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Background: Few studies were found on the neurobehavioral toxicity of dinotefuran in mammals. This study was designed to evaluate the reproductive and neurobehavioral effects of maternal exposure to dinotefuran in mice. Methods: Dinotefuran was given in the diet at levels of 0% (control), 0.012% (18.2–50.6 mg/kg body weight [bw]/day), 0.03% (44.2–125.8 mg/kg bw/day), and 0.075% (111.3–311.0 mg/kg bw/day) in females (10/group) during the gestation (gestation day 1–5 to 15–19) and lactation periods (lactation day 0 to 24–28). Selected reproductive and neurobehavioral parameters were measured in the F1 generation. Results: Litter size and litter weight significantly increased in the high‐dose group. The average body weight of male and female offspring increased in treatment groups at postnatal day (PND) 21. In female offspring, surface righting on PND 4 was delayed in higher‐dose groups. Cliff avoidance on PND 7 was delayed in a dose‐related trend. The route of olfactory orientation on PND 14 was delayed in the high‐dose group. For exploratory behavior of the F1 generation, the frequencies of mice with urination increased in a dose‐related trend in male offspring. In female offspring, the related variables of rearing increased in dose‐related manners. The average rearing time lengthened and the number of defecations increased in the high‐dose group in adult males. In adult females, the rearing time shortened in the high‐dose group. Several variables differed in the high‐dose group for spontaneous behavior in adult females. Conclusions: The dose levels of dinotefuran produced several adverse effects on neurobehavioral parameters in mice. [ABSTRACT FROM AUTHOR]

The novel psychoactive compounds derived from amphetamine have been illegally abused as recreational drugs, some of which are known to be hepatotoxic in humans and experimental animals. The cytotoxic effects and mechanisms of 5-(2-aminopropyl)benzofuran (5-APB) and N-methyl-5-(2-aminopropyl)benzofuran (5-MAPB), both of which are benzofuran analogues of amphetamine, and 3,4-methylenedioxy- N-methamphetamine (MDMA) were studied in freshly isolated rat hepatocytes. 5-MAPB caused not only concentration-dependent (0-4.0 m m) and time-dependent (0-3 h) cell death accompanied by the depletion of cellular ATP and reduced glutathione and protein thiol levels, but also accumulation of oxidized glutathione. Of the other analogues examined at a concentration of 4 m m, 5-MAPB/5-APB-induced cytotoxicity with the production of reactive oxygen species and loss of mitochondrial membrane potential was greater than that induced by MDMA. In isolated rat liver mitochondria, the benzofurans resulted in a greater increase in the rate of state 4 oxygen consumption than did MDMA, with a decrease in the rate of state 3 oxygen consumption. Furthermore, the benzofurans caused more of a rapid mitochondrial swelling dependent on the mitochondrial permeability transition than MDMA. 5-MAPB at a weakly toxic level (1 m m) was metabolized slowly: levels of 5-MAPB and 5-APB were approximately 0.9 m m and 50 μ m, respectively, after 3 h incubation. Taken collectively, these results indicate that mitochondria are target organelles for the benzofuran analogues and MDMA, which elicit cytotoxicity through mitochondrial failure, and the onset of cytotoxicity may depend on the initial and/or residual concentrations of 5-MAPB rather than on those of its metabolite 5-APB. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233-239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (highdose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes. [ABSTRACT FROM AUTHOR]

The genotoxic effects of multi-walled carbon nanotubes (MWCNTs) were examined by using in vitro and in vivo assays. MWCNTs significantly induced micronuclei in A549 cells and enhanced the frequency of sister chromatid exchange (SCE) in CHO AA8 cells. When ICR mice were intratracheally instilled with a single dose (0.05 or 0.2 mg/animal) of MWCNTs, DNA damage of the lungs, analysed by comet assay, increased in a dose-dependent manner. Moreover, DNA oxidative damage, indicated by 8-oxo-7,8-dihydro-2′-deoxyguanosine and heptanone etheno-deoxyribonucleosides, occurred in the lungs of MWCNT-exposed mice. The gpt mutation frequencies significantly increased in the lungs of MWCNT-treated gpt delta transgenic mice. Transversions were predominant, and G:C to C:G was clearly increased by MWCNTs. Moreover, many regions immunohistochemically stained for inducible NO synthase and nitrotyrosine were observed in the lungs of MWCNT-exposed mice. Overall, MWCNTs were shown to be genotoxic both in in vitro and in vivo tests; the mechanisms probably involve oxidative stress and inflammatory responses. [ABSTRACT FROM AUTHOR]

