Safety Evaluation of Unani Formulation: Capsule Shaqeeqa in Albino Wistar Rats

Capsule Shaqeeqa, Unani formulation, is prescribed for the clinical treatment of diseases like sinusitis, headache, and migraine. The safety evaluation data of it is not available; in order to provide the safety data the present study was carried out. The study was carried out on four groups of rats (n=5). Two groups (one male and one female group) as normal controls were orally given water while the other two groups were orally given daily doses of drug at the dose level of 150 mg/kg of body weight for duration of 90 days. Physiological parameters like body weight, feed consumption, water consumption, and clinical signs were regularly monitored and recorded. Organs were collected, examined, and weighed and specimens were taken for histopathological studies. The results showed that the drug did not alter the physiological parameters. There was no mortality or any morbidity found in drug treated rats. There was no statistical significant change found in any haematological or biochemical parameter of rats orally fed with Shaqeeqa. A statistically insignificant association verified that haematological and biochemical parameters were rendered unaffected by the drug. Moreover histological investigations of essential key organs demonstrated that the drug did not prompt any histopathological change. These observations demonstrate the safety of Capsule Shaqeeqa at the studied dosage levels.

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Safety evaluation of fructooligosaccharide (FOSSENCETM): Acute, 14-day, and subchronic oral toxicity study in Wistar rats

Toxicology Research and Application ◽

10.1177/2397847318787750 ◽

2018 ◽

Vol 2 ◽

pp. 239784731878775 ◽

Cited By ~ 1

Author(s):

Manish Jain ◽

Manoj Gote ◽

Ashok Kumar Dubey ◽

S Narayanan ◽

H. Krishnappa ◽

...

Keyword(s):

Body Weight ◽

Wistar Rats ◽

Clinical Chemistry ◽

Clinical Signs ◽

Safety Evaluation ◽

Toxicity Study ◽

Feed Consumption ◽

Oral Toxicity ◽

Trophic Effect ◽

Neurological Effects

Fructooligosaccharide (FOS) has been used in infant formula and conventional foods as prebiotics. Short chain FOS (FOSSENCETM) is produced by a patented process of biotransformation of sucrose by the action of enzyme from live microbial cells, hence toxicology studies were initiated to assess its safety. The objective of the present study was to determine safety of FOSSENCETM in acute, 14-day, and subchronic (90-day) toxicity studies. In acute and 14-day studies, administration of the FOSSENCETM to Wistar rats did not cause any mortality or clinical signs and changes in body weights, feed consumption, and gross pathology at the doses of 2000, 5000, and 9000 mg/kg body weight. In the subchronic (90-day) toxicity study, FOSSENCETM was administered by oral gavage to Wistar rats at the doses of 0, 2000, 5000, and 9000 mg/kg/day for 90 days. No treatment-related clinical signs or mortalities were observed. Similarly, no treatment-related toxicologically or biologically significant changes in body weight, feed consumption, ophthalmological findings, neurological effects, hematology, clinical chemistry, urinalysis, and gross pathological findings were noticed. However, statistically significant increase in weight of cecum (without correlative microscopic change) was noted at all the test item-treated groups in males and females and was considered to be a trophic effect and not a toxic effect in rats.

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Safety evaluation of galacto-oligosaccharides

Toxicology Research and Application ◽

10.1177/2397847317715864 ◽

2017 ◽

Vol 1 ◽

pp. 239784731771586

Author(s):

Yuting Zhou ◽

Claire Kruger ◽

GS Ravi ◽

DP Santhosh Kumar ◽

SK Vijayasarathi ◽

...

