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

Chambers, Janice E; Greim, Helmut; Kendall, Ronald J; Segner, Helmut; Sharpe, Richard M; Van Der Kraak, Glen (2014). Human and ecological risk assessment of a crop protection chemical: a case study with the azole fungicide epoxiconazole. Critical Reviews in Toxicology, 44(2), pp. 176-210. Informa Healthcare 10.3109/10408444.2013.855163

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Center for Fish and Wildlife Health (FIWI)

UniBE Contributor:

Segner, Helmut

Subjects:

600 Technology > 630 Agriculture

ISSN:

1547-6898

Publisher:

Informa Healthcare

Language:

English

Submitter:

Lucia Gugger-Raaflaub

Date Deposited:

31 Mar 2015 13:42

Last Modified:

31 Mar 2015 13:42

Publisher DOI:

10.3109/10408444.2013.855163

PubMed ID:

24274332

URI:

https://boris.unibe.ch/id/eprint/65496

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