2026-10-29T17:41:13Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/119872026-09-04T00:05:21Zcom_10259_6168com_10259_5086com_10259_2604com_10259_4323col_10259_6169col_10259_4330

Huerta Sainz, Sergio de la 845 600 0000-0002-6843-1419 Diez Cabanes, Valentin de6f08a3-922f-4441-b35a-ae2da8240e5c 600 Gutiérrez Vega, Alberto 271 600 0000-0003-2000-7413 Martel Martín, Sonia 790 600 0000-0001-9080-0877 Fernández Pampín, Natalia 810 600 Rumbo Lorenzo, Carlos 505 600 0000-0002-5038-0334 Marcos Villa, Pedro A. 336 600 0000-0002-6890-8088 Bol Arreba, Alfredo 70 600 0000-0003-4641-4826 Marson, Domenico 8f1e98a2-f2f4-4574-9a5b-e2e4f9f57e9c 500 Laurini, Erik 08112944-ee00-46cc-ad81-ed606c9ee28e 500 Aparicio Martínez, Santiago 30 600 0000-0001-9996-2426 2026-09-02T07:37:25Z 2026-09-02T07:37:25Z 2026-09 2468-1113 https://hdl.handle.net/10259/11987 10.1016/J.COMTOX.2026.100440 Essential-oil nanocapsules are bio-based antimicrobial formulations central to agri-food sustainability, yet their human and environmental hazard as formulated products cannot be assessed by conventional molecular QSAR, which ignores controlled release kinetics, nano-specific bio-interactions, and shell-material contributions. We apply a systems toxicology approach — integrating molecular QSAR (Tier 1), Korsmeyer–Peppas release kinetics (Tier 2), and a nano-specific bioavailability correction layer (Tier 3) — to produce the first quantitative integrated hazard prediction for two clove-oil advanced-material (AdMa) nanocapsule formulations: AdMa EO@PEC-GEL (pectin–gelatin shell, CaCl₂ crosslinker) and AdMa EO@Chi (chitosan shell, formaldehyde crosslinker).Eugenol (∼90 wt% core) is the principal toxicophore. Release parameters were scaled from published eugenol–chitosan kinetic data to the 1 μm target particle size; nano-correction factors were calibrated from published surface-charge and uptake relationships. The integrated model predicts AdMa EO@PEC-GEL to be 9.1× safer than free eugenol (IC₅₀ ∼3.5 mM vs. 0.38 mM), driven by anionic surface charge and 80% encapsulation efficiency. AdMa EO@Chi retains toxicity close to the free molecule (IC₅₀ ∼0.91 mM; 2.4×) because cationic surface charge offsets the encapsulation benefit. The formaldehyde crosslinker introduces independent sensitisation, genotoxicity, and IARC Group 1 carcinogenicity flags — quantified via the concentration-addition mixture model — entirely absent from PEC-GEL.Sensitivity analysis identifies zeta potential as the dominant model uncertainty driver. Tier 2 is retrospectively validated against published release kinetics (R2 = 0.997). The Korsmeyer–Peppas tier applies directly to environmental fate scenarios — pH-dependent shell dissolution in soil and aquatic compartments — providing a unified architecture for human–environment integrated hazard assessment aligned with planetary health priorities. An interactive, browser-based digital twin is provided as Supplementary Information: it recomputes all integrated predictions in real time as the user adjusts the model inputs (zeta potential, particle size, encapsulation efficiency, eugenol fraction, release time and pH/enzyme condition), enabling transparent scenario analysis and progressive refinement as experimental data become available, in line with the iterative Safe-and-Sustainable-by-Design (SSbD) workflow. This work was funded by SUNRISE project (HORIZON-EU, HORIZON-CL4-2023-RESILIENCE-01- SUNRISE-GA 101137324). application/pdf eng Elsevier Computational Toxicology. 