Toxicity Profiles

RAGs A Format for Bis(2-ethylhexyl)phthalate - CAS Number 117817

Bis(2-ethylhexyl)phthalate or di(2-ethylhexyl)phthalate (DEHP) is a clear oily liquid and is practically insoluble in water. Bis(2-ethylhexyl)phthalate is primarily used in the plastics industry as a plasticizer with such varied applications as wire insulation, food packaging and biomedical applications such as tubing and blood containers. Other uses include vacuum pump oil and as a dielectric fluid in capacitors. The combined annual production of dioctyl phthalates in the United States exceeds 300 million pounds. The wide-spread uses of bis(2-ethylhexyl)phthalate have made the compound, along with other phthalic acid esters, ubiquitous in the environment. It has been detected in ground water, surface water, drinking water, air, soil, plants, fish and animals.

There is no evidence that DEHP causes serious health effects in humans. Most of what we know about the health effects of DEHP comes from high exposures to rats and mice. Brief exposure to very high levels of DEHP in food or water damaged sperm, but the effect reversed when DEHP was removed from the diet. Longer exposures to high doses affected the ability of both males and females to reproduce and caused birth defects. High levels of DEHP damaged the livers of rats and mice. Long exposures of rats to DEHP caused kidney damage similar to the damage seen in the kidneys of long-term dialysis patients. Whether or not DEHP contributes to human kidney damage, is unclear at present. Health effects from skin contact with products containing DEHP do not cause harmful effects because it cannot be taken up easily through the skin.

There is no direct evidence in any study on humans exposed to bis(2-ethylhexyl)phthalate that it causes cancer. Bis(2-ethylhexyl)phthalate is known to induce the proliferation of peroxisomes, which has been associated with carcinogenesis. Dose-dependent, statistically-significant increases in the incidences of hepatocellular carcinomas and combined carcinomas and adenomas were seen in mice and rats exposed to bis(2-ethylhexyl)phthalate in their diet. An increased incidence of neoplastic nodules and hepatocellular carcinomas was also reported in exposed rats.

Based on U.S. EPA guidelines, bis(2-ethylhexyl)phthalate was assigned to weight-of-evidence Group B2, probable human carcinogen, on the basis of an increased incidence of liver tumors in rats and mice.

The following is a presentation of the toxicity information associated with Bis(2-ethylhexyl)phthalate:

• The Oral Chronic Reference Dose is 2.00E-02 (mg/kg-day).
• The Oral Chronic Reference Dose has a modifying factor of 1.
• The Oral Chronic Reference Dose has an uncertainty factor of 1000.
• The Oral Chronic Reference Dose is based on the Carpenter et al. study from 1953.
• The Oral Chronic Reference Dose study target organ is liver.
• The Oral Chronic Reference Dose study critical effect is increased relative weight.
• The overall confidence in the Oral Chronic Reference Dose is medium.
• The Dermal Chronic Reference Dose is 3.80E-03 (mg/kg-day).
• The Dermal Chronic Reference Dose is based on a gastrointestinal absorption factor of 0.1900.

• The Oral Slope Factor is 1.40E-02 (mg/kg-day)^-1.
• The Oral Slope Factor study target organ is liver.
• The Oral Slope Factor study cancer type is carcinoma and adenoma.
• The Oral Slope Factor is based on the NTP study from 1982.
• The Dermal Slope Factor is 7.37E-02 (mg/kg-day)^-1.
• The Dermal Slope Factor is based on a gastrointestinal absorption factor of 0.1900.