Navigating the Nonylphenol Hazard: Insights into Toxicity Mechanisms and Mitigation Approaches

Nonylphenol (NP), a prototypical endocrine-disrupting chemical and persistent organic pollutant, is ubiquitously detected in water, soil, and atmosphere as a degradation product of nonylphenol polyoxyethylene ethers (NPEO) widely used in industrial and consumer products. Its environmental persistence, low metabolic clearance, and high lipophilicity drive bioaccumulation in wildlife and humans, posing sustained risks to ecosystems and public health. Guided by a systematic literature search strategy across Web of Science and PubMed databases up to January 2026, this review synthesizes current knowledge on the environmental fate, toxicokinetics, multi-organ toxic effects, molecular mechanisms, and existing risk management strategies of NP. The synthesized evidence reveals that NP exposure induces systemic toxicity affecting the nervous, reproductive, endocrine, hepatic, renal, gastrointestinal, respiratory, and immune systems. Mechanistically, despite its chemical simplicity, NP converges on shared pathophysiological pathways defined by oxidative stress-driven mitochondrial dysfunction, endoplasmic reticulum stress, and programmed cell death via apoptosis, autophagy, and ferroptosis. Under environmentally realistic conditions, NP frequently coexists with microplastics, heavy metals, and other pollutants, often eliciting synergistic toxicity. Regarding risk mitigation, microbial degradation and advanced oxidation processes have demonstrated potential at the laboratory scale, while experimental studies have identified several natural compounds and trace elements as candidate protective agents. Despite substantial progress in characterizing NP's toxicity network, significant gaps remain in isomer-specific toxicology, combined exposure assessment, and translation of remediation technologies to field applications. Future research should integrate high-resolution isomer-resolved toxicity profiling, multi-pollutant joint risk assessment models, and long-term human cohort monitoring to establish a more robust scientific framework for NP management and control.