THE ACUTE ORAL TOXICITY OF SPIRAMYCIN

1958 ◽  
Vol 36 (1) ◽  
pp. 103-110 ◽  
Author(s):  
Eldon M. Boyd
Keyword(s):  
Body Weight ◽  
Lethal Dose ◽  
Young Male ◽  
Surface Epithelium ◽  
Albino Rats ◽  
Clinical Effects ◽  
Oral Toxicity ◽  
Hepatic Cells ◽  
Usual Therapeutic Dose ◽  
Tunica Propria

Spiramycin was administered as a suspension by stomach tube in a range of doses to 46 young male albino rats, with 16 controls, and to 14 small mongrel bitches, with eight controls. The oral acute LD50 was found to be 9.4 ± 0.8 g. (mean ± S.D.) per kg. body weight in rats and 5.2 ± 1.6 g. per kg. body weight in dogs. From these values, the oral acute LD50 in man was estimated to be of the order of 1 to 2 g. per kg. body weight or 20 to 40 times the usual therapeutic dose. The clinical effects of these acutely toxic oral doses in rats and dogs were anorexia, vomiting (dogs only), diarrhea, and lassitude, progressing to prostration, pallor, a fall in body temperature, cessation of respiration, and death usually within 48 hours. At autopsy the stomach and intestines were distended with gas and liquid, the tunica propria and submucosa were acutely congested, and there was excessive necrosis and desquamation of the surface epithelium. Areas of acute necrosis were found in the hepatic cells and sinusoids of the liver, and in the (mostly distal) convoluted tubules of the kidney. The cause of death, therefore, was an acute fulminating gastroenteritis accompanied by acute regional necrosis of the liver and kidneys, produced by the orally administered lethal dose of spiramycin.

THE ACUTE ORAL TOXICITY OF SPIRAMYCIN

1958 ◽  
Vol 36 (1) ◽  
pp. 103-110 ◽  
Author(s):  
Eldon M. Boyd
Keyword(s):  
Body Weight ◽  
Lethal Dose ◽  
Young Male ◽  
Surface Epithelium ◽  
Albino Rats ◽  
Clinical Effects ◽  
Oral Toxicity ◽  
Hepatic Cells ◽  
Usual Therapeutic Dose ◽  
Tunica Propria

Spiramycin was administered as a suspension by stomach tube in a range of doses to 46 young male albino rats, with 16 controls, and to 14 small mongrel bitches, with eight controls. The oral acute LD50 was found to be 9.4 ± 0.8 g. (mean ± S.D.) per kg. body weight in rats and 5.2 ± 1.6 g. per kg. body weight in dogs. From these values, the oral acute LD50 in man was estimated to be of the order of 1 to 2 g. per kg. body weight or 20 to 40 times the usual therapeutic dose. The clinical effects of these acutely toxic oral doses in rats and dogs were anorexia, vomiting (dogs only), diarrhea, and lassitude, progressing to prostration, pallor, a fall in body temperature, cessation of respiration, and death usually within 48 hours. At autopsy the stomach and intestines were distended with gas and liquid, the tunica propria and submucosa were acutely congested, and there was excessive necrosis and desquamation of the surface epithelium. Areas of acute necrosis were found in the hepatic cells and sinusoids of the liver, and in the (mostly distal) convoluted tubules of the kidney. The cause of death, therefore, was an acute fulminating gastroenteritis accompanied by acute regional necrosis of the liver and kidneys, produced by the orally administered lethal dose of spiramycin.

Acute and subacute toxicity assessment of Madhulai Manappagu (Siddha herbal syrup formulation) in animal model

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Meenakshi Sundaram Malayappan ◽  
Gayathri Natarajan ◽  
Logamanian Mockaiyathevar ◽  
Meenakumari Ramasamy
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Oral Route ◽  
Toxicity Assessment ◽  
Toxicity Study ◽  
Female Rats ◽  
Albino Rats ◽  
Oral Toxicity ◽  
Gross Pathology ◽  
Toxicity Studies

