Parabens, which are a homologous series of
esters of p-
hydroxybenzoic acid, have been used as preservatives in
cosmetics, medicines and foods because of their antimicrobial activity. However,
parabens in
cosmetics have been suspected to cause
allergic contact dermatitis. In this study, we examined
paraben-induced histamine release from rat peritoneal mast cells and skin reaction in guinea pigs using a series of 17
parabens with different alcohol side chains, ranging from
methylparaben to dodecylparaben. Octylparaben showed the greatest histamine release-inducing activity from mast cells, and the activity was decreased in shorter- and longer-side-chain
parabens. Octyl
benzoate, octyl o-hydroxybenzoate and phenyloctane caused no significant degranulation of mast cells, whereas octyl m-hydroxybenzoate, octyl
p-hydroxybenzoate and octyl
phenol induced concentration-related degranulation. Metabolites of these
parabens (p-
hydroxybenzoic acid and
alcohols) did not show histamine release-inducing activity. In the guinea pig skin reaction test,
heptylparaben induced a typical strong skin reaction, while
butylparaben induced a typical weak skin reaction, and
methylparaben and dodecylparaben were inactive. Metabolites of
parabens (p-
hydroxybenzoic acid and
alcohols) were also inactive. These results indicate that interaction of
parabens with rat mast cells requires a minimum length and adequate lipophilicity of the alkyl side chain. Since metabolites of
parabens were inactive,
parabens appear to be direct-acting
allergens.