CRA

What Are Margin of Exposure (MOE) and Margin of Safety (MOS) and How to Calculate

Little Pro on 2018-07-06 Views:  Update:2018-10-17

Margin of exposure(MOE) and margin of safety (MOS) are two very important concepts in chemical risk assessment. They are both used to characterize chemical exposure risks.  In this article, we will summarize their definition, compare their difference and show you how to calculate them.

Definition of Margin of Exposure (MOE)

Margin of exposure (MOE) is the ratio of  no-observed-adverse-effect level (NOAEL) obtained from animal toxicology studies to the predicted, or estimated human exposure level or dose. It is commonly used in human health risk assessment (i.e, assessing the safety of a cosmetic ingredient or a food impurity ). 

For a chemical substance with health thresholds (i.e, not genotoxic and not carcinogenic), a MOE >= 100 is generally considered to be protective. 

  • MOE = NOAEL/Estimated Exposure Dose
  • Unit of NOAEL: mg/kg bw/day or ppm

Sometimes, a higher MOE than 100 is needed when: 

  • the NOAEL is not obtained from chronic toxicity studies while exposure is chronic;
  • only a LOAEL but not a NOAEL was identified. 
  • there are uncertainties regarding the quality of the available data
  • there is a probability for underestimation of exposure 
  • there is a need to protect sensitive group of people 

For genotoxic and carcinogenic compounds, you need to use the following equation to calculate the MOE since NOAEL values cannot be identified for those substances. In general a MOE >= 10,000 is considered to be protective. The approach below has been used by EFSA to assess genotoxic and carcinogenic impurities in food.

  • MOE = BMDL/Estimated Exposure Dose
  • BMDL = Benchmark-dose lower bound. It is a reference value derived from the Benchmark dose (BMD) which extends the use of response data from animal studies.
  • Unit of BMDL: mg/kg bw/day or ppm.

Definition of Margin of Safety (MOS)

Unlike MOE, different experts may have different understandings of the margin of safety (MOS). There are 3 definitions. All of them are correct.

Definition 1: Margin of Safety (MOS) is the ratio of the lethal dose to 1% of population to the effective dose to 99% of the population (LD1/ED99). It is used to measure drug safety in pharma industry.

  • MOS = LD1/ED99
  • Bigger is better. 

Definition 2: Margin of safety (MOS) is the ratio of  no-observed-adverse-effect level (NOAEL) obtained from animal toxicology studies to the predicted, or estimated human exposure level or dose. It is equivalent to MOE. It is often used to assess the safety of cosmetic ingredients. For example, CFDA uses this appraoch. 

  • MOS = NOAEL/Estimated Exposure Dose

For a chemical substance with health thresholds (i.e, not genotoxic and not carcinogenic), a MOS >= 100 is generally considered to be protective. 

Definition 3: Margin of safety (MOS) is the ratio of derived reference dose (i.e, ADI, RfD, DNEL) to the predicted, or estimated human exposure level or dose. This definition is less common.

  • MOS = Derived Reference Dose/Estimated Exposure Dose
  • Bigger is better. Minimum requirement is >1.

Example: MOE/MOS Calculation

If 2 NOAEL values have been identified from long-term rat studies (10mg/kg bw/day for reproductive toxicity, 50mg/kg bw/day for dietary chronic toxicity), the lowest NOAEL(10mg/kg bw/d) will be used to calculate the MOE/MOS. If estimated human intake is 1mg/kg bw/d, then the MOE/MOS will be equal to 10. Since this value is <100, the chemical exposure risk is not likely to be acceptable.

References

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 Tags: Topics - CRAToxicology and Health Risk Assessment

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