Rat Metabolism Study Suggests 3-(3,5-Di-tert-butyl-4-hydroxyphenyl)propionic Acid as a Potential Urinary Biomarker of Human Exposure to Representative 3-(3,5-Di-tert-butyl-4-hydroxyphenyl)propionate Antioxidants

Abstract

propionate antioxidants, a family of synthetic phenolic antioxidants (SPAs) widely used in polymers, have recently been identified in indoor and outdoor environments. However, limited information is available concerning human exposure to these novel contaminants. In the present study, seven 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants were analyzed in human urine samples of donors from the United States. None of the target SPAs were initially detected in the urine samples either before or after hydrolysis by β-glucuronidase, prompting us to probe the major metabolites of these SPAs. We conducted rat metabolism studies with two representative congeners, tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate) (AO1010) and N,N′-bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionyl]hydrazine (AO1024). Neither AO1010 nor AO1024 was detected in rat urine, while 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid (fenozan acid) was identified as a urinary biomarker for these 3-(3,5-di-tert-butyl-4hydroxyphenyl)propionate antioxidants. Surprisingly, fenozan acid was detected in 88% of the human urine samples before hydrolysis (geometric mean: 0.69 ng/mL) and 98% of the samples after hydrolysis (geometric mean: 10.2 ng/mL), indicating prevalent human exposure to 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants. To our knowledge, this is the first study reporting the occurrence of fenozan acid in urine, where it can act as a potential biomarker of human exposure to 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants.

A Collision Cross Section Database for Extractables and Leachables from Food Contact Materials

“…This compound can be further oxidized into 7,9-di- tert -butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione ([M + H] + 173.9 Å 2 , [M + Na] + 185.2 Å 2 ). 48 Many of the TW CCS N2 values of degradation products are reported here for the first time, which contribute a lot to the application of IMS in the analysis of FCCs.…”

“…3-(3,5-Di- tert -butyl-4-hydroxyphenyl)­propionic acid ([M + Na] + 175.6 Å 2 ) can be produced from Irganox 245, Irganox 1076, Irganox 1035, and Irganox 1098. This compound can be further oxidized into 7,9-di- tert -butyl-1-oxaspiro­(4,5)­deca-6,9-diene-2,8-dione ([M + H] + 173.9 Å 2 , [M + Na] + 185.2 Å 2 ) . Many of the TW CCS N2 values of degradation products are reported here for the first time, which contribute a lot to the application of IMS in the analysis of FCCs.…”

“…TW CCS N2 Values of Sodiated Adducts of Isomeric Phthalate-Based Plasticizers (n = 3) 173.9 Å 2 , [M + Na] + 185.2 Å 2 ) 48. Many of the TW CCS N2 values of degradation products are reported here for the first time, which contribute a lot to the application of IMS in the analysis of FCCs.There are 33 TW CCS N2 values for 24 photoinitiators included in the TW CCS N2 database.…”

Carcinogenic Risk of 2,6-Di-tert-Butylphenol and Its Quinone Metabolite 2,6-DTBQ Through Their Interruption of RARβ: In Vivo, In Vitro, and In Silico Investigations

“…More details of exposure design and all sequences data have been described in our previous work . The quantification method and measured concentrations of 2,6-DTBP and 2,6-DTBQ in mice livers and serums are provided in Text S1 and Table S1. − Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed based on differential expressed genes (DEGs) induced by 2,6-DTBP and 2,6-DTBQ.…”

Field Evaluation of a Potential Exposure Biomarker of Methylated Polycyclic Aromatic Hydrocarbons: Association between Urinary Phenanthrene-2-carboxylic Acid and Personal Exposure to 2-Methylphenanthrene

“…On one hand, PAHs have been shown to induce the phase I enzymes (e.g., CYPs) and alter the metabolite profile (e.g., (1+2)-/4-OH-PHEs ratio). , In this study, we observed increased (1+2)-/4-OH-PHEs ratios from the nonheating to heating seasons, in association with personal exposure to PAHs (Figure S4), suggesting a possible seasonal difference in CYP activities. On the other hand, PAHs have been shown to inhibit phase II enzymes (e.g., glucuronosyltransferases), which may potentially slow the urinary excretion of OH-PHEs and 2-PHECA, since we and others have previously shown that a predominant fraction of hydroxylated and carboxylic acid metabolites were in conjugated forms. ,, Unfortunately, in the present, we did not assess the fraction of conjugated metabolites, so the direct evidence supporting the phase II metabolic alteration is lacking.…”