Two-Generation Oral (Diet) Reproductive Toxicity Study of Resorcinol Bis-Diphenylphosphate (Fyrolflex RDP) in Rats

2000 ◽  
Vol 19 (4) ◽  
pp. 243-255 ◽  
Author(s):  
R. Henrich ◽  
B. M. Ryan ◽  
R. Selby ◽  
S. Garthwaite ◽  
R. Morrissey ◽  
...  
Keyword(s):  
Body Weight ◽  
Sperm Count ◽  
Clinical Signs ◽  
Control Group ◽  
High Dose ◽  
Test Substance ◽  
Sprague Dawley ◽  
Mating Period ◽  
Flavor Aversion ◽  
Significant Difference

Fyrolflex resorcinol bis-diphenylphosphate (RDP) was evaluated in a two-generation reproductive study as part of a program to assess the overall toxicology of this flame retardant. RDP was administered to male and female Sprague-Dawley rats in the diet at concentrations of 1000, 10,000 or 20,000 ppm. The control group was given diet alone. Parental (P1) animals were treated for 10 weeks prior to mating, during the 2-week mating period, throughout gestation, and through lactation until sacrifice. The F1 generation (P1 offspring) was treated following a regimen similar to P1. The F2 generation was not treated. No significant difference in Utter survival was observed between the control and treated groups. Body weights were significantly decreased in P1 rats during the 1st week due to an initial flavor aversion of the test substance in the diet. Body weight, weight gains, and food consumption were decreased in the test substance-treated pups (F1) during lactationand after weaning. These changes were also attributed to a flavor aversion. Anogenital distance was similar in the control and high-dose groups, whereas vaginal opening and preputial separation were delayed in the 10,000 and 20,000 ppm groups, and were considered to be secondary to the reduction in F1 body weight. Neither parents nor offspring exhibited any test substance-related clinical signs of toxicity. Vaginal cytology and cyclicity and male reproductive functions (sperm count, motility, and morphology) were unaffected by treatment. Mating performance was similar in the treated groups relative to the control. No treatment-related lesions were noted in the reproductive organs. Increased liver weight and associated hepatic periportal hypertrophy were observed in the RDP-treated animals (P1 and F1). In conclusion, there were no adverse effects on reproductive performance or fertility parameters associated with RDP administration in the diet. Fyrolflex RDP administered for greater than 13 weeks and up to the entire life span (i.e., F1, from conception to euthanasia) resulted in increased liver weights with associated periportal hypertrophy. This change was considered an adaptive process associated with RDP metabolism in the liver.

Studies of the Toxicological Potential of Capsinoids: IV. Teratology Studies of CH-19 Sweet Extract in Rats and Rabbits

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 41-57 ◽  
Author(s):  
Bruce K. Bernard ◽  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Body Weight ◽  
Sex Ratio ◽  
Food Consumption ◽  
Clinical Signs ◽  
Pathological Finding ◽  
High Dose ◽  
Corpora Lutea ◽  
Test Substance ◽  
Sprague Dawley ◽  
Adverse Effect Level

