Sample Calculation of Margin of Exposure (MOE)

MOE: Margin of Exposure: First the average human daily intake of rodent carcinogen is divided by 70 kg body weight to give estimated human intake in mg/kg/day. Second, LTD10 is calculated from the Carcinogenic Potency Database as the lower 95% confidence limit on the tumorigenic dose-rate for 10% of rodents (mg/kg/day). Third, MOE is calculated as

LTD10 in the rodent (mg/kg/day)
Human exposure (mg/kg/day)

For statistical methods to estimate LTD10, see http://potency.berkeley.edu/ltd10.html.

The example below is for the naturally-occurring chemical acrylamide, which is formed by cooking starch-rich foods at high temperature. In the graphic and the table, the MOE is reported for the total intake of acrylamide in the average US diet and also for consumption of just French fried potatoes in restaurants.

MOE (LTD10/Human Exposure) Average Daily US Exposure Human Intake of Rodent Carcinogen
Amount per Day   [Amount in mg/kg/day]		 Rodent Cancer Dose LTD10 [mg/kg/day] References for Human Exposure
Rats Mice
900 Acrylamide in total diet Acrylamide, 28 µg [0.0004 mg/kg/day] 0.365 . (DiNovi and Howard 2004)
6,000 French fries (restaurant), 12.2 g Acrylamide, 4.06 µg [0.000058 mg/kg/day] 0.365 . (DiNovi and Howard 2004)

For Acrylamide in the total diet:
  1. Human Exposure for Acrylamide in total diet = 28 µg/day expressed as 0.0004 mg/kg/day (28 µg daily intake / 70 kg human). Consumption of acrylamide in the total diet is reported in the reference in the table above.
  2. LTD10: the chronic dose-rate in mg/kg body weight/day which would induce tumors in 10% of test animals = 0.365 mg/kg/day for rats. The LTD10 values used in MOE are averages for rats and mice separately, calculated by taking the harmonic mean of the LTD10 values from positive experiments. For acrylamide the only experiments in the Carcinogenic Potency Database are in rats, indicated by “.” for mice in the table. The LTD10 in rats is 0.365 mg/kg/day, which is a harmonic mean of the most potent values from several positive experiments in rats in the CPDB.
  3. MOE = (LTD10 in mg/kg/day / Human Exposure in mg/kg/day):
    0.365 mg/kg/day / 0.0004 mg/kg/day = 912.5
  4. MOE is rounded to one digit; for acrylamide the value is 900.
For Acrylamide in French fried potatoes in restaurants

Both the average concentration of acrylamide in restaurant French fries (333 µg/kg = 0.333 ppm) and the average US consumption of French fries in restaurants (12.2 gm/day) are used, and are from the reference.

Consumption of the food (gm/day) × Chemical concentration (ppm) = Exposure of chemical (µg/day)

12.2 gm/day × 0.333 ppm = 4.06 µg/day

The consumption of acrylamide in French fries in mg/day is as follows:

  1. Consumption of French fries in restaurants averages 12.2 g/day (column 1 of table). From the concentration of acrylamide in French fries, the amount consumed in 12.2 g is calculated as 4.06 µg [0.00406 mg]. This amount is calculated as 0.000058 mg/kg/day for a 70 kg person.
  2. LTD10: the chronic dose-rate in mg/kg body weight/day which would induce tumors in 10% of test animals = 0.365 mg/kg/day for rats.
  3. MOE = (LTD10 in mg/kg/day / Human Exposure in mg/kg/day):
    0.365 mg/kg/day / 0.0000058 mg/kg/day = 6,293
  4. MOE is rounded to one digit; for acrylamide in French fries the value is 6,000.

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Last updated: September 25, 2008