Toxicological review and oral risk assessment of terephthalic acid (TPA) and its esters: A category approach

Ball, Gwendolyn L.; McLellan, Clifton J.; Bhat, Virunya S.

doi:10.3109/10408444.2011.623149

Cited by 62 publications

(39 citation statements)

References 96 publications

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“…For example, chronic dietary exposure caused general toxicity in rats (Ball et al 2012). Female Sprague–Dawley rats administered DEHTP in the diet for 90 days showed no major organ or systemic toxicity at 0.5% (v/v) dose levels, but some effects on hematology parameters and increase in relative liver weights were observed at the 1.0% dose (Barber and Topping 1995).…”

Section: Introductionmentioning

confidence: 99%

Exposure to di-2-ethylhexyl terephthalate in a convenience sample of U.S. adults from 2000 to 2016

et al. 2017

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Di-2-ethylhexyl terephthalate (DEHTP), a structural isomer of di-2-ethylhexyl phthalate (DEHP), is a plasticizer used in a variety of commercial applications, but data on Americans’ exposure to DEHTP do not exist. We investigated the exposure to DEHTP in a convenience group of U.S. adults by analyzing urine collected anonymously in 2000 (N = 44), 2009 (N = 61), 2011 (N = 81), 2013 (N = 92), and 2016 (N = 149) for two major DEHTP oxidative metabolites: mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP). For comparison, we also quantified the analogous DEHP metabolites mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) and mono-2-ethyl-5-carboxypentyl phthalate (MECPP). We detected MECPTP, MEHHP, and MECPP in all samples collected in 2016 with geometric means of 13.1, 4.1, and 6.7 ng/mL, respectively; we detected MEHHTP in 91% of the samples (geometric mean = 3.1 ng/mL). Concentrations of MECPTP correlated well with those of MEHHTP (R2= 0.8, p < 0.001), but did not significantly correlate with those of MEHHP (p > 0.05) suggesting different sources of exposure to DEHP and DEHTP. We also evaluated the fraction of the metabolites eliminated in their free (i.e., unconjugated) form. The median percent of unconjugated species was lower for the DEHP metabolites (MECPP [45.5%], MEHHP [1.9%]) compared to the DEHTP metabolites (MECPTP [98.8%], MEHHTP [21.2%]). Contrary to the downward trend from 2000 to 2016 in urinary concentrations of MEHHP and MECPP, we observed an upward trend for MEHHTP and MECPTP. These preliminary data suggest that exposure to DEHTP may be on the rise. Nevertheless, general population exposure data using MEHHTP and MECPTP as exposure biomarkers would increase our understanding of exposure to DEHTP, one of the known DEHP alternatives.

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Section: Introductionmentioning

confidence: 99%

Exposure to di-2-ethylhexyl terephthalate in a convenience sample of U.S. adults from 2000 to 2016

et al. 2017

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“…Terephthalic acid was originally reported to be nontoxic (Hoshi et al 1968), but later studies involving higher levels of exposure to this compound suggested that it may impair testicular functions (Cui et al 2004). An extensive review on terephthalic acid has been recently published (Ball et al 2011). Although terephthalic acid has a certain resemblance in terms of molecular structure to DEHP, it cannot leach out of the final product and is chemically distinct from DEHP.…”

Section: Varieties Of Phthalates: Phthalates and Terephthalatesmentioning

confidence: 99%

Leaching of the plasticizer di(2-ethylhexyl)phthalate (DEHP) from plastic containers and the question of human exposure

Erythropel

Marić

Nicell

et al. 2014

Appl Microbiol Biotechnol

346

182

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Di(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizer to render poly(vinyl chloride) (PVC) soft and malleable. Plasticized PVC is used in hospital equipment, food wrapping, and numerous other commercial and industrial products. Unfortunately, plasticizers can migrate within the material and leach out of it over time, ending up in the environment and, frequently, the human body. DEHP has come under increased scrutiny as its breakdown products are believed to be endocrine disruptors and more toxic than DEHP itself. DEHP and its breakdown products have been identified as ubiquitous environmental contaminants, and daily human exposure is estimated to be in the microgram per kilogram level. The objective of this review is to summarize and comment on published sources of DEHP exposure and to give an overview of its environmental fate. Exposure through bottled water was examined specifically, as this concern is raised frequently, yet only little exposure to DEHP occurs through bottled water, and DEHP exposure is unlikely to stem from the packaging material itself. Packaged food was also examined and showed higher levels of DEHP contamination compared to bottled water. Exposure to DEHP also occurs in hospital environments, where DEHP leaches directly into liquids that passed through PVC/DEHP tubing and equipment. The latter exposure is at considerably higher levels compared to food and bottled water, specifically putting patients with chronic illnesses at risk. Overall, levels of DEHP in food and bottled water were below current tolerable daily intake (TDI) values. However, our understanding of the risks of DEHP exposure is still evolving. Given the prevalence of DEHP in our atmosphere and environment, and the uncertainty revolving around it, the precautionary principle would suggest its phaseout and replacement. Increased efforts to develop viable replacement compounds, which necessarily includes rigorous leaching, toxicity, and impact assessment studies, are needed before alternative plasticizers can be adopted as viable replacements.

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“…However, as mentioned above, TPA is the primary metabolite of DMT (Heck and Kluwe, 1980; Moffitt et al, 1975) and our study shows that DMT has no endocrine activity in any of the assays performed. TPA also showed no evidence of estrogenic activity in a two-generation reproduction study (Ball et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

Polyester monomers lack ability to bind and activate both androgenic and estrogenic receptors as determined by In Vitro and In Silico methods

Osimitz¹,

Welsh²,

Ni³

et al. 2015

Food and Chemical Toxicology

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The paper presents results from the screening of seven monomers used by Eastman Chemical to make various polymers. Ethylene glycol, diethylene glycol, polytetramethylene glycol, isophthalic acid, monosodium-5-sulfoisophthalic acid, 1,4-cyclohexanedicarboxylic acid, and dimethylcyclohexanedicarboxylate were screened for potential androgenicity or estrogenicity. The following studies were conducted: QSAR for binding to the AR and ER, in vitro Androgen Receptor Binding Assay, in vitro Estrogen Receptor Binding Assays (alpha and beta isoforms), in vitro Androgen Receptor Transactivation Assay in human cells, and in vitro Estrogen Receptor Transactivation Assay in human cells. None of the QSAR models predicted that any of the monomers possessed appreciable binding affinity for either AR or ER. Binding assays showed no evidence of interaction with either the AR or the alpha or beta ER receptors. Similarly, the AR and ER transactivation assays were negative. Moreover, six of the seven monomers have been subjected to 13-week and developmental toxicity studies in rats with no androgen- or estrogen-related effects being noted. Given the negative results of the in vitro screening assays (except PMG which demonstrated cytotoxicity) as well as available repeated dose and developmental and reproductive studies, the data suggest that none of the monomers tested exhibit androgenic or estrogenic hazards.

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Toxicological review and oral risk assessment of terephthalic acid (TPA) and its esters: A category approach

Cited by 62 publications

References 96 publications

Exposure to di-2-ethylhexyl terephthalate in a convenience sample of U.S. adults from 2000 to 2016

Exposure to di-2-ethylhexyl terephthalate in a convenience sample of U.S. adults from 2000 to 2016

Leaching of the plasticizer di(2-ethylhexyl)phthalate (DEHP) from plastic containers and the question of human exposure

Polyester monomers lack ability to bind and activate both androgenic and estrogenic receptors as determined by In Vitro and In Silico methods

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