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Cited by 212Effects and risks of endocrine disrupting chemicalsEpigenetics and DNA MethylationBirth, Development, and Health

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Phthalate Exposure and Long-Term Epigenomic Consequences: A Review

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Dutta, Sudipta, Haggerty, Diana K., Rappolee, Daniel A., Ruden, Douglas M.·2020·Frontiers in Genetics
DOI 10.3389/fgene.2020.00405PMC PMC7218126
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Abstract

Phthalates are esters of phthalic acid widely used as plasticizers to soften and increase the flexibility in polyvinyl chloride (PVC) plastics. They are also used in cosmetics and other daily personal care products. Phthalates are not covalently bound to plastics and easily leach into the environment and enter the human body by dermal absorption, ingestion or inhalation. Several in vitro and in vivo studies suggest that phthalates can act as endocrine disruptors and cause moderate reproductive and developmental toxicities. Furthermore, phthalates can cross the placental barrier and affect the developing fetus. Thus, phthalates are ubiquitous food and environmental contaminants with potential adverse health effects in humans. This review focusses on studies conducted in the field of toxicogenomics of phthalates and discusses possible transgenerational and multigenerational effects caused by phthalate exposure during any point of the life-cycle.

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Crossref · 10.3389/fgene.2020.00405

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Figure 1 Potential Sources of Phthalate Exposure in daily life. Phthalates have widespread applications in consumer products- they are used in a wide range of daily use household and personal care items starting from soaps, body lotions, and plastic containers to blood transfusion units. They can enter the human body through different routes like ingestion of foods, air inhalation, dust ingestion or dermal absorption. Phthalates can also cross the placenta and affect the developing fetus in a pregnant woman. Infants and neonates are also subjected to phthalate exposure via breast milk and from infant toys like pacifiers, bottle nipples, teethers, and neonatal medical care units.
Figure 1 Potential Sources of Phthalate Exposure in daily life. Phthalates have widespread applications in consumer products- they are used in a wide range of daily use household and personal care items starting from soaps, body lotions, and plastic containers to blood transfusion units. They can enter the human body through different routes like ingestion of foods, air inhalation, dust ingestion or dermal absorption. Phthalates can also cross the placenta and affect the developing fetus in a pregnant woman. Infants and neonates are also subjected to phthalate exposure via breast milk and from infant toys like pacifiers, bottle nipples, teethers, and neonatal medical care units.CC BY · PubMed Central
Figure 2 Pathway of phthalate metabolism in human body. LMW phthalates are mainly excreted in urine and feces as a monoester, no further metabolism is required. During phase I hydrolysis, diester phthalates are hydrolyzed by the enzymes like esterases and lipases in the intestine and parenchyma to their respective monoesters. High molecular weight (HMW) phthalates such as diisononyl phthalate (DINP), diisodecyl phthalate (DIDP), and dipropylheptyl phthalate (DPHP) have 9–13 carbon atoms in their chemical backbone and undergo further metabolism from monoesters via hydroxylation or oxidation and produce several oxidative metabolites which are excreted in urine within 24 h of exposure. Oxidative metabolites can also undergo phase II conjugation to form hydrophilic glucuronide conjugates which are excreted. Urinary phthalate metabolite is the most important biomarker for phthalate exposure [Adapted from the article, Metabolism of phthalates in humans by (Frederiksen et al., 2007)].
Figure 2 Pathway of phthalate metabolism in human body. LMW phthalates are mainly excreted in urine and feces as a monoester, no further metabolism is required. During phase I hydrolysis, diester phthalates are hydrolyzed by the enzymes like esterases and lipases in the intestine and parenchyma to their respective monoesters. High molecular weight (HMW) phthalates such as diisononyl phthalate (DINP), diisodecyl phthalate (DIDP), and dipropylheptyl phthalate (DPHP) have 9–13 carbon atoms in their chemical backbone and undergo further metabolism from monoesters via hydroxylation or oxidation and produce several oxidative metabolites which are excreted in urine within 24 h of exposure. Oxidative metabolites can also undergo phase II conjugation to form hydrophilic glucuronide conjugates which are excreted. Urinary phthalate metabolite is the most important biomarker for phthalate exposure [Adapted from the article, Metabolism of phthalates in humans by (Frederiksen et al., 2007)].CC BY · PubMed Central
Figure 3 Chemical structures of the top 10 major phthalates and their corresponding metabolites [adapted from the article, A Review of Biomonitoring of Phthalate Exposures by (Wang et al., 2019)].
Figure 3 Chemical structures of the top 10 major phthalates and their corresponding metabolites [adapted from the article, A Review of Biomonitoring of Phthalate Exposures by (Wang et al., 2019)].CC BY · PubMed Central

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Research works printed but not linked: 4

  1. Bayley, 1993, Bayley Scales of Infant Development, 2nd Edn.
  2. 2019, Fourth Report on Human Exposures to Environmental Chemicals, Updated Tables, Centers for Disease Control and
  3. 2019, NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di(2-ethylhexyl) Phthalate (DEHP), 06
  4. Park, 2006, Korean Bayley Scales of Infant Development. Interpretation Manual, 2nd Edn

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Metadata

Authors
Dutta, S., Haggerty, D. K., Rappolee, D. A., & Ruden, D. M.
Affiliations
  • University of Nebraska Medical Center (US)
  • Michigan State University (US)
  • Wayne State University (US)
Corresponding author
Ruden, Douglas M.
ORCID
Venue
Frontiers in Genetics
Publisher
Frontiers Media SA
Published
2020-05-06
Volume
11
Pages
405-405
ISSN
1664-8021 (ISSN-L)
DOI
10.3389/fgene.2020.00405
PMC
PMC7218126
OpenAlex
W3023341510
Cited by
212
References
234
Citations by year
2026: 29 · 2025: 49 · 2024: 35 · 2023: 38 · 2022: 35 · 2021: 25 · 2020: 1
FWCI
2.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Genetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Foundation for the National Institutes of Health
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
phthalates, plasticizers, endocrine disruptors, epigenetics, toxicogenomics, transgenerational epigenetic inheritance, multigenerational effects, reproductive toxicity, developmental toxicity, placental transfer, dermal exposure, environmental pollutants, food contaminants

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