Why does orthocresol behave as a skin irritant?

Question

o-Cresol or ortho-Cresol or 2-methylphenol is a constituent of tobacco smoke, and, like most other phenols, behaves as a skin irritant, causing a burning sensation when it comes in direct contact, or upon inhaling it in.

What is the biochemical reaction that causes our skin to produce such a reaction to orthocresol? Is there any correlation with orthocresol being an acidic compound? Can this be explained by +I effect or Hyperconjugation effect of the $\ce{-CH3}$ group?

Unlike Vinegar or Alcohol, which have different effects (vinegar feels like water to me, and alcohol has a cooling sensation), why do cresols and phenols in general have a stingy sensation on touching?

Answer 1

It is the phenol moiety of ortho-cresol that causes this. Phenol is classified as toxic because of the way it can penetrate the skin and cause damage.

In its neutral state, the phenol molecule is a slighlty polar but generally organic compound. Since our skin is designed to mainly keep water and water-soluble compounds out, it is lipophilic; this in turn helps lipophilic compounds to penetrate it and be absorbed by the body. As soon as phenol has been absorbed, it is again in an aquaeous environment. Here, phenol’s acidic properties ($\mathrm pK_\mathrm a = 9.95$) start playing a role: it can be deprotonated to the phenolate anion. This is hydrophilic and so will be able to dissolve in the water inside your body. If any membrane needs to be crossed, just add a proton to regenerate the lipophilic free phenol.

Another way in which phenol can often react is the single electron transfer mechanism to generate a phenol radical which can then cause havoc in cells. And finally, phenol should also be able to intercalate into DNA further causing damage.

So the stingy sensation is caused by the slight burns that you encounter once phenol has penetrated your skin. since neither ethanol nor vinegar can penetrate your skin as well as phenols can (they are too polar), these react differently and give you a different sensation.