 day oral), repeated dose toxicity (90 day oral), and genotoxicity (reverse mutation, chromosomal abnormality, in vivo micronucleus test) tests were performed. The pharmacokinetic profile was also obtained. The test results are as follows: in the pharmacokinetic study, it was confirmed that single oral exposure to BPF resulted in systemic exposure; in single oral dose toxicity test, the approximate lethal dose was found to be 4000 mg/kg and confusion and convulsion was shown in the test animals; NOAEL was determined to be 2 mg/kg/day for male and 5 mg/kg/day for female, and the no-observed-effect level (NOEL) was determined to be 2 mg/kg/day for males and 1 mg/kg/day for females, and the target organ was the small intestine; genotoxicity tests confirmed that BPF does not induce genotoxicity.

Acute and subacute repeated oral toxicity study of fragmented microplastics in Sprague-Dawley rats.

Polypropylene (PP) is the second most highly produced plastic worldwide, and its microplastic forms are found in water and food matrices. However, the effects of PP microplastics on human health remain largely unknown. Here, we prepared 85.2 µm-sized weathered PP (w-PP) microplastics by sieving the microplastic particles after fragmentation and accelerated weathering processes. The prepared particles are irregular in shape and no chemical additives including phthalates and bisphenol A were not released in simulated body fluids. Then, the w-PP samples were gavaged to rats for acute and subacute toxicity testing in accordance to the Organization for Economic Co-operation and Development (OECD) test guidelines under good laboratory practice regulations. The highest dose for gavaging to rats was 25 mg/kg bw/day, which was the maximum feasible dose based on the dispersibility of microplastics. Both toxicity testings for w-PP microplastics showed no adverse effects and mutagenicity. Thus, the no observed adverse effect level (NOAEL) of w-PP microplastics is higher than 25 mg/kg bw/day. Furthermore, the w-PP microplastics did not show any skin or eye irritation potentials in the 3-dimensional reconstructed human skin or corneal culture model. The dose of 25 mg/kg of w-PP microplastics is roughly equal to 2.82 × 105 particles/kg, which suggests that human exposure to w-PP microplastics in a real-life situation may not have any adverse effects.

Oral toxicity of titanium dioxide P25 at repeated dose 28-day and 90-day in rats.

BACKGROUND: Nanotechnology is indispensable to many different applications. Although nanoparticles have been widely used in, for example, cosmetics, sunscreen, food packaging, and medications, they may pose human safety risks associated with nanotoxicity. Thus, toxicity testing of nanoparticles is essential to assess the relative health risks associated with consumer exposure. METHODS: In this study, we identified the NOAEL (no observed adverse effect level) of the agglomerated/aggregated TiO2 P25 (approximately 180 nm) administered at repeated doses to Sprague-Dawley (SD) rats for 28 and 90 days. Ten of the 15 animals were necropsied for toxicity evaluation after the repeated-dose 90-day study, and the remaining five animals were allowed to recover for 28 days. The agglomerated/aggregated TiO2 P25 dose levels used included 250 mg kg- 1 d- 1 (low), 500 mg kg- 1 d- 1 (medium), and 1000 mg kg- 1 d- 1 (high), and their effects were compared with those of the vehicle control. During the treatment period, the animals were observed for mortality, clinical signs (detailed daily and weekly clinical observations), functional observation battery, weekly body weight, and food and water consumption and were also subjected to ophthalmological examination and urinalysis. After termination of the repeated-dose 28-day, 90-day, and recovery studies, clinical pathology (hematology, blood coagulation time, and serum biochemistry), necropsy (organ weights and gross findings), and histopathological examinations were performed. RESULTS: No systemic toxicological effects were associated with the agglomerated/aggregated TiO2 P25 during the repeated-dose 28-day, 90-day, and recovery studies in SD rats. Therefore, the NOAEL of the agglomerated/aggregated TiO2 P25 was identified as 1000 mg kg- 1 d- 1, and the substance was not detected in the target organs. CONCLUSION: Subacute and subchronic oral administration of the agglomerated/aggregated TiO2 P25 was unlikely to cause side effects or toxic reactions in rats.

