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Toxics
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Phthalate Exposure: From Quantification to Risk Assessment
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Phthalate Exposure: From Quantification to Risk Assessment

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Exposome Analysis and Risk Assessment".

Deadline for manuscript submissions: closed (20 May 2022) | Viewed by 44989

Special Issue Editors

Dr. Lidia Caporossi

E-Mail Website
Guest Editor
Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL-National Institute for Insurance against Accidents at Work, 00078 Monteporzio Catone, Italy
Interests: endocrine disrupters; occupational exposure to chemicals; reprotoxicity
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Maria Marino

E-Mail Website
Guest Editor
Dipartimento di Scienze, Università Roma Tre, Rome, Italy
Interests: endocrine disrupters; phthalate; alkylphenols; BPA; organohalogenates; environmental monitoring; biological monitoring; reprotoxicity; thyroid; metabolic effects
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Phthalates, the diesters of phthalic acid, are industrial chemicals widely used in commercial products. The ubiquitous use of phthalates results in human exposure from food, dermal absorption, inhalation, and parenteral use of medical—in addition to possible occupational—exposure.

Phthalates have been evaluated as possible human toxicants, and their toxicity has been extensively reviewed. Mainly phthalates possess endocrine-disrupting properties, with evidence for involvement in reproductive toxicity (both for men and women); they seem to be involved in metabolic disease, and there is interest in the scientific literature in a possible role played by phthalates in the onset of other illnesses linked to female hormones (e.g., endometriosis).

The environmental and biological monitoring of phthalates is a starting point to understand the real level of exposure for humans—first of all, distinguished between the base level in the environment and other sources of exposure (e.g., occupational). An important target is the proposal of analytical methods able to quantify low concentrations in different complex matrixes, particularly in human biomonitoring.

Any contribution to the clarification of the mechanisms of action of these chemical compounds in the human body and to the understanding of the role they play in producing adverse effects on health is necessary for the scientific community to orient itself and propose risk-prevention measures.

Dr. Lidia Caporossi
Professor Maria Marino
Guest Editor

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Keywords

  • endocrine disrupters
  • phthalates
  • adverse health impacts
  • source of exposure
  • analytical methods
  • reproductive disorders
  • dysmetabolic disorders
  • gender

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Published Papers (11 papers)

