Toxins: Screening

Toxicological testing of compounds is performed to deter-

mine the minimum concentration or dose of a compound

required to elicit a response from a biological system,

the causative factors in eliciting this response, and the

mechanisms by which the biological entity responds.

While elucidating the mechanisms of damage and response

often requires multiple types of extensive analyses, the

dose-response relationship, providing the most basic of

information, is derived by evaluating how a population

responds to a chemical.[1] A population typically shows a

variety of sensitivities to chemicals, with some individuals

being very sensitive, showing effects at low concentrations,

while other individuals may be insensitive and respond only

at very high concentrations. Such variable responses are

quantified by exposing multiple individuals to a compound

and recording that concentration at which effective pharma-

cological (such as a desired efficacious response), toxicolo-

gical (displaying some degree of cellular or systemic

damage), or lethal (causing morbidity) effects are observed

in 50% of the population. These specific concentrations are

represented as theED50, TD50, andLD50 levels, respectively.

Fig. 1 presents a representation of the effective, toxicologi-

cal, and lethal response obtained for one model pharmaceu-

tical compound. The ED50 represents the concentration

likely to be applied to generate the beneficial effects of the

compound, whereas concentrations approaching the TD50 should be avoided. Significant effort in toxicological testing

is based on determining these ED50, TD50, and LD50 con-

centrations while providing an appropriate margin of safety.

METHODS