Paracelcius in 1473 ‘all substances are poison, no non-poisonous substances. The dose taken determines the toxicity and usefulness of a substance ’. The effects of these substances on health have been investigated by long-term, comprehensive, detailed and expensive tests involving many disciplines. The procedure applied in the researches;
1.Experimental animals are given a lethal dose (lethal dose (LD50): the dose causing 50% of the experimental animals to die).
a. The dose-response relationship is investigated by slowly reducing the dose. At each dose; absorption, metabolism and excretion of the additive.
b. Carcinogenic, mutagenic, teratogenic and allergic effects of experimental animals are investigated.
2.If a dose cannot be found in which the additive has no effect, it is not allowed to be added to the food.
3.Determine NOAEL (concentration at which no effect is observed). With the dose of NOAEL found, daily dose amounts of carcinogenic, mutagenic, teratogenic and allergic effects in various organs of their bodies are determined as milligrams per kilogram of animal weight to cover 85% of the life span of the experimental animals. Since the experiment cannot be performed on people for ethical reasons, a safety factor is used. In other words, 1/100 of the dose which shows no effect in the experimental animal is accepted for human. ADI (Acceptable Daily Intake) = NOAEL / 100. The ADI value is determined in milligrams per kilogram of human body weight. Maximum daily intake = ADI x Body weight.
4.The second step in determining the maximum amount of additive to be added to the food is to determine the quantity required by the production technology of the food (GMP = Suitable Production Technology) within the framework of ADI. If the GMP amount and ADI value are exceeded, the use of the additive is not permitted.