Diisohexyl phthalate is a type of dialkyl phthalate showing agonistic activity via estrogen receptor α (ERα) with a REC20 value of 2.8×10-6M and antagonistic activity via estrogen receptor β (ERβ) with an RIC20 value of 3.2×10−6M[1]. Diisohexyl phthalate is primarily used as a plasticizer, particularly in the production of plastics such as PVC[2].
In vitro, Diisohexyl phthalate (10-7-10-5M) treated CHO-K1 for 24h induced ERα-mediated transcriptional activity, but simultaneously inhibited ERβ- and human androgen receptor (AR)-mediated transcriptional activities[1]. Diisohexyl phthalate (0.1, 1, 10μM) exposure for 24h did not induce significant luciferase activity in MCF-7 cells transiently transfected with the Gal4-human estrogen receptor chimera (Gal4-HEGO) and the Gal4-regulated luciferase reporter gene (17m5-G-Luc). This result indicated that Diisohexyl phthalate did not exhibit significant estrogen receptor-mediated activity in this cell assay[3].
In vivo, Diisohexyl phthalate (20, 200, and 2000mg/kg) administered orally daily for 4 consecutive days in OVX rats didn’t exert reproducible effect on uterine wet weight or induce significant vagianl epithelial cell cornifaction at any of the tested doses. The results suggested that diisohexyl phthalate lacks significant estrogenic activity in vivo[3]. Diisohexyl phthalate (25μM) treated B6C3F1 mice administered through ear five times weekly for two weeks had no significant effect on levels of serum IgE, IL-4, or IL-13 protein, or IL-4 or IL-13 mRNA, which indicated that Diisohexyl phthalate has little, if any, potential to produce antibody-mediated respiratory allergy[4].
References:
[1] Takeuchi S, Iida M, Kobayashi S, et al. Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor. Toxicology. 2005 Jun 1;210(2-3):223-33.
[2] Fung YS, Tang A.S. Liquid chromatographic determination of the plasticizer di(2-ethylhexyl) phthalate (DEHP) in PVC plastics. Fresenius' Journal of Analytical Chemistry. 1994, Volume 350, Issue 12, pp 721-723.
[3] Zacharewski T.R., Meek M.D., Clemons J.H., et al.Examination of the in Vitro and in Vivo Estrogenic Activities of Eight Commercial Phthalate Esters Toxicological Sciences. 1998; 46, 282–293
[4] Butala JH, David RM, Gans G, et al.Phthalate treatment does not influence levels of IgE or Th2 cytokines in B6C3F1 mice.Toxicology. 2004 Sep 1;201(1-3):77-85.