Evaluation of subchronic oral dose toxicity and allergen of freeze-dried powder of Locusta migratoria (Orthoptera: Acrididae) as a novel food source.

The migratory locust, Locusta migratoria (Orthoptera: Acrididae), is a well-known edible insect which may serve as new source of human food and animal feed. However, potential toxicity and food safety of L. migratoria had not been investigated extensively until now. Therefore, in this study, we aimed to investigate toxicity of freeze-dried powder of L. migratoria (fdLM) and identify allergic components in ELISA and PCR techniques. In this subchronic study, fdLM was administered once daily by oral gavage at the doses of 750, 1500, and 3000 mg/kg/day. No toxicological changes were observed in both sexes of rats for 13 weeks in accordance with the OECD guidelines and GLP conditions. In addition, fdLM did not induced increases of serum immunoglobulin E and 21 homologous proteins were not detected under our present conditions. In conclusion, the NOAEL (no-observed-adverse-effect level) was 3000 mg/kg/day and no target organ was identified in both sexes. In conclusion, we found that fdLM is safe with no adverse effects and offers the potential of its use as an edible ingredient or other biological uses.

Establishment of particulate matter-induced lung injury model in mouse.

BACKGROUND: Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice. RESULTS: PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group. CONCLUSIONS: In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.

Subacute Oral Toxicity Evaluation of Freeze-Dried Powder of Locusta migratoria.

Novel food sources have enormous potential as nutritional supplements. For instance, edible insects are considered as an alternative food source due to their higher protein content; moreover, they are economically efficient reproducers and have high in nutritional value. In this study, we investigated the toxicity of the freeze-dried powder of Locusta migratoria (fdLM), known to contain rich proteins as well as fatty acids. The objective of the present study was to evaluate the subacute toxicity of fdLM in male and female Sprague-Dawley (SD) rats. The SD rats were divided into four groups based on the dosage of fdLM administered: dosage of 0 (vehicle control), 750, 1,500, and 3,000 mg/kg/day were administered for 28 days. Toxicological assessments including observations on food consumption, body and organ weights, clinical signs, mortality, ophthalmologic tests, urinalyses, hematologic tests, clinical chemistry tests, gross findings, and histopathology tests were performed. Clinical signs, urinalyses, hematology, serum biochemistry tests, and organ weight examinations revealed no fdLM-related toxicity. The no-observed-adverse-effect level for fdLM was higher than 3,000 mg/kg/day in rats of both sexes; therefore, fdLM, in conclusion, can be considered safe as an edible alternative human and animal food source material.

Ginsenosides Rg5 and Rk1 Enriched Cultured Wild Ginseng Root Extract Bioconversion of Pediococcus pentosaceus HLJG0702: Effect on Scopolamine-Induced Memory Dysfunction in Mice.

Wild ginseng is known to contain additional physiologically and pharmacologically active substances than common ginseng. The utilization of this herb can be maximized by altering its composition via tissue culture generating adventitious roots. We enriched the content of specific ginsenosides and investigated their role in ameliorating memory impairment. Cultured wild ginseng root was subjected to extraction, steaming, and fermentation using Pediococcus pentosaceus HLJG0702 to enhance the levels of ginsenosides Rg5 /Rk1. The analysis of product, HLJG0701, confirmed target ginsenosides. We analyzed the inhibitory effect of ginsenoside Rg5/Rk1, HLJG0701 and the raw material on acetylcholinesterase. Further, we performed Morris water maze, Y-maze, and passive avoidance tasks with mice exhibiting memory deficit induced by scopolamine, and we analyzed the concentrations of acetylcholinesterase and acetylcholine in their brains. Studies showed that the levels of ginsenosides Rg5 /Rk1, not found in the raw material, were enhanced in HLJG0701. Ginsenosides and HLJG0701 significantly inhibited acetylcholinesterase unlike the raw material. In all behavioral tasks, HLJG0701 showed memory improvement. It reduced acetylcholinesterase, whereas, it preserved acetylcholine in brain. In conclusion, cultured wild ginseng root extract fermented by P. pentosaceus HLJG0702 contains the distinctive ginsenosides Rg5/Rk1, which may ameliorate memory impairment via inhibition of acetylcholinesterase resulting in increased acetylcholine levels in the brain.