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16 pages, 280 KiB  
Article
Phthalate Exposures in the Neonatal Intensive Care Unit
by Randall Jenkins, Devlynne Ondusko, Luke Montrose, Ryan Forbush and David Rozansky
Toxics 2021, 9(5), 90; https://doi.org/10.3390/toxics9050090 - 21 Apr 2021
Cited by 10 | Viewed by 3145
Abstract
Background: Di-2-ethylhexyl phthalate (DEHP), a phthalate compound found in medical devices, may cause toxic effects in premature infants. In this study, the objective is to quantify DEHP exposures from various intravenous and respiratory therapy devices, and to use these values to predict typical [...] Read more.
Background: Di-2-ethylhexyl phthalate (DEHP), a phthalate compound found in medical devices, may cause toxic effects in premature infants. In this study, the objective is to quantify DEHP exposures from various intravenous and respiratory therapy devices, and to use these values to predict typical exposure for an infant in a neonatal unit. Methods: Common IV products used on infants are directed through various types of IV tubing (IVT) and analyzed for DEHP content. DEHP exposure for infants receiving respiratory therapy was determined indirectly through analysis of urine DEHP metabolites. By deriving these values for DEHP we calculated the daily exposure to DEHP from common IV fluids (IVF) and respiratory devices during hospitalization in a neonatal unit. Results: IVF labeled DEHP-positive showed very high concentrations of DEHP, but when passed through IVT, substantial amounts were adsorbed. DEHP was undetectable with all DEHP-negative IVF tests, except when passed through DEHP-positive IVT. The DEHP leached from most respiratory devices was relatively modest, except that detected from bubble CPAP. In 14 very low birthweight infants, the mean DEHP exposure was 182,369 mcg/kg over 81.2 days of the initial hospitalization. Ninety-eight percent of the exposure was from respiratory devices, with bubble CPAP accounting for 95% of the total DEHP exposure in these infants. Conclusions: The DEHP exposure in our neonatal unit can be reduced markedly by avoiding or modifying bubble CPAP equipment and avoiding IV tubing containing DEHP. Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
16 pages, 7429 KiB  
Article
Effects of Phthalate Esters (PAEs) on Cell Viability and Nrf2 of HepG2 and 3D-QSAR Studies
by Huan Liu, Huiying Huang, Xueman Xiao, Zilin Zhao and Chunhong Liu
Toxics 2021, 9(6), 134; https://doi.org/10.3390/toxics9060134 - 5 Jun 2021
Cited by 10 | Viewed by 3647
Abstract
Phthalate esters (PAEs) are a widespread environmental pollutant, and their ecological and environmental health risks have gradually attracted attention. To reveal the toxicity characteristics of these compounds, ten PAEs were selected as research objects to establish a cell model. CCK-8 was used to [...] Read more.
Phthalate esters (PAEs) are a widespread environmental pollutant, and their ecological and environmental health risks have gradually attracted attention. To reveal the toxicity characteristics of these compounds, ten PAEs were selected as research objects to establish a cell model. CCK-8 was used to determine cell viability, Western blots were used to determine the content of Nrf2 in HepG2, and the LD50 collected for the 13 PAEs administered to rats. On this basis, 3D-QSAR models of IC50, LD50 and Nrf2 were established. The experimental results showed that as the time of PAEs exposure increased (24, 48 and 72 h), cell viability gradually decreased. The test concentration (62.5 /125/250 μM) of PAEs exposed for 48 h could significantly increase the content of Nrf2, and the 1000 μM PAEs could inhibit the content of Nrf2. The model is relatively stable and predicts well that the introduction of large and hydrophobic groups may significantly affect the toxic effects of PAEs on cells. The present study provided a potential tool for predicting the LD50 and Nrf2 of new PAEs, and provide a reference for the design of new less toxic PAEs in the future. Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
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26 pages, 2056 KiB  
Review
Comprehensive Insight from Phthalates Occurrence: From Health Outcomes to Emerging Analytical Approaches
by Catarina Luís, Manuel Algarra, José S. Câmara and Rosa Perestrelo
Toxics 2021, 9(7), 157; https://doi.org/10.3390/toxics9070157 - 1 Jul 2021
Cited by 29 | Viewed by 5915
Abstract
Phthalates are a group of chemicals used in a multitude of important industrial products (e.g., medical devices, children’s toys, and food packages), mainly as plasticizers to improve mechanical properties such as flexibility, transparency, durability, and longevity of polyvinyl chloride (PVC). The wide occurrence [...] Read more.
Phthalates are a group of chemicals used in a multitude of important industrial products (e.g., medical devices, children’s toys, and food packages), mainly as plasticizers to improve mechanical properties such as flexibility, transparency, durability, and longevity of polyvinyl chloride (PVC). The wide occurrence of phthalates in many consumer products, including foods (e.g., bottled water, soft drinks, wine, milk, and meat) brings that most people are exposed to phthalates every day, which raises some concerns. Adverse health outcomes from phthalates exposure have been associated with endocrine disruption, deformities in the human reproductive system, increased risk of preterm birth, carcinogen exposure, among others. Apprehension related to the health risks and ubiquitous incidence of phthalates in foods inspires the development of reliable analytical approaches that allow their detection and quantification at trace levels. The purpose of the current review is to provide information related to the presence of phthalates in the food chain, highlighting the health risks associated with their exposure. Moreover, an overview of emerging extraction procedures and high-resolution analytical approaches for a comprehensive quantification of phthalates is presented. Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
