Diisononyl phthalate

Diisononyl phthalate (DINP) is an orally active polyvinyl chloride plasticizer and indirect food additive. Diisononyl phthalate activates the ACE/AT1R axis and inhibits the production of NO. Diisononyl phthalate reduces the expression of eNOS. Diisononyl phthalate induces increased blood pressure in mice. Diisononyl phthalate induces monocytic leukemia in rats. Diisononyl phthalate can be used in hypertension-related research^[1][2]. In Vitro:Diisononyl phthalate shows no genotoxic activity in bacterial and mammalian cells^[2]. In Vivo:Exposure to diisononyl phthalate alone (0.15-15 mg/kg/day; intragastric administration; daily; 42 days) induces dose-dependent elevation of blood pressure, increased heart rate (at 15 mg/kg/day), and cardiovascular/renal tissue damage in C57/BL6 mice, accompanied by upregulated expression of ACE and AT1R in the aorta, downregulated expression of eNOS in the aorta, and reduced serum NO production^[1].
Exposure to diisononyl phthalate (0.15-15 mg/kg/day; oral gavage; daily; 42 days; with simultaneous daily subcutaneous administration of 1 mg/kg/day dexamethasone for 42 days) dose-dependently exacerbates dexamethasone-induced hypertension, cardiovascular/renal tissue damage, and dysregulation of the ACE/AT1R and eNOS/NO pathways in C57/BL6 mice, and this effect is reversible by treatment with an ACE inhibitor^[1].
Dietary intake of diisononyl phthalate (DINP) at doses of 0.03-0.6 wt% daily for 2 years induces a dose-dependent increase in liver, kidney and spleen weights in Fischer 344 rats. Male rats in the high-dose group show a slight decrease in body weight, and rats in the middle- and high-dose groups exhibit a statistically significant increase in the incidence of monocytic leukemia over the 2-year experimental period^[2].