Hepatic Toxicity of Diethyl Phthalate (DEP): A Systematic Review of Animal Toxicology Studies-poster
On this page:
Diethyl phthalate (DEP) is widely used in many commercially available products. Human exposure to DEP is among the highest of all the phthalates, so the potential toxicity of DEP is a concern. One of the primary targets of systemic DEP exposure is the liver. To evaluate the evidence for hepatic toxicity, we performed a systematic review to characterize effects in the liver following DEP exposure in laboratory animals. A literature search was conducted in five online scientific databases (PubMed, Web of Science, Toxline, TSCATS and Toxcenter) and augmented by review of online regulatory sources as well as forward and backward searches. Studies were selected for inclusion using PECO (Population, Exposure, Comparator, Outcome) criteria and evaluated for reporting quality, risk of bias, and sensitivity using a domain-based approach. Then each study was rated as high, medium, or low confidence. Evidence was synthesized and strength of evidence was summarized into categories of robust, moderate, slight, indeterminate, or compelling evidence of no effect, using a structured framework. Findings in the liver included changes in liver weight, changes in clinical chemistry, and, histopathological findings suggestive of liver damage. The evidence for liver effects was considered moderate, based on consistent changes in liver weight in medium and high confidence studies. The strongest evidence of an effect on liver enzymes and histopathological changes was observed in exposures to low doses of DEP over long durations; however, these studies were generally considered to be low confidence due to risk of bias concerns. Conversely, no histopathological effects were observed at higher doses in medium or high confidence studies. Differences in animal models, route, and study design between the lower and higher dose studies may contribute to the inconsistent pattern of findings. These conflicting findings suggest that additional research needs to be conducted on DEP following low dose exposures, which are more likely to be relevant to humans. The views expressed in this abstract are those of the authors and do not necessarily reflect the views or policies of the U.S. EPA.