The toxic effects of chlorophenols and associated mechanisms in fish

Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent studies on the alteration of DNA methylation by CPs through high-throughput DNA sequencing analysis provide new insights into our understanding of the epigenetic mechanisms underlying CPs toxicity.