Maximum tolerated dose , definition

Toxicology studies are conducted to define the safety profile of a candidate and include definition of the no-observable-toxic-effect dose, maximum tolerated dose or MTD, potential organs of toxicity, and potential biochemical markers to detect and track toxic events. Most developmental compounds that do not become therapeutic products have unacceptable toxicity in animals and/or humans. Before the definitive toxicology studies needed to support an IND submission are initiated, a number of in vitro and animal experiments can be conducted to characterize the potential toxicity of the candidate. These early toxicology evaluations are usually conducted in the same species as used in pharmacology evaluations. As mentioned earlier, the lowest dose that has no toxicity, or an acceptable level of toxicity, is compared with the dose that gives the desired pharmacological response in the same animal species to obtain a therapeutic ratio or index for that species. 

Sulfonylurea herbicides are generally applied to crops as an early post-emergent herbicide. Crops that are tolerant to these herbicides quickly metabolize them to innocuous compounds. At maturity, residues of the parent compound in food and feed commodities are nondetectable. Metabolites are not considered to be of concern, and their levels are usually nondetectable also. For this reason, the residue definition only includes the parent compound. Tolerances [or maximum residue limits (MRLs)] are based on the LOQ of the method submitted for enforcement purposes and usually range from 0.01 to 0.05 mg kg (ppm) for food items and up to O.lmgkg" for feed items. There is no practical need for residue methods for animal tissues or animal-derived products such as milk, meat, and eggs. Sulfonylurea herbicides are not found in animal feed items, as mentioned above. Furthermore, sulfonylurea herbicides intentionally dosed to rats and goats are mostly excreted in the urine and feces, and the traces that are absorbed are rapidly metabolized to nontoxic compounds. For this reason, no descriptions of methods for animal-derived matrices are given here. 

Amphetamines are definitely drugs which have been and are abused. Notice that the organic modifications in the fundamental amphetamine structure are to make the compound more lipophilic and so speed its delivery to the CNS as well as heighten the stimulant and euphoric effect. Therapeutic doses of amphetamines range from 5 to 10 mg for a maximum of 60 mg per day while abusive doses may be as high as 500-1000 mg every 2-3 hours. The side effects of abuse include tolerance, addiction, malnutrition, heart arrthymias, and... 

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