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 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 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.

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.

scholarly journals Evaluation of the Toxicological Profile of Yagari

2021 ◽  
pp. 29-45
Author(s):  
Uzuazokaro Mark-Maria Agatemor ◽  
Okwesili Fred Chiligue Nwodo
Keyword(s):  
Chronic Toxicity ◽  
Histopathological Examination ◽  
The Body ◽  
Toxicity Study ◽  
Albino Rats ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Herbal Products ◽  
Toxicological Profile ◽  
Hematological Analysis

Background and Objective: Data from researches have shown a rise in disease, ill health and death linked with the utilization of herbal products, thereby raising global awareness in the last few years. On that account, the safety and toxicity evaluations of herbal products and preparations was essential. This study evaluated the toxicological profile of Yagari – a herbal mixture. Materials and Methods: Acute oral toxicity (LD50) was carried out in Swiss mice according to Lorke’s method while sub-chronic toxicity study was carried out with 20 adult albino rats which were divided into 4 groups of 5 animals each. Group one served as control and received normal saline while Groups 2 to 4 received 250, 500 and 1000 mg/kg yagari respectively for 28 days. The body weights of the rats were monitored while on day 29, the rats were sacrificed and blood samples and organs were collected for biochemical/hematological analysis and histopathological examination respectively. Results: Results showed that Yagari is not noxious up to 5000 mg/kg following acute oral toxicity study. The sub-chronic toxicity test divulged that Yagari had no serious end results on the biochemical, hematological and histopathological parameters, although the body weight of the animals significantly increased. Conclusion: It was concluded that Yagari is not toxic, still further investigations on a large number of animals are essentially needed to denote safety and efficacy of the herbal formulation.

scholarly journals Cytoplasmic Vacuolation and Tapetal Changes Induced by a Novel Analgesic Agent in Beagle Dogs

2019 ◽  
Vol 47 (4) ◽  
pp. 494-503
Author(s):  
Kei Takahashi ◽  
Yasuhiro Morita ◽  
Shuji Udagawa ◽  
Seiki Yamakawa ◽  
Dai Watanabe ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Recovery Period ◽  
Dependent Manner ◽  
Beagle Dogs ◽  
Oral Toxicity ◽  
Drug Induced ◽  
Once Daily ◽  
Cytoplasmic Vacuolation ◽  
Light Microscopic Observation ◽  
Dose Dependent

Drug-induced unique cytoplasmic vacuolation was found in the subchronic oral toxicity study of 4-dimethylamino-1-{3-(1-methyl-1H-imidazole-2-yl)propanoyl}piperidine (DMIP), a potential therapeutic agent for neuropathic pain, in beagle dogs. In the first study, DMIP was administered at a dose of 250, 500, or 1,000 mg/kg/day once daily for 14 days. Discoloration of tapetum lucidum accompanied by tapetal swelling was observed at ≥250 mg/kg/day. The tapetal swelling was correlated to the light microscopic observation of cytoplasmic vacuolation in tapetal cells, and similar vacuolation was observed in several other tissues, including the coronary artery and aortal arch, in a dose-dependent manner. Immunohistochemistry for lysosomal-associated membrane protein 2 indicated that the vacuoles were enlarged lysosomes. However, the nature of these vacuoles was different from that of phospholipidosis because no lamellar bodies were observed. In the second study, DMIP was administered at a dose of 10, 50, or 250 mg/kg/day once daily for 14 days followed by a 14-day recovery period. Tapetal changes and systemic vacuolation were not observed at ≤50 mg/kg/day, and vacuolation observed at 250 mg/kg/day was reversible. A few reports have described the enlargement of lysosomes not attributable to phospholipid accumulation. Our findings provide further information about the toxicological implications of drug-induced lysosomal swelling.

THE CHRONIC ORAL TOXICITY OF CAFFEINE

1965 ◽  
Vol 43 (6) ◽  
pp. 995-1007 ◽  
Author(s):  
Eldon M. Boyd ◽  
Mortimer Dolman ◽  
Lois M. Knight ◽  
E. Patricia Sheppard
Keyword(s):  
Water Levels ◽  
Gastric Ulcers ◽  
Albino Rats ◽  
Oral Toxicity ◽  
Glucose Content ◽  
Toxic Reaction ◽  
Drinking Habits ◽  
Self Mutilation ◽  
Daily Dose ◽  
Colonic Temperature

