scholarly journals Safety Assessment of TGT Primaage using Wistar Rats through Oral Gavage Administration

2021 ◽  
Vol 10 (5) ◽  
pp. 298-315
Author(s):  
Kunjan Shah ◽  
◽  
Sudhakar Jadhav ◽  
Manish Patel ◽  
Jaydip Mistry ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Wistar Rats ◽  
Clinical Pathology ◽  
Centella Asiatica ◽  
Control Group ◽  
High Dose ◽  
Delayed Effect ◽  
Adverse Effect Level ◽  
Effect Level

TGT Primaage is one of the astonishing extracts, obtained from a combination of Moringa oleifera and Centella asiatica. At present, there is no finding reported regardin g the repeated exposure of this extract. This study investigates the No Observed Adverse Effect Level (NOAEL) and effects of repeated-dose administration of Astragalin and Isoquercetin (components of interest) present in TGT Primaage on Wistar rats. Rats were divided into 3 treatment and a control group (10 rats/sex/group). To assess reversibility, persistence, or delayed effect, additional control and high dose groups were treated similarly and observed further without any treatment. TGT Primaage was administered orally, through gavage for 90 days, at 0, 250, 500, and 1000 mg/kg body weight/day. No mortality, morbidity, and clinical sign of toxicity was observed. Abnormality related to neurological and functional parameters was not seen. No change in body weight and food consumption was observed. Treatment did not lead to any adverse effect in clinical pathology parameters and organ weights. TGT Primaage did not alter morphological and histopathological characteristics of organs. From these results, it is evident that TGT Primaage appears to be safe and devoid of any toxicity. The No Observed Adverse Effect Level (NOAEL) of TGT Primaage for both sexes were found to be 1000 mg/kg body weight/day

A 90-Day Oral Gavage Toxicity Study of d-Methylphenidate and d, I-Methylphenidate in Beagle Dogs

2003 ◽  
Vol 22 (3) ◽  
pp. 215-226 ◽  
Author(s):  
Steve K. Teo ◽  
David I. Stirling ◽  
Steve D. Thomas ◽  
Mark G. Evans ◽  
Vikram D. Khetani
Keyword(s):  
Body Weight ◽  
Recovery Period ◽  
Clinical Pathology ◽  
Body Weight Loss ◽  
High Dose ◽  
Beagle Dogs ◽  
Weight Changes ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Therapeutic Doses

d-Methylphenidate ( d-MPH) was approved as a treatment for attention deficit hyperactivity disorder (ADHD) in children. The repeated-dose toxicity of the d enantiomer of d, l-methylphenidate ( d, l-MPH) was assessed in male and female Beagle dogs. Dogs were orally dosed twice a day in equally divided doses 6 hours apart for total daily doses of 1, 3, and 10 mg/kg/day d-MPH or 20 mg/kg/day d, l-MPH for 90 days, followed by a 30-day recovery period. The top d-MPH dose of 10 mg/kg was equimolar to 20 mg/kg d, l-MPH in d-MPH content. The 10-mg/kg d-MPH and d, l-MPH doses were at least 13 times the maximum therapeutic dose giving rise to systemic exposures that were equivalent to or at least 2 times greater than those at the maximum therapeutic doses in children. The 10-mg/kg d-MPH and 20-mg/kg d, l-MPH doses had systemic exposures that were equivalent to or two to five times greater than the maximum therapeutic plasma levels in children respectively. There was no treatment-related mortality in all doses tested. Reversible salivation, hyperactivity, and diarrhea were seen in the high-dose d-MPH and d, l-MPH groups. Significant body weight loss and reduction in food consumption were observed in males for both high-dose groups with weights comparable to control values by the end of the recovery period. There were no abnormal clinical pathology or macroscopic or microscopic findings. Based on body weight changes, the no-observed-adverse-effect level (NOAEL) of d-MPH in beagle dogs was 3 mg/kg/day.

scholarly journals Subacute Toxicity Profile of Lacidipine Nanoformulation in Wistar Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Rupesh Shirodkar ◽  
Chandrasekhar Misra ◽  
Chethan GH ◽  
Pallavi Shetty ◽  
Zenab Attari ◽  
...  
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Testis Weight ◽  
Delayed Effect ◽  
Male And Female Rats

The present study was aimed at investigating the safety of Lacidipine (LCDP) loaded nanostructured lipid carriers (NLCs) in Wistar rats. NLCs were formulated using ultrasound dispersion technique. Animals were orally treated once daily with NLCs containing 0.140 mg, 0.350 mg, and 0.875 mg of LCDP as low, medium, and high dose per kg body weight, respectively, during 28 days along with blank formulation and pure LCDP. Control rats were fed with water. Animals were observed throughout experiment period and their body weight was recorded once weekly. Overnight fasted rats were sacrificed on the 29th day. Study revealed no signs or symptoms of toxicity or morbidity. No significant changes in the body weight were observed between treated and control group. Significant increase in left testis weight and liver weight was observed in male and female rats, respectively. Haematological estimation revealed significant decrease in haemoglobin count in male rats while female rats showed significant increase in granulocyte count. All the serum clinical parameters were within the normal range and no gross histopathological changes were observed. No delayed effect was noted in satellite group. The results indicate that developed LCDP loaded NLCs are safe when administered orally in rats.

