ArticleArchives of toxicology2024
The evaluation of skin sensitization potential of the UVCB substance diisopentyl phthalate by in silico and in vitro methods.
Article in Archives of toxicology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Advancing chemical mixture toxicity assessment using advanced in vitro NAMs: current status and future perspectives.Frontiers in toxicology · 2026Review
- Spot-on phage therapy: stable formulations, smarter dosing for topical phage application.Frontiers in cellular and infection microbiology · 2026Review
- Assessing the sensitisation hazard of microbial pesticides: potential value of New Approach Methodologies (NAMs) to overcome current challenges.Archives of toxicology · 2025Review
- Molecular Mechanisms of Phthalates in Depression: An Analysis Based on Network Toxicology and Molecular Docking.International journal of molecular sciences · 2025Article
- Review
- Development of image analysis tool to evaluate Langerhans cell migration after exposure to isothiazolinones.Archives of toxicology · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Diisopentyl phthalate (DiPeP) is primarily used as a plasticizer or additive within the production of polyvinyl chloride (PVC), and has many additional industrial applications. Its metabolites were recently found in urinary samples of pregnant women; thus, this substance is of concern as relates to human exposure. Depending upon the nature of the alcohol used in its synthesis, DiPeP may exist either as a mixture consisting of several branched positional isomers, or as a single defined structure. This article investigates the skin sensitization potential and immunomodulatory effects of DiPeP CAS No. 84777-06-0, which is currently marketed and classified as a UVCB substance, by in silico and in vitro methods. Our findings showed an immunomodulatory effect for DiPeP in LPS-induced THP-1 activation assay (increased CD54 expression). In silico predictions using QSAR TOOLBOX 4.5, ToxTree, and VEGA did not identify DiPeP, in the form of a discrete compound, as a skin sensitizer. The keratinocyte activation (Key Event 2 (KE2) of the adverse outcome pathway (AOP) for skin sensitization) was evaluated by two different test methods (HaCaT assay and RHE assay), and results were discordant. While the HaCaT assay showed that DiPeP can activate keratinocytes (increased levels of IL-6, IL-8, IL-1α, and ILA gene expression), in the RHE assay, DiPeP slightly increased IL-6 release. Although inconclusive for KE2, the role of DiPeP in KE3 (dendritic cell activation) was demonstrated by the increased levels of CD54 and IL-8 and TNF-α in THP-1 cells (THP-1 activation assay). Altogether, findings were inconclusive regarding the skin sensitization potential of the UVCB DiPeP-disagreeing with the results of DiPeP in the form of discrete compound (skin sensitizer by the LLNA assay). Additional studies are needed to elucidate the differences between DiPeP isomer forms, and to better understand the applicability domains of non-animal methods in identifying skin sensitization hazards of UVCB substances.
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