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23 pages, 2284 KiB  
Review
Review on Toxic Effects of Di(2-ethylhexyl) Phthalate on Zebrafish Embryos
by Wing Sum Kwan, Vellaisamy A. L. Roy and Kwan Ngok Yu
Toxics 2021, 9(8), 193; https://doi.org/10.3390/toxics9080193 - 21 Aug 2021
Cited by 19 | Viewed by 5037
Abstract
Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in consumer products. People are continuously exposed to DEHP through ingestion, inhalation and dermal absorption. From epidemiological studies, DEHP has been shown to associate with various adverse health effects, such as reproductive abnormalities and [...] Read more.
Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in consumer products. People are continuously exposed to DEHP through ingestion, inhalation and dermal absorption. From epidemiological studies, DEHP has been shown to associate with various adverse health effects, such as reproductive abnormalities and metabolic diseases. Health concerns have been raised regarding DEHP exposures; therefore, relevant risk assessment has become necessary through toxicological testing of DEHP. In the past 10 years, an increasing number of DEHP toxicity studies have been using zebrafish embryos as an in vivo model due to their high fecundity, rapid embryonic development as well as optical transparency, which have now been established as an alternative of the more conventional rodent model. The aim of the present paper is to review the effects of acute (from embryo stage to ≤1 week) and chronic (from embryo stage to >1 week) DEHP exposures on zebrafish, which start from the embryonic stage, and to analyze acute and potential long-term effects induced by acute exposure and effects induced by chronic exposure of DEHP upon subjecting to exposures, starting from the embryonic stage to different developmental stages, with a view to facilitate risk assessments on DEHP exposures. Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
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16 pages, 2508 KiB  
Article
Analysis of Phthalates and Alternative Plasticizers in Gloves by Gas Chromatography–Mass Spectrometry and Liquid Chromatography–UV Detection: A Comparative Study
by Kelly Poitou, Tiphaine Rogez-Florent, Marie Lecoeur, Cécile Danel, Romain Regnault, Philippe Vérité, Christelle Monteil and Catherine Foulon
Toxics 2021, 9(9), 200; https://doi.org/10.3390/toxics9090200 - 28 Aug 2021
Cited by 16 | Viewed by 5931
Abstract
Gloves represent an essential feature for hand protection because it is a requirement in the professional framework to comply with both hand hygiene standards and the principles of good laboratory practice. Despite their wide use, there is a knowledge gap regarding their composition, [...] Read more.
Gloves represent an essential feature for hand protection because it is a requirement in the professional framework to comply with both hand hygiene standards and the principles of good laboratory practice. Despite their wide use, there is a knowledge gap regarding their composition, including phthalates. The purpose of the present study was to develop two orthogonal methods, GC–MS and HPLC–DAD, for the screening of plasticizers in gloves. Performances of these two methods were compared in terms of ease of use, number of analyzed plasticizers, and sample preparation. The two methods were validated and applied for the identification and quantification of plasticizers in ten gloves made with different materials (vinyl, nitrile, latex, and neoprene). Results revealed the presence of three main ones: DEHP, DEHT, and DINP. Additionally, the contents of plasticizers were extremely variable, depending on the glove material. As expected, the results point out a predominant use of plasticizers in vinyl gloves with an amount that should be of concern. While DEHP is classified as a toxic substance for reproduction 1B, it was, however, quantified in the ten different glove samples studied. This study provides new data regarding the plasticizers’ content in protective gloves, which could be useful for risk assessment. Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
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15 pages, 1554 KiB  
Article
The Peculiar Estrogenicity of Diethyl Phthalate: Modulation of Estrogen Receptor α Activities in the Proliferation of Breast Cancer Cells
by Marco Fiocchetti, Giovanna Bastari, Manuela Cipolletti, Stefano Leone, Filippo Acconcia and Maria Marino
Toxics 2021, 9(10), 237; https://doi.org/10.3390/toxics9100237 - 25 Sep 2021
Cited by 15 | Viewed by 3593
Abstract
Phthalates comprise a group of synthetic chemicals present in the environment because of their wide use as plasticizers and as additives in products for personal care. Among others, diethyl phthalate (DEP) is largely used in products for infants, children, and adults, in which [...] Read more.