Keyword(s):

Body Weight ◽

Clinical Chemistry ◽

Clinical Signs ◽

Safety Evaluation ◽

Feed Consumption ◽

Sprague Dawley ◽

Entire Treatment Period ◽

Toxic Response ◽

Sprague Dawley Rats ◽

Conventional Foods

Galacto-oligosaccharides (GOS) have been added to infant formulas and conventional foods as prebiotics all over the world. The present study was conducted to assess the subchronic toxicity of a GOS syrup (VITAGOS™) when administered orally by gavage daily at 0, 1020, 2041, and 4082 mg GOS syrup/kg/day to male and female Sprague-Dawley rats to deliver doses of 0, 500, 1000, and 2000 mg GOS/kg/day for 90 days. Throughout the entire treatment period, no abnormal clinical signs or mortalities were observed. Similarly, no test article-related toxicologically adverse findings were seen in body weight, feed consumption, ophthalmological findings, hematology, coagulation, clinical chemistry, urinalysis, organ weights, and gross pathology or histopathology. Significant increases in the cecum weight of males and females treated with 2000 mg GOS/kg/day were associated with mucosal hypertrophy/hyperplasia; no changes in the cecum were noted at lower doses. The organ weight and histopathological changes noted in the cecum are consistent with findings in rats administered other poorly digestible and fermentable substances; thus, this is considered to be an adaptive rather than toxic response. The No-Observed-Adverse-Effect-Levels for VITAGOS™ is 4082 mg GOS syrup/kg body weight/day or 2000 mg GOS/kg body weight/day.

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TOCOSH FLOUR (Solanum tuberosum L.): A Toxicological Assessment of Traditional Peruvian Fermented Potatoes

Foods ◽

10.3390/foods9060719 ◽

2020 ◽

Vol 9 (6) ◽

pp. 719

Author(s):

Jonas Roberto Velasco-Chong ◽

Oscar Herrera-Calderón ◽

Juan Pedro Rojas-Armas ◽

Renán Dilton Hañari-Quispe ◽

Linder Figueroa-Salvador ◽

...

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Biochemical Parameters ◽

Solanum Tuberosum L ◽

Lethal Dose ◽

Clinical Signs ◽

Control Group ◽

Toxicological Assessment ◽

Hematological And Biochemical Parameters ◽

Histopathological Studies

Potato tocosh is a naturally processed potato for nutritional and curative purposes from traditional Peruvian medicine. The aim of this study was to investigate the acute and sub-acute toxicity of tocosh flour (TF). For sub-acute toxicity, TF was administered orally to rats daily once a day for 28 days at doses of 1000 mg/kg body weight (BW). Animals were observed for general behaviors, mortality, body weight variations, and histological analysis. At the end of treatment, relative organ weights, histopathology, hematological and biochemical parameters were analyzed. For acute toxicity, TF was administered orally to mice at doses of 2000 and 5000 mg/kg BW at a single dose in both sexes. Body weight, mortality, and clinical signs were observed for 14 days after treatment. The results of acute toxicity showed that the median lethal dose (LD50) value of TF is higher than 2000 g/kg BW but less than 5000 mg/Kg BW in mice. Death and toxicological symptoms were not found during the treatment. For sub-acute toxicity, we found that no-observed-adverse-effect levels (NOAEL) of TF in rats up to 1000 g/kg BW. There were statistically significant differences in body weight, and relative organ weight in the stomach and brain. No differences in hematological and biochemical parameters were observed when compared with the control group. For sub-acute toxicity, histopathological studies revealed minor abnormalities in liver and kidney tissues at doses of 5000 mg/Kg. Based on these results, TF is a traditional Peruvian medicine with high safety at up to 1000 mg/kg BW for 28 days in rats.

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Tamarind Seed Polysaccharide

International Journal of Toxicology ◽

10.1177/1091581813484069 ◽

2013 ◽

Vol 32 (3) ◽

pp. 198-208 ◽

Cited By ~ 5

Author(s):

