scholarly journals LyophilizedB. subtilisZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study in Wistar Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
B. Appala Naidu ◽  
Kamala Kannan ◽  
D. P. Santhosh Kumar ◽  
John W. K. Oliver ◽  
Zachary D. Abbott
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Clinical Signs ◽  
Albumin Level ◽  
Repeat Dose ◽  
Oral Gavage ◽  
Toxicological Evaluation ◽  
Body Weights ◽  
Adverse Effect Level ◽  
Dose Oral

A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on lyophilized spores of the novel genetically modified strainB. subtilisZB183. Lyophilized spores at doses of 109, 1010, and 1011 CFU/kg body weight/day were administered by oral gavage to Wistar rats for a period of 90 consecutive days.B. subtilisZB183 had no effects on clinical signs, mortality, ophthalmological examinations, functional observational battery, body weights, body weight gains and food consumption in both sexes. There were no test item-related changes observed in haematology, coagulation, urinalysis, thyroid hormonal analysis, terminal fasting body weights, organ weights, gross pathology and histopathology. A minimal increase in the plasma albumin level was observed at 1010and 1011 CFU/kg/day doses without an increase in total protein in males or females and was considered a nonadverse effect. The “No Observed Adverse Effect Level (NOAEL)” is defined at the highest dose of 1011 CFU/kg body weight/day for lyophilizedB. subtilisZB183 Spores under the test conditions employed.

scholarly journals Lyophilized B. subtilis ZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study In Wistar Rats

2019 ◽  
Author(s):  
Appala Naidu. B ◽  
Kamala Kannan ◽  
D. P. Santhosh Kumar ◽  
John W.K. Oliver ◽  
Zachary D. Abbott
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Wistar Rats ◽  
Clinical Signs ◽  
Albumin Level ◽  
Repeat Dose ◽  
Oral Gavage ◽  
Toxicological Evaluation ◽  
Body Weights ◽  
Dose Oral

AbstractA 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on lyophilized spores of the novel genetically modified strain B. subtilis ZB183. Lyophilized spores at doses of 109, 1010, and 1011 CFU/kg body weight/day were administered by oral gavage to Wistar rats for a period of 90 consecutive days. B.Subtilis ZB183 had no effects on clinical signs, mortality, ophthalmological examinations, functional observational battery, body weights, body weight gains and food consumption in both sexes. There were no test item-related changes observed in haematology, coagulation, urinalysis, thyroid hormonal analysis, terminal fasting body weights, organ weights, gross pathology and histopathology. A minimal increase in the plasma albumin level was observed at 1010 and 1011 CFU/kg/day doses without an increase in total protein in males or females and was considered a non-adverse effect. The “No Observed Adverse Effect Level (NOAEL)” is defined at the highest dose of 1011 CFU/kg body weight/day for lyophilized B.Subtilis ZB183 Spores under the test conditions employed.

scholarly journals A 90-day toxicity and genotoxicity study with high-purity phenylcapsaicin

2018 ◽  
Vol 2 ◽  
pp. 239784731877306 ◽  
Author(s):  
Torbjørn Rage Paulsen ◽  
Sebastian Stiller ◽  
Klaus Weber ◽  
Claudia Donath ◽  
Gudrun Schreiband ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Clinical Chemistry ◽  
Human Lymphocytes ◽  
Recovery Period ◽  
Clinical Signs ◽  
Gene Mutations ◽  
Oral Gavage ◽  
Adverse Effect Level ◽  
Dose Oral ◽  
Effect Level

