Potential mechanisms of tumorigenic action of diethanolamine in mice

Area of Science:

• Toxicology
• Carcinogenesis
• Biochemistry

Background:

• Diethanolamine (DEA), a common secondary amine in consumer products, is suspected of inducing liver tumors in mice.
• Understanding the mechanism of DEA-induced tumorigenesis is crucial for public health and safety.

Purpose of the Study:

• To investigate the in vivo formation of N-nitrosodiethanolamine (NDELA) following DEA administration.
• To examine the potential development of choline deficiency as a result of DEA exposure.
• To elucidate the underlying mechanism of DEA's carcinogenic effects in mice.

Main Methods:

• B6C3F1 mice were administered Diethanolamine (DEA) via dermal application or oral gavage for two weeks, with or without sodium nitrite supplementation.
• Blood, urine, and gastric contents were analyzed for the presence of N-nitrosodiethanolamine (NDELA).
• Levels of choline, phosphocholine, and glycerophosphocholine in mice were quantified and correlated with blood DEA levels.

Main Results:

• No N-nitrosodiethanolamine (NDELA) was detected in any biological samples from DEA-treated mice, regardless of administration route or nitrite supplementation.
• Significant depletion of choline, phosphocholine, and glycerophosphocholine (up to 84%) was observed in mice.
• Choline compound levels decreased in inverse proportion to measured blood DEA concentrations.

Conclusions:

• The study failed to demonstrate in vivo formation of N-nitrosodiethanolamine (NDELA) as a mechanism for Diethanolamine (DEA)-induced liver tumors in mice.
• A pronounced depletion of essential choline-containing compounds was observed, suggesting a potential role in DEA's carcinogenicity.
• Choline deficiency is proposed as the likely mechanism underlying Diethanolamine (DEA) tumorigenesis in the mouse model.