James T. Heimbach ◽

Hiroshi Egawa ◽

Palma Ann Marone ◽

Mark R. Bauter ◽

Elke Kennepohl

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Consumption ◽

Body Weight Gain ◽

Clinical Chemistry ◽

Clinical Signs ◽

Female Rats ◽

Feed Consumption ◽

Test Substance ◽

Tamarind Seed

Forty male and 40 female Crl:SD® CD® IGS rats were fed diets containing 0, 40 000, 80 000, or 120 000 ppm tamarind seed polysaccharide (equivalent to 3450.8, 6738.9, or 10 597.1 mg/kg bw/day and 3602.1, 7190.1, or 10 690.7 mg/kg bw/day for males and females, respectively) for 28 days. Animals were observed for adverse clinical signs, body weight, feed consumption, hematology and clinical chemistry parameters, urinalysis values were recorded, and at the end of the study the rats underwent a full necropsy. Functional Observational Battery (FOB) and Motor Activity (MA) tests were performed on all animals. There were no mortalities, no clinical or ophthalmologic signs, body weight, body weight gain, food consumption and food efficiency, FOB or MA findings associated with the administration of tamarind seed polysaccharide. Initial statistically significant decreases in body weight gain and food consumption resolved after the first week and were considered the result of reduced palatability. There were no adverse changes in hematology, coagulation, clinical chemistry or urinalysis parameters in male or female rats considered the result of test substance administration. At necropsy, there were no macroscopic, histopathological findings, estrus cycle, or organ weight changes deemed related to administration of the test substance. Under the conditions of this study and based on the toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) for tamarind seed polysaccharide in the diet was the highest concentration tested of 120 000 ppm (equivalent to 10 597 mg/kg bw/day and 10 691 mg/kg bw/day for male and female rats, respectively).

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Evaluation of the Developmental Toxicity of Acetyl Cedrene

International Journal of Toxicology ◽

10.1080/10915810600870575 ◽

2006 ◽

Vol 25 (5) ◽

pp. 423-428 ◽

Cited By ~ 5

Author(s):

Aurelia Lapczynski ◽

Daniel A. Isola ◽

Mildred S. Christian ◽

Robert M. Diener ◽

Anne Marie Api

Keyword(s):

Body Weight ◽

Soft Tissue ◽

Corn Oil ◽

Developmental Toxicity ◽

Clinical Signs ◽

Feed Consumption ◽

Corpora Lutea ◽

Sprague Dawley ◽

Body Weights ◽

Weight Gains

The developmental toxicity of acetyl cedrene (AC), a widely used fragrance ingredient, was evaluated in pregnant Sprague-Dawley rats (25/group). Gavaged dosages of 0 (corn oil), 25, 50, or 100 mg/kg/day were administered on days 7 through 17 of gestation (GDs 7 to 17). First and last day dosing suspensions were analyzed for AC content. All rats were observed daily for viability, clinical signs, abortions, and premature deliveries. Body weights were recorded at frequent intervals. Cesarean-sectioning and necropsy examinations were performed on GD 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. The number of corpora lutea in each ovary was also recorded. Fetuses were weighed and examined for gender and gross external changes and soft tissue or skeletal alterations. Totals of 25, 23, 21, and 24 rats became pregnant in the 0 (control), 25, 50 and 100 mg/kg/day groups, respectively, and analysis of dosage preparations verified that administered dosages reflected calculated dosages ±10%. No deaths or premature deliveries occurred in the study. Clinical signs included excessive salivation, which was attributed to the administration of AC. When compared to controls, significant reductions in feed consumption and body weight gains occurred only at 100 mg/kg/day. Both absolute (g/day) and relative (g/kg/day) feed consumption values were significantly decreased on GDs 7 to 12. Relative values were decreased significantly on GDs 15 to 18. Body weight gains were significantly reduced on GDs 7 to 10. Mean maternal body weights remained significantly lower than controls on GDs 9 to 14, but a marked compensatory increase in feed consumption on GDs 15 to 18 prevented further deterioration in body weight gains. No cesarean-sectioning or litter parameters were affected by dosages of AC and necropsy of the dams after cesarean section did not reveal any gross changes attributable to AC. No gross external, soft tissue, or skeletal fetal alterations (malformations or variations) were attributed by dosages AC. The average number of ossifications sites per fetus per litter did not differ among the groups. Based on these data, maternal and developmental no-observable-adverse-effect levels (NOAELs) of 50 and 100 mg/kg/day, respectively, were established for AC.

