Toxicologic Evaluation of Cellulon™ Fiber; Genotoxicity, Pyrogenicity, Acute and Subchronic Toxicity

CellulonTM fiber, a cellulose produced by a bacterial fermentation process employing a strain of Acetobacter aceti subsp. xylinum, was tested for genotoxicity in four assays: (1) microbial reverse mutation assay in Salmonella typhimurium (Ames assay), (2) an assay for chromosomal aberrations in Chinese hamster ovary (CHO) cells, (3) an assay for induction of unscheduled DNA synthesis (UDS) in rat primary hepatocytes, and (4) the CHO/HGPRT forward mutation assay. Each assay was conducted at a wide range of dose levels, both with and without metabolic activation (assay 1, 2, and 4). Test results gave no indication that Cellulon fiber possessed any genotoxic potential. The pyrogenicity of five batches of Cellulon fiber was tested in the Limulus Amebocyte Lysate assay, gel-clot method. Test results were negative for the presence of gram-negative bacterial endotoxin. The primary eye and dermal irritation potential of Cellulon fiber were examined in New Zealand White rabbits. The Draize method was employed to evaluate and grade ocular and dermal irritation as a result of test material administration. Test results indicated that Cellulon fiber is a minor ocular irritant up to 1 hour postadministration. However, the resultant irritation was considered to be mechanical and related to the dry, granular form of the test material. In addition, test results indicated that Cellulon fiber is not a dermal irritant in the rabbit. The acute oral toxicity of Cellulon fiber was determined in Sprague-Dawley rats, and the LD50 was found to be greater than 2000 mg/kg of body weight. The subchronic toxicity of Cellulon fiber was examined in Sprague-Dawley rats fed diets containing 0, 5, and 10% Cellulon fiber or microcrystalline cellulose for 13 weeks. No dose-related effects on survival, growth, hematology, blood chemistry, organ weights, or pathologic lesions were observed. The results of these studies indicate that Cellulon fiber and microcrystalline cellulose are toxicologically equivalent and that Cellulon fiber does not possess genotoxic potential, is nonpyrogenic, and that animals are not adversely affected by acute or subchronic exposure to Cellulon fiber.

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Toxicological Evaluation of the ketogenic ester Bis Hexanoyl (R)-1,3-Butanediol: Subchronic Toxicity in Sprague Dawley Rats

Food and Chemical Toxicology ◽

10.1016/j.fct.2021.112084 ◽

2021 ◽

pp. 112084

Author(s):

Brianna J. Stubbs ◽

Andrey I. Nikiforov ◽

Marisa O. Rihner ◽

Sari L. Weston ◽

Nancy Higley ◽

...

Keyword(s):

Sprague Dawley ◽

Subchronic Toxicity ◽

Toxicological Evaluation ◽

Sprague Dawley Rats

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The in vivo Pig-a gene mutation assay is applied to study the genotoxicity of procarbazine hydrochloride in Sprague-Dawley rats

Fundamental Toxicological Sciences ◽

10.2131/fts.3.167 ◽

2016 ◽

Vol 3 (4) ◽

pp. 167-175 ◽

Cited By ~ 2

Author(s):

Jiang Pu ◽

Yuanyuan Deng ◽

Xiaoyan Tan ◽

Gaofeng Chen ◽

Cong Zhu ◽

...

Keyword(s):

Gene Mutation ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Mutation Assay ◽

Gene Mutation Assay

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Subchronic Toxicity of Lunasin Targeted Extract (ET-Lun) from Soybean Seed (Glycine max (L.) Merr.): Perspective from Liver Histopathology, SGOT, and SGPT Levels in Sprague Dawley Rats

Pharmacognosy Journal ◽

10.5530/pj.2021.13.175 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1384-1388

Author(s):

Numlil Khaira Rusdi ◽

Weri Lia Yuliana ◽

Erni Hernawati Purwaningsih ◽

Andon Hestiantoro ◽

Kusmardi Kusmardi

Keyword(s):

Glycine Max ◽

Soybean Seed ◽

Sprague Dawley ◽

Subchronic Toxicity ◽

Liver Histopathology ◽

Sprague Dawley Rats ◽

Glycine Max L

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Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies

Journal of Toxicology ◽

10.1155/2019/3680757 ◽

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.

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Subchronic Toxicity of S-111-S-WB in Sprague Dawley Rats

International Journal of Toxicology ◽

10.1177/1091581810370372 ◽

2010 ◽

Vol 29 (4) ◽

pp. 358-371 ◽

Cited By ~ 6

Author(s):

Jozef J. W. M. Mertens ◽

Daniel W. Sved ◽

Gary B. Marit ◽

Nichole R. Myers ◽

Phil L. Stetson ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Steady State ◽