scholarly journals Safety Evaluation for Restorin® NMN, a NAD+ Precursor

2021 ◽  
Vol 12 ◽  
Author(s):  
John Turner ◽  
Albert Licollari ◽  
Emil Mihalcea ◽  
Aimin Tan
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Recovery Period ◽  
The Body ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Adverse Effect Level ◽  
Effect Level

NAD+ is an abundant molecule in the body and vital to all living cells. NAD+ levels decline with age, and this decline correlates with age-related diseases. Therefore, sustaining NAD+ levels offers potential benefits to healthspan and longevity. Here we conducted toxicity studies to evaluate the safety of Restorin® NMN, a high purity form of the direct NAD+ precursor, β-nicotinamide mononucleotide (NMN). Based on the preliminary toxicity study and a 14-days repeated dose toxicity study at a higher dose level exposure, Restorin® NMN was administered orally to Sprague-Dawley rats for 91 days followed by a 14-days recovery period. The oral doses of 500, 1,000, and 2000 mg/kg/day were compared. There were no test item-related findings that could be considered adverse events in animals dosed at 500 mg/kg/day. The findings in the Restorin® NMN high dose group (2000 mg/kg/day) were similar to the reference item (Nicotinamide Riboside Chloride) dosed at 1740 mg/kg/day: reduced body weight, reductions in body weight gains, and diminished food consumption. In conclusion, the No-Observed-Adverse-Effect-Level (NOAEL) for Restorin® NMN is 1,000 mg/kg/day in female rats and 500 mg/kg/day in male rats, and the Low-Observed-Adverse-Effect-Level (LOAEL) for Resotrin® NMN is 2000 mg/kg/day.

scholarly journals Palmitoylethanolamide: Prenatal Developmental Toxicity Study in Rats

2021 ◽  
pp. 109158182098607
Author(s):  
Narendra S. Deshmukh ◽  
Shailesh Gumaste ◽  
Silma Subah ◽  
Nathasha Omal Bogoda
Keyword(s):  
Body Weight ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Toxicity Study ◽  
High Dose ◽  
Pregnant Rats ◽  
Human Dose ◽  
Adverse Effect Level ◽  
Female Wistar Rats ◽  
Effect Level

Palmitoylethanolamide (PEA) is an endogenous ethanolamine playing a protective and homeodynamic role in animals and plants. Prenatal developmental toxicity of PEA was tested following oral administration to pregnant female Wistar rats, from days 0 to 19 of gestation, at dosage of 250, 500, or 1,000 mg/kg body weight, according to Organisation for Economic Co-operation and Development Test Guideline No. 414. On gestation day 20, cesarean sections were performed on the dams, followed by examination of their ovaries and uterine contents. The fetuses were further examined for external, visceral, and skeletal abnormalities. Palmitoylethanolamide did not cause any alterations at any of the given dosages in the measured maternal parameters of systemic toxicity (body weight, food consumption, survival, thyroid functions, organ weight, histopathology), reproductive toxicity (preimplantation and postimplantation losses, uterus weight, number of live/dead implants and early/late resorptions, litter size and weights, number of fetuses, their sex ratio), and fetal external, visceral, or skeletal observations. Any alterations that were recorded were “normal variations” or “minor anomalies,” which were unrelated to treatment with PEA. Under the condition of this prenatal study, the no-observed-adverse-effect level of PEA for maternal toxicity, embryotoxicity, fetotoxicity, and teratogenicity in rats was found to be >1,000 mg/kg body weight/d. It indicates that PEA is well tolerated by and is safe to pregnant rats even at a high dose of 1,000 mg/kg body weight/d, equivalent to a human dose of greater than 9.7 g/d. This prenatal developmental toxicity study contributes greatly in building a robust safety profile for PEA.

Toxicity Assessment of 4-Amino-2-Nitrotoluene

2013 ◽  
Vol 32 (2) ◽  
pp. 113-122 ◽  
Author(s):  
John T. Houpt ◽  
Glenn J. Leach ◽  
Larry R. Williams ◽  
Mark S. Johnson ◽  
Gunda Reddy
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
Toxicity Data ◽  
Adverse Effect Level ◽  
Effect Level

