Human biological monitoring of diisononyl phthalate and diisodecyl phthalate: a review

Abstract

High molecular-weight phthalates, such as diisononyl phthalate (DINP), and diisodecyl phthalate (DIDP), are widely used as plasticizers in the manufacturing of polymers and consumer products. Human biological monitoring studies have employed the metabolites of DINP and DIDP as biomarkers to assess human exposure. In this review, we summarize and analyze publicly available scientific data on chemistry, metabolism, and excretion kinetics, of DINP and DIDP, to identify specific and sensitive metabolites. Human biological monitoring data on DINP and DIDP are scrutinised to assess the suitability of these metabolites as biomarkers of exposure. Results from studies carried out in animals and humans indicate that phthalates are metabolised rapidly and do not bioaccmulate. During Phase-I metabolism, ester hydrolysis of DINP and DIDP leads to the formation of hydrolytic monoesters. These primary metabolites undergo further oxidation reactions to produce secondary metabolites. Hence, the levels of secondary metabolites of DINP and DIDP in urine are found to be always higher than the primary metabolites. Results from human biological monitoring studies have shown that the secondary metabolites of DINP and DIDP in urine were detected in almost all tested samples, while the primary metabolites were detected in only about 10% of the samples. This indicates that the secondary metabolites are very sensitive biomarkers of DINP/DIDP exposure while primary metabolites are not. The NHANES data indicate that the median concentrations of MCIOP and MCINP (secondary metabolites of DINP and DIDP, resp.) at a population level are about 5.1 μg/L and 2.7 μg/L, respectively. Moreover, the available biological monitoring data suggest that infants/children are exposed to higher levels of phthalates than adults.

Figure 1

Proposed metabolic transformation of DINP and DIDP based on studies conducted in rodents and humans [6]. For simplicity, the linear side chains are depicted in phthalate structures in this figure. Legends: DIDP: diisodecyl phthalate; DINP: Diisononyl phthalate; MIDP: monoisodecyl phthalate; MINP: monoisononyl phthalate; MHIDP: monohydroxy isodecyl phthalate; MCINP: monocarboxy isononyl phthalate; MCIOP: monocarboxy isooctyl phthalate; MHINP: monohydroxy isononyl phthalate; MOIDP: monooxoisodecyl phthalate; MCIHPP: monocarboxy isoheptyl phthalate; MCIHXP: monocarboxy isohexyl phthalate; MOINP: monooxoisononyl phthalate; MCIPEP: monocarboxy isopentyl phthalate; MCIBP: monocarboxy isobutyl phthalate; MCPP: monocarboxy propyl phthalate; MCEP: monocarboxy ethyl phthalate [13, 14, 22, 23].