Abstract Objectives Madhulai Manappagu – a well-known sastric and widely prescribed Siddha herbal syrup formulation indicated for treating Veluppu Noi (Anaemia especially Iron deficiency Anaemia) has been in day today practice in Tamil Nadu for a quite longer decades. The syrup is a herbal preparation which has a sweet pleasant odour and a palatable taste, contain the juice of pomegranate (Punica granatum L.) as the main ingredient. Though the formulation is a fruit juice, the safety profile of the syrup is not established and is being marketed without toxicological evaluation. The study is aimed at ascertaining the acute and sub-acute toxicity assessment of Madhulai Manappagu in Wistar Albino rats. Methods The acute and sub-acute (28day repeated oral) toxicity studies were performed as per the guidelines mentioned in the Organization for Economic Cooperation and Development (OECD) 423 (adopted on December 2001) and TG 407 (adopted on October 2008) with slight modifications respectively. For acute toxicity study, three female rats were randomly selected as control; three female rats were randomly selected and were administered a single dose of 5,000 mg/kg body weight per oral route. For sub-acute (28day repeated oral) toxicity studies, three doses of test drug MM of 500 mg/kg/day (low dose), 750 mg/kg/day (intermittent dose) and 1,000 mg/kg/day (high dose) were selected for administration. Both sexes of Wistar Albino rats were randomized into four groups of 10 animals each (five males, five females). Group I was kept as control group. Group II, III and IV served as low, intermittent and high doses of MM respectively. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In the acute toxicity study, rats showed no toxicological signs on behavior, gross pathology and body weight of rats when treated with a single dose of 5,000 mg/kg body weight per oral route. In the subacute (28 days repeated oral) toxicity study, rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters when treated with Madhulai Manappagu in three different doses. Conclusions The toxicity studies which include both acute and 28 days repeated (subacute) oral toxicity studies, revealed no observed adverse effect level (NOAEL) of Madhulai Manappagu in animals. Thus the safety of the drug in human usage was ensured.

scholarly journals Delving into the Antiurolithiatic Potential of Tribulus terrestris Extract Through –In Vivo Efficacy and Preclinical Safety Investigations in Wistar Rats

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jyoti Kaushik ◽  
Simran Tandon ◽  
Rishi Bhardwaj ◽  
Tanzeer Kaur ◽  
Surinder Kumar Singla ◽  
...  
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Kidney Stones ◽  
Wistar Rats ◽  
Lethal Dose ◽  
Tribulus Terrestris ◽  
Oral Toxicity ◽  
Preclinical Safety

Abstract Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.

scholarly journals ACUTE ORAL TOXICITY STUDY OF ETHANOLIC EXTRACT OF ACTINOSCIRPUS GROSSUS (L.F.) GOETGH. AND D.A. SIMPSON

2018 ◽  
Vol 11 (7) ◽  
pp. 321
Author(s):  
Savin Chanthala Ganapathi ◽  
Rajendra Holla ◽  
Shivaraja Shankara Ym ◽  
Ravi Mundugaru
Keyword(s):  
Body Weight ◽  
Lethal Dose ◽  
Ethanolic Extract ◽  
Female Rats ◽  
Test Substance ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Healthy Female ◽  
Ld50 Value ◽  
Toxic Potential

Objective: To study the acute oral toxicity of ethanolic extract of Actinoscirpus grossus (L.f.) Goetgh. and D.A. Simpson in Wistar albino rats.Methods: Ethanolic extract of the plant was assessed for single dose acute toxicity by employing Organisation for Economic Co-Operation and Development(OECD) guidelines 425 using Acute Oral Toxicity(AOT) software. The dosed (up or down as per the requirement) rats were observed for 14 days for general appearance, behavior, mortality, and necropsy. A total of 5 healthy female rats of body weight 225±25 g were used.Results: The test substance did not produce any mortality up to the dose of 2000 mg/kg per oral.Conclusion: Test substance is without any toxic potential even at the dose of 2000 mg/kg in animals and the Lethal Dose (LD50) value of A. grossus (L.f.) Goetgh. and D.A. Simpson was found to be more than 2000 mg/kg body weight.

scholarly journals Acute, Subacute, and Genotoxicity Assessments of a Proprietary Blend of Garcinia mangostana Fruit Rind and Cinnamomum tamala Leaf Extracts (CinDura®)

