Subacute and Subchronic Oral Toxicity of p-Chlorotoluene in the Rat

1990 ◽  
Vol 9 (5) ◽  
pp. 487-495
Author(s):  
James B. Terrill ◽  
Merrel Robinson ◽  
Gary W. Wolfe ◽  
Leonard H. Billups
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Dose Group ◽  
Corn Oil ◽  
Clinical Laboratory ◽  
Clinical Signs ◽  
High Dose Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Oral Toxicity

p-Chlorotoluene was administered by corn oil gavage for 14 and 90 days to male and female Sprague-Dawley-derived rats at dosages of 200, 600, and 1800 mg/kg per day and 50, 200, and 800 mg/kg per day, respectively. In the 14-day study, 8 of 10 animals of each sex in the high-dose group died due to treatment. Other treatment-related signs for these animals included an adverse effect upon body weight and clinical signs of salivation, tremors, and prostration. In the 200 and 600 mg/kg per day groups there were no apparent treatment-related effects. In the 90-day study, 4 of 10 males and 2 of 10 females in the high-dose group died due to treatment. Other signs for this treatment group included an adverse effect upon body weight and clinical signs of languid behavior, prostration, tremors, sensitivity to touch, epistaxis, and respiratory distress. Increases in alkaline phosphatase and creatinine (males only), and increases in adrenal (absolute and relative, females), kidney (relative, both sexes), and liver (relative, both sexes) weights were also noted. Histopathologic findings of centrilobular hepatocellular hypertrophy, adrenal cortical hyperplasia, and exacerbation of chronic progressive nephropathy confirmed the clinical laboratory and organ weight results as being treatment related for the animals receiving 800 mg/kg per day for 90 days. Animals receiving 50 or 200 mg/kg per day (90 days) did not exhibit treatment-related findings.

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.

Subchronic Hepatotoxicity Evaluation of 1,2,4-Tribromobenzene in Sprague-Dawley Rats

2012 ◽  
Vol 31 (3) ◽  
pp. 250-256 ◽  
Author(s):  
Darol E. Dodd ◽  
Linda J. Pluta ◽  
Mark A. Sochaski ◽  
Kathleen A. Funk ◽  
Russell S. Thomas
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Exposure Time ◽  
Clinical Signs ◽  
Liver Weight ◽  
Sprague Dawley ◽  
Significant Incidence ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Male Sprague-Dawley rats were exposed to 1,2,4-tribromobenzene (TBB) by gavage for 5 days, 2, 4, and 13 weeks at 0, 2.5, 5, 10, 25, or 75 mg/kg per d. There were no TBB exposure-related clinical signs of toxicity or changes in body weight. Liver weight increases were dose and exposure time related and statistically significant at ≥10 mg/kg per d. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were dose and time related. The 75 mg/kg per d group had minimally increased mitoses within hepatocytes (5 days only). Hepatocyte vacuolation was observed (13 weeks) and was considered TBB exposure related at ≥25 mg/kg per d. Concentrations of blood TBB increased linearly with dose and at 13 weeks, ranged from 0.5 to 17 µg/mL (2.5-75 mg/kg per d). In conclusion, rats administered TBB doses of 10-75 mg/kg per d for 13 weeks had mild liver effects. A no observed adverse effect level of 5 mg/kg per d was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥10 mg/kg per d.

scholarly journals Role of Pediococcus Acidilactici J9 in Decreasing the Occurrence of Gastritis Caused by H.pylori Infection and Two-week Repeated-dose Oral Toxicity Study in Mice

2020 ◽  
Author(s):  
Mijung Lee ◽  
Jin-Young Chung ◽  
Ka Yeun Kim ◽  
Wooseok Im ◽  
Manho Kim
Keyword(s):  
Dose Group ◽  
Clinical Signs ◽  
Dosage Level ◽  
Repeated Dose ◽  
High Dose ◽  
Pediococcus Acidilactici ◽  
Oral Toxicity ◽  
Gastric Cancer Cells ◽  
Male And Female ◽  
Female Mice