To evaluate the safety of the synthetic capsaicin analogue phenylcapsaicin (PheCap; 7-phenylhept-6-yne-acid-hydroxy-3-mathoxylbenzylamide, CAS no 848127-67-3), a 90-day repeated dose oral gavage of 0, 30, 100 or 250 mg/kg body weight (bw)/day toxicity study with a 28-day recovery period was conducted using Wistar rats. Examinations of clinical signs, body and organ weight, haematology, urinalysis, clinical chemistry, food consumption and macroscopic, as well as histopathological tissue examinations were carried out for signs of toxicity. Degenerative, but reversible changes in the liver at 250 mg/kg bw/day, and local irritating effects in the stomach at 100 and 250 mg/kg bw/day were found. These findings were associated with test item-related clinical symptoms, that is, diarrhoea, salivation and moving of bedding material. PheCap did neither cause gene mutations by base pair changes or frame shifts in the genome of the tester stains Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 or TA 102 nor induce structural and/or numerical chromosomal damage in human lymphocytes. Therefore, it can be concluded that PheCap is not genotoxic. The No Observed Adverse Effect Level (NOAEL) of PheCap for systemic toxicity is considered to be at 100 mg/kg bw/day which is based on degenerative changes in the liver. Due to irritating effects in the stomach, the NOAEL for local effects was established at 30 mg/kg bw/day.

scholarly journals Toxicological evaluation of alpha-galacto-oligosaccharides shows no adverse effects over a 90-day study in rats

2017 ◽  
Vol 1 ◽  
pp. 239784731771640
Author(s):  
Claire Kruger ◽  
Nicole Beauchamp ◽  
Virginie Modeste ◽  
Fanny Morel-Despeisse ◽  
Eric Chappuis
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Toxicological Evaluation ◽  
Organ Weights ◽  
Naturally Occurring ◽  
Adverse Effect Level ◽  
Effect Level

AlphaGOS®, an alpha-galacto-oligosaccharides product, is a mixture of bi-, tri- and tetrasaccharides derived from oligosaccharides in the raffinose family of oligosaccharides (RFOs), naturally occurring plant-derived sugars. RFOs are alpha α-1,6-linked chains of D-galactose attached to the 6-position of D-glucose and differ from the currently commercially available beta-galacto-oligosaccharides products in the chirality and glyosidic bonds. In order to determine the safety of AlphaGOS, rats were given 2000 mg AlphaGOS/kg/day daily via gavage over 90 days. Daily assessments of the animals showed no adverse clinical signs. No adverse treatment-related changes in feed consumption, body weight, clinical chemistry or hematology were noted. There were no adverse treatment-related changes in organ weights, gross or histopathology. Given these findings, it can be concluded that the no observed adverse effect level for AlphaGOS is greater than 2000 mg/kg/day.

Developmental Toxicity of Homobrassinolide in Wistar Rats

2010 ◽  
Vol 29 (5) ◽  
pp. 517-522 ◽  
Author(s):  
Yogeshkumar V. Murkunde ◽  
P. Balakrishna Murthy
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Dose Group ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Oral Gavage ◽  
Fetal Toxicity ◽  
Skeletal Malformations ◽  
Teratogenic Potential

Brassinosteroids (BRs) are close analogues of animal cholesterol. Brassinosteroids have shown their great value as yield promoters of a variety of plants. In view of its steroidal moiety and recent use in agriculture in many countries, the teratogenic potential of homobrassinolide (HBR) was evaluated in Wistar rats. Homobrassinolide was administered by oral gavage at doses 0, 100, and 1000 mg/kg body weight in water during gestation days (GD) 6 to 15 in groups of 20 mated females. Maternal and embryo-fetal toxicity was analyzed by studying the effects such as clinical signs, mortality/morbidity, abortions, body weight, feed consumption, and pregnancy data, gravid uterine weights, implantation losses, litter size, external, visceral, and skeletal malformations. No treatment-related effect was observed on any of the maternal/fetal end points in any dose group. From the results, it can be concluded that HBR is nonteratogenic at doses as high as up to 1000 mg/kg body weight in Wistar rats.

