Di(2-ethylhexyl) phthalate (DEHP)
Di(2-ethylhexyl) phthalate (DEHP) is a widely used organic compound with the molecular formula C24H38O4, primarily functioning as a plasticizer in polyvinyl chloride (PVC) to enhance flexibility and softness in products. Though classified as a "reasonably anticipated human carcinogen" since 1983, studies indicate that DEHP does not appear to cause cancer in humans, with toxicological mechanisms observed in animals being irrelevant to human health. DEHP can leach from plastic products, and potential exposure routes include inhalation, ingestion, and medical procedures involving IV bags or tubing.
Significant exposure risks may be encountered by newborns and infants in medical settings, as well as individuals living near hazardous waste sites or working in PVC production. While DEHP exposure has been associated with decreased sperm quality and potential links to allergies and asthma, the evidence remains inconclusive and necessitates further investigation. Although its use has decreased in some applications, DEHP's presence in everyday items like children's toys and food packaging raises concerns about health implications. Overall, while DEHP is still regarded with caution, particularly regarding infants, the direct risk to human health appears limited under typical exposure conditions.
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Subject Terms
Di(2-ethylhexyl) phthalate (DEHP)
ROC STATUS: Reasonably anticipated human carcinogen since 1983
ALSO KNOWN AS: Diethylhexyl phthalate, bis(2-ethylhexyl) phthalate
RELATED CANCERS: DEHP does not seem to cause cancer in humans. The mechanism by which cancers are induced in experimental animals by prolonged high doses of DEHP is not relevant to humans.
DEFINITION: DEHP is a water-insoluble organic compound, a widely used phthalate with the molecular formula of C24H38O4. It is used as a plasticizer, mainly in the plastic polyvinyl chloride (PVC), for flexibility and softness of the final product.
Exposure routes: Inhalation, ingestion, dermal contact, and medical procedures such as intravenous (IV) drug administration, hemodialysis, and blood transfusion
Where found: DEHP is mainly used in plastic products such as children’s toys, vinyl upholstery, raincoats, and food packaging. Because DEHP is not chemically attached to the plastic, it can leach out. DEHP release is found in IV bags, blood bags, dialysis bags, medical tubing products, atmosphere, soil, and water. Some manufacturers have begun not to use DEHP in their products.
At risk: DEHP may cause toxicity in humans. Because of its minimum exposure to humans, however, it does not present a general risk to human health. Newborns and infants are particularly at risk for toxicity in the hospital setting. Thus, this subpopulation has a greater risk of developmental and reproductive abnormalities. Individuals who reside near municipal landfills or hazardous waste disposal sites are at higher risk than the average population of DEHP exposure from drinking water or ambient air. However, studies are lacking. Additionally, individuals working in producing or using PVC-containing products are more likely to be exposed through inhalation. Adverse health effects are determined by the duration and amount of DEHP exposure.
Etiology and symptoms of associated cancers: Studies in animals indicate DEHP exposure results in initial distribution in muscle, fat, kidney, lung, liver, and intestine as well as the placenta and fetal tissues in pregnant animals. The hepatocarcinogenesis (potential to cause liver cancer) of DEHP in rats has been proven. DEHP-induced peroxisome proliferation in rats is a phenomenon in which peroxisomes in hepatocytes (liver cells) are increased in number. Peroxisomes, also called microbodies, are intracellular respiratory organelles like mitochondria. Peroxisome proliferation protects the cell from increased oxidation. Failure to do so results in carcinogenesis cell replication and tumor formation. No such peroxisomal route of carcinogenesis has been demonstrated in humans, and thus, no form of cancer due to DEHP. It may be because there are fundamental differences in metabolism between rats and humans. Also, prolonged exposure to higher doses of DEHP in humans is unlikely. Some studies found exposure to DEHP lowers serum testosterone and sperm quality in men, and others posit an association between DEHP exposure to allergies and asthma in humans, though further research is needed to confirm these findings.
History: Plasticized PVC was invented in 1926. DEHP was implicated in animal hepatocarcinogenesis in 1982, which was followed by the classification of DEHP as an anticipated human carcinogen. DEHP’s possible removal from the twelfth Report on Carcinogens was based on expert conclusions that the chemical cannot be reasonably anticipated to cause cancer in humans. It is important to note, however, that human carcinogenicity data remain incomplete. DEHP remains listed as an anticipated human carcinogen, and the US Environmental Protection Agency (EPA) and the International Agency for Research on Cancer consider DEHP to likely pose a threat to human health.
Bibliography
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"Di(2-ethylhexyl) Phthalate." Report on Carcinogens, Fifteenth Edition, National Toxicology Program, Department of Health and Human Services, 2021, ntp.niehs.nih.gov/sites/default/files/ntp/roc/content/profiles/diethylhexylphthalate.pdf.
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"ToxGuideTM for Di(2-ethylhexyl) Phthalate C24H38O4." Agency for Toxic Substances and Disease Registry, Jan. 2022, www.atsdr.cdc.gov/toxguides/toxguide-9.pdf. Accessed 20 June 2024.