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.

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.

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 Protective Effect of Ethanolic Extract ofTabernaemontana divaricata(L.) R. Br. against DEN and Fe NTA Induced Liver Necrosis in Wistar Albino Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Kannappan Poornima ◽  
Palanisamy Chella Perumal ◽  
Velliyur Kanniappan Gopalakrishnan
Keyword(s):  
Ethanolic Extract ◽  
Treated Group ◽  
Hepatic Necrosis ◽  
Hepatoprotective Activity ◽  
Albino Rats ◽  
Protective Effects ◽  
Liver Necrosis ◽  
Standard Drug ◽  
Tabernaemontana Divaricata ◽  
Wistar Albino Rats

This study is an attempt to evaluate the hepatoprotective activity ofTabernaemontana divaricataagainst DEN and Fe NTA induced liver necrosis in rats. Ethanolic extract of the whole plant ofTabernaemontana divaricataat doses of 200 and 400 mg/kg body weight and 5-fluorouracil (standard drug) was orally administered to male Wistar Albino rats once daily for 24 weeks, simultaneously treated with the carcinogen DEN and Fe NTA. In simultaneously treated animals, the plant extract significantly decreased the levels of uric acid, bilirubin, AST, ALT, and ALP in serum and increased the levels of liver marker enzymes in liver. Treatment with the extracts resulted in a significant increase in the levels of antioxidants accompanied by a marked reduction in the levels of malondialdehyde when compared to DEN and Fe NTA treated group. When compared with 200 mg/kg bw rats, 400 mg/kg bw rats and 5-fluorouracil treated rats showed better results in all the parameters. The histopathological studies confirmed the protective effects of extract against DEN and Fe NTA induced liver necrosis. Thus, it could be concluded that the use ofTabernaemontana divaricataextract in the treatment of carcinogen induced hepatic necrosis.

The toxicity of Indigofera enneaphylla L. in rats

1965 ◽  
Vol 16 (4) ◽  
pp. 713 ◽  
Author(s):  
LR Murray ◽  
T Moore ◽  
IM Sharman
Keyword(s):  
Vitamin E ◽  
Chemical Analysis ◽  
Young Male ◽  
Tocopheryl Acetate ◽  
Albino Rats ◽  
Liver Lesions ◽  
Feeding Trial ◽  
Microscopic Evidence ◽  
Nitropropionic Acid ◽  
Plant Chemical

The inclusion of 50% of dried Indigofera enneaphylla in the diet arrested the growth of young male albino rats, caused incoordination of their limbs, and was fatal to them. Microscopic evidence of liver cellular abnormality was consistently observed in rats fed on the plant. Chemical analysis of I. Enneaphylla indicated the presence of combined G-nitropropionic acid, paralleling the findings of other workers in respect of I. Spicata, which, in addition, produced liver lesions. Dried I. Enneaphylla contained about 12 p.p.m. of α-tocopherol. According to haemolysis tests, the poisoned rats were not deficient in vitamin E. The administration of liberal doses of α-tocopheryl acetate did not counteract the poisoning. In preliminary experiments, dosing with L-arginine appeared to be partially protective against poisoning by I. Enneaphylla. Autoclaving the dried plant, according to a single feeding trial, resulted in loss of toxicity.

Long-term effect of a sheep antiserum to rat growth hormone in vivo in rats is explained by the rat anti-sheep immunoglobulin response

1991 ◽  
Vol 128 (2) ◽  
pp. 229-237 ◽  
Author(s):  
R. J. Madon ◽  
D. M. Panton ◽  
D. J. Flint
Keyword(s):  
Milk Yield ◽  
Young Male ◽  
High Response ◽  
Male Rats ◽  
Inhibition Of Growth ◽  
Igf I ◽  
Rat Growth ◽  
Response Group ◽  
High Responders

ABSTRACT A specific antiserum to rat GH (anti-rGH) raised in sheep was used in young male and lactating rats. In both models a group of rats was found which appeared to generate a low response (low responders) to the injected sheep immunoglobulin, and was characterized by the ability of the antiserum to cause inhibition of growth for more than 21 days in the male rats, and to abolish milk yield when prolactin concentrations were lowered in the females. In the groups which generated a high response to the anti-rGH (high responders), growth was retarded for only 2–3 days in male rats, with a moderate milk yield maintained in lactating animals. The low-response animals were found to have a significantly longer half-life for circulating anti-rGH, when compared with the high-response animals. After 21 days, in the age-matched male rats, levels of anti-rGH were undetectable in the high-responders, whereas the low-response animals, which were nearly 160 g lighter, still had approximately 4·5 ml anti-rGH/1 in their circulation. This anti-rGH was still capable of neutralizing GH, as concentrations of insulin-like growth factor-I (IGF-I) were 13·6±3·5 (mean ± s.e.m.) and 76·9±2·0 nmol/l in the low-response and high-response groups respectively. The reason for these differences would appear to be that the immune response mounted by these low-response animals to the exogenous sheep immunoglobulin (i.e. rat anti-sheep) 7 days after treatment was less than 10% of that seen in the high-response group. In male animals the concentration of IGF-I was positively correlated with growth rate. It is concluded that the effectivenes of the anti-rGH was related to its clearance rate which in turn depended on the ability of the animal to mount an effective anti-sheep response. Journal of Endocrinology (1991) 128, 229–237

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