Phthalates comprise a group of synthetic chemicals present in the environment because of their wide use as plasticizers and as additives in products for personal care. Among others, diethyl phthalate (DEP) is largely used in products for infants, children, and adults, in which its exposure has been correlated with an increased risk of breast cancer. The adverse health outcomes deriving from phthalate exposure have been associated with their activity as endocrine disruptors (EDCs) of the steroid and thyroid hormone signaling by affecting developmental and reproductive health, and even carcinogenicity. However, the estrogen disruptor activities of DEP are still controversial, and the mechanism at the root of the estrogenic-disrupting action of DEP remains to be clarified. Here, we evaluated the DEP mechanism of action on the activation status of estrogen receptor α (ERα) by analyzing the receptor’s phosphorylation as well as both nuclear and extra-nuclear pathways triggered by the receptor to modulate the proliferation of breast cancer cells. Although DEP does not bind to ERα, our results suggest that this phthalate ester exerts multiple parallel interactions with ERα signaling and emphasize the importance to determine an appropriate battery of in vitro methods that will include specific molecular mechanisms involved in the endocrine disruption. Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
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13 pages, 1877 KiB  
Article
Fast and Reliable Determination of Phthalic Acid Esters in the Blood of Marine Turtles by Means of Solid Phase Extraction Coupled with Gas Chromatography-Ion Trap/Mass Spectrometry
by Ivan Notardonato, Cristina Di Fiore, Alessia Iannone, Mario Vincenzo Russo, Monica Francesca Blasi, Gabriele Favero, Daniela Mattei, Carmela Protano, Matteo Vitali and Pasquale Avino
Toxics 2021, 9(11), 279; https://doi.org/10.3390/toxics9110279 - 22 Oct 2021
Cited by 7 | Viewed by 2618
Abstract
The presence of phthalic acid esters (PAEs) in marine environments is an important issue. These chemicals are able to affect marine organisms, particularly marine turtles, and to act as endocrine disrupters. In this paper, for the first time, a simple and reproducible analytical [...] Read more.
The presence of phthalic acid esters (PAEs) in marine environments is an important issue. These chemicals are able to affect marine organisms, particularly marine turtles, and to act as endocrine disrupters. In this paper, for the first time, a simple and reproducible analytical method based on solid-phase extraction (SPE) coupled with gas chromatography—ion trap/mass spectrometry (GC-IT/MS) was developed for the extraction of phthalates from the blood of marine turtles. The extraction was obtained by using C18 phthalates-free as the stationary phase. In order to individuate the best working conditions for the extraction, the adsorption isotherms and breakthrough curves were studied. The overall analytical methodology was validated in terms of limit of detection (LOD, 0.08–0.6 ng mL−1), limit of quantification (LOQ, 0.4–0.8 ng mL−1), and correlation coefficients (>0.9933). By using this procedure, percentage recoveries ranging from 89 to 103% were achieved. The precision parameters (intra-day and inter-day) were studied, and the obtained values were smaller than 12.5%. These data confirm the goodness of the proposed analytical methodology, which is applied to real samples. Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
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15 pages, 337 KiB  
Article
Female Reproductive Health and Exposure to Phthalates and Bisphenol A: A Cross Sectional Study
by Lidia Caporossi, Paola Viganò, Enrico Paci, Silvia Capanna, Alessandra Alteri, Giovanni Campo, Daniela Pigini, Mariangela De Rosa, Giovanna Tranfo and Bruno Papaleo
Toxics 2021, 9(11), 299; https://doi.org/10.3390/toxics9110299 - 11 Nov 2021
Cited by 19 | Viewed by 4203
Abstract
The xenoestrogenicity of some plasticisers (phthalates and bisphenol A) is documented in the literature and may pose a risk to female reproductive health. The aim of this study was to assess exposure to six phthalates. This was achieved by measuring their respective metabolites [...] Read more.
The xenoestrogenicity of some plasticisers (phthalates and bisphenol A) is documented in the literature and may pose a risk to female reproductive health. The aim of this study was to assess exposure to six phthalates. This was achieved by measuring their respective metabolites (mono-ethylphthalate (MEP); mono-n-butylphthalate (MnBP); mono-n-ottylphthalate (MnOP); and monobenzylphthalate (MBzP)), as well as the sum of two of the diethyl-hexyl phthalate metabolites-(∑DEHP) and bisphenol A (BPA) in a female population with infertility problems, and by conducting a correlation analysis between infertility factors, work activities, and lifestyle habits, in order to formulate a causal hypothesis. A cross-sectional epidemiological study was carried out and women under 43 years of age were recruited from an assisted reproduction technology (ART) center; the sample of 186 women was given a specific questionnaire and a spot urine sample was collected. Phthalate metabolites and urinary BPA were analyzed by HPLC/MS/MS. The results showed significantly higher mean values for MEP in women with recurrent pregnancy loss (RPL) (820.5 ± 1929.5 µg/g of creatinine) and idiopathic infertility (230.0 ± 794.2 µg/g of creatinine) than in women with other infertility factors (76.9 ± 171.8 µg/g of creatinine). Similarly, for MnOP levels, women with idiopathic infertility (2.95 ± 3.44 µg/g of creatinine) showed significantly higher values than women with the other infertility factors taken together (1.35 ± 2.05 µg/g of creatinine). Women with tubal factors of infertility, RPL, and endocrine dysfunctions show higher values of DEHP (p = 0.032). Considering occupations, women working in commerce showed more than twice as much urinary BPA levels (1.10 ± 0.48 µg/g of creatinine) compared to women working in other industries (0.45 ± 0.35 µg/g of creatinine). The presence of significantly higher values of certain phthalates, DEHP in particular, especially in women with RPL and idiopathic infertility, suggests a possible involvement of these compounds as competing factors in reproductive issues. The study of sources of exposure suggested that the working activity in trade, as a casher in particular, represents a major one for BPA (p = 0.015). Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
