Safety assessment of propyl paraben: a review of the published literature

Propyl paraben (CAS no. 94-13-3) is a stable, non-volatile compound used as an antimicrobial preservative in foods, drugs and cosmetics for over 50 years. It is an ester of p-hydroxybenzoate. Propyl paraben is readily absorbed via the gastrointestinal tract and dermis, It is hydrolyzed to p-hydroxybenzoic acid, conjugated and the conjugates are rapidly excreted in the urine. There is no evidence of accumulation. Acute toxicity studies in animals indicate that propyl paraben is relatively non-toxic by both oral and parenteral routes, although it is mildly irritating to the skin. Following chronic administration, no-observed-effect levels (NOEL) as high as 1200-4000 mg/kg have been reported and a no-observed-adverse-effect level (NOAEL) in the rat of 5500 mg/kg is posited. Propyl paraben is not carcinogenic, mutagenic or clastogenic. It is not cytogenic in vitro in the absence of carboxyesterase inhibitors. The mechanism of propyl paraben may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation. Sensitization has occurred when medications containing parabens have been applied to damaged or broken skin. Parabens have been implicated in numerous cases of contact sensitivity associated with cutaneous exposure, but high concentrations of 5-15% in patch testing are needed to elicit reaction in susceptible individuals. Allergic reactions to ingested parabens have been reported, although rigorous evidence of the allergenicity of ingested paraben is lacking. (C) 2001 Elsevier Science Ltd. All rights reserved.