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Objective To characterize the oral toxicity of Shufeng Jiedu Capsule (SFJD) in SD rats during peri-weaning period, and provide reference for the clinical application of SFJD in infants. Methods Ten-day-old healthy SD rats were exposed to 0 and 4 g/kg of SFJD once per day for 14 d via intra-gastric administration. Mortality, general physical signs, body weights, spontaneous motor activity, learning and memory functions, hematology (with T and B lymphocyte subgroups included), serum chemistry, serum testosterone, insulin-like growth factor, organ weights, as well as gross pathological findings were evaluated between the control and exposure group. Physical development indicators such as pinna unfolding, coat growth, incisor eruption, and eyes opening time, were also recorded. The body length and tail length of rats under anesthesia were detected. Results After SFJD administration, loose stools and orange colored urine were found in rats, and the color of the urine was related to the color of drugs. The body weight growth rates were decreased compared with the control group. Urine specific gravity was increased in rats. RBC and Ret concentrations were decreased in two of the 16 tested animals. Liver, spleen, and kidney ratios to body and brain weight were increased in rats; The weight of spleen was also increased compared with the control group. Conclusion It was well tolerated to peri-weaning rats after the ig administration of 4 g/kg SFJD. The concerns of diarrhea, mild body weight growth rate, as well as RBC and Ret decrease should be noted for long term and high dose usage in infants and toddlers.
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Objective To learn the toxic effects on rats repeatedly exposed to dichloromethane by dermal route at the same dose for 28 days.Methods Seventy two Sprague Dawley rats were divided into six groups:a solvent control group (oliver oil),four exposure groups (0.75,1.5,3.0 and 6.0 g/kg·BW)and a recovery group.Each group included six female and six male rats.The exposure groups were dermal exposed to DCM at 1.5,3.0 and 6.0 g/kg·BW,6 hours/day,5 days/week for four weeks.The recovery group was dermal exposed to 6.0 g/kg BW of DCMduring the same period then recovered for 2 weeks.Clinical signs including body weight and food consumption of each group were observed.After rats were sacrificed,the hematological and serum biochemical parameters were determined.Histopathological examination was performed on selected tissues for all animals.Results The male rats in test groups including four exposure groups and a recovery group,showed decreased body weight gain.Neutrophilia and lymphocytopenia were determined in females of 3.0 and 6.0 g/kg BW groups and males of 1.5,3.0 and 6.0 g/kg BW groups by blood routine test (P <0.05).The mean levels of serum ALT and AST significantly increased in males of 3.0 and 6.0 g/kg BW groups (P <0.05).Only the mean level of serum TG in males of 6.0 g/kg BW group decreased (P <0.05).No significant differences of these indexes were shown in female rats of all exposure groups compared to control group.The exposure -related significant increases on the incidences of epidermis and dermis lesion,hepatocellular degeneration and necrosis were observed in test groups compared to the control group.The rats of recovery group were exhibited normal percentages of lymphocytes and neutrophils,levels of ALT,AST and TG. The skin and hepatocellular lesion were improved to some extent, but not recovered exactly.Conclusion In a 4 -week repeated -dose toxic study,DCM induce dose -related effects in rats involving skin lesion and liver injury with adverse changes in body weight gain of male rats,part parameters of hematology and serum biochemistry .
