Examining the feasibility of mixture risk assessment: A case study using a tiered approach with data of 67 pesticides from the Joint FAO/WHO Meeting on Pesticide Residues (JMPR)

Food Chem Toxicol. 2015 Oct;84:260-9. doi: 10.1016/j.fct.2015.08.015. Epub 2015 Sep 4.


The way in which mixture risk assessment (MRA) should be included in chemical risk assessment is a current topic of debate. We used data from 67 recent pesticide evaluations to build a case study using Hazard Index calculations to form risk estimates in a tiered MRA approach in line with a Framework proposed by WHO/IPCS. The case study is used to illustrate the approach and to add detail to the existing Framework, and includes many more chemicals than previous case studies. A low-tier MRA identified risk as being greater than acceptable, but refining risk estimates in higher tiers was not possible due to data requirements not being readily met. Our analysis identifies data requirements, which typically expand dramatically in higher tiers, as being the likely cause for an MRA to fail in many realistic cases. This forms a major obstacle to routine implementation of MRA and shows the need for systematic generation and collection of toxicological data. In low tiers, hazard quotient inspection identifies chemicals that contribute most to the HI value and thus require attention if further refinement is needed. Implementing MRA requires consensus on issues such as scope setting, criteria for performing refinement, and decision criteria for actions.

Keywords: Dose addition; Hazard index; JMPR; Mixture risk assessment; Mixture toxicology; Pesticide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Carcinogens, Environmental / chemistry
  • Carcinogens, Environmental / toxicity
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / toxicity
  • Databases, Chemical
  • Endocrine Disruptors / chemistry
  • Endocrine Disruptors / toxicity
  • Feasibility Studies
  • Food Contamination
  • Humans
  • Irritants / chemistry
  • Irritants / toxicity
  • Models, Biological*
  • Molecular Structure
  • Mutagens / chemistry
  • Mutagens / toxicity
  • Pesticide Residues / chemistry
  • Pesticide Residues / toxicity*
  • Pesticides / chemistry
  • Pesticides / toxicity*
  • Risk Assessment
  • Toxicology / methods*
  • Toxicology / standards
  • United Kingdom
  • United Nations
  • World Health Organization


  • Carcinogens, Environmental
  • Cholinesterase Inhibitors
  • Endocrine Disruptors
  • Irritants
  • Mutagens
  • Pesticide Residues
  • Pesticides