Biochemical Basis of Endocrine Disruption by Phthalates in Urban Populations: A Multi-Generational Cohort Study in Benue State

Phthalate esters are ubiquitous environmental endocrine disruptors present in plastic food packaging, cosmetics, and household materials that interfere with steroidogenesis and thyroid hormone signalling through biochemically defined receptor-mediated mechanisms. This study investigates the biochemical mechanisms of endocrine disruption by di(2-ethylhexyl) phthalate and dibutyl phthalate in a multi-generational urban cohort in Benue State, North Central Nigeria. A longitudinal cohort design was employed, recruiting 150 mother-child dyads in the Makurdi urban area with exposure assessment during pregnancy and at child age 2 years. Urinary phthalate metabolites (MEHP, MBP, and MCPP) were quantified by LC-MS/MS in both generations. Hormonal disruption was characterised by measuring TSH, free T4, testosterone, oestradiol, progesterone, and cortisol in mothers and children. Steroidogenesis enzyme activity was assessed in vitro using H295R adrenal carcinoma cells treated with study-relevant phthalate concentrations. Oxidative stress indices including 8-OHdG and 4-HNE were measured to characterise phthalate-mediated reactive oxygen species generation. A structural causal model integrating exposure, biochemical pathway disruption, and clinical endocrine outcomes was constructed. This study constitutes an original multi-generational biochemical investigation of phthalate endocrine disruption in Nigeria. Keywords: phthalates, endocrine disruption, steroidogenesis, thyroid hormones, Benue State.