Abstract BACKGROUND Helicobacter pylori (H. pylori) is an important pathogen that causes chronic gastritis and peptic ulcer, and is related to the development of gastric carcinoma. Several chemicals, including antibiotics, have been used to eradicate H.pylori. However, more studies are yet requred to accomplish a sufficient therapy. Pediococcus acidilactici J9 were studied for inhibition of binding of H.pylori binding to human gastric cell lines. This study was performed in order to investigate the repeated-dose toxicity of Pediococcus acidilactici J9 in male and female mice.RESULTS C57BL/6 male and female Mus musculus were divided into four groups (n = 10 in each group). Pediococcus acidilactici J9 was administered daily by oral injection of vehicle control at dosage levels to a low-dose group (500 mg/kg/day), middle-dose group (1000 mg/kg/day), and high-dose group (2000 mg/kg/day) for two weeks. After 14 days of exposure, the blood biochemistry and hematology were investigated, along with a histopathology exam. There were no bacterial-related deaths or abnormal clinical signs in either gender of mouse. The data was observed during the period in terms of body weight, food, intake, and water consumption. Also, no alterations in organ weights upon administration of Pediococcus acidilactici J9 alone were observed.CONCLUSIONS These results suggest that the oral application of Pediococcus acidilactici J9, up to a dosage level of 2,000 mg/kg/day, causes no adverse effects in both male and female mice. Pediococcus acidilactici J9 inhibits the adhesion of H.pylori to AGS gastric cancer cells. When used as probiotics, Pediococcus acidilactici J9 may help decrease the occurrence of gastritis and reduce the risk of H.pylori infection with promising safety issues.

scholarly journals A 90-Day Oral Toxicity Study of the Ethanol Extract from Eupatorium japonicum Thunb and Foeniculum vulgare in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Guangcheng Dai ◽  
Chenglu Wang ◽  
Wei Tang ◽  
Jiangyun Liu ◽  
Boxin Xue
Keyword(s):  
Body Weight ◽  
Safety Information ◽  
Clinical Signs ◽  
Ethanol Extract ◽  
Male Rats ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Foeniculum Vulgare ◽  
Hematological Indices ◽  
Eupatorium Japonicum

Eupatorium japonicum Thunb and Foeniculum vulgare are two of the most widely used folk herbs and constituents in many traditional Chinese herbal formulas. Nonetheless, little toxicological and safety information associated with following daily repeated exposure is obtained according to previous research. The present study was performed to assess the toxicity of ethanol extract from Eupatorium japonicum Thunb and Foeniculum vulgare (EFE) in male rats administered by dietary oral gavage at target doses of 0.39, 0.78, and 1.56 g/kg body weight/day for 90 days. There were no significant adverse effects on clinical signs, body weight, food conversion efficiency, and vital hematological indices. However, some hematology and biochemical indices such as WCV, MCH, MCHC, LY, MPV, T-CHO, as well as TG revealed significant changes in Sprague–Dawley rats and organ weights in lung and spleen showed diminished in male rats. Necropsy and histopathology findings suggested that no significant differences in absolute weights were found in all organs except lung and spleen, and no treatment-related alteration was identified in any organs. All results obtained in the present study indicated that the proper use of EFE in traditional medicine at oral dosages up to 1.56 g/kg/day body weight may harbor no prolonged toxicity to rats. However, further studies of EFE are still necessary to assess its oral safety in patients.

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.

