scholarly journals A Test of Dietary Monosodium Glutamate Developmental Neurotoxicity in Rats: A Reappraisal

2018 ◽  
Vol 73 (Suppl. 5) ◽  
pp. 36-42 ◽  
Author(s):  
Charles V. Vorhees
Keyword(s):  
Monosodium Glutamate ◽  
Daily Intake ◽  
Developmental Neurotoxicity ◽  
The Other ◽  
High Dose ◽  
Functional Tests ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

In 1979, we tested dietary monosodium glutamate (MSG) for developmental neurotoxicity in rats. The study was recently cited for establishing a No Observable Adverse Effect Level (NOAEL) for MSG as a food additive resulting in a change in the acceptable daily intake (ADI). Therefore, I re-evaluated the study [Vorhees et al.: Toxicol Appl Pharmacol 1979; 50: 267–282]. Sprague-Dawley rats were fed diets containing 0, 1.7, 3.4, or 5.1% MSG prior to conception, throughout gestation and lactation, and the same diets were fed to the offspring until 90 days of age. About 18–20 L were tested per dose with litter and sex factors in data analyses. There were 21 functional tests with 36 dependent variables and 10 body weight and histological outcomes. Of the functional tests, 4 were significant involving 6 effects. Two effects were on swimming ontogeny: one was an improvement and the other an atypical minor delay of no significance. Two effects were on active avoidance: one was a low-dose female-only extinction effect and the other a high-dose male-only acquisition effect, neither providing evidence of consistency. One was on passive avoidance, but was an improvement not a deficit. The last was on open-field rearing in the absence of its normal association with locomotion changes. Thus, it can be concluded, as was done in 1979 and by the U.S. Food and Drug Administration who sponsored the study, that there is no evidence in these data that dietary MSG is developmentally neurotoxic, hence, the study provides no basis for the establishment of a NOAEL and changing the ADI for dietary MSG.

scholarly journals Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-25
Author(s):  
Gajanan Deshmukh ◽  
Suresh B. Venkataramaiah ◽  
Chandrashekar M. Doreswamy ◽  
Mohan C. Umesh ◽  
Rajesh B. Subbanna ◽  
...  
Keyword(s):  
Biologically Active ◽  
High Dose ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Endogenous Antioxidant ◽  
In Vitro Genotoxicity

Coenzyme Q10 (CoQ10) is a lipid soluble, endogenous antioxidant present at highest levels in the heart followed by the kidney and liver. The reduced CoQ10 ubiquinol is well known for its chemical instability and low bioavailability. The present study was designed to synthesize ubiquinol acetate, which is more stable and biologically active, and further evaluate its safety and genotoxic potential. Synthesized ubiquinol acetate showed better stability than that of ubiquinol at the end of 3 months. In vitro genotoxicity studies (AMES test, in vitro micronucleus and chromosomal aberration) showed ubiquinol acetate as nongenotoxic with no clastogenic or aneugenic effects at high dose of 5000 and 62.5 μg/mL, respectively. In subchronic toxicity study, ubiquinol acetate was administered orally to Sprague Dawley rats at 150, 300, and 600 mg/kg/day for 90 days. No treatment related adverse effects were observed in males at 600 mg/kg/day; however, females showed treatment related increase in AST and ALT with small focal irregular white-yellow spots in liver on gross necropsy examination. Histopathological evaluation revealed hepatocellular necrosis in high dose females which was considered as adverse. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of ubiquinol acetate in males and females was determined as 600 and 300 mg/kg/day, respectively.

scholarly journals Subchronic Oral Toxicity of Sodium Tungstate in Sprague-Dawley Rats

2015 ◽  
Vol 34 (4) ◽  
pp. 336-345 ◽  
Author(s):  
Wilfred C. McCain ◽  
Lee C. B. Crouse ◽  
Mathew A. Bazar ◽  
Laurie E. Roszell ◽  
Glenn J. Leach ◽  
...  
Keyword(s):  
Food Consumption ◽  
Male Rats ◽  
High Dose ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Male And Female ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