23 pages, 3153 KiB  
Article
Proficiency and Interlaboratory Variability in the Determination of Phthalate and DINCH Biomarkers in Human Urine: Results from the HBM4EU Project
by Hans G. J. Mol, Ingrid Elbers, Claudia Pälmke, Daniel Bury, Thomas Göen, Marta Esteban López, Stefanie Nübler, Vincent Vaccher, Jean-Philippe Antignac, Darina Dvořáková, Jana Hajšlová, Amrit Kaur Sakhi, Cathrine Thomsen, Katrin Vorkamp, Argelia Castaño and Holger M. Koch
Toxics 2022, 10(2), 57; https://doi.org/10.3390/toxics10020057 - 26 Jan 2022
Cited by 18 | Viewed by 3314
Abstract
A quality assurance/quality control program was implemented in the framework of the EU project HBM4EU to assess and improve the comparability of biomarker analysis and to build a network of competent laboratories. Four rounds of proficiency tests were organized for 15 phthalate and [...] Read more.
A quality assurance/quality control program was implemented in the framework of the EU project HBM4EU to assess and improve the comparability of biomarker analysis and to build a network of competent laboratories. Four rounds of proficiency tests were organized for 15 phthalate and two DINCH urinary biomarkers (0.2–138 ng/mL) over a period of 18 months, with the involvement of 28 laboratories. A substantial improvement in performance was observed after the first round in particular, and by the end of the program, an average satisfactory performance rate of 90% was achieved. The interlaboratory reproducibility as derived from the participants’ results varied for the various biomarkers and rounds, with an average of 24% for the biomarkers of eight single-isomer phthalates (e.g., DnBP and DEHP) and 43% for the more challenging biomarkers of the mixed-isomer phthalates (DiNP, DiDP) and DINCH. When the reproducibility was based only on the laboratories that consistently achieved a satisfactory performance, this improved to 17% and 26%, respectively, clearly demonstrating the success of the QA/QC efforts. The program thus aided in building capacity and the establishment of a network of competent laboratories able to generate comparable and accurate HBM data for phthalate and DINCH biomarkers in 14 EU countries. In addition, global comparability was ensured by including external expert laboratories. Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
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13 pages, 315 KiB  
Article
Phthalate Exposure and Biomarkers of Oxidation of Nucleic Acids: Results on Couples Attending a Fertility Center
by Daniela Pigini, Lidia Caporossi, Enrico Paci, Silvia Capanna, Paola Viganò, Alessandra Alteri, Elisa Rabellotti, Flavia Buonaurio, Bruno Papaleo and Giovanna Tranfo
Toxics 2022, 10(2), 61; https://doi.org/10.3390/toxics10020061 - 29 Jan 2022
Cited by 7 | Viewed by 3272
Abstract
Phthalates are substances used as plasticizing agents and solvents that can increase the risk of infertility and that appear to induce oxidative stress. The aim of the study was to show the possible relationship between urinary concentrations of phthalates metabolites, namely MEP, MBzP, [...] Read more.
Phthalates are substances used as plasticizing agents and solvents that can increase the risk of infertility and that appear to induce oxidative stress. The aim of the study was to show the possible relationship between urinary concentrations of phthalates metabolites, namely MEP, MBzP, MnBP, MEHP, MEHHP, and MnOP and biomarkers of nucleic acids oxidation, methylation, or protein nitroxidation. The oxidative stress biomarkers measured in human urine were 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, 8-oxo-7,8-dihydro-2′-deoxyguanosine, 3-nitrotyrosine, and 5-methylcytidine. Two hundred and seventy-four couples were enrolled, undergoing an assisted reproduction technology (ART) treatment, urine samples were analyzed in HPLC/MS-MS, and then two sub-groups with urinary concentration > 90th or <10th percentile were identified, reducing the sample size to 112 subjects. The levels of oxidative stress biomarkers were measured in both groups, reduced to 52 men and 60 women. A statistically significantly difference for 8-oxoGuo and 3-NO2Tyr between men and women, with higher levels in men, was found. The levels of oxidative stress biomarkers were directly correlated with some phthalate concentrations in both sexes. Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
4 pages, 220 KiB  
Editorial
Phthalate Exposure: From Quantification to Risk Assessment
by Lidia Caporossi and Maria Marino
Toxics 2022, 10(6), 330; https://doi.org/10.3390/toxics10060330 - 16 Jun 2022
Cited by 1 | Viewed by 1955
Abstract
Phthalates (di-esters of phthalic acid) are a group of synthetic organic compounds present in the environment because of their wide use in a multitude of important industrial products (e [...] Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
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