Facial malformations represent one of the most frequent abnormality in humans. The adverse outcome pathway involved in facial defects seems to be related to retinoic acid (RA) pathway imbalance. Environmental agents inducing craniofacial malformations in experimental models include pesticides (especially azole fungicides). By using the in vitro alternative method postimplantation rat whole embryo culture (WEC), we evaluated the intrinsic embryotoxic activity of some azole antifungals (cyproconazole, CYPRO; triadimefon, FON; flusilazole, FLUSI; and prochloraz, PCZ), in comparison to RA. All the tested molecules induced in a dose-related manner specific defects of the craniofacial structures (fused branchial arches), similar to those induced by RA. Collected data were modelled using PROAST 65.5 software to characterise the relative potency factors (RPFs) versus RA. In comparison to RA, all the evaluated azoles were less potent, showing among them a similar potency. Our data suggest a possible azole-related RA signalling perturbation to be further investigated. Moreover, the present results indicate the approach used in this work to be an interesting tool applicable to the hazard evaluation of novel compounds or the assessment of combined exposure to azoles or other dismorphogens.

Relative potency ranking of azoles altering craniofacial morphogenesis in rats : an in vitro data modelling approach / F. Di Renzo, F. Metruccio, M. Battistoni, A. Moretto, E. Menegola. - In: FOOD AND CHEMICAL TOXICOLOGY. - ISSN 0278-6915. - 123(2019 Jan), pp. 553-560.

Relative potency ranking of azoles altering craniofacial morphogenesis in rats : an in vitro data modelling approach

F. Di Renzo;F. Metruccio;M. Battistoni;A. Moretto
;
E. Menegola
2019-01

Abstract

Facial malformations represent one of the most frequent abnormality in humans. The adverse outcome pathway involved in facial defects seems to be related to retinoic acid (RA) pathway imbalance. Environmental agents inducing craniofacial malformations in experimental models include pesticides (especially azole fungicides). By using the in vitro alternative method postimplantation rat whole embryo culture (WEC), we evaluated the intrinsic embryotoxic activity of some azole antifungals (cyproconazole, CYPRO; triadimefon, FON; flusilazole, FLUSI; and prochloraz, PCZ), in comparison to RA. All the tested molecules induced in a dose-related manner specific defects of the craniofacial structures (fused branchial arches), similar to those induced by RA. Collected data were modelled using PROAST 65.5 software to characterise the relative potency factors (RPFs) versus RA. In comparison to RA, all the evaluated azoles were less potent, showing among them a similar potency. Our data suggest a possible azole-related RA signalling perturbation to be further investigated. Moreover, the present results indicate the approach used in this work to be an interesting tool applicable to the hazard evaluation of novel compounds or the assessment of combined exposure to azoles or other dismorphogens.
Azole; Malformation; Potency; PROAST; Retinoic acid; Animals; Azoles; Craniofacial Abnormalities; Embryonic Development; Face; Female; Fungicides, Industrial; Imidazoles; Logistic Models; Male; Morphogenesis; Rats; Skull; Food Science; Toxicology
Settore BIO/06 - Anatomia Comparata e Citologia
Assessing the health risks of combined human exposure to multiple food-related toxic substances
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/625486
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