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Developmental Toxicity of Levo-Alpha-Acetylmethadol (LAAM) in Tolerant Rats

International Journal of Toxicology ◽

10.1080/10915810252866105 ◽

2002 ◽

Vol 21 (2) ◽

pp. 147-159 ◽

Cited By ~ 5

Author(s):

Raymond G. York ◽

Kevin H. Denny ◽

David E. Moody ◽

Mario E. Alburges

Keyword(s):

Body Weight ◽

Body Weight Gain ◽

Fetal Liver ◽

Developmental Toxicity ◽

Clinical Signs ◽

Fetal Brain ◽

Female Rats ◽

Feed Consumption ◽

Fetal Plasma ◽

Range Finding

Mated Crl:CD VAF/Plus female rats, in a range-finding study ( n = 5–6 per dose) and a subsequent definitive study ( n = 30 per dose) were used to determine the developmental toxicity, including the teratogenic potential of levo-alpha-acetyhnethadol (LAAM) hydrochloride, in tolerant rats. Tolerance was induced by initially administering the drug by gavage (10 ml/kg) at 2 mg/kg/day and increasing the dose every 2 weeks for 12 weeks until the doses of 2, 6, 9, 12, and 15, or 2, 6, and 12 mg/kg/day were achieved in the range-finding or definitive study, respectively. Females were then mated to stock males and treated throughout mating and gestation. Controls received distilled water on a similar regimen. The range-finding experiment was used for initial clinical evaluations and to determine tissue concentrations of LAAM and metabolites. In plasma, liver, and brain collected from dams and fetuses pooled by litter on gestation day 20, LAAM and its two N-demethylated metabolites, norLAAM and dinorLAAM, showed dose-dependent increases in concentration and in tissue to plasma ratios. Tissue to dam plasma ratios were highest in dam liver (17–60), intermediate in fetal liver (3–16), and fetal brain (3–14), and lowest in dam brain (0.8–5.6) and fetal plasma (0.3–2.1). In the definitive study, caesarean section examinations were performed following euthanization on gestation day 20 on all surviving females followed by teratologic examination of the fetuses. Drug-related outcomes, including increased activity, secondary hair loss, scabbing, focal swelling, and material around the nose, were exhibited by all groups receiving LAAM. Maternal toxicity was evident as decreased body weights, with maximum reduction at the 6-mg/kg/day dose, and reduction in feed consumption. There was also evidence of developmental toxicity in the form of postimplantaüon losses at all doses of LAAM. There were no deaths attributable to LAAM. No grossly observable visceral or skeletal anomalies related to LAAM were observed in the fetuses. In conclusion, the no-observable-effect level when administered to tolerant rats was less than 2 mg/kg/day with regard to clinical signs, body weight, body weight gain, and feed consumption, and with regard to developmental toxicity as reflected by postimplantaüon losses. Despite maternal and developmental toxicity, there was no evidence of selective fetal toxicity or teratogenic activity attributable to LAAM.

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ACUTE TOXICITY EVALUATION OF PROTODIOSCIN RICH EXTRACT OF TRIGONELLA FOENUM-GRAECUM L IN RATS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2016.v9s3.14706 ◽

2016 ◽

Vol 9 (9) ◽

pp. 152

Author(s):