Evaluation of the Developmental Toxicity of Acetyl Cedrene

2006 ◽  
Vol 25 (5) ◽  
pp. 423-428 ◽  
Author(s):  
Aurelia Lapczynski ◽  
Daniel A. Isola ◽  
Mildred S. Christian ◽  
Robert M. Diener ◽  
Anne Marie Api
Keyword(s):  
Body Weight ◽  
Soft Tissue ◽  
Corn Oil ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Body Weights ◽  
Weight Gains

The developmental toxicity of acetyl cedrene (AC), a widely used fragrance ingredient, was evaluated in pregnant Sprague-Dawley rats (25/group). Gavaged dosages of 0 (corn oil), 25, 50, or 100 mg/kg/day were administered on days 7 through 17 of gestation (GDs 7 to 17). First and last day dosing suspensions were analyzed for AC content. All rats were observed daily for viability, clinical signs, abortions, and premature deliveries. Body weights were recorded at frequent intervals. Cesarean-sectioning and necropsy examinations were performed on GD 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. The number of corpora lutea in each ovary was also recorded. Fetuses were weighed and examined for gender and gross external changes and soft tissue or skeletal alterations. Totals of 25, 23, 21, and 24 rats became pregnant in the 0 (control), 25, 50 and 100 mg/kg/day groups, respectively, and analysis of dosage preparations verified that administered dosages reflected calculated dosages ±10%. No deaths or premature deliveries occurred in the study. Clinical signs included excessive salivation, which was attributed to the administration of AC. When compared to controls, significant reductions in feed consumption and body weight gains occurred only at 100 mg/kg/day. Both absolute (g/day) and relative (g/kg/day) feed consumption values were significantly decreased on GDs 7 to 12. Relative values were decreased significantly on GDs 15 to 18. Body weight gains were significantly reduced on GDs 7 to 10. Mean maternal body weights remained significantly lower than controls on GDs 9 to 14, but a marked compensatory increase in feed consumption on GDs 15 to 18 prevented further deterioration in body weight gains. No cesarean-sectioning or litter parameters were affected by dosages of AC and necropsy of the dams after cesarean section did not reveal any gross changes attributable to AC. No gross external, soft tissue, or skeletal fetal alterations (malformations or variations) were attributed by dosages AC. The average number of ossifications sites per fetus per litter did not differ among the groups. Based on these data, maternal and developmental no-observable-adverse-effect levels (NOAELs) of 50 and 100 mg/kg/day, respectively, were established for AC.

The Subchronic Oral Toxicity of Ethane, 1,2-Bis(pentabromophenyl) (Saytex 8010) in Rats

2002 ◽  
Vol 21 (3) ◽  
pp. 165-170 ◽  
Author(s):  
M. L. Hardy ◽  
D. Margitich ◽  
L. Ackerman ◽  
R. L. Smith
Keyword(s):  
Corn Oil ◽  
Clinical Chemistry ◽  
Recovery Period ◽  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Low Grade ◽  
Oral Toxicity ◽  
Effect Level

Ethane, 1,2-bis(pentabromophenyl) (EBP; CAS no. 8452–53–9) dose levels of 0, 100, 320 and 1000 mg/kg/day administered to rats by gavage in corn oil for 90 consecutive days produced no compound-related clinical signs of systemic toxicity, ocular lesions, or alterations in urinalysis, clinical chemistry, and hematology values in the treated or recovery groups. No biologically or toxicologically significant differences were observed in body weights, body weight gains, and food consumption. Statistically significant differences were found between control and high-dose animals in mean absolute or relative liver weights. Histomorphological evaluation showed in male rats low-grade liver changes consisting of minimal to slight hepatocellular vacuolation (high-dose males) and minimal to slight centrilobular hepatocytomegaly (high- and possibly mid-dose males). These changes had resolved by the end of the 28-day recovery period. No treatment-related changes were found in the livers of female rats. No treatment-related histomorphologic changes were present in any of the other tissues examined in either sex, except for evidence of aspirated test article in individual rats. The 90-day EBP no-adverse-effect level in the rat was 1000 mg/kg/day, and was consistent with that of the preceding 28-day study (no-effect level 1250 mg/kg/day). EBP's lack of toxicity is likely related to poor bioavailability due to its high molecular weight and low solubility.

scholarly journals Nutritional and 13-Week Subchronic Toxicological Evaluation of Lignosus rhinocerotis Mycelium in Sprague-Dawley Rats