The subchronic toxicity of sodium tungstate dihydrate aqueous solution in male and female Sprague-Dawley rats was evaluated by daily oral gavage of 0, 10, 75, 125, or 200 mg/kg/d for 90 days. Measured parameters included food consumption, body weight measurements, hematology, clinical chemistry, and histopathological changes. There was a significant decrease in food consumption and body weight gain in males at 200 mg/kg/d from days 77 to 90; however, there was no effect in food consumption and body weights in females. There were no changes in the hematological and clinical parameters studied. Histopathological changes were seen in kidney of male and female and epididymis of male rats. Histopathological changes were observed in the kidneys of male and female rats dosed at 125 or 200 mg/k/d consisting of mild to severe cortical tubule basophilia in 2 high-dose groups. Histological changes in epididymides included intraluminal hypospermia with cell debris in the 200 mg/kg/d dosed male rats. Histopathological changes were observed in the glandular stomach including inflammation and metaplasia in the high-dose groups (125 or 200 mg/kg/d) of both sexes of rats. Based on histopathology effects seen in the kidneys, the lowest observable adverse effect level was 125 mg/kg/d and the no observable adverse effect level was 75 mg/kg/d in both sexes of rats for oral subchronic toxicity.

scholarly journals A 4-Week Repeated Oral Dose Toxicity Study of Ssanghwa-Tang in Crl:CD Sprague Dawley Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Sae-Rom Yoo ◽  
Hyekyung Ha ◽  
Mee-Young Lee ◽  
Hyeun-kyoo Shin ◽  
Su-Cheol Han ◽  
...  
Keyword(s):  
Safety Information ◽  
Experimental Period ◽  
Serum Biochemistry ◽  
Toxicity Study ◽  
Herbal Formula ◽  
Sprague Dawley ◽  
Organ Weights ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Ssanghwa-tang (SHT), a traditional herbal formula, has been widely used to recover fatigue or consumptive disease after an illness. Along with much attention to herbal formula, the concerns about the safety and toxicity have arisen. To establish the safety information, SHT was administrated in Crl:CD Sprague Dawley rats at a daily dose of 0, 1000, 2000, and 5000 mg/kg for 4 weeks. During the test periods, we examined the mortality, clinical observation, body weight change, food consumption, organ weights, hematology, serum biochemistry, and urinalysis parameters. No changes of mortality and necropsy findings occurred in any of the groups during the experimental period. In either sex of rats treated with SHT at 5000 mg/kg/day, changes were observed in food intake, reticulocyte, total bilirubin, some urinalysis parameters, and relative organ weights. The results indicated that SHT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. This dosage was considered no observed adverse effect level (NOAEL) and was appropriate for a 13-week subchronic toxicity study.

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.

Oral (Drinking Water) Developmental Toxicity Study of Ammonium Perchlorate in Sprague-Dawley Rats

2003 ◽  
Vol 22 (6) ◽  
pp. 453-464 ◽  
Author(s):  
Raymond G. York ◽  
Kathleen A. Funk ◽  
Michael F. Girard ◽  
David Mattie ◽  
Joan E. Strawson
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Developmental Toxicity ◽  
Thyroid Stimulating Hormone ◽  
Toxicity Study ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Maternal Thyroid

A developmental toxicity study was conducted with ammonium perchlorate (AP) in the drinking water at doses of 0.0, 0.01, 0.1, 1.0, and 30.0 mg/kg-day beginning 14 days before cohabitation and continuing through sacrifice. Twenty-four rats/group were cesarean-sectioned on day of gestation (DG) 21 and fetuses examined for visceral and skeletal alterations. An additional 16 litters/group were sacrificed on DG 21 for maternal and fetal serum TSH, T3, and T4 (thyroid-stimulating hormone, triiodothyronine, and thyroxine) levels and thyroid histopathology. Clinical and necropsy observations, body weights, feed and water consumption, and cesarean-sectioning parameters were comparable among the groups with only delays in ossification observed in the 30 mg/kg-day group. Maternal thyroid weights were increased in the 30.0 mg/kg-day group. Decreased colloid was present in male and female fetal thyroids in the 1.0 and 30.0 mg/kg-day groups. Maternal TSH was increased and T4 was decreased at all levels, and T3 was reduced at 30.0 mg/kg-day. Fetal TSH was increased at 1.0 and 30.0 mg/kg-day, T4 was reduced at 30.0 mg/kg-day, and T3 was decreased at all levels. The maternal no-observable-adverse-effect level (NOAEL) was 1.0 mg/kg-day; exposures of 30.0 mg/kg-day increased absolute and relative maternal thyroid weights and histopathology findings. The developmental NOAEL was 1.0 mg/kg-day; developmental delays in ossification occurred in the 30.0 mg/kg-day group. The colloid depletion in the thyroids and increased TSH and decreased T3 and T4 levels at lower exposures were considered adaptive and not adverse. No adverse effects on development at occurred levels that did not cause maternal toxicity. AP is not a selective developmental toxicant.