Ammonium Salts ◽

Serum Concentrations ◽

Sprague Dawley ◽

Subchronic Toxicity ◽

Lower Serum ◽

Sprague Dawley Rats ◽

Steady State Serum ◽

Effect Level

S-111-S-WB, a mixture of perfluoro fatty acid ammonium salts (C6-C13), was administered orally to Crl:CD (SD)IGS-BR rats. Higher hepatic β-oxidation and liver weights with hepatocellular hypertrophy were present at the 0.125 and 0.6 mg/kg/d dosage. The 0.6 mg/kg/d males developed hepatocellular degeneration and necrosis. Lower serum protein and higher bilirubin and BUN were seen in the 0.6 mg/kg/d males and lower globulin and higher alkaline phosphatase in the 0.125 mg/kg/d males and 0.6 mg/kg/d animals. After 2 weeks, serum concentrations of pentadecafluorooctanoic acid (C8), heptadecafluorononanoic acid (C9), perfluoroundecanoic acid (C11), and perfluorotridecanoic acid (C13) were constant for at least 8 hours. After 90 days, only C9 in the 0.025 mg/kg/d females had reached steady state. Serum C8 and C9 concentrations in the males were 10-fold higher than in the females, whereas C11 and C13 were similar for both genders. The main elimination was via the urine for C8 (males) and C9 (females), and via the feces for C11 and C13. The no-observed-effect level (NOEL) was 0.025 mg/kg/d for the males and 0.125 mg/kg/d for the females.

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SUBCHRONIC TOXICITY OF MALAYSIAN ACALYPHA INDICA: BIOCHEMISTRY AND HAEMATOLOGY ANALYSIS OF RAT

Jurnal Teknologi ◽

10.11113/jt.v78.8570 ◽

2016 ◽

Vol 78 (5-5) ◽

Author(s):

Norazlanshah Hazali ◽

Nurul Nadia Mohd Nazri ◽

Muhammad Ibrahim ◽

Mashita Masri

Keyword(s):

Body Weight ◽

Skin Diseases ◽

Female Rats ◽

Control Group ◽

Dosage Group ◽

Sprague Dawley ◽

Subchronic Toxicity ◽

High Dosage Group ◽

Sprague Dawley Rats ◽

Acalypha Indica

Acalypha indica is one of the medicinal plants that have been used since ages to treat various diseases such as pneumoniae, asthma and skin diseases. This study aimed to explore the subchronic toxicity effect of Acalypha indica on Sprague Dawley rats based on haematological and biochemical parameters. The extract of Acalypha indica was prepared by aqueous extraction technique. 48 Sprague Dawley rats aged 7 weeks, weighing 150-200g were randomly divided into four groups, 6 animals per gender. A control group received water vehicle while three treated groups received the extract at dosage of 100 (low dosage group), 200 (medium dosage group) and 300 (high dosage group) mg/kg body weight. The sample was administered orally by using oral gavage daily for 90 days. No sign of toxicity and mortality was recorded in all groups throughout the study. There were no significant different (p>0.05) in body weight gain, food and water intake between control and treatment group. However, there was significant different in uric acid between control and high dosage group of male and female rats but the mean were in normal range. There were also reduced in mean of urea and creatinine in all dosage group of male and urea for all dosage group of female. Statistically significant reduced in urea was recorded between control and high dosage group of male only. Other parameters showed no significant different between control and treatment groups. Therefore, Acalypha indica is safe for human consumption and might be potential in reducing kidney damage problem.

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Acute and subchronic toxicity of FCD, a soybean extract combined with l-carnitine, in Sprague–Dawley rats

Regulatory Toxicology and Pharmacology ◽

10.1016/j.yrtph.2010.11.001 ◽

2011 ◽

Vol 59 (2) ◽

pp. 285-292 ◽

Cited By ~ 2

Author(s):

Jeong-Hwan Che ◽

Euna Kwon ◽

Seung-Hyun Kim ◽

Ji-Ran You ◽

Bae-Hwan Kim ◽

...

Keyword(s):

Sprague Dawley ◽

Subchronic Toxicity ◽

Sprague Dawley Rats ◽

Soybean Extract

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Cocoa Pod Husk Pectin Intended as a Pharmaceutical Excipient Has No Adverse Effects on Haematological Parameters in Sprague Dawley Rats

Journal of Pharmaceutics ◽

10.1155/2018/1459849 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Ofosua Adi-Dako ◽

Kwabena Ofori-Kwakye ◽

Kennedy Kwami Edem Kukuia ◽

Jerry Asiedu-Larbi ◽

Alexander Kwadwo Nyarko ◽

...

Keyword(s):

Total Bilirubin ◽

Natural Polymer ◽

Sprague Dawley ◽

Subchronic Toxicity ◽

Sprague Dawley Rats ◽

Novel Drugs ◽

Cocoa Pod Husk ◽

Polymer Research ◽

Haematological Indices ◽

Haematopoietic System

Natural polymer research has recently become the focus of intensive research in the quest for new enabling excipients for novel drugs in pharmaceutical formulation for optimal treatment outcomes. Evaluations of some excipients have shown deleterious haematological effects of varying extents on the safety profile of these excipients. A 90-day subchronic toxicity study was conducted to evaluate the influence of cocoa pod husk (CPH) pectin on indicators for haematotoxicity. Male and female Sprague Dawley rats (SDRs) were fed with CPH pectin in doses up to 71.4 mg/kg. The effects of CPH pectin on the haematological indices, direct and total bilirubin, and the spleen were determined. The results indicated that CPH pectin did not induce any untoward toxic effects on the haematological indices, bilirubin levels, and the spleen. There were, however, elevations in MCV at day 30, which was not sustained after the 90 days. The data obtained from this study did not reveal any remarkable findings of toxicological relevance to the haematopoietic system.

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