Due to health concerns about
phthalate esters, the use of alternative
plasticizers is being considered.
Phthalate esters enhance skin sensitization to
fluorescein isothiocyanate (
FITC) in mouse models. We have demonstrated that
phthalate esters stimulate transient receptor potential
ankyrin 1 (TRPA1)
cation channels expressed on sensory neurons. We also found a correlation between TRPA1 activation and the enhancing effect on
FITC-induced
contact hypersensitivity (CHS) when testing various types of
phthalate esters. Here we investigated the effects of an alternative
plasticizer,
diisopropyl adipate (
DIA). Activation of TRPA1 by
DIA was demonstrated by
calcium mobilization using Chinese hamster ovary cells expressing TRPA1 in vitro. The effect of
DIA was inhibited by a TRPA1-specific antagonist,
HC-030031. The presence of
DIA or
dibutyl phthalate (DBP; positive control) during skin sensitization of BALB/c mice to
FITC augmented the CHS response, as revealed by the level of ear-swelling. The enhancing effect of
DIA was inhibited by in vivo pretreatment with
HC-030031.
FITC-presenting CD11c(+) dendritic cell (DC)-trafficking to draining lymph nodes was facilitated both by
DIA and by DBP. DBP and
DIA were similarly active in the enhancement of
interferon-γ production by draining lymph nodes, but the effect on
interleukin-4 production was weaker with
DIA. Overall,
DIA activated TRPA1 and enhanced
FITC-induced CHS, as DBP did. The adjuvant effects of
adipate esters may need to be considered because they are used as ingredients in
cosmetics and
drug formulations topically applied to the skin.