scholarly journals Toxicological Evaluation of β-Caryophyllene Oil

2016 ◽  
Vol 35 (5) ◽  
pp. 558-567 ◽  
Author(s):  
D. Schmitt ◽  
R. Levy ◽  
B. Carroll
Keyword(s):  
Clinical Chemistry ◽  
Recovery Period ◽  
Dosage Level ◽  
Female Rats ◽  
High Dose ◽  
Toxicological Evaluation ◽  
Male And Female Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Major Treatment

In a subchronic toxicity study, administration of β-caryophyllene (BCP) oil by oral gavage to Wistar rats at dosages of 0, 150, 450, or 700 mg/kg/d for 90 days, including a 21-day recovery period, did not produce any significant toxicologic manifestations. The study design also included a 28-day interim sacrifice in the control and high-dose groups. The BCP oil test article was well tolerated as evidenced by the absence of major treatment-related changes in the general condition and appearance of the rats, neurobehavioral end points, growth, feed and water intake, ophthalmoscopic examinations, routine hematology and clinical chemistry parameters, urinalysis, and necropsy findings. The no observed adverse effect level was the highest dosage level administered of 700 mg/kg body weight/d for both male and female rats. The study was conducted as part of an investigation to examine the safety of BCP oil for its proposed use in medical food products.

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 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 14-Day Repeated Intraperitoneal Toxicity Test of Ivermectin Microemulsion Injection in Wistar Rats

2020 ◽  
Vol 7 ◽  
Author(s):  
Zhen Dong ◽  
Shou-ye Xing ◽  
Ji-yu Zhang ◽  
Xu-zheng Zhou
Keyword(s):  
Toxicity Test ◽  
Wistar Rats ◽  
Histopathological Examination ◽  
Clinical Chemistry ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Toxic Injury ◽  
Male And Female Rats ◽  
Initial Stage

To evaluate the safety of ivermectin microemulsion injection, 100 Wistar rats were injected intraperitoneally at 0.38 g/kg, 0.19 g/kg, and 0.1 g/kg for 14 days. The 14-day repeated toxicity test of ivermectin microemulsion injection was systematically evaluated by clinical observation, organ coefficient, hematological examination, clinical chemistry examination, and histopathological examination. The results showed that no rats died during the test. At the initial stage of treatment, the rats in the high dose group had mild clinical reaction, which disappeared after 4 days. Clinical chemistry showed that the high dose of ivermectin microemulsion could cause significant changes in ALT and LDH parameters in male rats; high and medium doses could increase the liver coefficients of male and female rats. The toxic target organ may be the liver as indicated by histopathological findings. No significant toxic injury was found in the heart, liver, spleen, lung, kidney, brain, ovary, and testes of all groups of rats. No drug-related toxic effects were found at low doses, and thus the NOVEL of ivermectin microemulsion injection was 0.19 g/kg.

scholarly journals Acute and 30-day oral toxicity studies of a novel coccidiostat – ethanamizuril

2019 ◽  
Vol 8 (5) ◽  
pp. 686-695 ◽  
Author(s):  
Wenlong Xiao ◽  
Xiaoyang Wang ◽  
Chunmei Wang ◽  
Mi Wang ◽  
Chenzhong Fei ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
Wall Thickening ◽  
High Dose ◽  
Alveolar Wall ◽  
Oral Toxicity ◽  
Male And Female Rats ◽  
Adverse Effect Level ◽  
Ld50 Value

Abstract Ethanamizuril is a novel triazine compound that exhibits remarkable anticoccidial activity. Owing to its pharmacological properties, this study was conducted to evaluate the acute and 30-day oral toxicity of ethanamizuril. In the acute study, ethanamizuril was administered once by oral gavage to mice and rats. The calculated LD50 values for mice and rats were 5776 and 4743 mg per kg b.w, respectively, but the LD50 value for male rats was higher than that of female rats. In the subchronic study, male and female rats were fed with diets supplemented with 0, 20, 60 or 120 mg kg−1 ethanamizuril for 30 days. Treatment related clinical signs of alopecia on the back and neck of the animals were observed in the 60 and 120 mg kg−1 dose groups from the third week of treatment. Significant differences in haematological and biochemical parameters as well as organ-to-body weight ratios were detected between the 60 and 120 mg kg−1 groups. Histopathological observations revealed that 60 and 120 mg kg−1 ethanamizuril could induce focal hepatocellular necrosis and split phase. Slight renal tubule protein casts in the kidneys and alveolar wall thickening in the lungs were also observed in the high dose groups of both genders. The dietary no-observed-adverse-effect level (NOAEL) of ethanamizuril for 30 days was 20 mg kg−1 feed.