Vijaykumar Kunvarji Parmar ◽

Ketan Variya ◽

Sandip Patel

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Clinical Signs ◽

Oral Gavage ◽

Adult Rats ◽

Trigonella Foenum Graecum ◽

Biochemical Analyses ◽

Histopathological Studies ◽

Trigonella Foenum Graecum L

ABSTRACTObjectives: The objective of this study was to investigate the acute toxicity of standardized protodioscin rich extract (PRE) of Trigonella foenumgraecumL (26.63% w/w; PRE).Methods: To evaluate the toxicity of PRE, the acute toxicity of the extract on adult rats were investigated. A fixed large dose of 2 g/kg body weight ofPRE was administrated by a single oral gavage, and 1 g/kg body weight of PRE was administered by intravenous according to the Organisation forEconomic Co-operation and Development guidelines.Results: In 2 weeks, PRE showed no obvious acute toxicity. There were no deaths in either group and no change in the clinical signs. The hematologicaland biochemical analyses showed some changes that returned to reference levels without impairment of homeostasis. The treatment did not induceuntoward changes in organs as shown by histological studies. The in vivo results showed that has low toxicity.Conclusion: PRE is safe and can be potentially used as an aphrodisiac in future studies.Keywords: Protodioscin, Aphrodisiac, Trigonella foenum-graecum, Organisation for Economic Co-operation and Development, Toxicity,Histopathological studies.

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Toxicological evaluation of alpha-galacto-oligosaccharides shows no adverse effects over a 90-day study in rats

Toxicology Research and Application ◽

10.1177/2397847317716402 ◽

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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Developmental Toxicity of Homobrassinolide in Wistar Rats

International Journal of Toxicology ◽

10.1177/1091581810375620 ◽

2010 ◽

Vol 29 (5) ◽

pp. 517-522 ◽

Cited By ~ 7

Author(s):

Yogeshkumar V. Murkunde ◽

P. Balakrishna Murthy

Keyword(s):

Body Weight ◽

Wistar Rats ◽

Dose Group ◽

Developmental Toxicity ◽

Clinical Signs ◽

Feed Consumption ◽

Oral Gavage ◽

Fetal Toxicity ◽

Skeletal Malformations ◽

Teratogenic Potential

Brassinosteroids (BRs) are close analogues of animal cholesterol. Brassinosteroids have shown their great value as yield promoters of a variety of plants. In view of its steroidal moiety and recent use in agriculture in many countries, the teratogenic potential of homobrassinolide (HBR) was evaluated in Wistar rats. Homobrassinolide was administered by oral gavage at doses 0, 100, and 1000 mg/kg body weight in water during gestation days (GD) 6 to 15 in groups of 20 mated females. Maternal and embryo-fetal toxicity was analyzed by studying the effects such as clinical signs, mortality/morbidity, abortions, body weight, feed consumption, and pregnancy data, gravid uterine weights, implantation losses, litter size, external, visceral, and skeletal malformations. No treatment-related effect was observed on any of the maternal/fetal end points in any dose group. From the results, it can be concluded that HBR is nonteratogenic at doses as high as up to 1000 mg/kg body weight in Wistar rats.

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Safety evaluation of α-galacto-oligosaccharides for use in infant formulas investigated in neonatal piglets

Toxicology Research and Application ◽

10.1177/2397847317722828 ◽

2017 ◽

Vol 1 ◽

pp. 239784731772282 ◽

Cited By ~ 1

Author(s):

Claire Kruger ◽

Yuting Zhou ◽

Bjorn A Thorsrud ◽

Fanny Morel-Despeisse ◽

Eric Chappuis

Keyword(s):

Clinical Chemistry ◽

Clinical Signs ◽

Safety Evaluation ◽

Feed Consumption ◽

Common Finding ◽

Infant Formulas ◽

Organ Weights ◽

Neonatal Piglets ◽

Body Weights ◽

Milk Replacers

Galacto-oligosaccharide (GOS), comprising galactoses with a glucose or sucrose, is a family of nondigestible oligosaccharides. The present study evaluates the safety of an α-GOS product (P-GOS® P) in a neonatal piglet model for 3 weeks. Three days after birth, neonatal piglets were divided into control and treated groups and provided with swine milk replacers in the absence and presence of 8 mg/mL—of the α-GOS product, respectively. An increase in the weight of the large intestines in treated males was noted, which is a common finding in studies of animals fed nondigestible oligosaccharides. There were no α-GOS product-related adverse effects in the piglets in terms of clinical signs, body weights, feed consumption, clinical chemistry, hematology, organ weights, or histopathology. The study demonstrated that formula supplemented with 8 mg/mL of P-GOS P is safe and well tolerated in neonatal piglets and supports the safe use of P-GOS P in infant formulas.

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