it makes a negligible incremental contribution to total exposure. Nitrate from all sources is mixed in extracellular body water. Losses and removal occur as a result of urinary excretion of nitrate and by conversion to reduced or reactive forms that are ultimately lost in feces. The half-life for clearance of nitrate from blood is about 5 hours, and the fraction lost by urinary excretion is 30-50%.

An important component of human physiology is the ability of salivary glands to transport nitrate from blood into saliva. The process is either absent or diminished in all nonhuman species studied; only humans have the capacity to introduce substantial amounts of nitrite into an acidic stomach. (The optimal pH for nitrosation is 2.5-3.3.)

Several considerations should be included in model development:

  • Endogenous nitrate synthesis in the absence of infection or inflammation is constant over 24 hours.

  • Intake of exogenous nitrate from food and water occurs as a bolus.

  • Nitrate exposure from food is accompanied by exposure to antioxidants that inhibit N-nitrosation in the stomach.

Estimating human cancer risk associated with nitrate in drinking water requires a physiologically based pharmacokinetic model that could be used to compute the relative input of nitrate from all sources, rates of input, and potential for N-nitroso compound formation. Data adequate to develop such a model are available.

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