The effects of the phthalate DiNP on reproduction†

Abstract

Di-isononyl phthalate (DiNP) is a high molecular weight, general purpose, plasticizer used primarily in the manufacture of polymers and consumer products. It can be metabolized rapidly and does not bioaccumulate. The primary metabolite of DiNP is monoisononyl-phthalate (MiNP) and the secondary metabolites include three oxidative derivatives of DiNP, which have been identified mainly in urine: mono-oxoisononyl phthalate (MOINP or oxo-MiNP), mono-carboxyisooctyl phthalate (MCIOP, MCOP or cx-MiNP), and mono-hydroxyisononyl phthalate (MHINP or OH-MiNP). The secondary metabolites are very sensitive biomarkers of DiNP exposure while primary metabolites are not. As the usage of DiNP worldwide increases, studies evaluating its potential reproductive toxicity are becoming more prevalent in the literature. In studies on female animals, the researchers found that the exposure to DiNP appears to induce negative effects on ovarian function and fertility in animal models. Whether or not DiNP has direct effects on the uterus is still controversial, and the effects on human reproduction require much more research. Studies on males indicate that DiNP exposure has disruptive effects on male reproduction and fertility. Occupational studies also indicate that the exposure to DiNP might induce negative effects on male reproduction, but larger cohort studies are needed to confirm this. This review presents an overview of the literature regarding the reproductive effects of exposure to DiNP.

Keywords: DiNP; metabolite; ovary; phthalate; reproductive toxicity; testis.

Figure 1

Schematic diagram of DiNP exposure, metabolism, excretion and biomonitoring. DiNP is absorbed by the gastrointestinal system where it is hydrolyzed to MiNP quite rapidly, or by inhalation or by dermal contact. It is mostly metabolized in the liver, and further oxidized into the secondary metabolites, oxo-MiNP, cx-MiNP and OH-MiNP. These metabolites are mainly excreted in the urine, which can be used to monitor exposure. Other body fluids, such as blood, amniotic fluid, breast milk and cord blood can also be used for biomonitoring in conditional circumstances. Since blood cannot be used as an excretion method but can be used for biomonitoring, we indicated this with the dashed line box. For bile, since it is a method for excretion, but cannot be used for biomonitoring, we used a light gray color.