Risk characterization of N-nitrosodimethylamine in pharmaceuticals


Dr. Dennis Paustenbach and Mr. Jonathan Heywood co-authored the article “Risk characterization of N-nitrosodimethylamine in pharmaceuticals,” recently published in Food and Chemical Toxicology.

Paustenbach and Associates, President and Chief Scientist Dr. Paustenbach and Senior Toxicologist Mr. Heywood have extensive expertise in toxicology and human health risk assessment. The article evaluated the appropriateness of the FDA’s acceptable intake (AI) of 96 ng/day for NDMA based on the toxicological literature. Significantly, humans may be exposed to over 1,000,000 ng of NDMA per day due to endogenous production within the body, which highlights that human DNA repair abilities are superior to those of test animals. This makes the FDA’s AI unduly conservative. In the analysis by Dr. Paustenbach and Mr. Heywood, a permissible daily exposure (PDE) of 5,800 ng/day was estimated for NDMA based on animal data from Peto et al. (1984), Peto et al. (1991a), and Peto et al. (1991b) and the benchmark dose 10% (BMD10) from Zeilmaker et al. (2010), which yielded a point of departure (POD) of 29,000 ng/day. The proposed PDE of 5,800 ng/day represents an exposure below which no adverse effects, notably liver carcinogenicity, are expected among humans exposed to NDMA. As a conservative estimate, it is likely that doses an order of magnitude or more above this would also yield no adverse carcinogenic effects.

Join us in thanking Dr. Dennis Paustenbach and Mr. Jonathan Heywood for their contribution to the field of toxicology. To read the article in the Food and Chemical Toxicology journal. Click here.