Evaluation of the endocrine disrupting potential of Di-isononyl phthalate

Overview

This weight-of-evidence (WoE) assessment evaluates the endocrine disrupting potential of di-isononyl phthalate (DINP) using the ECHA/EFSA Endocrine Disruptor Guidance (2018) framework, examining estrogen (E), androgen (A), thyroid (T), and steroidogenesis (S) pathways. Based on analysis of 110 articles and 105 high-throughput assays, the authors conclude DINP does not meet ECHA/EFSA criteria to be considered an endocrine disruptor. DINP did not elicit thyroid- or estrogen-related apical outcomes in vivo; for the A and S pathways, limited adverse apical evidence was found and no biologically plausible adverse outcome pathway (AOP) was established. A data gap exists for thyroid hormone levels in vivo, preventing a conclusion on the T-pathway.

Key numbers

Evidence base: 110 articles; 105 high-throughput assays from EPA ToxCast (downloaded May 2024). EFSA NOAEL for DINP: 15 mg/kg bw/day (liver effects); NOEL for reproductive/developmental: 50 mg/kg bw/day. ECHA 2018 concluded DINP does not warrant reproductive toxicity classification under CLP. EFSA 2019 identified DINP as having effects on reproductive system and liver. DINP CAS numbers: 28553-12-0, 68515-48-0.

Methods (brief)

Systematic literature search (PubMed, Embase, EPA HERO) without date limits; PECO framework (mammalian and non-mammalian species, any life stage); data extraction and quality assessment per OHAT RoB guidance; AOP framework (OECD GD150) for MoA assessment; in silico QSAR assessment for DINP metabolites.

Implications

Certification: DINP is a plasticizer relevant to food contact materials and packaging; the conclusion that DINP is not an endocrine disruptor under ECHA/EFSA criteria informs food contact material safety assessments. This study is not within the core heavy metals scope of the wiki.

Courses: useful as a methodological reference for weight-of-evidence AOP frameworks in chemical safety assessment.

App: not applicable.

Wiki pages updated on ingest

None. DINP is a phthalate plasticizer, not a heavy metal. This paper falls outside the heavy metals focus of this wiki and is classified as a misclassified P3 paper (not agency-affiliated; it is an industry-sponsored review). No wiki pages require updating.

Update history

The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.