Question

What do you understand by the statement “the dose makes the poison”? Describe "the dose-response assessment" used in toxicity studies (give specific examples).

Answer 1

All things are poison, and nothing is without poison, the dosage alone makes it so a thing is not a poison.

PARACELSUS

• The dose makes the poison is an adage intended to indicate a basic principle of toxicology.
• It means that a substance can produce the harmful effects associated with its toxic properties only if it reaches a susceptible biological system within the body inna high enough concentration.
• The principle relies on the finding that all chemicals even water and oxygen can be toxic if too much is eaten, drunk or absorbed.
• The toxicity of any chemical depends on many factors Which includes the extent to which it enters an individual's body.

E.g. The substance in question is solanin and is found in potatoes and yes it can cause solanine poisoning. Tomatoes, paprika, eggplant, beet, okra also contain solanin.

Dose response assessment explores the relationship between the dose of an agent administered or received and the incidence of an adverse health effect on human or animal.

• It helps us to understand what happens in the human body at different levels of exposure to a chemical and it allows us to see that relationship presented graphically.
• It allows us to derive toxicity values that become important when we develop a complete risk assessment.

• It incorporates both qualitative data( eg. Does a lesion exist and if so what is its severity grade) and quantitative data ( eg. Organ weight, cell numbers and othe end points) .
• The intended goal of a dose response assessment is to define a threshold of exposure above which the test article will cause adverse effects.
• Many calculated values have been defined to provide a numerical estimate of this threshold including " benchmark dose " ( BMD commonly used for chemical) and the " no observed adverse effects level" ( NOAEL typically employed for drug candidate.
• It is based on high dose animal ( toxicology) studies and then extra polated to human.

Eg: In the laboratory, a population of organism is exposed to various dose of hazardous substance, typically measured in concentration of oarts per million (ppm) . Over the course of many trials, the health effects observed at the varying dose are then synthesized and plotted graphically. The resulting dose response curve gives an illustration of how increased dosage of a harmful substance may alter the incidence and severity of adverse health effect. This can then be used to comoare the toxicity of one substance to another for estimating possible health effect in human population.