The toxicity of caffeine administered daily by intragastric cannula to female albino rats was determined over 100 days, i.e., 1/10 of the animal's life-span. The maximal LD0(0.1L) or maximal daily dose producing no deaths over 100 days was 110 ± 2.5 mg/kg; the LD50(0.1L), 150 ± 3.1 mg/kg; and the minimal LD100(0.1L), 191 ± 5.7 mg/kg. Doses of the order of the LD0(0.1L) produced a mild cerebral hyperemia, occasional psychotic-like self mutilation, gastric ulcers, and inhibition of oogenesis; hypertrophy of the salivary glands, gastrointestinal tract, liver, heart, kidneys, and lungs; a stressor reaction in the adrenal and thymus glands; minor changes in organ water levels; an occasional death apparently from bronchopneumonia; but in general a normal appearance, and no change in growth rate, eating and drinking habits, or in the volume, pH, and protein and glucose content of the urine. Doses of the order of the LD50(0.1L) also produced a polydipsia and diuresis and an occasional dermatitis; some degree of toxic nephritis, hepatitis, myositis, thyroiditis, and loss of red pulp in the spleen. Doses of the order of the minimal LD100(0.1L) and higher produced an increasingly more toxic reaction, which was similar to that seen in the syndrome at the acute oral LD50 dose and that due to fortnight partial starvation. Abrupt withdrawal of caffeine was followed for 1 week by decreased locomotor activity, a slight decrease in colonic temperature, and proteinuria and glycosuria.

Investigation of antiulcer activity of Pergularia extensa Linn

2020 ◽  
Vol 9 (2) ◽  
pp. 23-26
Author(s):  
Pavani C H
Keyword(s):  
Cardiac Glycosides ◽  
Methanol Extract ◽  
Methanolic Extract ◽  
Antiulcer Activity ◽  
Acute Oral Toxicity ◽  
Gastric Lesions ◽  
Oral Toxicity ◽  
Control Groups ◽  
Dose Dependent

This study was based on determination of the antiulcer activity from methanol extract was prepared by using barks of pergularia extensa linn.. Priliminary investigations showed presence of saponins, terpenes, cardiac glycosides, alkaloids and sterols. Based on OECD-423 Guidelines, the pharmacology and acute oral toxicity studies were conducted by using methanolic extract. Ulcer development was prevented by Tannins because of their vasoconstriction effects and due to protein precipitation. Similarly, the Methanolic extract of Pergularia extensa Linn shows triterpenoids and saponins. The phytoconstituents are present in the extract and these could be possible agents which are involved in order to prevent gastric lesions induced by aspirin. When compared to ulcerative control groups, this Pergularia extensa Linn., shows a dose dependent curative ratio. The extracts exhibited an inhibition percentage of 27.18, 45.47 and 61.28 at doses of 100, 200 and 400mg/kg doses respectively. 

scholarly journals Antidiabetic and antiulcerative potential of Garcinia lanceifolia Roxb. bark

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Nilutpal Sharma Bora ◽  
Partha Sarathi Bairy ◽  
Abdus Salam ◽  
Bibhuti Bhusan Kakoti
Keyword(s):  
Body Weight ◽  
Serum Levels ◽  
Northeast India ◽  
Scientific Data ◽  
Antidiabetic Activity ◽  
Histological Evaluation ◽  
Albino Rats ◽  
Antiulcer Activity ◽  
Dose Dependent

Abstract Background Garcinia lanceifolia Roxb. has been used by many ethnic communities of Northeast India to mitigate various disorders like dyspepsia, ulcers, diabetes, etc. However, a robust scientific study on its antidiabetic and antiulcer potential is unavailable till date. The aim of this present study is to scientifically validate if the antidiabetic and antiulcer effects reported by the ethnic tribes of Assam has any scientific value or not. The effects were tested in adult Wistar albino rats using approved animal models for preclinical testing of pharmacological activities. Results The hydroalcoholic extract of the bark of Garcinia lanceifolia Roxb. was prepared and its LD50 was calculated. The LD50 was determined to be greater than 5000 mg/kg body weight. The extract at doses of 250 mg/kg body weight and 500 mg/kg body weight was found to exhibit a very potent dose-dependent antidiabetic activity. The results were backed by a battery of test including analysis of serum levels of blood glucose, lipid profiles, in vivo antioxidant enzymes, and histopathological studies. Evidence of dose-dependent antiulcer activity of the extract was backed by robust scientific data. It was found that HAEGL induced a significant dose-dependent increase in the ulcer index in both alcohol-induced and acetic acid-induced ulcer models, which was evident from the macroscopic observation of the inner lining of the gastric mucosa and the histological evaluation of the extracted stomach. Conclusion The results suggested that the bark of Garcinia lanceifolia (Roxb.) has significant antidiabetic and antiulcer potential. Further studies with respect to the development herbal dosage forms and its safety evaluation are required.

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.

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