4-Amino-2-nitrotoluene (4A2NT; CAS 119-32-4) is a degradation product of 2,4-dinitrotoluene. The toxicity data on 4A2NT are limited. Therefore, we collected toxicity data from rats to assess environmental and human health effects from exposures. The approximate lethal dose for both sexes was 5000 mg/kg. A 14-day toxicity study in rats was conducted with 4A2NT in the feed at concentrations of 0, 125, 250, 500, 1000, and 2000 ppm. Based on a 14-day oral dose range toxicity study with 4A2NT in the feed, 2000 ppm was selected as highest concentration for a subsequent 90-day study. An oral 90-day subchronic toxicity study in rats was conducted with concentrations of 0, 500, 1000, or 2000 ppm of 4A2NT in the feed. The calculated consumed doses of 4A2NT in the feed were 0, 27, 52, or 115 mg/kg/d for males and 0, 32, 65, or 138 mg/kg/d for females. A no-observed adverse effect level could not be determined. The lowest observed adverse effect level was 27 mg/kg/d for males and 32 mg/kg/d for female rats based upon decreased body weight gain. The decreased body weight gain in male rats was the most sensitive adverse event observed in this study and was used to derive a benchmark dose (BMD). A BMD of 23.1 mg/kg/d and BMD with 10% effect level of 15.5 mg/kg/d were calculated for male rats, which were used to derive an oral reference dose (RfD). The human RfD of 1.26 μg/kg/d was derived using current United States Environmental Protection Agency guidelines.

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 Imbalance in the Blood Concentrations of Selected Steroids in Pre-pubertal Gilts Depending on the Time of Exposure to Low Doses of Zearalenone

Toxins ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 561 ◽  
Author(s):  
Anna Rykaczewska ◽  
Magdalena Gajęcka ◽  
Ewa Onyszek ◽  
Katarzyna Cieplińska ◽  
Michał Dąbrowski ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Biological Effect ◽  
Control Group ◽  
Low Doses ◽  
Blood Concentrations ◽  
Qualitative And Quantitative ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Quantitative Changes ◽  
Control Group Group

Zearalenone (ZEN) is a mycotoxin that not only binds to estrogen receptors, but also interacts with steroidogenic enzymes and acts as an endocrine disruptor. The aim of this study was to verify the hypothesis that low doses, minimal anticipated biological effect level (MABEL), no-observed-adverse-effect level (NOAEL) and lowest-adverse-effect level (LOAEL), of ZEN administered orally for 42 days can induce changes in the peripheral blood concentrations of selected steroid hormones (estradiol, progesterone and testosterone) in pre-pubertal gilts. The experiment was performed on 60 clinically healthy gilts with average BW of 14.5 ± 2 kg, divided into three experimental groups and a control group. Group ZEN5 animals were orally administered ZEN at 5 μg ZEN/kg BW, group ZEN10 — at 10 μg ZEN/kg BW, group ZEN15 — at 15 μg ZEN/kg BW, whereas group C received a placebo. Five gilts from every group were euthanized on analytical dates 1, 2 and 3 (days 7, 14 and 42 of the experiment). Qualitative and quantitative changes in the biotransformation of low ZEN doses were observed. These processes were least pronounced in group ZEN5 (MABEL dose) where ZEN metabolites were not detected on the first analytical date, and where β-ZEL was the predominant metabolite on successive dates. The above was accompanied by an increase in the concentration of estradiol (E2) which, together with “free ZEN”, probably suppressed progesterone (P4) and testosterone (T) levels.

scholarly journals Vulnerability of the Neural Circuitry Underlying Sexual Behavior to Chronic Adult Exposure to Oral Bisphenol A in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 502-512 ◽  
Author(s):  
Marie Picot ◽  
Lydie Naulé ◽  
Clarisse Marie-Luce ◽  
Mariangela Martini ◽  
Kalina Raskin ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Sexual Behavior ◽  
Androgen Receptor ◽  
Bisphenol A ◽  
Neural Circuitry ◽  
Male Sexual Behavior ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Adult Exposure

There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 μg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only. Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action. This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.

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.

scholarly journals The Oral NOAEL of Flurochloridone in Male Wistar Rats in Ninety-Day Subchronic Toxicity Test Was 3mg/kg/day

2019 ◽  
Vol 16 (4) ◽  
pp. 553 ◽  
Author(s):  
Hongyan Zhu ◽  
Rui Li ◽  
Su Zhou ◽  
Suhui Zhang ◽  
Yu Wang ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Wistar Rats ◽  
Serum Testosterone ◽  
Male Rats ◽  
Subchronic Toxicity ◽  
Sperm Abnormalities ◽  
Testicular Weight ◽  
Adverse Effect Level ◽  
Male Wistar Rats ◽  
Effect Level

A ninety-day toxicity and toxicokinetics of flurochloridone (FLC) were studied in male Wistar rats with oral administration at doses of 3 mg/kg and 10 mg/kg respectively, following the previous study. Apparent toxicity to reproductive system of male rats was still observed at the dose of 10 mg/kg, trace amounts of FLC were still detected 24 hours after administration, testicular weight, epididymal weight and serum testosterone were significantly reduced and sperm abnormalities in epididymis were significantly increased. No abnormalities were found in 3 mg/kg group, it indicated that no-observed-adverse-effect level (NOAEL) of FLC in male rats was 3 mg/kg/day, far below the dose of 20 mg/kg/day reported by European Food Safety Authority (EFSA). Therefore, more attention should be paid to this herbicide.

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