In order to evaluate the safety of CH-19 Sweet extract that contains capsinoids, teratology studies were conducted in pregnant Sprague-Dawley rats (20 rats per group) and pregnant New Zealand white rabbits (17 to 22 animals per group). The test substance was administered to rats by gavage for 11 days on gestation days 7 to 17 at doses of 0 (vehicle), 1.25, 2.5, and 5.0 ml/kg and to rabbits for 13 days on gestation days 6 to 18 at doses of 0 (vehicle), 0.25, 0.5, and 1.0 ml/kg. As the concentration of capsinoids in CH-19 Sweet extract was 72.2 to 75.05 mg/ml, the resulting dose of capsinoids administered to rats was 90.25, 180.5, and 361 mg/kg, and to rabbits was 18.76, 37.53, and 75.05 mg/kg in the vehicle, low-, mid-, and high-dose groups, respectively. In the rat study, no deaths occurred in any group and there were no test substance–related changes or abnormalities in clinical signs, body weight, food consumption, or gross pathological findings. There were no test substance–related changes in the number of corpora lutea, number or index of implantations, index of embryofetal deaths, number of live fetuses, sex ratio, fetal body weight at the end of the gestation period, or abnormalities in the placenta of live fetuses. There were no test substance–related abnormalities or variations in the external, skeletal, or visceral examinations of live fetuses. It was concluded that the test article caused neither teratogenic effects nor abnormalities in the progression of ossification. In the rabbit study, there were no test substance–related effects on clinical signs, body weight, food consumption, or necropsy findings. There were neither test substance–related abortions nor test substance–related effects on the number of corpora lutea, or number or index of implantations. There were no test substance–related effects on the number of dead embryos/fetuses, the number of live fetuses, sex ratio, body weight of live fetuses, or gross pathological finding in the placentas. There were no test substance–related external abnormalities or incidences of visceral or skeletal abnormalities or variations, and there were no test substance–related effects on the progress of ossification in any group. The authors concluded the no observed adverse effect level (NOAEL) of CH-19 Sweet extract containing capsinoids on pregnant animals and fetal development/growth was >5.0 ml/kg/day (>361 mg/kg/day as capsinoids) in rats and >1.0 ml/kg/day (>75.05 mg/kg/day as capsinoids) in rabbits.

scholarly journals The Effect of Single and Triple Testicular Biopsy Using Biopty Gun on Spermatogenesis in Pubertal Rats

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1569
Author(s):  
Tomislav Šušnjar ◽  
Ivana Kuzmić Prusac ◽  
Ivan Švagelj ◽  
Anđela Jurišić ◽  
Tomislav Šušnjar ◽  
...  
Keyword(s):  
Sperm Count ◽  
Semen Analysis ◽  
Study Groups ◽  
Testicular Biopsy ◽  
Male Rats ◽  
Lower Percentage ◽  
Control Group ◽  
Sprague Dawley ◽  
Left Testis ◽  
Significant Difference

Background: The aim of this study was to compare consequences in single and triple testicular biopsy by biopty gun in pubertal rats using histological and immunohistochemical analysis. Methods: Thirty-two Sprague-Dawley male rats were used as the experimental model. The rats were randomly divided into three study groups. The rats from the first group (n = 12) received a single-biopsy of upper pole of the left testis, while the rats from the second group (n = 10) received triple-biopsy of upper and lower poles and lateral surface of left testis. The third group (n = 10) was a control group. On the eightieth day after the biopsy in all rats bilateral orchiectomy and funiculectomy were performed to obtain testicular tissue and sperm for analysis. The consequences of the puncture were observed by pathohistology, immunohistochemistry and semen analysis. Results: The results of the study showed lower percentage of sperm count (14.5 mill/mL vs. 16 mill/mL, p = 0.130), sperm motility (24.6% vs. 32.7%, p > 0.05), abnormal sperm (30% vs. 27%, p > 0.05), atrophic tubules (21% vs. 6%, p < 0.001), volume (1.7 mL vs. 2.28 mL, p < 0.01) and apoptotic index (1.56 vs. 1.19, p = 0.650) in the testes with a triple-biopsy compared to the testes with a single-biopsy. Semen analysis showed a borderline significant difference between the group with triple-biopsy where sperm count was lower than it in the control group (14.5 mill/mL vs. 17.5 mill/mL, p = 0.05). A single-biopsy has little effect on the testis, especially on overall fertility. A triple-biopsy showed higher degree of the testicular damage but without a significant impact on overall fertility. Semen analysis showed that single- and triple-biopsies did not have a significant effect on sperm count, motility and morphology. Conclusion: Biopty gun procedure is a cheap, simple and reliable method for testicular biopsy in rats without a significant effect on sperm count, motility and morphology.

scholarly journals Toxicity Evaluation of a Traditional Polyherbal Unani Formulation Jawarish Shahi in Rats

2018 ◽  
Vol 7 (5) ◽  
pp. 412-418
Author(s):  
Mohd Urooj ◽  
◽  
Mohammad Ahmed Khan ◽  
G. Thejaswini ◽  
Munawwar Husain Kazmi ◽  
...  
Keyword(s):  
Body Weight ◽  
Feed Intake ◽  
Clinical Signs ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Male And Female ◽  
Salix Caprea ◽  
Male And Female Rats ◽  
Dose Levels