14-Day Repeat-Dose Oral Toxicity Evaluation of Oxazyme in Rats and Dogs

2009 ◽  
Vol 29 (1) ◽  
pp. 20-31 ◽  
Author(s):  
Aaron B. Cowley ◽  
Duane W. Poage ◽  
Robin R. Dean ◽  
Carol L. Meschter ◽  
Majid Ghoddusi ◽  
...  
Keyword(s):  
High Dose ◽  
Repeat Dose ◽  
Mutant Form ◽  
Oral Toxicity ◽  
Oral Gavage ◽  
Test Article ◽  
Adverse Effect Level ◽  
Dose Oral ◽  
Effect Level ◽  
Dietary Oxalate

Oxazyme (OC4) is an orally administered formulation that has as an active component a recombinant mutant form of Bacillus subtilis oxalate decarboxylase (OxDC) enzyme C383S, designed to degrade dietary oxalate in the stomach. Fourteen-day repeat-dose studies were conducted in rats and dogs to evaluate toxicity and determine a no observed adverse effect level (NOAEL). Animals were administered OC4 by oral gavage twice daily for 14 consecutive days. Reversibility, progression, and delayed appearance of any observed changes were evaluated in a subset of animals that underwent a recovery of 7 days following 14 days of control or test-article. There were no test-article-related adverse effects or deaths in either species. Results indicate that the NOAEL under the conditions used in the studies was 720.8 mg/kg/d in rats and 187.2 mg/kg/d in dogs, the high dose tested in each species.

Evaluation of the Developmental Toxicity of Methyl Dihydrojasmonate (MDJ) in Rats

2008 ◽  
Vol 27 (3) ◽  
pp. 295-300 ◽  
Author(s):  
Valerie T. Politano ◽  
Elise M. Lewis ◽  
Alan M. Hoberman ◽  
Mildred S. Christian ◽  
Robert M. Diener ◽  
...  
Keyword(s):  
Body Weight ◽  
Soft Tissue ◽  
Corn Oil ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Sprague Dawley ◽  
Body Weights ◽  
Adverse Effect Level ◽  
Sparse Hair

Methyl dihydrojasmonate (MDJ) is a widely used fragrance ingredient. MDJ was evaluated for developmental toxicity in presumed pregnant Sprague-Dawley rats (25/group) at oral dosages of 0, 40, 80 or 120 mg/kg/day in corn oil administered on gestational days 7–20. Dams were observed for viability, clinical signs, body weights, and feed consumption. Caesarean-sectioning and necropsy occurred on gestational day 21. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. No maternal or fetal deaths occurred. MDJ-related maternal clinical signs included an increased incidence of sparse hair coat and ungroomed appearance at 120 mg/kg/day. Two dams in this group also had tan areas in the liver and a pale spleen. The 120 mg/kg/day dosage also caused reduced mean maternal body weight gains and body weights during the dosage period and reduced absolute and relative maternal feed consumption for the entire dosage period. No Caesarean-sectioning or litter parameters were affected by dosages of MDJ as high as 120 mg/kg/day, although at the highest dosage a tendency toward slightly reduced, but not statistically significant, fetal mean body weight was observed. No fetal gross external, soft tissue or skeletal changes were attributable to dosages of MDJ as high as 120 mg/kg/day. Based on these data, maternal No-Observable-Adverse-Effect-Level (NOAEL) of 80 and developmental NOAEL of equal to or greater than 120 mg/kg/day were established for MDJ. It is concluded that MDJ is not a developmental toxicant in rats under the conditions of this study.

scholarly journals A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Amy Clewell ◽  
Gábor Hirka ◽  
Róbert Glávits ◽  
Philip A. Palmer ◽  
John R. Endres ◽  
...  
Keyword(s):  
Body Weight ◽  
Histological Examination ◽  
Food Consumption ◽  
Feed Efficiency ◽  
Wistar Rats ◽  
Toxicological Evaluation ◽  
Hepatocellular Necrosis ◽  
Purine Alkaloid ◽  
Dose Oral ◽  
Mature Spermatozoa

A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.

