Development of a tolerable daily intake for N-nitrosodimethylamine using a modified benchmark dose methodology

Area of Science:

• Environmental Science
• Toxicology
• Risk Assessment

Background:

• N-Nitrosodimethylamine (NDMA) is an environmental contaminant detected in Australian drinking water, primarily from chloramination.
• NDMA is acutely toxic, genotoxic, and carcinogenic, necessitating risk assessment for public health protection.

Purpose of the Study:

• To develop tolerable daily intakes (TDIs) and guideline values for NDMA in environmental media using an Australian modified benchmark dose (mBMD) methodology.
• To apply the mBMD methodology to NDMA rat liver tumor data for low-dose cancer risk assessment.

Main Methods:

• Utilized a modified benchmark dose (mBMD) approach on rat liver tumor data (hepatocellular carcinomas and hemangiosarcomas).
• Applied a suite of mathematical models to incidence data, averaging the 5% extra risk dose (mBMD(0.05)).
• Incorporated modifying factors for endpoint seriousness, database adequacy, and inter/intraspecies differences to derive TDIs.

Main Results:

• The study determined an mBMD(0.05) range of 0.020-0.028 mg/kg/d for NDMA.
• Derived a tolerable daily intake (TDI) range of 4.0 to 9.3 ng/kg/d for NDMA.

Conclusions:

• The established TDI range provides a basis for developing guideline values for NDMA in environmental media.
• The mBMD methodology offers a robust approach for carcinogen risk assessment in the low-dose region.