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Phthalate Exposure and Long-Term Epigenomic Consequences: A Review
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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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![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)].](/paper-figures/9a1fa933e7c143988f4698889e9b5f69/phthalate-exposure-and-long-term-epigenomic-consequences-a-review-figure-2.jpg)
![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)].](/paper-figures/77c864ae36cf4b7da8b084b716bd458b/phthalate-exposure-and-long-term-epigenomic-consequences-a-review-figure-3.jpg)
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“Moreover, phthalates can influence gene expression patterns, further complicating their effects on the body’s intricate regulatory processes.”
From The dark side of beauty: an in-depth analysis of the health hazards and toxicological impact of synthetic cosmetics and personal care products (2024) · cites this paper as [65]
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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.
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2020-05-06
- Volume
- 11
- Pages
- 405-405
- ISSN
- 1664-8021 (ISSN-L)
- 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
- gold
- doi.org
- 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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