Dose-Response Relationships interactive effects

It is important to note that the T1 screening program will not determine dose-response relationships, mechanism of action, or the adversity of a chemical s effect, if any. Rather, it is designed to demonstrate interaction with components of the endocrine system. 

The feasibility of informative experiments, whether in vitro or, if necessary, in vivo will depend mainly on the availability of model systems that are sufficiently well understood, and the coverage of the broad types of investigation, as in conventional toxicity experiments where the objective is to try to detect any effect and subsequently to decide whether it is toxic or pharmacological . The need to explore such major features as the concentration-response or dose-response relationship, speed of onset, duration of action and reversibility of effects and their upstream and downstream consequences on other physiological mechanisms, potential interactions with the physiological and pathophysiological status of the patient, and other treatments administered at the same time, will all affect the nature and number of the most relevant experiments. 

Interactive toxicity is defined as effects of mixtures deviating from the additive toxic response expected based on the dose-response relationships obtained from individual components. 

Interaction Effect of a mixture that is different from additivity based on the dose-response relationships of the individual components. 

Antagonistic interactions also occur, reversing the direction of these effects, such as occurs with enzyme inhibition, etc. Concerns of interactions are critical in the area of pharmacy and medicine in the guise of drug interactions. Serious health effects occur when improper combinations of drugs are administered, such as occurred recently with dietary pills. However, all of these effects are detectable in laboratory animal studies and follow well-defined dose-response relationships. Like any other toxicological effect discussed in earlier chapters, a no-effect level is defined, and the safety of chemical exposure should then be interpreted relative to these levels which have appropriate safeguards built in. 

That drug or chemical interactions might be constrained by hormetic dose response relationships possessing ceiling effect limitations is a phenomenon that may extend to broad research areas and biology in general. For the pharmaceutical industry this... 

Multiple agents inducing hormetic dose response relationships display interactions that are equal to or greater than additive responses. However, a key feature of hormetic drug-drug interactions is that they would be expected to be constrained by the response ceiling effect. Thus, the resultant interactions likely would not increase the response beyond that imposed on the system by its inherent plasticity. The maximum interaction response therefore likely would be within two-fold of the control value. However, the doses of individual agents needed to achieve the effect could be profoundly lowered by the interaction. 

The dose response relationship between seven commonly used herbicides and four luminescence-based bacterial biosensors was characterised. As herbicide concentration increased the light emitted by the test organism declined in a concentration dependent manner. These dose responses were used to compare the predicted vs. observed response of a biosensor in the presence of multiple contaminants. For the majority of herbicide interactions, the relationship was not additive but primarily antagonistic and sometimes synergistic. These biosensors provide a sensitive test and are able to screen a large volume and wide range of samples with relative rapidity and ease of interpretation. In this study biosensor technology has been successfully applied to interpret the interactive effects of herbicides in freshwater environments [12]. 

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