Mechanism of the NMDR phenomenon induced by “receptor desensitization”. At low concentrations, EDC binds to some receptors and induces the observed effect. At high concentrations, numerous receptors are bound, resulting in a down-regulation phenomenon characterized by receptor desensitization. Consequently, the intensity of the effect is decreased, resulting in an NMDR. Note: (-) = negative effect; R = receptor; xe = xenobiotic (e.g., EDC).