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Sundararaju Dodda ◽  
Venkata Krishnaraju Alluri ◽  
Trimurtulu Golakoti ◽  
Krishanu Sengupta
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Lethal Dose ◽  
Toxicity Study ◽  
Mouse Bone Marrow ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Garcinia Mangostana ◽  
Cinnamomum Tamala ◽  
Fruit Rind

The present communication describes a battery of toxicity studies that include an acute oral toxicity, a subacute twenty-eight-day repeated oral dose toxicity, and genotoxicity studies on a herbal formulation CinDura® (GMCT). This proprietary herbal composition contains the extracts of the Garcinia mangostana fruit rind (GM) and the Cinnamomum tamala leaf (CT). The toxicological evaluations were performed following the Organization for Economic Cooperation and Development (OECD) guidelines. The acute oral toxicity study in Wistar rats suggests that the median lethal dose of CinDura® is at least 2000 mg/kg body weight. Acute dermal and eye irritation tests in New Zealand white rabbits indicate that the test item is nonirritant to the skin and eyes. A twenty-eight-day repeated dose oral toxicity study was conducted in male and female Wistar rats using daily doses of 250, 500, and 1000 mg/kg body weight, followed by a fourteen-day reversal period for two satellite groups. The CinDura®-supplemented animals did not show any sign of toxicity on their body weights, organ weights, and on the hematobiochemical parameters. The gross pathology and histopathological examinations indicated no treatment-related changes in the experimental animals. Overall, the no-observed-adverse-effect level (NOAEL) of the herbal blend is 1000 mg/kg body weight, the highest tested dose. Also, the results of the bacterial reverse mutation test and the erythrocyte micronucleus assay in mouse bone marrow suggest that CinDura® (GMCT) is neither mutagenic nor clastogenic.

scholarly journals Evaluation of Median Lethal Dose and Subchronic Oral Toxicity Assessment of Ethanolic Leaf Extract of Phyllanthus amarus

2019 ◽  
pp. 1-8
Author(s):  
O. E. Adolor ◽  
I. Onyesom ◽  
A. O. Opajobi ◽  
J. C. Mordi
Keyword(s):  
Body Weight ◽  
Total Antioxidant Capacity ◽  
Liver Tissue ◽  
Leaf Extract ◽  
Lethal Dose ◽  
Phyllanthus Amarus ◽  
Oral Toxicity ◽  
Weight Group ◽  
Total Antioxidant ◽  
Ethanolic Leaf Extract

Aims: To determine the median lethal dose (LD50) of crude ethanolic leaf extract of Phyllanthus amarus and evaluate its sub-chronic oral toxicity in experimental mice (BALB/C strain). Study Design: One-factor, one-control, one-test group experimental design. Place and Duration of Study: Department of Medical Biochemistry, Delta State University, Abraka, Nigeria, between December, 2014 and November, 2015. Methodology: Crude ethanolic leaf extract of P. amarus was prepared as previously described and twenty (20) Swiss albino mice (BALB/C strain) were randomly and equally divided into two (2) groups and administered 2000 mg/kg body weight (Group A) and 5000 mg/kg body weight (Group B) of the prepared extract as single oral dose in line with the limit dose method of determining LD50. For the sub-chronic oral toxicity study, ten (10) mice were assigned into control (n=5) and experimental (n=5). The control animals were given placebo-normal saline, but the experimental mice were administered with nocebo – 300 mg/kg body weight of P. amarus crude ethanolic extract for twenty one (21) days. Thereafter, the animals in each group were sacrificed and then, serum and liver homogenate were obtained for the assay of total antioxidant capacity (TAC) and oxidative damage (Malondialdehyde-MDA) Using documented methods. Liver tissue was also processed for histopathological examination using H&E stain. Results: Data showed LD50 of the extract to be greater than 5000 mg/kg. Assessment of the herb’s sub-chronic oral toxicity indicates that the leaf extract significantly (P=.03) enhanced total antioxidant capacity (TAC) in both serum (Control: TAC = 0.10±0.03 mM, Experimental: TAC = 0.33±0.05 mM) and liver (Control: TAC = 0.12±0.09 mM, Experimental: TAC = 0.34±0.06 mM) but reduced (P = .01) the biomarker for liver tissue damage (Control: MDA = 41.89±3.36 µM, Experimental: MDA = 4.67±4.04 µM). In addition, hepatic cells were invigorated by P. amarus treatment as suggested by the histopathological features. Conclusion: Collectively, P. amarus crude ethanolic leaf extract possesses high degree of tolerance and hepatic tonic potential with no identifiable toxic or side effects.

