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Heavy Metal Index

Infants' Dermal Exposure to Phthalates from Disposable Baby Diapers and Its Association with DNA Oxidative Damage

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This Toxics paper quantifies six phthalates (DEP, DiBP, DnBP, DEHP, and two non-detectable isomers) in inner-layer disposable-diaper samples from 66 Guangzhou infants and nine urinary phthalate monoester metabolites (mEP, miBP, mnBP, mEHP, mEHHP, mEOHP plus the non-detectable mBzP and mMP) ...

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Cited by6 pages
Evidence tierA
Year2025

Overview

This Toxics paper quantifies six phthalates (DEP, DiBP, DnBP, DEHP, and two non-detectable isomers) in inner-layer disposable-diaper samples from 66 Guangzhou infants and nine urinary phthalate monoester metabolites (mEP, miBP, mnBP, mEHP, mEHHP, mEOHP plus the non-detectable mBzP and mMP) and 8-hydroxydeoxyguanosine (8-OHdG) in paired spot urine. Authors estimate the daily intake (DI) of each phthalate via dermal absorption from diapers and the proportion that diaper-derived dermal absorption contributes to the total daily intake (TDI back-calculated from urinary metabolites). DEHP was the predominant phthalate in diapers (median 1670 ng/g, 48.8 % of ΣPAEs); urinary mEHP-derived DEHP metabolites were the most abundant (Σ mDEHP 87.1 ng/mL median). Diaper DnBP correlated weakly with urinary mnBP (r = 0.259, p = 0.035), and urinary metabolites correlated with the oxidative-DNA-damage biomarker 8-OHdG (r = 0.265-0.316, p < 0.01). The paper measures no heavy metals and contributes no occurrence data to the HMI corpus; it is ingested as a methodology and exposure-pathway reference for diaper-derived dermal absorption in infants — the paired diaper + urine + biomarker design and the body-burden / TDI ratio framework are reusable for HMI heavy-metals modeling if/when comparable analyte data become available.

Key numbers

  • Diaper phthalate concentrations (Table 2, p. 4; inner-layer, ng/g; n = 66, all four reported phthalates 100 % detection frequency):
    • DEP — median 252 (range 116-3350); mean 309 ± 386
    • DiBP — median 333 (range 16.1-4910); mean 680 ± 908
    • DnBP — median 948 (range 189-5980); mean 1270 ± 904
    • DEHP — median 1670 (range 678-5200); mean 1830 ± 934
    • ΣPAEs — median 3420 (range 1870-12,500); mean 4090 ± 2150; DEHP = 48.8 % of median ΣPAEs
    • Two other targeted phthalates (mBzP- and mMP-parent isomers) were non-detectable in all samples.
  • Diaper-vs-other-product cross-comparison (Table 2, pp. 4-5; ng/g; medians or ranges as reported by cited studies):
    • Japan diapers (n = 10, Ishii et al. 2015): DiBP < LOD; DnBP 100-200; DEHP 200-600; DEP and ΣPAEs n.a.
    • Six-country diapers (n = 12, Park et al. 2019): DEP 0.8-2.9; DnBP 13.4-1610; DEHP 12.6-62.8
    • Sanitary napkins, six countries (n = 48, Park 2019): DEP < LOD-134; DnBP 52.1-7820.4; DEHP 5.5-197.4
    • Sanitary napkins, China 2017-2018 (n = 64): DEP 80 (< LOD-1710); DiBP 230 (< LOD-1590); DnBP 240 (< LOD-2380); DEHP 440 (< LOD-8040); ΣPAEs 1430 (250-8760)
    • Panty liners, New York, US 2019 (n = 13): DEP 386 (45.6-1070); DiBP 299 (25.1-5500); DnBP 393 (21.3-6070); DEHP 164 (11.1-23,400); ΣPAEs 1830 (168-34,500)
    • Sanitary napkins, New York US 2019 (n = 18): DEP 82 (50.9-1200); DiBP 73 (25.9-5400); DnBP 83.3 (22.0-3630); DEHP 38.7 (14.9-858); ΣPAEs 362 (205-11,200)
    • Sanitary napkins, six countries (n = 72): DiBP 905; DnBP 711; DEHP 822; ΣPAEs 1859 (464-8380)
    • Sanitary napkins, China 2016 (n = 40): DiBP 1270; DnBP 991; DEHP 1086; ΣPAEs 4974 (2705-13,779)
  • Urinary metabolites in infants (Table 3, p. 5; ng/mL; detection frequencies DF in %):
    • DEP → mEP: DF 89; mean 65.5 ± 80.4; median 33.1; 95th 229; range < MDL-386; Spearman r(mEP, 8-OHdG) = 0.265 (p = 0.031)
    • DiBP → miBP: DF 100; mean 17.4 ± 13.8; median 13.9; 95th 44; range 0.75-71.3; r(miBP, 8-OHdG) = 0.316 (p = 0.010)
    • DnBP → mnBP: DF 100; mean 60.2 ± 68.8; median 44.6; 95th 196; range 3.99-451; r(mnBP, 8-OHdG) = 0.297 (p = 0.016)
    • DEHP → mEHP: DF 100; mean 70.6 ± 136; median 27.7; 95th 278; range 0.14-736
    • DEHP → mEHHP: DF 96; mean 71.9 ± 170; median 13.8; 95th 240; range < MDL-1220
    • DEHP → mEOHP: DF 100; mean 37.2 ± 62.2; median 10.2; 95th 180; range 0.34-293
    • Σ mDEHP: DF 100; mean 177 ± 212; median 87.1; range 0.78-1750; 41.5 % of total ΣmPAEs
    • Σ mPAEs: DF 100; mean 313 ± 309; median 238; range 14.8-1860; r(ΣmPAEs, 8-OHdG) = 0.318 (p = 0.009)
    • 8-OHdG: DF 100; mean 1.58 ± 0.84; median 1.38; range 0.016-5.066. No significant sex difference.
    • mBzP and mMP non-detectable in all samples.
  • ΣmPAEs composition by metabolite (Section 3.2, p. 5): mEHP 41.5 %; mnBP 29.8 %; mEP 20.2 %; miBP 8.5 %.
  • Breastfeeding sub-analysis (Section 3.2, p. 6): mEP median 48.1 ng/mL in breastfed infants < 1 y old (n = 29) vs 27.7 ng/mL in non-breastfed infants > 1 y (n = 37); Mann-Whitney U, p < 0.05. Authors attribute to mEHP near-exclusive presence in breast-milk samples per refs 33-34.
  • Estimated daily intake from dermal diaper contact (Table 4, p. 8; ng/kg-bw/day; medians):
    • Total (n = 66): DEP 19.6 (range 2.1-561; 95th p 95.4); DiBP 23 (0.18-764; 95th p 178); DnBP 61.7 (4.5-523; 95th p 231); DEHP 46.3 (6.1-349; 95th p 161); ΣPAEs 159 (21.2-1220; 95th p 690)
    • 0-0.5 y (n = 21): DEP 61.3 (41-561); DiBP 38.2 (2.5-764); DnBP 130 (34.7-523); DEHP 117 (52-349); ΣPAEs 380 (169-1220)
    • 0.5-1.0 y (n = 10): DEP 26.7 (18.8-70.5); DiBP 20.6 (1.1-80.2); DnBP 65.9 (31.8-182); DEHP 74.2 (20-131); ΣPAEs 211 (82.1-405)

