Lea et al. 2018 — DINP endocrine disruption: weight-of-evidence assessment
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.