THE CHRONIC ORAL TOXICITY OF SODIUM CHLORIDE AT THE RANGE OF THE LD50(0.1L)

1966 ◽  
Vol 44 (1) ◽  
pp. 157-172 ◽  
Author(s):  
Eldon M. Boyd ◽  
Miriam M. Abel ◽  
Lois M. Knight
Keyword(s):  
Sodium Chloride ◽  
Chronic Toxicity ◽  
Young Male ◽  
Albino Rats ◽  
Oral Toxicity ◽  
Stomach Tube ◽  
Once Daily ◽  
Daily Dose ◽  
Slight Fever ◽  
Dose Dependent

The chronic toxicity of sodium chloride was studied in young male albino rats given 2.57–6.14 g/kg in water by stomach tube once daily for 100 days or until half the animals had died, whichever occurred first. The LD50(0.1 L) or daily dose which killed 50% of the animals after administration for 100 days, i.e. 1/10 the animal's normal lifespan (0.1 L), was 2.69 ± 0.12 g/kg. It is suggested that the LD50(0.1 L) expressed as a percentage of the acute LD50 would provide a useful index of chronic toxicity; this is termed the C/A LD50(0.1 L) index, C meaning chronic and A acute. The value of this index was 72 for sodium chloride, 62 for benzylpenicillin, and 13 for atropine. Rats which survived doses of the order of the LD50(0.1 L) had no change in food intake but lost some body weight as daily dose increased. They had a dose-dependent polydipsia and polyuria. In the initial month of drug administration the rats developed a slight fever, proteinuria, and alkalinuria, and in the terminal month a slight hypothermia and aciduria, all of which were statistically significant but not dose-dependent. When deaths occurred within the first week or two, they were similar clinically and pathologically to those seen in studies on the acute oral toxicity of sodium chloride. Other deaths followed a period of hypothermic cachexia and were due to bronchopneumonia, associated with hepatitis, nephritis, arteriolitis, and occasionally encephalopathy, and accompanied by degeneration of the thymus, adrenals, and testes. Animals which survived for 100 days had developed a hypertrophied gastrointestinal mucosa but most other organs had lost weight, and there was some arteriolitis, myocarditis, pulmonary edema, and nephritis.

The chronic oral toxicity of paracetamol at the range of the LD50 (100 days) in albino rats

1968 ◽  
Vol 46 (2) ◽  
pp. 239-245 ◽  
Author(s):  
Eldon M. Boyd ◽  
Susan E. Hogan
Keyword(s):  
Young Male ◽  
Hepatic Necrosis ◽  
Testicular Atrophy ◽  
Albino Rats ◽  
Many Body ◽  
Oral Toxicity ◽  
Cardiac Stomach ◽  
Susceptibility To Infection ◽  
Inhibition Of Growth ◽  
A Minor

The LD50 (100 days) ± S.E. (oral dose of paracetamol which killed 50% of young male albino rats when given daily for 100 days) was found to be 0.77 ± 0.02 g/kg per day. The maximal LD0 (100 days) was estimated to be 0.4 g/kg per day, and the minimal LD100 (100 days) 1.1 g/kg per day. Signs of toxicity at the LD0 (100 days) were hyperreflexia, aciduria, hypertrophy of the cardiac stomach, atrophy of the testes, minor degrees of hepatic necrosis and nephritis, and augmented susceptibility to infection. Signs at the LD50 (100 days) were listlessness, pallor, inhibition of growth, diuresis, aciduria, a stress reaction, testicular atrophy, hepatic necrosis, tubular and calyxial nephritis, augmented susceptibility to infection, dehydration, and capillary–venous congestion of many body organs. Doses at and above the minimal LD100 (100 days) produced a toxicity syndrome which included in addition anorexia, hypothermia, hyporeflexia, prostration, and degenerative changes in several body organs. The abrupt withdrawal of paracetamol in survivors at 100 days was followed by a minor abstinence syndrome, with recovery within 2 weeks apart from residual testicular atrophy.