Iron nanomaterials are of considerable interest for application to nanotechnology-related fields including environmental catalysis, biomedical imaging, drug delivery and hyperthermia, because of their superparamagnetic characteristics and high catalytic abilities. However, information about potential risks of iron nanomaterials is limited. The present study assessed pulmonary responses to a single intratracheal spray instillation of triiron tetraoxide nanoparticles (magnetite) in rats. Ten-week-old male and female Fischer 344 rats (n=5/group) were exposed to a single intratracheal spray instillation of 0 (vehicle), 5.0, 15.0 or 45.0 mg/kg body weight (BW) of magnetite. After 14 days, the rats were sacrificed, and biological consequences were investigated. The lung weights of the 15.0 and 45.0 mg/kg BW male and female groups were significantly higher than those of the control groups. The lungs of treated rats showed enlargement and black patches originating from the color of magnetite. The typical histopathological changes in the lungs of the treated rats included infiltration of macrophages phagocytosing magnetite, inflammatory cell infiltration, granuloma formation and an increase of goblet cells in the bronchial epithelium. The results clearly show that instilled magnetite causes foreign body inflammatory and granulating lesions in the lung. These pulmonary responses occur in a dose-dependent manner in association with the increase in lung weight. [ABSTRACT FROM AUTHOR]

Background: Few studies were found on the neurobehavioral toxicity of dinotefuran in mammals. This study was designed to evaluate the reproductive and neurobehavioral effects of maternal exposure to dinotefuran in mice., Methods: Dinotefuran was given in the diet at levels of 0% (control), 0.012% (18.2-50.6 mg/kg body weight [bw]/day), 0.03% (44.2-125.8 mg/kg bw/day), and 0.075% (111.3-311.0 mg/kg bw/day) in females (10/group) during the gestation (gestation day 1-5 to 15-19) and lactation periods (lactation day 0 to 24-28). Selected reproductive and neurobehavioral parameters were measured in the F 1 generation., Results: Litter size and litter weight significantly increased in the high-dose group. The average body weight of male and female offspring increased in treatment groups at postnatal day (PND) 21. In female offspring, surface righting on PND 4 was delayed in higher-dose groups. Cliff avoidance on PND 7 was delayed in a dose-related trend. The route of olfactory orientation on PND 14 was delayed in the high-dose group. For exploratory behavior of the F 1 generation, the frequencies of mice with urination increased in a dose-related trend in male offspring. In female offspring, the related variables of rearing increased in dose-related manners. The average rearing time lengthened and the number of defecations increased in the high-dose group in adult males. In adult females, the rearing time shortened in the high-dose group. Several variables differed in the high-dose group for spontaneous behavior in adult females., Conclusions: The dose levels of dinotefuran produced several adverse effects on neurobehavioral parameters in mice., (© 2022 Wiley Periodicals LLC.)

A chronic feeding study to evaluate the safety of genetically modified glyphosate-tolerant soybeans (GM soybeans) was conducted using F344 DuCrj rats. The rats were fed diet containing GM soybeans or Non-GM soybeans at the concentration of 30% in basal diet. Non-GM soybeans were a closely related strain to the GM soybeans. These two diets were adjusted to an identical nutrient level. In this study, the influence of GM soybeans in rats was compared with that of the Non-GM soybeans, and furthermore, to assess the effect of soybeans themselves, the groups of rats fed GM and Non-GM soybeans were compared with a group fed commercial diet (CE-2). General conditions were observed daily and body weight and food consumption were recorded. At the termination (104 weeks), animals were subjected to hematology, serum biochemistry, and pathological examinations. There were several differences in animal growth, food intake, organ weights and histological findings between the rats fed the GM and/or Non-GM soybeans and the rats fed CE-2. However, body weight and food intake were similar for the rats fed the GM and Non-GM soybeans. Gross necropsy findings, hematological and serum biochemical parameters, and organ weights showed no meaningful difference between rats fed the GM and Non-GM soybeans. In pathological observation, there was neither an increase in incidence nor any specific type of nonneoplastic or neoplastic lesions in the GM soybeans group in each sex. These results indicate that long-term intake of GM soybeans at the level of 30% in diet has no apparent adverse effect in rats.

A chronic feeding study to evaluate the safety of the genetically modified glyphosate-tolerant soybeans (GM soybeans) was conducted using rats. F344 DuCrj rats were fed diet containing GM soybeans or Non-GM soybeans at the concentration of 30% in basal diet. Non-GM soybeans were closely related strain of GM soybeans. These two diets were adjusted to an identical nutrient level. In this study, the influence of GM soybeans on rats was compared with that of the Non-GM soybeans, and furthermore, to assess the effect of soybeans themselves, the groups of rats fed GM and Non-GM soybeans were compared with a group fed commercial diet (CE-2). General conditions were observed daily and body weight and food consumption were recorded. At the intermediate examination (26 weeks), and at the termination (52 weeks), animals were subjected to hematology, serum biochemistry, and pathological examination. There were several differences in animal growth, food intake, serum biochemical parameters and histological findings between the rats fed the GM and/or Non-GM soybeans and the rats fed CE-2. However, body weight and food intake were similar for the rats fed the GM and Non-GM soybeans. Gross necropsy findings, hematological and serum biochemical parameters, organ weights, and pathological findings showed no meaningful difference between rats fed the GM and Non-GM soybeans. These results indicate that long-term intake of GM soybeans at the level of 30% in diet has no apparent adverse effect in rats.