Jawarish Shahi (JS) is a compound polyherbal Unani pharmacopoeial formulation indicated for Khafqan (Palpitation), Nafkh-e-Shikam (Flatulence) and Waswas (Insanity; false perception and hallucinations). Jawarish Shahi contains herbs like Halela (Terminalia chebula), Amla (Emblica officinalis), Kishneez (Coriandrum sativum), Elaichi Khurd, (Elettaria cardamomum), and Bed Mushk (Salix caprea). The present study was carried out as per OECD 408 guidance to evaluate 90 days repeated oral dose toxicity in male and female Sprague Dawley rats. The study was performed at dose levels 1028 and 2000 mg/kg bw. No adverse effects were reported with respect to body weight, feed intake, behavior and clinical signs indicative of systemic toxicity. The expected growth pattern was observed in body weight and feed intake as compared to control group at both dose levels in male and female rats. There were few significant alterations with respect to hematology, and clinical biochemistry, however the results were within normal range thus considered toxicologically insignificant. The microscopic examination of different organ/tissue showed that no histopathological changes were observed. The findings of the study showed that No Observed Adverse Effect Level (NOAEL) for JS is greater than 2000 mg/kg body weight

scholarly journals Thirteen-Week Oral Toxicity Study of HVC1 in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Kyungjin Lee ◽  
Ho-Young Choi
Keyword(s):  
Hematological Parameters ◽  
Clinical Signs ◽  
Ethanol Extract ◽  
New Drugs ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Weight Changes ◽  
Oral Toxicity ◽  
Blood Biochemical

Studies on the safety of herbal medicine are essential for the development of new drugs. The aim of this study was to evaluate the no-observed-adverse-effect-level (NOAEL) of HVC1 (Gamisamhwangsasim-tang, a 30% ethanol extract of a mixture of Pruni Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rhei Rhizoma) and identify its target organs after oral administration to Sprague-Dawley (SD) rats repeatedly for 13 weeks. Three test groups were treated with HVC1 at a dose of either 500 (low-dose), 1,000 (middle-dose), or 2,000 (high-dose) mg/kg/day. Another group received high-dose HVC1 and was observed for 4 weeks following treatment to examine recovery from the effects of the extract. All treatment groups were compared to a vehicle control group. During the study, mortality, clinical signs, body weight changes, food consumption, abnormal lesions in the eye, urinary parameters, hematological parameters, blood coagulation time, blood biochemical parameters, changes in organ weight, gross findings, and histopathological changes were examined. No systemic toxicity related to HVC1 was observed in any group, and it was concluded that the NOAEL of HVC1 was 2,000 mg/kg/day. No target organ was identified.

scholarly journals Enhanced intestinal 2-deoxy-2-[18F]fluoro-D-glucose uptake under metformin is not fully suppressed by loperamide

2018 ◽  
Vol 52 (4) ◽  
pp. 185-191
Author(s):  
Tomomi Nobashi ◽  
Tsuneo Saga ◽  
Yuji Nakamoto ◽  
Yoichi Shimizu ◽  
Sho Koyasu ◽  
...  
Keyword(s):  
Body Weight ◽  
Small Intestine ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Fdg Uptake ◽  
Significant Difference ◽  
Mouse Small Intestine ◽  
Long Acting ◽  
And Control

