Azole fungicides are widely used chemicals in agriculture and medicine. Their antifungal activity involves inhibition of steroid biosynthesis via inhibition of several cytochrome p450 enzymes. Evidence is accumulating in fish species to suggest azole fungicides perturb multiple hormone signaling pathways. The objective of this review was to comprehensively review data for azole-mediated impacts on the teleost endocrine system. We emphasize aspects of azole-induced endocrine disruption in several fish species, with special focus on the hypothalamic-pituitary-gonadal (HPG), hypothalamus-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axis. Histopathological, physiological, and molecular data suggest azole fungicides at environmentally relevant concentrations and above are endocrine disruptors in fish. Endocrine disruption has been well documented for some azoles (e.g., difenconazole, fadrozole, ketoconazole, tebuconazole, triadimefon), but there are little data for others (e.g., cyproconazole, expoxiconazole, imidazole, metoconazole, nocodazole) in fish, revealing a knowledge gap in our understanding of azole toxicity. Based upon literature, computational analyses of transcriptome responses revealed progesterone-mediated oocyte maturation, insulin signaling pathway, adrenergic signaling, and metabolism of angiotensinogen may be processes disrupted by azoles. However, hormonal regulation of the sympathetic nervous system and the cardiovascular system in response to azole exposure has yet to be investigated in fish. Recommendations for studies moving forward include focus on non-steroid endocrine pathways, mechanisms of neuroendocrine disruption, and transgenerational effects of azoles on fish. This critical review identifies knowledge gaps and future directions for environmental studies focused on the effects of azoles in aquatic species.
Keywords: Agrochemical; Development; Ecotoxicology; Endocrine disruption; Pesticide.
Copyright © 2022 Elsevier B.V. All rights reserved.