Safety Assessment of Zigbir®: A Polyherbal Formulation in Sprague-Dawley Rats

The safety of Zigbir®, a polyherbal formulation intended for use as food supplement, was evaluated in Sprague-Dawley rats treated orally at the dose of 2000 mg/kg in acute and at 250, 500, and 1000 mg/kg for 90 days in subchronic toxicity study. The median lethal dose of Zigbir® was found to be more than 2000 mg/kg, and fourteen-day repeated dose toxicity study revealed it to be safe up to 1000 mg/kg. The subchronic study did not show any mortality or treatment-related adverse clinical signs. The treated animals exhibited normal feed intake and comparable body weight gain except for a decrease in females of 500 and 1000 mg/kg groups. Ocular examination revealed no abnormalities. Further, Zigbir® administration in rats did not induce any major changes in urinalysis, hematological, and biochemical evaluations except for minor alterations in few parameters at different dose levels. Gross and histopathological findings did not show any lesions attributable to Zigbir® administration. The no observed effect level of Zigbir® was found to be 500 and 250 mg/kg in male and female Sprague-Dawley rats.

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Acute and Subchronic Oral Toxicity of Oil Palm Puree in Sprague–Dawley Rats

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17103404 ◽

2020 ◽

Vol 17 (10) ◽

pp. 3404

Author(s):

Zaida Zainal ◽

Augustine Ong ◽

Choo Yuen May ◽

Sui Kiat Chang ◽

Afiqah Abdul Rahim ◽

...

Keyword(s):

Lethal Dose ◽

Pharmaceutical Formulations ◽

Toxicity Study ◽

Sprague Dawley ◽

Oral Toxicity ◽

Subchronic Toxicity ◽

Organ Weights ◽

Sprague Dawley Rats ◽

Adverse Effect Level ◽

Effect Level

Palm puree is rich in antioxidants and is produced via blending various proportions of mesocarp fibre and crude palm oil. The aim of this study was to assess the acute and subchronic toxicity of palm puree in male and female Sprague–Dawley rats. For the acute toxicity study, animals administered single palm-puree doses (2000 mg kg−1) by gavage were observed daily for 14 d. For the subchronic toxicity study, the rats were administered 500, 1000, or 2000 mg kg−1 palm puree daily for 28 d. We evaluated body and organ weights; performed haematological, biochemical, and histopathological analyses of blood and organ samples during and after treatment; and calculated the oral no-observed-adverse-effect level (NOAEL). The toxicity studies showed no signs of toxicity or mortality. The haematological, biochemical, and histopathological analyses and body and organ weights indicated no evidence of substantial toxicity at any dose of palm puree. The oral lethal dose and NOAEL for the palm puree were greater than 2000 mg kg−1 d−1 over 28 d. To the best of our knowledge, the present study is the first to confirm the safety of palm puree as a novel functional food. These encouraging results warrant further studies to elucidate its potential for pharmaceutical formulations.

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180 Day Repeated-Dose Toxicity Study on Forchlorfenuron in Sprague–Dawley Rats and Its Effects on the Production of Steroid Hormones

Journal of Agricultural and Food Chemistry ◽

10.1021/acs.jafc.9b03855 ◽

2019 ◽

Vol 67 (36) ◽

pp. 10207-10213 ◽

Cited By ~ 3

Author(s):

Qian Bu ◽

Xiaoyan Wang ◽

Hongcheng Xie ◽

Kai Zhong ◽

Yanping Wu ◽

...

Keyword(s):

Steroid Hormones ◽

Toxicity Study ◽

Repeated Dose ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Repeated Dose Toxicity

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/2135351 ◽

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.

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Subchronic Hepatotoxicity Evaluation of 1,2,4-Tribromobenzene in Sprague-Dawley Rats

International Journal of Toxicology ◽

10.1177/1091581812437974 ◽

2012 ◽

Vol 31 (3) ◽

pp. 250-256 ◽

Cited By ~ 4

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.

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Prenatal Oral (Gavage) Developmental Toxicity Study of Decabromodiphenyl Oxide in Rats

International Journal of Toxicology ◽

10.1080/10915810252866051 ◽

2002 ◽

Vol 21 (2) ◽

pp. 83-91 ◽

Cited By ~ 30

Author(s):

M. L. Hardy ◽

R. Schroeder ◽

J. Biesemeier ◽

O. Manor

Keyword(s):

Body Weight ◽

Flame Retardant ◽

Corn Oil ◽

Body Weight Gain ◽

Developmental Toxicity ◽

Clinical Signs ◽

Toxicity Study ◽

Wide Range ◽

Effect Level ◽

Effect Of Treatment

Decabromodiphenyl oxide (DBDPO) is a highly effective flame retardant that is primarily used in electrical and electronic equipment with a secondary, but important, application in upholstery textiles. DBDPO, the second largest volume brominated flame retardant in use today, has undergone a wide range of toxicology tests in mammalian species with the results indicating a no-adverse-effect level of ∼1000 mg/kg/day in oral repeated-dose studies. An oral prenatal developmental toxicity study of the commercial DBDPO product (97% purity) was performed under current EPA OPPTS and OECD guidelines. Female Sprague-Dawley rats (25 mated females/group) received 0, 100, 300 or 1000 mg DBPDO/kg/day via gavage in corn oil during gestation days 0 through 19. All females survived until scheduled sacrifice. No clinical signs of toxicity were observed. Pregnancy rates in the control and treated groups ranged from 96% to 100% and provided 23 or more litters in each group for evaluation on gestation day 20. No effect of treatment was seen in maternal gestational parameters (body weight, body weight gain, and food consumption), uterine implantation data, liver weight, or necropsy findings. Likewise, no effect of treatment was seen in fetal body weights, fetal sex distribution, or during the fetal external, visceral, or skeletal examinations. The NOEL (noobservable-effect level) for maternal and developmental toxicity was 1000 mg DBPDO/kg/day, the highest dose level administered on gestation days 0 to 19.

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

International Journal of Toxicology ◽

10.1177/109158180302200606 ◽

2003 ◽

Vol 22 (6) ◽

pp. 453-464 ◽

Cited By ~ 21

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.

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Repeated Dose Toxicity Study of a Live Attenuated Oral Cholera Vaccine in Sprague Dawley Rats

Archives of Medical Research ◽

10.1016/j.arcmed.2009.09.003 ◽

2009 ◽

Vol 40 (7) ◽

pp. 527-535 ◽

Cited By ~ 5

Author(s):

Sergio Sifontes-Rodríguez ◽

Juan Francisco Infante-Bourzac ◽

Daiyana Díaz-Rivero ◽

Yulieé López-Feria ◽

Merlin Pérez-Pérez ◽

...

Keyword(s):

Toxicity Study ◽

Repeated Dose ◽

Cholera Vaccine ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Repeated Dose Toxicity ◽

Oral Cholera Vaccine

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

International Journal of Toxicology ◽

10.1080/10915810802513379 ◽

2008 ◽

Vol 27 (3_suppl) ◽

pp. 11-27 ◽

Cited By ~ 7

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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