Exposure response function for nitrate and iMetHb

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To define the exposure response factor for nitrate exposure from drinking water causing iMetHb

  • European countries
  • Infants 0-6 months old
  • Oral exposure from drinking water via baby food formula or drinking water.





Accoding to US EPA IRIS (Integrated Risk Information System) NOAEL for nitrate is 10 mg nitrate-nitrogen/L (1.6 mg/kg/day) and LOAEL is 11-20 mg nitrate-nitrogen/L (1.8-3.2 mg/kg/day). Conversion Factor for nitrate-nitrogen is expressed as the amount of nitrogen within the nitrite molecule commonly shown as mg nitrate-nitrogen/L (1 mg nitrate-nitrogen = 4.4 mg nitrate. The oral Reference Dose (RfD), which is based on the assumption that thresholds exist for certain toxic effects such as cellular necrosis, is 1.6E+0 mg/kg/day. This results in early clinical signs of methemoglobinemia in excess of 10% (0-3 months old infants formula). U.S. EPA has evaluated the noncancer oral data for nitrate and derived a reference dose (RfD) of 1.6 mg/kg-day with 10 % of risk to MetHb. [1]

The exposure response slope was calculated from the following equation:

1-e ^(x*1.6)= 0.1

x = 0.06585

The main assumptions for ERF slope area when concidering the background referenced are: [2] [3] [4]

  • Oral exposure is well water origin
  • Exposured population 0-3 months old infants in North-America in the 1950's
  • Exposure route: 0-3 months old infants formula

However, in the nitrate risk assessment the ERF slope factor is applied for a exposure situation excluding well water exposure and extended from 0-6 month old infants exposure orally to both baby food formula and pure drinking water. This may have the most importance in terms of magnitude of results.


The variable "Exposure response function for nitrate and iMetHb" is found in the Analytica version of the nitrate model. File:Nitrate.ANA


mg/kg/d / mg/l



  1. http://www.epa.gov/NCEA/iris/subst/0076.htm
  2. Bosch, H.M., A.B. Rosefield, R. Huston, H.R. Shipman and F.L. Woodward. 1950. Methemoglobinemia and Minnesota well supplies. Journal of American Water Works Association. 42, 161-170.
  3. Walton, G. 1951. Survey of literature relating to infant methemoglobinemia due to nitrate-contaminated water. American Journal of Public Health. 41, 986-996.
  4. USEPA 2008. Integrated Risk Information System (IRIS). Nitrate search, retrieved from the Internet on 29th of August 2008 http://www.epa.gov/NCEA/iris/subst/0076.htm