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Updated: Feb 9, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Diglycolic acid induces HepG2/C3A liver cell toxicity in vitro
Miriam E Mossoba1, Sanah Vohra1, Howard Toomer1
1U.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Applied Regulatory Toxicology (DART), 8301 Muirkirk Rd., Laurel, MD 20708, United States.
Diglycolic acid (DGA), a byproduct of carboxymethyl starch food additives, was tested for liver toxicity. Both in vitro and in vivo studies confirmed DGA is a hepatotoxin above a specific exposure threshold.
Area of Science:
- Food science
- Toxicology
- Biochemistry
Background:
- Carboxymethyl starches are common food additives used for thickening and as tablet binders.
- The synthesis of these starches produces diglycolic acid (DGA), a chemical byproduct with questionable toxicity.
- Previous reports indicate DGA may affect organs, particularly the kidneys and liver, following high-concentration exposure.
Purpose of the Study:
- To investigate the potential hepatotoxicity of diglycolic acid (DGA) using an in vitro model.
- To complement existing in vivo studies on DGA's toxic effects.
- To assess the dose-dependent hepatotoxic effects of DGA exposure.
Main Methods:
- Utilized the HepG2/C3A human liver cell line for in vitro testing.
- Exposed cells to escalating doses of DGA over a 24-hour period.
- Compared in vitro findings with results from a concurrent 28-day in vivo rat study.
Main Results:
- Diglycolic acid (DGA) demonstrated dose-dependent hepatotoxicity in the HepG2/C3A cellular model.
- Both in vitro cell-based assays and in vivo animal studies identified DGA as a hepatotoxin.
- A consistent threshold for DGA-induced hepatotoxicity was observed across both testing systems.
Conclusions:
- Diglycolic acid (DGA) is confirmed as a hepatotoxin when exposure exceeds a certain threshold.
- In vitro models, such as the HepG2/C3A system, are valuable tools for predicting in vivo toxicological outcomes.
- The findings support the need for careful consideration of DGA levels in food products containing carboxymethyl starches.
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