(120) Associations of Urinary Phthalate Levels with Oxidative Stress Biomarkers in Midlife Women

Zane Cutright Inman¹ , Taylor Seaton¹, Maria E. Cinzori^2,3 , Rita S. Strakovsky^2,3, Jodi A. Flaws¹

¹Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, Urbana, Illinois.

²Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan.

³Institute for Integrative Toxicology, Michigan State University, East Lansing, Michigan.  

Abstract Text:

Women are ubiquitously exposed to phthalates – endocrine disruptors and plasticizers used in consumer products including building materials, food and beverage containers, and personal care products. This continuous exposure is concerning because phthalates can leach out of products and enter the human body. Phthalates are linked to elevated oxidative damage in rodent models, but little is known about the relationship between phthalates and oxidative stress in aging women. Thus, we hypothesized that phthalate exposure is associated with oxidative stress in midlife women. Urine and sera samples were collected from midlife women (n=619) from Baltimore city, Maryland and the surrounding counties. Urine samples (four pooled samples across a menstrual cycle) were subjected to measurements of nine phthalate metabolites using LC-MS. Specifically, we measured: mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethyl- 5-oxohexyl) phthalate (MEOHP), mono-(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), and monoisobutyl phthalate (MiBP). In addition, four di(2-ethylhexyl) phthalate (DEHP) metabolites (MEHP, MEHHP, MEOHP, and MECPP) were molar-summed to approximate exposure to DEHP (ΣDEHP). Serum samples were used to measure 8-hydroxy-2′-deoxyguanosine (8-OHdG, a measure of oxidative DNA damage), and total antioxidant capacity (TAC, a measure of free radical removal), using enzyme-linked immunosorbent assays (ELISA). Covariate-adjusted linear regression models evaluated associations of specific gravity-adjusted phthalates with 8-OHdG and TAC (μM of copper reducing equivalents). All phthalates and 8-OHdG were natural log-transformed to improve model fit. In the current study, 64% of the participants were premenopausal, with the rest being perimenopausal. Each two-fold increase in ΣDEHP was associated with 2.9% higher 8-OHdG (95% confidence interval (CI): 0.0, 5.9), whereas each two-fold increase in MCPP was associated with -2.6% lower 8-OHdG (95%CI: -4.5, -0.6) in midlife women. In addition, two-fold increases in ΣDEHP and MBzP were associated with -77.4 μM (95%CI: -105.2, -49.6) and -29.7 μM (95%CI: -55.9, -3.5) lower TAC, respectively. However, two-fold increases in MCPP and MiBP were associated with higher TAC (β_MCPP: 46.2, 95%CI: 26.5, 65.8; β_MiBP: 50.8, 95%CI: 19.8, 81.9) in midlife women. These findings suggest that phthalate exposure may be associated with modulated oxidative stress pathways in midlife women, but the associations differ based on phthalate metabolite. Supported by NIH R01ES026956, the Wanda Haschek-Hock Travel Award, and the Aarush M. Patel Foundation Fellowship.