Subchronic Hepatotoxicity Evaluation of Hydrazobenzene in Fischer 344 Rats

2012 ◽  
Vol 31 (6) ◽  
pp. 564-571 ◽  
Author(s):  
Darol E. Dodd ◽  
Linda J. Pluta ◽  
Mark A. Sochaski ◽  
Henry G. Wall ◽  
Russell S. Thomas
Keyword(s):  
Body Weight ◽  
Serum Alkaline Phosphatase ◽  
Clinical Signs ◽  
Liver Weight ◽  
Fischer 344 ◽  
Liver Histopathology ◽  
Clinical Observations ◽  
Body Weights ◽  
Effect Level ◽  
F344 Rats

Male F344 rats were exposed to hydrazobenzene (HZB) by dietary feed at concentrations of 0, 5, 20, 80, 200, or 300 ppm for 5 days, 2 weeks, 4 weeks, or 13 weeks duration. End points evaluated included clinical observations, body weights, liver weights, serum chemistry, blood HZB, gross pathology, and liver histopathology. There were no HZB exposure-related clinical signs of toxicity. During study weeks 8 through 13, body weight means in rats of the 300 ppm group were 6% lower compared to control rat means. Serum alkaline phosphatase concentrations were decreased in rats of the 300 ppm group at all time points. Relative (to body weight) liver weight increases were observed in rats of the 200 and 300 ppm groups following 5 days (300 ppm only), 2 weeks, 4 weeks, and 13 weeks of exposure. Following 13 weeks of exposure, microscopic findings in the liver were observed only in rats of the 200 and 300 ppm groups and consisted of hypertrophy, macrovesiculation, eosinophilic granular cytoplasm, and bile duct duplication. Blood HZB concentrations ranged from 0.002 to 0.006 µg/mL in rats of the 200 or 300 ppm groups. A no observed effect level of 80 ppm (4.80 mg/kg per d) was selected based on the observation of microscopic hepatocyte alterations at ≥200 ppm HZB.

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.

The Toxicity of Cyclopiazonic Acid in Weaned Pigs

1984 ◽  
Vol 21 (4) ◽  
pp. 418-424 ◽  
Author(s):  
L. G. Lomax ◽  
R. J. Cole ◽  
J. W. Dorner
Keyword(s):  
Body Weight ◽  
Clinical Signs ◽  
Cyclopiazonic Acid ◽  
Gastric Ulcers ◽  
Reduced Body ◽  
Hepatocellular Necrosis ◽  
Body Weights ◽  
Renal Tubular ◽  
Crossbred Pigs ◽  
Small And Large Intestine

Five- to six-week-old crossbred pigs weighing 5 to 14 kg were given purified cyclopiazonic acid at dosages of 10, 1.0, 0.1, and 0.01 mg/kg body weight orally for 14 days. Clinical signs observed by day 7 in pigs given 10 mg/kg body weight were weakness, inactivity, anorexia, rough hair coats, and reduced body weights. These pigs also developed diarrhea during week 2 of the experiment. The pigs given 1.0 mg/kg body weight had rough hair coats and were moderately inactive during the second week of the experiment. At necropsy, lesions were observed only in pigs given 10 and 1.0 mg/kg body weight of cyclopiazonic acid. Lesions were gastric ulcers, mucosal hyperemia, and hemorrhage throughout the small and large intestine in pigs given 10 mg/kg body weight of cyclopiazonic acid. The pigs also had yellow, fibrinonecrotic material in the lumen of the small intestine and pale livers. One pig given 1.0 mg/kg body weight had gastric ulceration. Microscopic lesions in pigs given 10 mg/kg body weight were necrotizing gastroenteritis, focal hepatocellular necrosis, hepatic peripheral lobular fatty change, and focal renal tubular nephrosis with focal suppurative tubulointerstitial nephritis. Pigs given 1.0 mg/kg body weight of cyclopiazonic acid had necrotizing gastritis and villous blunting in the jejunum and ileum.

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