2021 ◽  
Vol 18 (3) ◽  
pp. 1271
Author(s):  
I-Chen Li ◽  
Bi-Hua Yang ◽  
Jing-Yi Lin ◽  
Shan Lin ◽  
Chin-Chu Chen
Keyword(s):  
Body Weight ◽  
Histopathological Examination ◽  
Clinical Signs ◽  
Female Rats ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Crude Lipid ◽  
Sprague Dawley Rats ◽  
Freeze Dried ◽  
Lignosus Rhinocerotis

Lignosus rhinocerotis (Tiger’s Milk mushroom) is a novel mushroom with sclerotium belonging to the Polyporaceae family and has been reported widely to possess anti-cancer, anti-cough, antioxidant, gastro-protective, immuno-modulating, and neurite-stimulating properties. As numerous studies have proven the tremendous medicinal values of L. rhinocerotis, it is necessary to understand its nutrition as well as its safety for the recipient. Previous research on L. rhinocerotis has mainly focused on the naturally occurring sclerotium and may have overlooked mushroom mycelia from submerged liquid fermentation, which ensures a high uniform quantitative biomass production as well as a high biological value. Hence, this is the first report on the evaluation of nutrition and 13-week repeated oral toxicity of L. rhinocerotis mycelium (LRM). The LRM powder contained 9.0 ± 4.2% moisture, 1.9 ± 1.3% ash, 1.6 ± 2.2% crude lipid, 8.4 ± 5.3% crude protein, 79.3 ± 4.6% carbohydrate, and 364 kcal/100 g energy. The total free amino acid ranged from 349 to 5636 mg/100 g and the umami index of freeze-dried LRM powder was 0.37. For safety assessment, ninety-six rats were divided into four groups, each consisting of twelve male and twelve female rats. Test articles were administered by oral gavage to rats at 850, 1700, and 3400 mg/kg body weight/day for 13 weeks and reverse osmosis water was used as the control. All animals survived to the end of the study. During the experiment period, no abnormal changes were observed in clinical signs, body weight, or ophthalmological examinations. No adverse or test article-related differences were found in urinalysis, hematology, or serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. According to the above results, the no-observed-adverse-effect level (NOAEL) of L. rhinocerotis was identified to be greater than 3400 mg/kg body weight (BW)/day in Sprague–Dawley rats.

scholarly journals Acute oral toxicity of squid and cuttlefish ink powder enzyme hydrolysates in Sprague-Dawley rats in accordance with the OECD Test Guideline 425

Food Research ◽  
2021 ◽  
Vol 5 (5) ◽  
pp. 259-264
Author(s):  
Ayu Shazwani Z. ◽  
Husnul Azan T. ◽  
Wan Ezumi M.F. ◽  
Rabeta M.S.
Keyword(s):  
Body Weight ◽  
Clinical Signs ◽  
Normal Structure ◽  
Female Rats ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Sprague Dawley Rats ◽  
Behavioural Patterns ◽  
Ld50 Value ◽  
Enzyme Hydrolysate

The objectives of this study were to determine LD50 and establish the safety of ink squid and cuttlefish hydrolysates. In the acute toxicity study, three groups of female rats were randomly assigned. One group served as the control and two groups orally received a single limiting dose (2000 mg/kg body weight) of ink hydrolysates. There were no signs of adverse toxicity observed in behavioural patterns, clinical signs, and no significant differences (p>0.05) between the control and treated rats regarding their food and water consumption and body weight for up to 14 days. The histopathological evaluation revealed a normal structure and the absence of noticeable lesions in the vital organs of treated animals. It can be concluded that LD50 value is greater than 2000 mg/kg. The results showed that the squid ink powder enzyme hydrolysate (SIPEHs) and cuttlefish ink powder enzyme hydrolysate (CIPEHs) possess low toxicity, as indicated in the rat model. The preliminary results suggested that it should be further evaluated for long-term use and repeated dose effects to support the safe use of these hydrolysates.

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.

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