Short-term Toxicity Study of ST-20 (NSC-741804) by Oral Gavage in Sprague-Dawley Rats

It is sometimes difficult to assess the relevance of tumors that occur in treated animals in short-term studies. This report is intended to establish a general profile of tumor occurrence in young control CD-1 mice and Sprague—Dawley rats. Data from 20 rat and 20 mouse carcinogenicity studies conducted between 1990 and 2002 at Huntingdon Life Sciences, UK, were collected and evaluated. The route of administration was either dietary or oral gavage, and the analysis was confined to sporadic deaths (decedents) in control groups occurring during the first 50 weeks of study. In addition, tumor occurrence between 50—80 weeks were compared. In mice, the most common tumor was lymphoma, followed by bronchiolo-alveolar adenoma. In rats, the most common tumor was adenoma of the pituitary gland, followed by mammary fibroadenoma, and adenocarcinoma. When studies of up to 50 weeks, between 50 and 80 weeks, and at 2-year termination were compared, there was no great difference in tumor occurrence except in male rats, in which the most common tumor up to 50 weeks on study was lymphoma, whereas the most common tumor between 50—80 weeks and at 2 years was pituitary adenoma.

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A 90-day oral gavage toxicity study of d-methylphenidate and d,l-methylphenidate in Sprague–Dawley rats

Toxicology ◽

10.1016/s0300-483x(02)00338-4 ◽

2002 ◽

Vol 179 (3) ◽

pp. 183-196 ◽

Cited By ~ 154

Author(s):

Steve Teo ◽

David Stirling ◽

Steve Thomas ◽

Alan Hoberman ◽

Anthony Kiorpes ◽

...

Keyword(s):

Toxicity Study ◽

Sprague Dawley ◽

Oral Gavage ◽

Sprague Dawley Rats

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Short-term perinatal toxicity study in sprague Dawley rats with the plasticizer and emerging contaminant N-Butylbenzenesulfonamide

Toxicology Letters ◽

10.1016/j.toxlet.2020.05.005 ◽

2020 ◽

Vol 330 ◽

pp. 159-166

Author(s):

Cynthia V. Rider ◽

Molly Vallant ◽

Chad Blystone ◽

Suramya Waidyanatha ◽

Natalie L. South ◽

...

Keyword(s):

Toxicity Study ◽

Emerging Contaminant ◽

Sprague Dawley ◽

Short Term ◽

Sprague Dawley Rats

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Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

Toxicological Sciences ◽

10.1093/toxsci/kfab049 ◽

2021 ◽

Author(s):

Shu-Chieh Hu ◽

Matthew S Bryant ◽

Estatira Sepehr ◽

Hyun-Ki Kang ◽

Raul Trbojevich ◽

...

Keyword(s):

Human Lung ◽

Inhalation Exposure ◽

Systemic Exposure ◽

Sprague Dawley ◽

Oral Gavage ◽

Sd Rats ◽

New Information ◽

Sprague Dawley Rats ◽

Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

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Safety Assessment of a Hydroethanolic Extract of Caralluma fimbriata

International Journal of Toxicology ◽

10.1177/1091581813492827 ◽

2013 ◽

Vol 32 (5) ◽

pp. 385-394 ◽

Cited By ~ 3

Author(s):

Antoinette Y. Odendaal ◽

Narendra S. Deshmukh ◽

Tennille K. Marx ◽

Alexander G. Schauss ◽

John R. Endres ◽

...

Keyword(s):

Developmental Toxicity ◽

Toxicity Study ◽

Developmental Study ◽

Sprague Dawley ◽

Oral Toxicity ◽

Toxicological Assessment ◽

Sprague Dawley Rats ◽

Chromosomal Aberration Test ◽

Hydroethanolic Extract

This toxicological assessment evaluated the safety of a hydroethanolic extract prepared from Caralluma fimbriata (CFE), a dietary supplement marketed worldwide as an appetite suppressant. Studies included 2 in vitro genotoxicity assays, a repeated dose oral toxicity study, and a developmental study in rats. No evidence of in vitro mutagenicity or clastogenicity surfaced in the in vitro studies at concentrations up to 5000 μg of extract/plate (Ames test) or 5000 μg of extract/mL (chromosomal aberration test). No deaths or treatment-related toxicity were seen in the 6-month chronic oral toxicity study in Sprague-Dawley rats conducted at 3 doses (100, 300, and 1000 mg/kg body weight (bw)/d). The no observed effect level for CFE in this study was considered to be 1000 mg/kg bw/d. A prenatal developmental toxicity study conducted at 3 doses (250, 500, and 1000 mg/kg bw/d) in female Sprague-Dawley rats resulted in no treatment-related external, visceral, or skeletal fetal abnormalities, and no treatment-related maternal or pregnancy alterations were seen at and up to the maximum dose tested. CFE was not associated with any toxicity or adverse events.

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Short-Term High Fat Intake Does Not Significantly Alter Markers of Renal Function or Inflammation in Young Male Sprague-Dawley Rats

Journal of Nutrition and Metabolism ◽

10.1155/2015/157520 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Catherine Crinigan ◽

Matthew Calhoun ◽

Karen L. Sweazea

Keyword(s):

Kidney Disease ◽

Renal Mass ◽

Early Stage ◽

Young Male ◽

Protective Effects ◽

Sprague Dawley ◽

High Fat ◽

Short Term ◽

Sprague Dawley Rats ◽

The Impact

Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD) is not well-understood. Six weeks of HFD result in indices of metabolic syndrome (increased adiposity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hyperleptinemia, and impaired endothelium-dependent vasodilation) compared to rats fed on standard chow. The hypothesis was that short-term HFD would induce early signs of renal disease. Young male Sprague-Dawley rats were fed either HFD (60% fat) or standard chow (5% fat) for six weeks. Morphology was determined by measuring changes in renal mass and microstructure. Kidney function was measured by analyzing urinary protein, creatinine, and hydrogen peroxide (H2O2) concentrations, as well as plasma cystatin C concentrations. Renal damage was measured through assessment of urinary oxDNA/RNA concentrations as well as renal lipid peroxidation, tumor necrosis factor alpha (TNFα), and interleukin 6 (IL-6). Despite HFD significantly increasing adiposity and renal mass, there was no evidence of early stage kidney disease as measured by changes in urinary and plasma biomarkers as well as histology. These findings suggest that moderate hyperglycemia and inflammation produced by short-term HFD are not sufficient to damage kidneys or that the ketogenic HFD may have protective effects within the kidneys.

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