Minimal Effect Levels , risk

Toxicologists generally posit that no threshold exists for some effects, notably for most carcinogens. Such effects are characterized by a derived minimal effect level (DMEL) in the European Union in the parlance used in the United States, risks are characterized using oral slope factors and oral or inhalation unit risks. A DMEL represents the exposure level that corresponds to a specified level of risk to the exposed population. In the case of a chemical known or suspected to be a human carcinogen, this exposure level corresponds to a risk of one excess case of cancer in an exposed population. For a hypothetically exposed population of one million people, for example, this risk level of one excess case of cancer in the population of one million is abbreviated... 

Tables (3-1, 3-2, and 3-3) and figures (3-1 and 3-2) are used to summarize health effects and illustrate graphically levels of exposure associated with those effects. These levels cover health effects observed at increasing dose concentrations and durations, differences in response by species, minimal risk levels (MRLs) to humans for noncancer end points, and EPA s estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to locate data for a specific exposure scenario. The LSE tables and figures should always be used in conjunction with the text. All entries in these tables and figures represent studies that provide reliable, quantitative estimates of No-Observed-Adverse-Effect Levels (NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs).

Cancer Effect Level - CEL (animals) [ Minimal risk level for effects 1 other than cancer V/... 

Once we know the chemical nature of the allelopathic agents and their effects on plant growth dynamics, as well as on health and environment, we can apply genetic manipulation and biotechnology to develop toxin-resistant plants and to reduce the toxin levels frcm the donor plants. These approaches serve a dual purpose because they contribute to increased agricultural productivity and help to minimize the potential risks on health and environment. 

For most chemicals, actual human toxicity data are not available or critical information on exposure is lacking, so toxicity data from studies conducted in laboratory animals are extrapolated to estimate the potential toxicity in humans. Such extrapolation requires experienced scientific judgment. The toxicity data from animal species most representative of humans in terms of pharmacodynamic and pharmacokinetic properties are used for determining AEGLs. If data are not available on the species that best represents humans, the data from the most sensitive animal species are used to set AEGLs. Uncertainty factors are commonly used when animal data are used to estimate minimal risk levels for humans. The magnitude of uncertainty factors depends on the quality of the animal data used to determine the no-observed-adverse-effect level (NOAEL) and the mode of action of the substance in question. When available, pharmocokinetic data on tissue doses are considered for interspecies extrapolation. 

If the drug proves safe and effective, phase III trials are initiated. (In the context of clinical trials, safe and effective are rarely used in the absolute sense. Safe generally refers to a favourable risk beneht ratio, i.e. the benefits should outweigh any associated risk. A drug is rarely 100 per cent effective in all patients. Thus, an acceptable level of efficacy must be defined, ideally prior to trial commencement. Depending upon the trial context, efficacy could be defined as prevention of death/prolonging of life by a specific time-frame. It could also be defined as alleviation of disease symptoms or enhancement of the quality of life of sufferers (often difficult parameters to measure objectively). An acceptable incidence of efficacy should also be defined (particularly for phase II and III trials), e.g. the drug should be efficacious in, say, 25 per cent of all patients. If the observed incidence is below the minimal acceptable level, then clinical trials are normally terminated. 

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