Lawrence, J. N., F. M. Dickson, and D. J. Benford. Skin Irritant-induced Cytotoxicity and Prostaglandin E₂ Release in Human Skin Keratinocyte Cultures. Toxic. in Vitro 1997. 11: 627-631. [Reprinted with permission from Elsevier Science]

phorbol -12-myristate-13-acetate - 16561-29-8; benzalkonium chloride - 08001-54-5; tributyltin chloride - 01461-22-9; 2-methoxyethanol - 00109-86-4; 2-butoxyethyl acetate - 00112-07-2; sodium dodecyl sulfate - 00151-21-3; acetic acid - 00064-19-7

Damage to the skin induced by chemical irritants is associated with the release of arachidonic acid metabolites, such as prostaglandin E₂ (PGE₂) which plays an important role in epidermal inflammation. This study investigated cytotoxicity and release of PGE₂ in human epidermal keratinocytes following an 18 hr exposure of confluent cultures to various skin irritants. The concentration-dependent release of PGE₂ into the extracellular medium appeared to fall into two categories, which was reflective of possible mechanisms of action. Potent skin irritants, such as phorbol-12-myristate-13-acetate, bezalkonium chloride and tributyltin chloride, elicited an increase in extracellular PGE₂ levels at concentration that did not produce overt cell damage (uptake of neutral red at these concentrations was comparable to control levels.) Non-irritants (2-methoxyethanol and 2-butoxyethanol acetate) and two less severe irritants (sodium dodecyl sulfate and acetic acid) stimulated release of PGE₂ only at concentrations that compromised cellular integrity (uptake of neutral red was at least 50% lower than that of control cultures).