    • 1.0-2.0 y (n = 20): DEP 14.3 (7.3-25.4); DiBP 14.6 (0.67-100); DnBP 38.2 (13.8-104); DEHP 28.7 (12.6-104); ΣPAEs 100 (34.4-334)

    • 2.0 y (n = 15): DEP 7.2 (2.1-10.1); DiBP 21.3 (0.18-188); DnBP 29 (4.5-229); DEHP 22.2 (6.1-40.5); ΣPAEs 79.6 (21.2-452)

    • Younger-vs-older monotonic decline driven primarily by higher diaper-change frequency in younger infants.
  • Dermal-vs-total-burden contribution (Section 3.5, p. 7): median DI-to-TDI ratio DEP 0.91 %; DiBP 1.88 %; DnBP 2.22 %; DEHP 0.11 %. At the 95th percentile of dermal absorption, the same ratios rise to DEP 44.9 %, DiBP 19.5 %, DnBP 15.1 %, DEHP 7.76 % of total exposure — the paper’s headline result on dermal exposure as a non-trivial pathway, especially for low-molecular-weight phthalates DEP, DiBP, DnBP.
  • Health-risk indices (Section 3.5, p. 7): median hazard quotients HQ DEP 0.063; DiBP 0.109; DnBP 0.351; DEHP 0.094. Median hazard index HI = 0.86. 37.9 % of infants had HI > 1 indicating “nonnegligible” risk from diaper-derived phthalates.
  • External-internal correlations (Section 3.3, p. 6): Diaper DnBP vs urinary mnBP r = 0.259 (p = 0.035) — the strongest external-internal link, attributable to LMW phthalate’s higher skin permeation rate (~ 1 µg/cm²/h for DnBP per ref 17). Diaper DnBP vs urinary miBP r = 0.297 (p = 0.015) ascribed to miBP↔mnBP cross-correlation. No significant correlation between diaper DEHP and urinary DEHP metabolites — attributed by authors to DEHP’s HMW (~0.0002 µg/cm²/h skin permeation rate per ref 17) limiting stratum-corneum penetration. Diaper-vs-diaper correlations: DiBP-DnBP-DEHP positively inter-correlated (r = 0.324-0.655, p < 0.01); DEP uncorrelated with others (attributed to DEP-as-essence-solvent vs DiBP/DnBP/DEHP-as-polypropylene-plasticizer distinct material origins per refs 1, 2, 10).
  • Dermal-DNA-damage link (Section 3.4, p. 6): Diaper DnBP vs urinary 8-OHdG r = 0.326 (p = 0.038) — the only diaper-side phthalate that correlated with the oxidative-DNA-damage biomarker. Urinary mEP, miBP, mnBP, ΣmPAEs each correlated with urinary 8-OHdG (r = 0.265-0.318, p < 0.05).
  • Permeation reference rates used by authors (Section 1, p. 2, per refs 15-17): DEP ~ 2 µg/cm²/h; DnBP ~ 0.1 µg/cm²/h; DEHP ~ 0.0002 µg/cm²/h — a four-order-of-magnitude penetration disparity that explains the asymmetric DI-vs-TDI contributions.