AbstractObjective. This study investigated whether the metformin (Met)-induced enhanced intestinal uptake of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) is reduced by loperamide, a long-acting anti-diarrheal agent. Methods. Mean18F-FDG uptake in the mouse small intestine and colon with Met exposure was compared with that in control mice. In the Met group, high-dose (1.0 mg/kg body weight) and low-dose (0.1 mg/kg body weight) loperamide were introduced, and18F-FDG uptake in the small intestine and colon was compared with that of control mice administered high-dose loperamide. The percent injected dose of18F-FDG per gram of tissue (%ID/g) in the extracted tissues was then determined. Results.18F-FDG uptake increased significantly in the small intestine (0.64±0.06 vs. 1.01±0.15, p=0.040) and, especially, the colon (0.46±0.13 vs. 2.16±0.51, p<0.001) after Met exposure. Neither high-dose nor low-dose loperamide significantly reduced18F-FDG uptake in the small intestine (0.82±0.31 vs. 0.84±0.22, p=0.93 and 0.78±0.25 vs. 0.70±0.15, p=0.13, respectively) or colon (2.13±0.41 vs. 1.67±0.55, p=0.063 and 1.77±0.39 vs. 1.80±0.25, p=0.56, respectively). The colonic %ID/g was significantly higher in Met groups irrespective of loperamide introduction than in control group, whereas the significant difference in the small intestine was observed only between Met and control groups. Conclusion. Metformin increased18F-FDG uptake in intestines especially in colon. Loperamide administration partially, but not sufficiently, suppresses the Met-induced increased colonic uptake of18F-FDG.

scholarly journals Acute and Subchronic Toxicity Study ofEuphorbia hirtaL. Methanol Extract in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kwan Yuet Ping ◽  
Ibrahim Darah ◽  
Yeng Chen ◽  
Subramaniam Sreeramanan ◽  
Sreenivasan Sasidharan
Keyword(s):  
Body Weight ◽  
Toxicity Study ◽  
Morphological Alteration ◽  
Control Group ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Methanolic Extracts ◽  
Sprague Dawley Rats ◽  
Significant Difference

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.

Lack of Oncogenicity of Wood Creosote, the Principal Active Ingredient of Seirogan, an Herbal Antidiarrheal Medication, in Sprague-Dawley Rats

2001 ◽  
Vol 20 (5) ◽  
pp. 297-305 ◽  
Author(s):  
Tomoo Kuge ◽  
Takashi Shibata ◽  
Michael S. Willett ◽  
Patricia Turck ◽  
Karl A. Traul
Keyword(s):  
Body Weight ◽  
Dose Level ◽  
Active Ingredient ◽  
Clinical Signs ◽  
Clinical Pathology ◽  
Maximum Tolerated Dose ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Wood Creosote

Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021–39–4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non-neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote.

scholarly journals Vitamin D Supplementation in Laboratory-Bred Mice: An In Vivo Assay on Gut Microbiome and Body Weight

2020 ◽  
Vol 13 ◽  
pp. 117863612094529
Author(s):  
Lorina Ineta Badger-Emeka ◽  
Zainab Yaseen AlJaziri ◽  
Cereen Fahad Almulhim ◽  
Asma Saleh Aldrees ◽  
Zainab Hamzah AlShakhs ◽  
...  
Keyword(s):  
Vitamin D ◽  
Body Weight ◽  
Vitamin D Supplementation ◽  
The Body ◽  
Automated System ◽  
Control Group ◽  
High Dose ◽  
Bacterial Colony ◽  
Normal Dose ◽  
Significant Difference

Saudi Arabia is in a tropical geographical region with a population that has access to adequate diet. There is, however, a high level of vitamin D deficiency in the Kingdom, comorbid with other disease. There is the postulation of a correlation between a healthy gut microbiota and balanced levels of serum vitamin D. This investigation looks into the effect of vitamin D supplementation on the gut flora of laboratory-bred mice as well as any possible association on body weight. BALB/C mice weighing between 34 and 35.8 g were divided into 4 groups and placed on daily doses of vitamin D of 3.75 µg (low dose), 7.5 µg (normal dose), and 15 µg (high dose). The fourth group was the control group that did not receive any supplementation with vitamin D. Body weights were monitored on weekly basis, while faecal samples from the rectum were obtained for microbial culturing and the monitoring of bacterial colony count using the Vitek 2 Compact automated system (BioMerieux, Marcy-l’Etoile, France) according to manufacturer’s guidelines. The data presented as mean ± SD, while significant differences were determined with 2-way analysis of variance in comparing differences within and between treatment groups. The different doses of vitamin D showed varying effects on the body weight and gut microbial colonies of the mice. There was a highly significant difference between the control, 15 µg (high), and 7.5 µg (normal) dose groups. This is suggestive that supplementation with vitamin D could a role in the gut microbial flora in the gut which could reflect in changes in body weight.