2026, V. 39, art. 100440 https://doi.org/10.1016/j.comtox.2026.100440 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Essential oil nanocapsules Systems toxicology Integrated hazard prediction Korsmeyer Peppas release kinetics Safe and sustainable by design Human and environmental health Esencias y aceites esenciales Química Essences and essential oils Chemistry A three-tier in silico toxicology framework for formulated essential-oil nanocapsules: integrating molecular hazard, release kinetics and nano-bioavailability for safe-and-sustainable-by-design assessment info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Computational Toxicology 39 100440 THUMBNAIL Gutierrez-Vega-CT_2026.pdf.jpg Gutierrez-Vega-CT_2026.pdf.jpg IM Thumbnail image/jpeg 4834 https://riubu.ubu.es/bitstream/10259/11987/4/Gutierrez-Vega-CT_2026.pdf.jpg 347e148fef1038826b90c87bf0c833ec MD5 4 Gutierrez-CT_2026.pdf.jpg Gutierrez-CT_2026.pdf.jpg IM Thumbnail image/jpeg 4834 https://riubu.ubu.es/bitstream/10259/11987/5/Gutierrez-CT_2026.pdf.jpg 347e148fef1038826b90c87bf0c833ec MD5 5 LICENSE license.txt license.txt text/plain; charset=utf-8 1362 https://riubu.ubu.es/bitstream/10259/11987/3/license.txt 5d013bfa6e473ff0db22cd82a4d71a70 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 805 https://riubu.ubu.es/bitstream/10259/11987/2/license_rdf 4460e5956bc1d1639be9ae6146a50347 MD5 2 ORIGINAL Gutierrez-CT_2026.pdf Gutierrez-CT_2026.pdf application/pdf 6342523 https://riubu.ubu.es/bitstream/10259/11987/1/Gutierrez-CT_2026.pdf 991ff89d02aa435772dd9d32aa8710e4 MD5 1 10259/11987 oai:riubu.ubu.es:10259/11987 2026-09-04 02:05:21.543 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es RWwgYXV0b3IgY29tbyDDum5pY28gdGl0dWxhciBkZSBsb3MgZGVyZWNob3MgZGUgcHJvcGllZGFkIGludGVsZWN0dWFsIGRlIGxhIG9icmEsIG8gZGlzcG9uaWVuZG8gZGUgbG9zIGRlYmlkb3MgcGVybWlzb3MgZGUgbG9zIG90cm9zIHRpdHVsYXJlcywgc2kgbG9zIGh1YmllcmEsIHkgZW4gdmlydHVkIGRlIGxvcyBkZXJlY2hvcyBxdWUgbGUgY29uZmllcmUgbGEgbGVnaXNsYWNpw7NuIHZpZ2VudGUgc29icmUgcHJvcGllZGFkIGludGVsZWN0dWFsIHkgZGVyZWNob3MgZGUgYXV0b3IsIApBVVRPUklaQSBhIGxhIFVuaXZlcnNpZGFkIGRlIEJ1cmdvcyBhIGRpZnVuZGlyLCBkZSBtYW5lcmEgZ3JhdHVpdGEsIGVsIGNvbnRlbmlkbyBkZSBsb3MgYXJjaGl2b3MgZGlnaXRhbGVzIHF1ZSBjb3JyZXNwb25kZW4gYWwgZG9jdW1lbnRvIGRlc2NyaXRvIGFudGVyaW9ybWVudGUsIGNvbiBjYXLDoWN0ZXIgbm8gZXhjbHVzaXZvIHkgZGUgbWFuZXJhIHDDumJsaWNhIGVuIGFjY2VzbyBhYmllcnRvIGEgdHJhdsOpcyBkZSBJbnRlcm5ldCwgcGFyYSBsbyBxdWUgbGEgQmlibGlvdGVjYSBwcm9jZWRlcsOhIGEgYXJjaGl2YXJsb3MgZW4gZWwgUmVwb3NpdG9yaW8gSW5zdGl0dWNpb25hbC4gQXNpbWlzbW8gYXV0b3JpemEgYSBsYSBVbml2ZXJzaWRhZCBkZSBCdXJnb3MgYSByZWFsaXphciBsYXMgdHJhbnNmb3JtYWNpb25lcyBuZWNlc2FyaWFzIGRlIGZvcm1hdG8sIG5vIGRlIGNvbnRlbmlkbywgcGFyYSBnYXJhbnRpemFyIGxhIHByZXNlcnZhY2nDs24geSBlbCBhY2Nlc28gZW4gZWwgZnV0dXJvLgoKRWwgYXV0b3IgZGlzcG9uZSwgZW4gdG9kbyBjYXNvLCBkZWwgZGVyZWNobyBhIHJldm9jYXIgZXN0YSBhdXRvcml6YWNpw7NuLgoKTGEgY2VzacOzbiBkZSBkZXJlY2hvcyBkZSBlc3RhIG9icmEgc2UgZW5jdWVudHJhIHN1amV0YSBhIGxhIGxlZ2lzbGFjacOzbiB2aWdlbnRlIHNvYnJlIHByb3BpZWRhZCBpbnRlbGVjdHVhbCB5IGRlcmVjaG9zIGRlIGF1dG9yLiBTdSBkaWZ1c2nDs24gZW4gZWwgUmVwb3NpdG9yaW8gc2Vyw6EgYmFqbyBsYSBtb2RhbGlkYWQgZGUgbGljZW5jaWEgQ3JlYXRpdmUgQ29tbW9ucyBvIGVxdWl2YWxlbnRlOiByZWNvbm9jaW1pZW50byDigJMgdXNvIG5vIGNvbWVyY2lhbCDigJMgc2luIG9icmEgZGVyaXZhZGEsIHBvciBsYSBxdWUgc2UgcGVybWl0ZSBoYWNlciBjb3BpYSwgZGlzdHJpYnVpciB5IGNvbXVuaWNhciBww7pibGljYW1lbnRlIGxhIG9icmEgc2llbXByZSBxdWUgc2UgY2l0ZSBhbCBhdXRvciwgZWwgdXNvIHF1ZSBzZSBoYWdhIGRlIGVsbGEgc2VhIG5vIGNvbWVyY2lhbCB5IG5vIHNlIGNyZWVuIG9icmFzIGRlcml2YWRhcyBhIHBhcnRpciBkZSBsYSBvcmlnaW5hbC4K