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Objective To observe toxic symptoms and signs , toxic damage extents and reversibility in rats after oral administration of Tangwang Mingmu granules .Methods Four dose groups with 40 rats in each group were designed in this study, including control group fed with distilled water and three groups at different dosages of the test drug .Tangwang Mingmu granules were orally administered to SD rats at the dosage of 8.4, 4.2 and 2.1 g/kg for 3 weeks and 14.0, 8.4 and 4.2 g/kg for 23 weeks, for 26 consecutive weeks .The general state of the rats was observed every day , while body mass and food consumption were calculated once a week .Halfway through and at the end of the administration (13 and 26 weeks) and after four weeks of recovery, parameters of body mass, hematology, hematological biochemistry, organ/body mass ratio and histopathology were measured .Results Compared with the control group at the same time-point, body mass of male rats in the other three groups was slightly reduced .Food consumption in high and medium dose groups was reduced (P<0.05), MCHC, ALT, TBIL and Na +in high dose group were decreased (P<0.05), TP, ALB and D-BIL were increased (P<0.05), the mean body mass and relative organ weight of thymus in medium dose male rats were decreased (P<0.05), relative organ weight of the liver and kidney in high dose male rats was increased (P<0.05), and focal chronic inflammation to different extent was observed in the liver , kidney and prostate gland .No dose-effect relationship was found in these perturbations that were all within the normal range of animals .No significant drug-related pathological changes were found.Conclusion The NOAEL of Tangwang Mingmu granules is considered to be 14.0 g/kg body mass/day (equal to 50 times the proposed clinical adult dosage ) for the 26-week repeated dose oral toxicity study in male andfemale rats.
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Objective To investigate the repeated dose toxicity of doxorubicin liposome injection and doxorubicin injection in rats. Methods Ninety SD rats ( body weight 180-220 g, male:female=1:1 ) were divided into 3 groups (30 rats in each group), and were administered intravenously with physiological saline, doxorubicin liposome injection (1 mg·kg-1 ) and doxorubicin injection ( 1 mg·kg-1 ) , respectively, once every three days for thirteen times. The body weight, blood biochemistry, hematology, organ coefficient and histopathology were analyzed for the overall toxicity assessment. Results The rats administered with doxorubicin liposome injection (1 mg/kg) showed hair loss and skin ulcer, significantly reduced growth of body weight, increased levels of urea nitrogen ( BUN ) , alanine aminotransferase ( ALT ) , blood platelet ( PLT ) , and kidney and heart coefficients, decreased thymus and testicular coefficients, myofibrillar rupture and lysis, and partial loss of cell nuclei, hyaline casts in the renal convoluted tubules, interstitial edema and loss of spermatogenic cells in the testicular tubules. Compared with the doxorubicin liposome injection group, similar abnormal changes were also observed in the doxorubicin injection group, but the hair loss and skin ulcer were milder and the heart and kidney toxicities were severer. Conclusions Compared with doxorubicin injection, the doxorubicin liposome injection causes milder heart and kidney toxicity but more serious skin toxicity.
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Objective: To re-evaluate the potential toxicity of Danshen Injection (DI) in Beagle's dogs by repeated iv injection. Methods: DI was iv given to the dogs at the doses of 0, 1.6, 5.4, and 16.0 g/(kg·d) (4 per sex per group) for 13 weeks. During the test period, the clinical signs, mortality, body weights, food consumption, rectal temperature, ophthalmoscopy, electrocardiography, urinalysis, hematology, serum biochemistry, organ weights, gross findings, and histopathology were examined. Results: Dogs iv given with DI at the doses of 0, 1.6, 5.4, and 16.0 g/(kg·d) for 13 weeks had no drug-related changes in mortality, body weight, food consumption, temperature, electrocardiography, ophthalmoscopy, urinalysis parameters, and organ weights. The hematological parameter data showed a significant decrease in red blood cells and hemoglobin concentration in the high-dose group and a significant increase in activated partial thromboplastin time suggesting an effect on haemopoiesis. For biochemical parameters, a significant decrease in glucose and a significant increase in total bilirubin were observed in the high-dose group, and the latter was considered to be toxicologically insignificant as lack of histopathological correlate. However, the histopathological examinations of the injection site showed that DI could cause dose-dependent focal inflammation. Conclusion: That the iv injection with DI into dogs at 16 g/(kg·d) for 13 weeks could cause the decreases in red blood cell parameters and glucose, as well as the lesions of the injection site. The no observed adverse effect level is 5.4 g/(kg·d), which suggests that safe clinical dosing be possible. © 2013 Tianjin Press of Chinese Herbal Medicines.
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The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent alpha-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.
