Current insights into the impact of plastic-derived pollutants (phthalates), microplastics, and nanoplastics on hypothalamic phenotype and molecular pathways: A scoping review

Plastic is a ubiquitous material worldwide, and its derivatives - such as phthalates as Endocrine-Disrupting Chemicals (EDCs) derived from plastics and Microplastics (MPs) and Nanoplastics (NPs) as plastics waste - have raised increasing concern due to their potential adverse effects on human health, particularly on the neuroendocrine system and hypothalamic regulatory pathways. This critical scoping review integrates experimental and theoretical evidence on the metabolic impacts of chemical additives (phthalates) and micro and nanometric plastic waste (MNPs), emphasizing hypothalamic alterations and their systemic consequences. The eligibility criteria were to select articles that specifically traced the correlation between exposure to phthalates or MPs/NPs on the hypothalamic structure or molecular aspects, from studies present in PubMed using the mapping method by Nanoplastics and hypothalamus, Microplastics and hypothalamus, and Phthalates and hypothalamus. Plastic-derived EDCs have been shown to impair energy homeostasis, eating behavior, reproduction, and neurodevelopment. Both gestational and chronic exposures promote hypothalamic inflammation and disrupt key metabolic pathways by altering the sensitivity of hormone receptors, axis pathways, reproductive parameters, and biological development. Evidence also highlights sex-specific differences in hypothalamic responses and the role of EDCs in inducing epigenetic changes with potential transgenerational transmission. Despite these advances, significant gaps remain, particularly regarding studies directly targeting the hypothalamus and its nuclei. Elucidating the neurotoxic mechanisms of plastics and their derivatives is essential to guide public health strategies and regulatory policies aimed at mitigating exposure risks.