Comparative Toxicology Studies in Sprague-Dawley Rats, Rhesus Monkeys, and New Zealand White Rabbits to Determine a No Observed Adverse Effect Level for 1,1′-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] Dimethanesulfonate

2013 ◽  
Vol 32 (4_suppl) ◽  
pp. 59S-74S ◽  
Author(s):  
Merrill R. Osheroff ◽  
Dean J. Kobs ◽  
Matthew Buccellato ◽  
Claire R. Croutch ◽  
Laura E. Elcock ◽  
...  
Keyword(s):  
Adverse Effect ◽  
New Zealand ◽  
Rhesus Monkeys ◽  
Clinical Pathology ◽  
Intramuscular Administration ◽  
Sprague Dawley ◽  
Single Dose Study ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Studies were conducted in Sprague-Dawley rats, New Zealand White (NZW) rabbits, and rhesus monkeys to characterize the toxicity of 1,1′-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) following intramuscular administration. Rats received MMB4 DMS once daily for 7 days at 100, 200, 400, and 800 mg/kg/d; rabbits received a range of dose levels in 3 separate 7-day studies from 3 to 800 mg/kg/d and in a single-dose study from 50 to 200 mg/kg; and monkeys received MMB4 DMS at 150 to 600 mg/kg/d. Mortality was noted in rats and rabbits administered ≥200 mg/kg. All monkeys survived until scheduled termination. Adverse clinical observations were noted in the rats at ≥400 mg/kg/d and in rabbits administered ≥200 mg/kg; no adverse findings were noted in the monkeys. Clinical pathology changes were noted in the rabbit related to cardiac and renal function. In the rabbit and monkey, elevations in myoglobin, alanine aminotransferase/aspartate aminotransferase, platelets, creatine kinase, and coagulation factors were related to local inflammation at the intramuscular administration site. Light microscopic examination at the injection sites revealed acute skeletal muscle necrosis in vehicle control and treated groups. Target tissues in the rabbit studies were identified as kidney, heart, and lungs at ≥100 mg/kg/d. All changes noted in all the species demonstrated partial to complete recovery comparable to control values or to a clinically irrelevant level of effect. The NZW rabbit was the most sensitive species, and the no observed adverse effect level (NOAEL) was determined as 50 mg/kg/d; the NOAEL in the rat was 100 mg/kg/d; and the NOAEL in rhesus monkeys was >600 mg/kg/d.

Ninety-Day Toxicity Study of Alpha-Iso-Methylionone in Rats

2012 ◽  
Vol 31 (6) ◽  
pp. 595-601 ◽  
Author(s):  
Valerie T. Politano ◽  
Aurelia A. Lapczynski ◽  
Gretchen Ritacco ◽  
Anne Marie Api
Keyword(s):  
Blood Chemistry ◽  
Tubular Epithelium ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Renal Tubular Epithelium ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Liver And Kidney ◽  
Effect Level ◽  
Renal Tubular

Alpha-iso-methylionone (AIM), a fragrance ingredient, was evaluated for systemic toxicity in rats. Male and female Sprague Dawley rats were administered 0, 5, 30, or 500 mg/kg/d AIM via gavage for 90 days. Statistically significant changes in blood chemistry parameters (reduced aspartate aminotransferase [AST], and increased cholesterol, creatinine, and total protein) were observed in both sexes at 500 mg/kg/d. There were statistically significant increases in liver and kidney weights in both sexes and in spleen weights in males at 500 mg/kg/d. Adaptive hepatocyte enlargement was observed in both sexes at 500 mg/kg/d. Globular accumulations of eosinophilic material were observed in the renal tubular epithelium in males at ≥30 mg/kg/d. Thyroid and bone marrow histopathological changes were observed in males at 500 mg/kg/d. The no-observed-effect level was 5 mg/kg/d for males and 30 mg/kg/d for females. Based on histopathological changes in the kidney in males, the no-observed-adverse-effect level was 30 mg/kg/d.

scholarly journals Biodistribution, Toxicology, and Radiation Dosimetry of 5-HT1A-Receptor Agonist Positron Emission Tomography Ligand [11C]CUMI-101

2011 ◽  
Vol 30 (6) ◽  
pp. 611-618 ◽  
Author(s):  
Dileep J. S. Kumar ◽  
Bing Bai ◽  
Hanna H. Ng ◽  
Jon C. Mirsalis ◽  
Kjell Erlandsson ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Radiation Dosimetry ◽  
Maximum Tolerated Dose ◽  
High Dose ◽  
Sprague Dawley ◽  
Dose Administration ◽  
Positron Emission ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Medical Internal Radiation Dose

Sprague Dawley rats (10/sex/group) were given a single intravenous (iv) dose of CUMI-101 to determine acute toxicity of CUMI-101 and radiation dosimetry estimations were conducted in baboons with [11C]CUMI-101. Intravenous administration of CUMI-101 did not produce overt biologically or toxicologically significant adverse effects except transient hypoactivity immediately after dose in the mid- and high-dose groups, which is not considered to be a dose-limiting toxic effect. No adverse effects were observed in the low-dose group. The no observed adverse effect level (NOAEL) is considered to be 44.05 µg/kg for a single iv dose administration in rats. The maximum tolerated dose (MTD) was estimated to be 881 µg/kg for a single iv dose administration. The Medical Internal Radiation Dose (MIRDOSE) estimates indicate the maximum permissible single-study dosage of [11C]CUMI-101 in humans is 52 mCi with testes and urinary bladder as the critical organ for males and females, respectively.

