>  Topics > CRA > Toxicology and Health Risk Assessment

CRA

How to Calculate Derived Minimal Effect Level (DMEL)

By Little Pro on 2016-09-04 Views:  Update:2017-01-18

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

  • T25: dose giving 25 % of the animals tumours (preferred starting point).
  • Allometric scaling factor: rat (4), mouse (7), dog (1.4)
  • BMD10: the statistically calculated bench mark dose at the 95% lower confidence limit producing a 10% response(cancer).
mg/kg/d or mg/m³ 
Large Assessment Factor Approach

DMEL =corrected BMDL10/10,000 or corrected T25/25,000

  • BMDL10: The benchmark dose level associated with a 10% extra risk of adverse effect (cancer) in the exposed test animals, as compared to control groups (preferred starting point).
  • T25: See above.
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

how to calculate DMEL

Good job. You have learned what DMEL is and how to calculate DMELs for human health. Please subscribe our newsletter to keep updated of our new articles.

"It does not matter how slowly you go as long as you do not stop. "
– Confucius

 

 Tags: Topics - CRAToxicology and Health Risk Assessment

Sponsored Content

Related Topics