Diethylhexyl phthalate magnifies deposition of ¹⁴ C-bisphenol A in reproductive tissues of mice

Abstract

Endocrine disrupting chemicals are found in diverse common products, including cosmetics, food packaging, thermal receipt paper and plastic containers. This exposes most people in developed countries through ingestion, skin absorption and inhalation. Two ubiquitous endocrine disrupting chemicals, bisphenol A (BPA) and diethylhexyl phthalate (DEHP) can interact in disrupting blastocyst implantation in inseminated females. We hypothesized that DEHP might increase the bioavailability of BPA in tissues by competing for metabolic enzymes. We injected 0, 3, 9 or 18 mg DEHP into female and male mice and allowed 30 min for the chemical to circulate before giving them a food supplement containing 50 μg kg C-BPA. Animals were dissected 1 h following C-BPA administration and various tissue samples were acquired. Samples were solubilized and radioactivity was measured via liquid scintillation counting. In cycling females, DEHP increased BPA deposition in the muscle, uterus, ovaries and blood serum relative to controls. In peri-implantation females, DEHP increased deposition of BPA in the uterus, ovaries and serum relative to controls. In males, DEHP doses increased BPA deposition in serum and epididymis relative to controls. These results are consistent with the hypothesis that DEHP competes with BPA for conjugating enzymes such as UDP-glucuronosyltransferase, thereby magnifying the presence of BPA in estrogen-binding reproductive tissues. Copyright © 2017 John Wiley& Sons, Ltd.

Toxic Effects of the Mixture of Phthalates and Bisphenol A—Subacute Oral Toxicity Study in Wistar Rats

“…These interactions were confirmed in an acute toxicity study on mice, which explored the influence of a single dose of DEHP injected subcutaneously (3, 9, and 18 mg) on the deposition of BPA received as a food supplement (50 µg/kg 14C-BPA). The results of this study indicated that DEHP increases the deposition of BPA in the epididymis of male mice compared to the control group [79]. The effects of the single phthalate on the testosterone production have been tested in various studies, but mostly after the prenatal exposure.…”

Endocrine Disruption by Mixtures in Topical Consumer Products

“…The number of potential endocrine active substances commonly used in consumer products and especially so in cosmetics, may be very high and the role of complex interaction and cumulative effects in mixtures is still too unclear to rule out potential endocrine adverse effects according to the concentration of individual ingredients. Some EDCs with very low activity are known or supposed to be able to act as multipliers for other endocrine actives by indirect modulatory effects [123]. While testing every existing product on the market for endocrine disruption is not feasible in the short term, a strategy to apply precautionary testing is needed in order to provide customer safety while EDCs research proceeds.…”

“…The most commonly used phthalate however, di-2-ethylhexyl phthalate (DEHP) have been linked with endocrine disrupting effects on the reproductive system due to his action as an androgen antagonist. DEHP has been correlated to lower fertility and sperm motility in males [90], to defective oocyte maturation [30,123], to anomalies in sexual development [122], to asthma [25], to breast cancer induction and to a wide range of other endocrine effects [124]. Recently, DEHP was categorized as a non-persistent endocrine disrupting compound by the world health organization (WHO).…”

“…Numerous studies of DEHP have shown changes in sexual function and development. More worryingly, DEHP has been reported to be able to increase the accumulation of other EDCs such as bisphenol A in reproductive tissues [123] indicating an indirect effect as a potential endocrine disruptor bioaccumulation promoter. A large study on male partners of subfertile couples found associations between monobutyl phthalate and below reference value sperm motility and sperm concentration.…”

Endocrine disrupting chemicals, 4‐nonylphenol, bisphenol A and butyl benzyl phthalate, impair metabolism of estradiol in male and female rats as assessed by levels of 15α‐hydroxyestrogens and catechol estrogens in urine

“…Metabolic enzymes that are related to the function of EDCs include conjugating enzymes. Diethylhexyl phthalate competes with BPA for UDP‐glucuronosyltransferase (Borman, Vecchi, Pollock, & DeCatanzaro, ). We believe that the influence of EDCs on E 2 metabolism, which was shown in this study, is also important.…”