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.

Evaluation of genotoxicity and subchronic toxicity of standardized rose hip extract

2017 ◽  
Vol 37 (7) ◽  
pp. 725-741 ◽  
Author(s):  
A Nagatomo ◽  
M Oguri ◽  
N Nishida ◽  
M Ogawa ◽  
A Ichikawa ◽  
...  
Keyword(s):  
Oral Dose ◽  
Chinese Hamster ◽  
Gene Mutations ◽  
Ethanol Extract ◽  
Female Rats ◽  
Toxicity Studies ◽  
Male And Female Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Rose Hip

Rose hip is the fruit of the rose plant, which is widely used in food, cosmetics and as a traditional medicine. Therefore, rose hip is considered safe and has a sufficient history of consumption as food. However, few studies have reported on the safety of rose hip extracts in toxicological analyses. Thus, to evaluate the safety of rosehip polyphenol MJ (RHPMJ), an aqueous ethanol extract standardized with the trans-tiliroside content, we performed genotoxicity and 90-day repeated oral dose toxicity studies in compliance with the Organisation for Economic Co-operation and Development-Good Laboratory Practice. RHPMJ did not induce gene mutations in reverse mutation tests of Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA strains and did not induce chromosomal aberrations in cultured Chinese hamster lung (CHL/IU) cells. Moreover, micronucleus tests using rat bone marrow showed RHPMJ had no micronucleus-inducing potential. Finally, 90-day repeated oral dose toxicity studies (100–1000 mg/kg) in male and female rats showed no treatment-related toxicity in rats. These data indicate that the RHPMJ had no genotoxicity and a no-observed-adverse-effect level greater than 1000 mg/kg in rats.

A Preliminary 13-Week Oral Toxicity Study of Ginger Oil in Male and Female Wistar Rats

2011 ◽  
Vol 30 (6) ◽  
pp. 662-670 ◽  
Author(s):  
Kottarapat Jeena ◽  
Vijayastelter B. Liju ◽  
Ramadasan Kuttan
Keyword(s):  
Wistar Rats ◽  
Hematological Parameters ◽  
Zingiber Officinale ◽  
Female Rats ◽  
Oral Toxicity ◽  
Male And Female ◽  
Male And Female Rats ◽  
Adverse Effect Level ◽  
Female Wistar Rats ◽  
Effect Level

Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).

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 Toxicity and Toxicokinetic Study of Subcutaneously Administered RPh201 in Minipigs

2018 ◽  
Vol 46 (6) ◽  
pp. 693-705 ◽  
Author(s):  
Yuval Ramot ◽  
Zadik Hazan ◽  
Andre Lucassen ◽  
Konstantin Adamsky ◽  
Vanessa Ross ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Recovery Period ◽  
Herbal Remedies ◽  
Drug Candidate ◽  
High Dose ◽  
Subcutaneous Injections ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Toxic Potential ◽  
Novel Drug

Mastic gum extracts are widely used as herbal remedies and are being tested for several clinical indications. Nevertheless, information on their safety is limited. RPh201 is an extract of the mastic gum, formulated and stabilized in a proprietary method, which is being developed as a novel drug candidate for neurological indications. The aim of this study was to assess the systemic toxic potential of RPh201, administered twice weekly by subcutaneous injections to minipigs, after 39 weeks of administration followed by a recovery period of 6 weeks. No clinical or dose-related signs were observed, but treatment-related findings were seen at the injection sites of the high-dose animals, composed of abscesses, chronic inflammation, and subcutaneous fibrosis. Abscesses >30 mm in size, graded as marked severity, were confined to the high-dose group and were considered as adverse. Minimal-slight subcutaneous and lymph nodes abscesses seen in control, low, and intermediate doses, related to the vehicle (cottonseed oil), were not considered as adverse. Additionally, minimal-to-slight cystic spaces or vacuolation related to the vehicle were observed in the skin, lymph nodes, kidney, and lungs. These findings were considered not to be adverse. The no-observed-adverse-effect level was considered to be 12.5 mg/kg/occasion.

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.

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