The effect of thyroid dysfunction on nesfatin-1 and adiponectin levels in rats

2017 ◽  
Vol 32 (3) ◽  
Author(s):  
Emine Atıci ◽  
Rasim Mogulkoc ◽  
Abdulkerim Kasım Baltaci ◽  
Esma Menevse
Keyword(s):  
Body Weight ◽  
Thyroid Hormone ◽  
Thyroid Dysfunction ◽  
The Other ◽  
High Dose ◽  
Fat Cells ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Sprague Dawley Rats ◽  
Experimental Thyroid

AbstractBackgroundChanges in thyroid hormone concentrations may affect adiponectin concentrations through various mechanisms. A molecule released primarily from the fat cells adiposities; adiponectin has important effects on the regulation of body weight.AimThe present study aimed to explore the effects of experimental thyroid dysfunction and its treatment on nesfatin-1 and adiponectin levels in rats.MethodsThe study included 40 adult male Sprague-Dawley rats which were grouped as follows: (1) control; (2) hypothyroidism [hypothyroidism was induced by intraperitoneal injection of 10 mg/kg/day propylthiouracil (PTU) for 3 weeks]; (3) hypothyroidism + thyroxine group [after hypothyroidism was induced by 2-week PTU injection, they were treated with high-dose L-thyroxine (1.5 mg/kg/day) for 1 week]; (4) hyperthyroidism [hyperthyroidism was induced by 3-weeks’ thyroxine injection (0.3 mg/kg/day)]; (5) hyperthyroidism + PTU (after hyperthyroidism was induced by 2-weeks’ thyroxine injection, the animals were given 10 mg/kg/day PTU for 1 week). Blood samples taken at the end of the study were analyzed to measure nesfatin-1 and adiponectin levels.ResultsIt was found that nesfatin-1 levels increased in hypothyroidism, while adiponectin levels decreased (p < 0.001). In experimental hyperthyroidism, on the other hand, both nesfatin-1 and adiponectin levels were found significantly elevated (p < 0.001).ConclusionThe results of the study indicate that nesfatin-1 and adiponectin levels were modified considerably in hypo- and hyperthyroidism, whereas with the restoration of the thyroid function, modified hormone levels went back to normal.

Studies of the Toxicological Potential of Capsinoids: II. A 26-Week Daily Gavage Dosing Toxicity Study of CH-19 Sweet Extract in Rats

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 11-27 ◽  
Author(s):  
Terutaka Kodama ◽  
Eri Watanabe ◽  
Takeshi Masuyama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Toxicity Study ◽  
High Dose ◽  
Test Substance ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Test Article ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Dose Levels

A 26-week oral toxicity study of capsinoids-containing CH-19 Sweet extract was conducted in Sprague-Dawley rats (20 males and 20 females per group) at 6 weeks of age. The test substance was administered by gavage for 26 weeks at dose levels of 0 (vehicle), 1.25, 2.5, and 5.0 ml/kg/day. The concentration of capsinoids in the CH-19 Sweet extract employed was 71.25 to 73.15 mg/ml, resulting in dose levels of capsinoids of 89.06 to 91.44, 178.13 to 182.88, and 356.25 to 365.75 mg/kg, respectively. Adverse test article–related changes were only observed in males, not in females, and within the males, only at the high dose (5.0 ml/kg). Within that group (high-dose males), increases were observed in the numbers of segmented neutrophils, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, liver weights, and in the incidence and severity of hepatocellular focal necrosis. No test substance–related changes were detected in clinical signs, body weight, food consumption, water intake, ophthalmology, or urinalysis. No adverse test article–related changes were observed in low- or mid-dose males or in females at any dose. Based on the results of this chronic gavage study, the target organ was the liver and the no observed adverse effect level (NOAEL) for CH-19 Sweet extract in the rat was 2.5 ml/kg/day in males and 5.0 ml/kg/day in females (178.13 to 182.88 mg/kg and 356.25 to 365.75 mg/kg as capsinoids, respectively).

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