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.

The potential use of diisononyl phthalate metabolites hair as biomarkers to assess long-term exposure demonstrated by a rat model

“…That may explain why the level of MINP was not significantly higher. A previous study showed that the level of MINP was lower than the secondary metabolites at all sampling time points (Saravanabhavan and Murray, 2012). However, in hair samples, the level of MINP was significantly different.…”

“…More than 18 billion pounds of phthalates are used each year. They are produced worldwide and are found in children's toys, food packaging, and medical devices (Crinnion, 2010;Colacino et al, 2011;Saravanabhavan and Murray, 2012). Phthalates are endocrine disruptors and affect reproductive outcomes, the development of the male reproductive tract (Waterman et al, 1999;Gray et al, 2000;Kavlock et al, 2002), and sexual differentiation in male rats (Gray et al, 2000;Tyl et al, 2004;Foster, 2006).…”

“…Due to the short elimination halflife of DINP, measuring exposure over weeks or months may require multiple measurements (Preau et al, 2010). DINP exposure assessments in epidemiologic studies are not consistent because of different sampling time points (Saravanabhavan and Murray, 2012). The general population is continually exposed to DINP through food packaging and personal products (Koch et al, 2013).…”

Exposure Marker Discovery of Phthalates Using Mass Spectrometry

“…[1][2][3][4] Because of their widespread use and biological e ects in animals, phthalates were included in the list of regulated (priority) pollutants by the US Environmental Protection Agency and the European Union. 5) Phthalates are easily released from plastic products because phthalates are not chemically bond to plastic products.…”

Ultrasound assisted extraction combined with dispersive liquid–liquid microextraction (US-DLLME)—a fast new approach to measure phthalate metabolites in nails

“…In addition, toxicity of PEs is associated with the length and branching of alkyl side-chain [8,9]. Nevertheless, several studies reported that the high molecular weight PEs are more quickly metabolized and excreted than low molecular weight (short chain) PEs and, consequently, high molecular weight PEs have rather low bioaccumulation potential in the human body [10,11]. Yet, the PEs (and in some cases their metabolites) are considered toxic for animals and/or humans, where the most common effects include hepatoxicity, carcinogenicity, endocrine disruption, fertility decrease (reproductive system), low birth weight, and decreased anogenital distance in children [5,[12][13][14][15].…”