scholarly journals ACUTE DERMAL TOXICITY STUDY OF ARECA CATECHU LINN. EXTRACT IN SPRAGUE-DAWLEY RATS

2016 ◽  
Vol 9 (9) ◽  
pp. 209
Author(s):  
Liza Meutia Sari ◽  
Frans D Suyatna ◽  
Gus Permana Subita ◽  
Elza Ibrahim Auerkar
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Lethal Dose ◽  
Clinical Signs ◽  
Treated Group ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Dermal Toxicity ◽  
Areca Catechu

ABSTRACTObjective: Areca catechu Linn. or biji pinang is one of the most widely used psychoactive substance with several hundred million users worldwide,predominantly in Southern Asia. However, details of the dermal toxicity of A. catechu L. are still undiscovered. The objective of this study is toinvestigate the in vivo acute dermal toxicity of aqueous extract of A. catechu L. at dose 15,000 mg/kg body weight in Sprague-Dawley rats.Methods: The acute dermal toxicity of A. catechu L. nut extract was investigated in rats, as per OECD Guidelines 402 for acute toxicity protocols. Thebody weight, possibility of death, general signs, and behavior activity parameters were measured for 14 days to ascertain the median lethal dose(LD50) of the extract. At the end of the study, all the animals in all the treated group were sacrificed.Results: The LD50 was found to be >15,000 mg/kg body weight. There was significant weight increase (p<0.05) in treated group when comparedto control group. No mortality was observed during whole 14 days study period. A single dose of 15,000 mg/kg of body weight did not producetreatment-related signs of toxicity in any of animal tested.Conclusion: A single dermal dose to A. catechu L. aqueous extract had no toxic effects on mortality, clinical signs, body weight changes, and grossfindings in female rats at a dose of 15,000 mg/kg of body weight. Subsequently, the concentrate can be employed for pharmaceuticals nutrient plants.Keywords: A. catechu L., Acute dermal toxicity, LD50.

scholarly journals Impact of Moriamin Forte on Testicular and Epididymal Damage in Rats with Oligoasthenospermia

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xing Zhou ◽  
Guo-Wei Zhang ◽  
Wei-Ning Liang ◽  
Yi-Ze Li ◽  
Song Xu ◽  
...  
Keyword(s):  
Group Treatment ◽  
Sperm Count ◽  
Testicular Tissue ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Antioxidase Activity ◽  
Motility Of Sperm ◽  
Related Proteins

To investigate the effect and mechanism of action of Moriamin Forte (MF) on oligoasthenospermia (OA) in rats exposed to multiglycosides of Tripterygium wilfordii (GTW), forty male Sprague Dawley rats were randomly divided into four groups. Rats in the control group were treated with 0.5% sodium carboxymethyl cellulose. The remaining rats were administered GTW (30 mg/kg/d) for 40 d to establish an OA model. Concurrently, the groups were treated with normal saline and low-dose (100 mg/kg/d) and high-dose (200 mg/kg/d) MF, respectively. After treatment, the number and motility of sperm cells were examined. Testicular and epididymal histomorphology changes were observed. Antioxidant indicators (SOD, CAT, MDA, TAC, and Nrf2) in testicular and epididymal tissues were detected. Apoptotic and antiapoptotic indicators (Bax and Bcl2 expression) in the testicular tissue were measured by immunohistochemistry. GTW decreased sperm count and motility, damaged testicular and epididymis tissues, impaired antioxidase activity, and increased tissue MDA levels. Meanwhile, GTW upregulated the expression of Bax and downregulated the expression of Bcl2. Western blot analysis demonstrated a decrease in the Nrf2 expression in the model group. Treatment with MF improved sperm count and motility, as well as inhibited the rate of apoptosis in the rat reproductive system. Moreover, MF improved the activity of antioxidants and increased the relative expression of the antioxidant pathway-related protein Nrf2. In conclusion, MF may reverse the GTW-induced OA by modulating the expression of apoptotic and antioxidant pathway-related proteins. This study may provide a pharmacological foundation for the use of MF in OA treatment.

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