Diclofenac is an anti-inflammatory drug used as an analgesic. It is often detected in various environmental sources around the world and is considered as one of the emerging contaminants (ECs). This paper reviews the distribution of diclofenac at high concentrations in diverse environments and its adverse ecological impact. Recent studies observed strong evidence of the hazardous effect of diclofenac on mammals, including humans. Diclofenac could cause gastrointestinal complications, neurotoxicity, cardiotoxicity, hepatotoxicity, nephrotoxicity, hematotoxicity, genotoxicity, teratogenicity, bone fractures, and skin allergy in mammals even at a low concentration. Collectively, this comprehensive review relates the mode of toxicity, level of exposure, and route of administration as a unique approach for addressing the destructive consequence of diclofenac in mammalian systems. Finally, the mitigation strategy to eradicate the diclofenac toxicity through green remediation is critically discussed. This review will undoubtedly shed light on the toxic effects of pseudo-persistent diclofenac on mammals as well as frame stringent guidelines against its common usage.
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