Human and ecological risk assessment of a crop protection chemical: A case study with the azole fungicide epoxiconazole

Janice E. Chambers, Helmut Greim, Ronald J. Kendall, Helmut Segner, Richard M. Sharpe, Glen Van Der Kraak

Research output: Contribution to journalReview articlepeer-review

67 Scopus citations


Conventional risk assessments for crop protection chemicals compare the potential for causing toxicity (hazard identification) to anticipated exposure. New regulatory approaches have been proposed that would exclude exposure assessment and just focus on hazard identification based on endocrine disruption. This review comprises a critical analysis of hazard, focusing on the relative sensitivity of endocrine and non-endocrine endpoints, using a class of crop protection chemicals, the azole fungicides. These were selected because they are widely used on important crops (e.g. grains) and thereby can contact target and non-target plants and enter the food chain of humans and wildlife. Inhibition of lanosterol 14α-demethylase (CYP51) mediates the antifungal effect. Inhibition of other CYPs, such as aromatase (CYP19), can lead to numerous toxicological effects, which are also evident from high dose human exposures to therapeutic azoles. Because of its widespread use and substantial database, epoxiconazole was selected as a representative azole fungicide. Our critical analysis concluded that anticipated human exposure to epoxiconazole would yield a margin of safety of at least three orders of magnitude for reproductive effects observed in laboratory rodent studies that are postulated to be endocrine-driven (i.e. fetal resorptions). The most sensitive ecological species is the aquatic plant Lemna (duckweed), for which the margin of safety is less protective than for human health. For humans and wildlife, endocrine disruption is not the most sensitive endpoint. It is concluded that conventional risk assessment, considering anticipated exposure levels, will be protective of both human and ecological health. Although the toxic mechanisms of other azole compounds may be similar, large differences in potency will require a case-by-case risk assessment

Original languageEnglish
Pages (from-to)176-210
Number of pages35
JournalCritical Reviews in Toxicology
Issue number2
StatePublished - Feb 2014
Externally publishedYes


  • Azole fungicides
  • Azoles
  • Endocrine disruption
  • Epoxiconazole
  • Risk assessment


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