scholarly journals Biochemical and Histopathological Effect of Detarium microcarpum Stem Bark Extract in Wistar Albino Rats

2020 ◽  
pp. 1-9
Author(s):  
Abubakar Bilyamini Mu’azu ◽  
Yusif Bello Baba ◽  
Adamu Idris Matinja
Keyword(s):  
Body Weight ◽  
Lethal Dose ◽  
Stem Bark ◽  
Bark Extract ◽  
Albino Rats ◽  
Cardiac Muscle Cells ◽  
Hepatocellular Necrosis ◽  
Detarium Microcarpum ◽  
Stem Bark Extract ◽  
Histopathological Studies

Aim: In this study, the methanol stem bark extract of Detarium microcarpum was evaluated for sub-chronic, biochemical and histopathological studies. Methodology: Sub-chronic toxicity studies was investigated in rats administered with 35, 70 and 140 mg/kg doses of the extract orally for 28 days using standard laboratory procedures after the acute toxicity was carried out. Results: The median lethal dose (LD50) of the extract was calculated to be equal to (≥) 5000 mg/kg body weight in rats orally. Serological studies revealed significant (p<0.05) decrease in Alanine aminotransferase (ALT) at all doses tested, while at 140 mg/kg it caused a significant (p<0.05) increase in Alkaline Phosphatase (ALP). At doses of 70 and 140 mg/kg there was a significant (p<0.05) reduction in creatinine level. Histopathological studies on the liver showed moderate hepatocellular necrosis at doses of 35 and 70 mg/kg, while at 140 mg/kg there was intense hepatocellular necrosis,  Kupffer cells and lymphocytes hyperplasia. The Kidney showed intense necrosis of tubules and glomerular necrosis with lymphocytes hyperplasia at all doses tested.  The spleen also showed intense lymphocyte hyperplasia at all doses with sinusoidal congestion at the lowest dose of 35 mg/kg. The heart showed slight necrosis of cardiac muscle cells at all doses with blood congestion at 35 and 70mg/kg body weight. Conclusion: The study indicates that prolong use of the extract in the management of disease conditions may be associated with some adverse effect of some vital organs.

scholarly journals Acute Toxicity Assessment of the methanolic leaf extract of Annona squamosa Bark in Male Albino Rats

2021 ◽  
Vol 10 (3) ◽  
pp. 151-155
Author(s):  
Jamila Saleh ◽  
◽  
Funsho Olowoniyi ◽  
Ekpa Emmanuel ◽  
Abdulrahman Abdullateef ◽  
...  
Keyword(s):  
Body Weight ◽  
Leaf Extract ◽  
Lethal Dose ◽  
Dose Effect ◽  
Control Group ◽  
Albino Rats ◽  
Annona Squamosa ◽  
Control Groups ◽  
Significant Difference ◽  
Different Doses

Throughout the history of man, traditional and herbal method of treatment of diseases has been used without considering the dose effect. Therefore, this present study is an attempt on investigating the effect of different doses of Annona squamosa methanolic leaf extract on male wistar Rats especially the delicate organs. The work involves oral administration of different doses (10, 100, 1000, 1600, 2900, 5000 mg/kg body weight) of the extract to groups of rats according to Lorkes method. The animals were monitored for 30 days at every 24 hours interval in order to find the median lethal dose (LD50) of the extract. Internal organ-body weight ratios (OBR) of animals in the test groups were determined and compared with those of the control group. LD50 was found to be greater than 5000mg/kg body weight without any significant decrease (p>0.05) in body weight. Biochemical analysis of Aspartate amino transferase (AST), Alanine amino transferase (ALT), Albumin and globulin of animals administered with extract showed no significant difference compared to the control groups (p>0.05) but concentration of Alkaline Phosphatase (ALP) indicated obvious changes in the treated groups compared to the control groups (p<0.05). Histopathology of the kidney revealed some inflammation at 1000, 1600, and 5000 mg/kg body weight. The implications of using this extract within safe doses in traditional medicine is hereby discussed

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