How to Calculate Derived Minimal Effect Level (DMEL)
Little Pro on 2016-09-04
Derived minimal effect level (DMEL) is defined as a level of exposure below which the risk levels of cancer become tolerable. Exposure levels below a DMEL are judged to be of very low concern. For non-threshold carcinogens, only DMELs may be obtained because even very low level of non-threshold carcinogens may lead to cancer (thus no DNEL can be derived). In this article, we will show you what the tolerable risk levels are and how to derive DMELs by taking two different approaches. Examples will be given.
Tolerable Cancer Risk Levels
Even though there is no EU legislation setting tolerable cancer risk levels, cancer risk levels of 10^(-5) and 10^(-6) are usually seen as indicative tolerable risks levels when setting DMELs for workers and the general population, respectively. A risk level of 10^(-5) means a life-time risk for cancer in 1 per 100.000 exposed individuals.
How to Calculate Derived Minimal Effect Level (DMEL)
There are 2 approaches to derive DMELs: the ‘Linearised’ approach and the ‘Large Assessment Factor’ approach (“EFSA” approach). For both approaches, DMELs are obtained by applying a large assessment factor to a suitable starting point from a rodent long-term cancer bioassay or from reliable human epidemiological studies.
| Method | Equation and Parameters | Unit |
|---|---|---|
| Linearised Approach |
DMEL representing a 10^(-5) risk=corrected T25/(allometric scaling factor*25,000) or BMD10/40,000
|
mg/kg/d or mg/m³ |
| Large Assessment Factor Approach |
DMEL =corrected BMDL10/10,000 or corrected T25/25,000
|
mg/kg/d or mg/m³ |
Note 1: For both methods, preferred dose descriptors such as T25 or BMDL10 are not always available. Which equation to use depends on available dose descriptors.
Note 2: Allometric scaling factor is only applied to dose descriptors with units mg/kg/d. For dose descriptors given in mg/m3, the default allometric scalling factor is 1.
Note 3: If there are differences in bio-availability, exposure limits or, exposure conditions between animals and human, dose descriptors such as T25 or BMD must be modified to a correct starting point. How to modify dose descriptors.
Example 1: Calculating DMEL for Oral Route Using Rat Oral T25
| Linearised Approach | Large Assessment Factor | |
|---|---|---|
| Dose descriptors | T25 (rat, oral)=10 mg/kg/d | T25 (rat, oral)=10 mg/kg/d |
| Modified dose descriptor (assuming 40% absorption in rat) | Corrected T25=4mg/kg/d | Corrected T25=4mg/kg/d |
| DMEL (oral) | Workers: 4/(4*25000)=0.00004mg/kg/d General=4/(4*250000)=0.000004mg/kg/d |
4/25000=0.00016mg/kg/d |
If you do not know how to modify toxicological dose descriptors, please read how to modify dose descriptors.
Example 2: Calculating DMEL for Inhalation Route Using Rat Oral T25
| Linearised Approach | Large Assessment Factor | |
|---|---|---|
| Dose descriptors | T25 (rat, oral)=10 mg/kg/d | BMDL10 (rat, oral)=5 mg/kg/d |
| Modified dose descriptor | Corrected T25=24.4 mg/m³ | Corrected T25=12.2 mg/m³ |
| DMEL (inhalation) | Workers: 24.4/(1*25000)=0.001 mg/m³ General=24.4/(1*250000)=0.0001mg/m³ |
12.2/10,000=0.0012 mg/m³ |
If you do not know how to modify toxicological dose descriptors, please read how to modify dose descriptors.
Main Reference
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