Systemic toxicity in mammals dermally exposed to field-collected weathered oil fragments from the largest South Atlantic spill: Experimental evidence from a realistic exposure scenario.

Oil spills represent an underestimated ecotoxicological risk to coastal mammals, particularly regarding dermal exposure to weathered oil fragments (WOFs). In this study, we provide the first comprehensive assessment of the multisystemic biochemical effects triggered by a single dermal exposure to WOFs collected from Brazilian beaches impacted by the 2019 oil spill, regarded as the largest environmental disaster in the recent history of the South Atlantic. To this end, C57BL/6 J mice (both males and females), employed as a translational model for ecotoxicological inferences in marine mammals, were exposed to a WOF dose calculated based on body surface area and evaluated at 24 and 144 h post-exposure. We analyzed behavioral biomarkers, oxidative stress parameters, energy metabolism indicators, digestive markers, and neurochemical endpoints across four target organs (liver, lung, intestine, and brain). Additionally, multivariate analyses, physiological network mapping, and inter-organ causal modeling were conducted. While no overt behavioral alterations were detected in neurological screening or social interaction tests, our findings revealed subclinical, time- and sex-dependent dysfunctions, with the liver emerging as the primary target organ and key integrator of systemic effects. Females evaluated 144 h post-exposure exhibited the highest functional complexity in biomarker networks, whereas males displayed greater neurochemical vulnerability. In silico analysis supported mechanistic plausibility by linking polycyclic aromatic hydrocarbons identified in the WOFs and/or petroleum derivatives to pathways of oxidative stress, inflammation, and xenobiotic metabolism. Although the experimental dose does not reflect realistic exposure scenarios, these findings provide valuable insights into potential systemic effects of WOFs. Caution is warranted in extrapolating the results to environmental contexts, but the data reinforce the importance of considering coastal and terrestrial mammals in future ecotoxicological monitoring and risk assessment frameworks.