Acute Subacute Chronic Toxicity Studies Pdf Free
The most significant lead exposure in adults usually occurs at the workplace, whereas for children, other forms of environmental exposure are more important. Although lead toxicity can occur after a single event, it is usually a result of chronic exposure.
Acute Subacute Chronic Toxicity Studies Pdf Free
Young children who are independently mobile are at greatest neurologic risk from chronic exposure to low or moderate levels of lead. From the time children are able to crawl until they enter school, they are at risk of ingesting lead-containing dust. Although this sometimes is associated with pica and intentional ingestion of paint chips, lead poisoning often occurs without such behavior. Children may also be at risk for lead toxicity if folk remedies are used or if their parents, siblings, or caregivers are involved in lead-related occupations.
Although no compelling evidence exists that any particular race is biologically predisposed to lead toxicity, covariant conditions such as poor nutrition and lower socioeconomic status clearly are associated with chronic lead poisoning.
Essentially, 2 syndromes of lead poisoning exist, depending on exposure: one syndrome is associated with acute or subacute high-level lead exposure, and the other is associated with chronic low-level lead exposure.
With chronic exposure to low or moderate levels of lead, subacute symptoms develop. Patients with chronic lead nephropathy may have a progressive decline in kidney function and eventually require renal replacement therapy.
A one-time exposure to relatively large amounts of the chemical can overwhelm the body. In the workplace, this exposure may happen through improper handling of the chemical, or when there is a spill or a leak from a valve or pipe carrying chemicals. It might also happen during maintenance or cleaning of equipment that normally contains chemicals (such as a solvent vat). The harmful effects caused by one-time, sudden, high exposures are often called acute toxicity effects. Some examples of acute toxicity are listed below:
A repeated exposure over a long period of time can also cause too much chemical to enter the body and produce poisoning. This kind of poisoning occurs because the exposure is repeated day after day over many years. The exposure levels may be too small to cause acute toxicity. Harmful effects caused in repeated exposure situations are sometimes called chronic toxicity effects. The following are some examples of chronic toxicity:
Most chemicals can cause both acute and chronic toxicity depending on the conditions of exposure. The adverse acute and chronic health effects caused by the chemical can be quite different. It is not usually possible to predict what the chronic toxicity of a chemical might be by looking at its acute toxicity, or vice versa.
In most cases, much more is known about the acute toxicity of a chemical than its chronic toxicity. The understanding of acute toxicity comes from studies with animals exposed to relatively high doses of the chemical, from tests that use animal, human or other cells, or from comparison of the effects of very similar chemicals. Accidental exposure, spills and emergencies add to our knowledge of acute toxicity in humans. The health effects may be temporary, such as skin irritation, dizziness or nausea, or they may be permanent: blindness, scars from acid burns, mental impairment and so on.
Much of the knowledge we have about chronic toxicity comes from animal experiments. In addition, much has been learned from studying groups of people occupationally exposed to a chemical for many years. As a general rule, chronic toxicity appears many years after exposure first began. The health effects occur only because the exposure has taken place repeatedly over many years. Chronic toxicity is thought to occur in one of two main ways. These two ways can be explained by using sodium fluoride and n-hexane as examples.
As per the regulatory requirements, the study was designed for acute (single dose - 14 days), sub-chronic (repeat dose - 28 days) and chronic (intended clinical dose - 120 days) toxicity tests using three dose levels, viz. therapeutic, average (2x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in monkeys. The selection of the model i.e. monkey was based on affinity and rapid higher antibody response during the efficacy studies. An attempt was made to evaluate all parameters which included physical, physiological, clinical, haematological and histopathological profiles of all target organs, as well as Tiers I, II, III immunotoxicity parameters.
In acute toxicity there was no mortality in spite of exposing the monkeys to 10XDRV. In sub chronic and chronic toxicity studies there were no abnormalities in physical, physiological, neurological, clinical parameters, after administration of test compound in intended and 10 times of clinical dosage schedule of DRV and CRV under the experimental conditions. Clinical chemistry, haematology, organ weights and histopathology studies were essentially unremarkable except the presence of residual DNA in femtogram level at site of injection in animal which received 10X DRV in chronic toxicity study. No Observational Adverse Effects Level (NOAEL) of DRV is 1000 ug/dose (10 times of therapeutic dose) if administered on 0, 4, 7, 14, 28th day.