BPharm Sixth Sem BP602T Subacute Toxicity Subacute toxicity studies are intended to evaluate a drugs toxic potential and pathological effects following a treatment repeated administration ID: 1027173
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1. Toxicology: Subacute and Chronic ToxicityB.Pharm. Sixth Sem.BP602T
2. Subacute ToxicitySubacute toxicity studies are intended to evaluate a drug's toxic potential and pathological effects following a treatment/repeated administration during a period of 14-90 days. During this type of study, data about observed effects, mortality, body weight, food/water consumption, physical examinations, hematology, bone marrow, coagulation, blood chemistry, urinalysis, organ weights, gross pathology, and histopathology are collected and analyzed.
3. This study access the nature of toxic dose under more realistic situation than the acute toxicity studies and 03 dose levels are normally used:1) Dose that is high enough to elicit definite signs of toxicity but not to kill many of the animals.2) Low dose that is expected to induce no toxic effect3) Intermediate dose.
4. METHOD –The subacute toxicity test is a continuation of the acute toxicity test. It mainly involves the continued observation of the test animals used for acute toxicity for a longer period. All animals administered the test substance (irrespective of dose administered) during the acute toxicity test and did not produce mortality are kept under further careful observation for 14 days. Signs of toxicity and mortality are recorded if any is observed (just as during acute toxicity test). Where mortality is observed within the 14 days of observation, the dose that gave mortality (or lowest lethal dose, in a situation that recorded more than one death) is administered to two animals (consisting of two different strains) and observed for 14 days. The observation of single mortality of any of the animals within the period of observation is a confirmation of its subacute toxicity at that dose.Calculation: The formula for calculating the subacute lethal dose is expressed as: Lethal Dose subacute=[Mo + M₁]/2
5. CHRONIC TOXICITY Chronic toxicity studies are performed for a period of 180 days to 1 year or lifelong. During this type of study, the potential risks in relation to the anticipated dose and period of drug treatment, potential targets of toxicity, reversibility of any observed toxicities, and No Observed Adverse Effect Levels are observed.Chronic toxicity represents cumulative damage to specific organ systems and takes many months or years to become a recognizable clinical disease.Examples of chronic toxic affects are:- cirrhosis in alcoholics who have ingested ethanol for several years; - chronic bronchitis in long-term cigarette smokers; - pulmonary fibrosis in coal miners (black lung disease)
6. METHOD: Chronic toxicity assessment can only be carried out for test doses that passed the subchronic test. It begins 24 h after administration of the last subchronic doses. Six animals each (consisting of three animals per strain) should be alive from both control and passing dose groups at the end of the subchronic procedure (including histological assessment). Administration of the test doses to the animals in the respective groups is continued for a period of 62 days (making a total of 92 days of administration), while the control group animals still receive the vehicle. All animals in the respective groups are carefully observed daily throughout the period of study. Weight taking across the groups is also done at 2 weeks interval. Mortality and other signs of toxicity are recorded. At any time mortality is observed, the vital organs (kidney, lung, liver, heart, spleen, small intestine, stomach, duodenum and adrenal gland) of such animal(s) should be isolated immediately for histological examination. Regarding test: The date of such mortality is also recorded. The mortality of two animals from the same strain in a particular group shows toxicity at that dose. At the end of the period of administration, all the animals from test groups and control are sacrificed 6 h after the last administration. The vital organs (kidney, lung, liver, heart, spleen, small intestine, stomach and duodenum, and adrenal gland) are isolated for histological examination.