NOAEL and LOAEL

Results from research studies establish the highest doses at which no toxic effects were identified and the lowest doses at which toxic or adverse effects were observed. The terms often used to describe these outcomes are:

  • No Observed Adverse Effect Level (NOAEL)
  • Lowest Observed Adverse Effect Level (LOAEL)

These terms refer to the actual doses used in human clinical or experimental animal studies. They are defined as follows:

  • NOAEL — Highest dose at which there was not an observed toxic or adverse effect.
  • LOAEL — Lowest dose at which there was an observed toxic or adverse effect.
Figure 1 shows a dose-response curve where the NOAEL occurs at 10 mg and the LOAEL occurs at 18 mg.
A dose response curve of a hypothetical example where NOAEL occurs at 10 mg and LOAEL is at about 18 mg.

Figure 1. A dose-response curve showing doses where the NOAEL and LOAEL occur for a substance
(Image Source: NLM)

Sometimes the terms No Observed Effect Level (NOEL) and Lowest Observed Effect Level (LOEL) are also used. NOELs and LOELs do not necessarily imply toxic or harmful effects and can be used to describe beneficial effects of substances.

The NOAEL, LOAEL, NOEL, and LOEL are commonly used in risk assessments and research. For example, this U.S. Food and Drug Administration (FDA) publication for industry describes a process for estimating the maximum safe starting dose of drugs tested in clinical trials. It provides extensive information about these concepts and their utility when developing new drugs.  

NOEALs and LOAELs are also included in the Noncarcinogenic Risk Assessment section where they are applied using the benchmark dose (BMD) method.

Knowledge Check

Which of the following is not one of the Three Rs of estimating acute toxicity?
The Therapeutic Index (TI) is used to:
The Margin of Safety (MOS) of a drug is the:
The No Observed Adverse Effect Level (NOAEL) is the:
The Lowest Observed Adverse Effect Level (LOAEL) is the: