Diisohexyl phthalate

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.

Diisohexyl phthalate是一类邻苯二甲酸二烷基酯，通过雌激素受体α（ERα）具有激动作用，其REC₂₀值为2.8×10^-6M，通过雌激素受体β（ERβ）具有拮抗作用，其RIC₂₀值为3.2×10⁻⁶M。Diisohexyl phthalate主要用作增塑剂，特别是在PVC等塑料的生产中^[2]。

在体外，Diisohexyl phthalate（10^-7-10^-5M）处理CHO-K1 24h，可诱导ERα介导的转录活性，但同时抑制ERβ和人雄激素受体（AR）介导的转录活性^[1]。Diisohexyl phthalate（0.1、1和10μM）处理瞬时转染了Gal4 -人雌激素受体嵌合体（Gal4-HEGO）和Gal4调控的荧光素酶报告基因（17m5-G-Luc）的MCF-7细胞24h后，荧光素酶活性不显著。这一结果表明Diisohexyl phthalate在该细胞试验中没有表现出显著的雌激素受体介导的活性^[3]。

在体内，在OVX大鼠连续4天每天口服Diisohexyl phthalate（20、200和2000mg/kg）对子宫湿重影响无法被反复证实，也没有引起阴道上皮细胞明显的角质化。结果表明，Diisohexyl phthalate在体内缺乏明显的雌激素活性^[3]。经耳给药的Diisohexyl phthalate（25μM）处理B6C3F1小鼠，每周经耳给药5次，持续两周，对血清IgE、IL-4或IL-13蛋白、IL-4或IL-13 mRNA水平没有显著影响，这表明Diisohexyl phthalate几乎没有可能产生抗体介导的呼吸道过敏^[4]。