Subject(s)
Animals , Mice , Rats , 1-Deoxynojirimycin , Biochemistry , Body Weight , Bombyx , Bone Marrow , Chromosome Aberrations , Diabetes Mellitus , Functional Food , Food, Organic , Hematology , Micronucleus Tests , Morus , Mutagenicity Tests , Organ Size , Rats, Sprague-Dawley , Toxicology , Urinalysis , DrinkingABSTRACT
In this study, aloe fermentation products were derived from mycelia from 3 mushrooms: Ganoderma lucidum (AG), Hericium erinaceum (AH), and Phellinus linteus (AP). Levels of aloin A and B increased with fermentation time. The highest levels were measured on the fifth day of fermentation. beta-Glucan levels decreased with fermentation time. The safety of aloe fermentation products were examined in male and female Sprague-Dawley rats. Rats were orally administered the three aloe fermentation products at dose levels of 1, 2 or 5 g/kg for single-dose toxicity test and 0.5, 1, or 2 g/kg for repeated-dose toxicity test. There were no significant differences in body weight gain between vehicle control and AG-, AH- or AP-treated rats. Also, significant changes in daily feed intake and water consumption were not observed. In hematological analysis, none of the parameters were affected by aloe fermentation products with mushroom mycelia. This suggests that there are no negative effects on homeostasis and immunity. In blood biochemistry analysis, none of the markers were affected by feeding rats with AG, AH or AP. Similarly, there were no significant effects on markers for liver, kidney, skeletal and heart muscle functions. No remarkable lesions were observed in these organs at histopathology. Since there were no adverse effects of AG, AH and AP in single- or repeated-dose toxicity tests, even at higher doses than normal, we conclude that the aloe fermentation products with mushroom mycelia possess long-term safety and could be candidates as multifunctional nutrients for the improvement of intestinal function and immunity.
Subject(s)
Animals , Female , Humans , Male , Rats , Agaricales , Aloe , Biochemistry , Body Weight , Drinking , Emodin , Fermentation , Homeostasis , Kidney , Liver , Myocardium , Rats, Sprague-Dawley , Reishi , Toxicity TestsABSTRACT
In repeated-dose 28-day oral toxicity study design, the low dose is fixed as the no observed effect level (NOEL). But, in practice the low dose usually shows significant difference in few measurable items in most of the studies. We investigated 109 of repeated-dose 28-day oral toxicity studies in rats conducted according to the Chemical Substance Control Law, Japan and examined the measurable items (functional observational battery, urinalysis, hematology, blood chemistry and absolute and relative organ weights) of the low dose group which showed a statistical significant difference (P<0.05) compared to the respective control groups. The investigation revealed that, 205/12,167 (1.6%) measurable items showed a significant difference in the low dose groups. The significant difference shown by urinalysis was high (3.3%), followed by clinical chemistry parameters, hematology, relative organ weights and absolute organ weights (1.8-1.1%). We conclude from the investigation that the low dose may be considered as NOEL, if the significant difference of measurable items of it is about 2% (maximum <5%), compared to the control. However, due consideration may be given to the clinical relevance of the items that showed a significant difference.
Subject(s)
Animals , Rats , Chemistry, Clinical , Hematology , Japan , Jurisprudence , No-Observed-Adverse-Effect Level , Organ Size , UrinalysisABSTRACT
In repeated-dose 28-day oral toxicity study design, the low dose is fixed as the no observed effect level (NOEL). But, in practice the low dose usually shows significant difference in few measurable items in most of the studies. We investigated 109 of repeated-dose 28-day oral toxicity studies in rats conducted according to the Chemical Substance Control Law, Japan and examined the measurable items (functional observational battery, urinalysis, hematology, blood chemistry and absolute and relative organ weights) of the low dose group which showed a statistical significant difference (P<0.05) compared to the respective control groups. The investigation revealed that, 205/12,167 (1.6%) measurable items showed a significant difference in the low dose groups. The significant difference shown by urinalysis was high (3.3%), followed by clinical chemistry parameters, hematology, relative organ weights and absolute organ weights (1.8-1.1%). We conclude from the investigation that the low dose may be considered as NOEL, if the significant difference of measurable items of it is about 2% (maximum <5%), compared to the control. However, due consideration may be given to the clinical relevance of the items that showed a significant difference.