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

"Compound Summary for CID 8343, Diethylhexyl Phthalate." PubChem Compound, National Center for Biotechnology Information, 8 May 2024, pubchem.ncbi.nlm.nih.gov/compound/Bis‗2-ethylhexyl‗-phthalate. Accessed 20 June 2024.

"Di(2-ethylhexyl) Phthalate (DEHP)." National Toxicology Program, 21 Dec. 2021, www.ncbi.nlm.nih.gov/books/NBK590781. Accessed 20 June 2024.

"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.

"Endocrine Disruptors." National Institute of Environmental Health Sciences, www.niehs.nih.gov/health/topics/agents/endocrine. Accessed 20 June 2024.

Pintér, Máté D., and Péter A. Varga. Consumer Product Safety Issues. Nova, 2009.

"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.