Zinc Oxide Eugenol

Zinc oxide eugenol is frequently used as a material in dentistry. It is generally considered bland or even therapeutic to the pulp and is routinely used as the nontoxic control in most in-vivo tooth tests of pulpal toxicity. It is highly cytotoxic in all tissue culture test systems that lack a dentin barrier. If it comes in direct contact with bone, the pain could be extremely severe so much so if extruded into the mandibular canal, it may damage the mandibular nerve.

Zinc oxide when mixed with eugenol lead to formation of zinc eugenolate matrix. The zinc eugenolate units are held together by vander- waal forces and particle interlocking. When exposed to aqueous media such as saliva or dentinal fluid, hydrolysis of zinc eugenolate occurs yielding eugenol and zinc hydroxide. Eugenol liberated from zinc eugenolate can diffuse through dentin and into the saliva. It has been established that concentration of 10-2 mol/L of eugenol is observed below the fillings in dentin and 10-4 mol/L in the pulp. These concentrations were maintained for more than 1 week. Calcium in the dentinal tubules chelates eugenol, limiting its ability to diffuse through dentin. Eugenol also binds with the organic matrix of dentin, especially collagen, which slows the diffusion rate.

Modified ZOE cements have demonstrated less release of eugenol and fewer cytotoxic effects. It has been observed that acid etched dentin may facilitate diffusion of potentially toxic amounts of eugenol to the pulp.

Eugenol is bactericidal at relatively high concentration of 10-2 to 10-3 mol/L. Brief exposure to 10-2 mol/L and prolonged exposure to 10-3 mol/L of eugenol can kill mammalian cells. Even lower concentrations can inhibit cell respiration and cell division. Inhibitory eugenol concentrations are significantly higher than the one required for anti-inflammatory effects. The zinc oxide eugenol placed in direct contact with the pulp tissue result in chronic inflammation and necrosis.

However, when placed against dentin, the cytotoxic effects are nil. Various mechanisms that explain the cytotoxicity of eugenol are:

• Eugenol can be oxidized by peroxidase enzyme; the product formed is toxic to hepatocytes.
• It has a high affinity to plasma membranes because of its lipid solubility, which can cause cell damage.
• Eugenol has shown to uncouple oxidative phosphorylation in mitochondria.

At concentration levels of 10-4 mol/L or just below it, eugenol has been shown to inhibit prostaglandin synthesis and sensory nerve excitability. At low concentrations the intradental nerve activity is blocked reversibly just like a local anaesthetic, whereas at high concentrations of eugenol, nerve conduction is irreversibly blocked, indicating a neurotoxic effect. It exerts an anti-inflammatory

effect by the following mechanisms:

• Protects tissue from damage by inhibiting neutrophil function and chemotaxis.
• Inhibits prostaglandin and leukotriene synthesis, which are important mediators of inflammation by increasing blood flow and vascular permeability and lowering pain threshold.
• Eugenol causes vasodilatation and decreases the response of these vessels to nor epinephrine and histamine. Vasodilatation would result in prevention of toxic accumulations and rapid removal of irritants.

Effects of Eugenol

Toxic(High Dose) 

– Induces cell death 

– Unknown vascular effect 

– Inhibits cell growth and respiration 

Beneficial(Low Dose)

– Inhibits white cell chemotaxis

– Inhibits prostaglandins synthesis

– Inhibits nerve activity

Thus, it can be seen that the effect of eugenol is dose dependent.