Methods (brief)

Cross-sectional paired-sample study, Guangzhou Women and Children’s Medical Center, ethics protocol 2022138A01 (IRB 12 July 2022). 66 infant subjects (age 0.1-4.0 y) recruited May-October 2021 from a child-healthcare clinic with ~ 30,000 patients/year. Inclusion required parental/guardian consent and completion of a PCP-usage questionnaire. Diaper samples: same brand/style of disposable diaper used in the prior week was obtained from the family; ~ 1 cm² of inner layer (in direct skin contact) was excised with stainless-steel scissors and weighed to 100 mg; ultrasonic extraction twice with 5 mL ethyl acetate (30 min each), combined extracts condensed; 1 mL spiked with 20 ng benzyl benzoate internal standard. Analysis on GC-MS/MS (GCMS-TQ8040, Shimadzu, Japan) in electron-impact ionization mode (full GC-MS/MS parameters in Supplementary Table S1). Paired spot urine collected in disposable infant urine bags, transferred to 50-mL HDPE bottles, shipped within 24 h, stored at −80 °C until analysis. Diaper samples wrapped in aluminium foil and stored at 4 °C. Urinary mPAEs determined by HPLC-MS/MS per Ma et al. 2022 method (ref 24; Supplementary Table S2). Urinary 8-OHdG determined per Kuang et al. 2019 method (ref 25). Statistical analysis (SPSS v13.0; Section 2.3 p. 3): analyte concentrations < instrument detection limit (IDL) set to 0; > IDL but < method detection limit (MDL) set to MDL / 2; analyses restricted to targets with DF ≥ 50 %. Normality by Kolmogorov-Smirnov; non-normal data → Spearman’s rank correlation. α = 0.05. Daily-intake calculation, total-daily-intake back-calculation from urinary metabolites, and DI/TDI-ratio and hazard-quotient/hazard-index formulae documented in Supplementary Text S2 (not extracted in this ingest).

Implications

  • Certification (HMTc): No direct relevance. This paper measures only organic plasticizers and does not contribute to heavy-metals threshold-setting under the HMTc 10-analyte panel (Pb, tAs, Cd, MeHg, tHg, iAs, Ni, Al, Cr-VI, Sn) for Category 9 Row 7 (diapers and diaper components). The methodological framework — paired diaper-inner-layer + spot-urine + DNA-damage biomarker, daily-intake estimation from dermal contact, DI / TDI ratio as “contribution of dermal pathway to body burden”, and hazard-index calculation — is reusable for future HMI work that quantifies metals in diaper inner-layer or absorbent core (e.g., if a future study measures Pb, Ni, Cr, or Sn in superabsorbent polymer hydrogels or printed-pattern dyes). Where the present paper’s permeation-rate disparity (DEP ~ 2 vs DEHP ~ 0.0002 µg/cm²/h) yielded a four-order-of-magnitude DI/TDI asymmetry, an analogous metal-permeation analysis would require ion-form-specific dermal absorption fractions (ABS_d) from ATSDR / OEHHA guidance rather than the lipophilic-organic permeation model used here.
  • Courses: Useful as a methodology reference for designing paired-sample dermal-exposure studies in infants — especially the diaper-change-frequency-by-age stratification (10.3, 5.2, 2.4 changes/day for ≤ 0.5, 0.5-1, ≥ 1 y) and the < 1 y vs > 1 y stratification when breast-feeding may confound urinary metabolites.
  • App: Not directly applicable to the heavy-metals consumer app.

Wiki pages this source may touch

  • (None directly; methodology / out-of-core-scope only. Routing to [[products/diapers-and-components]] per matrices: [diaper] so this source is discoverable as a non-metal exposure-pathway reference on the diaper page.)

Verification notes

  • No heavy-metal occurrence data. metals: [] is correct. Paper measures DEP, DiBP, DnBP, DEHP (parent phthalates) in diapers and mEP, miBP, mnBP, mEHP, mEHHP, mEOHP, ΣmDEHP, ΣmPAEs (metabolites) plus 8-OHdG in urine. Two further targets (mBzP-parent and mMP-parent isomers) were below detection. Phthalates are organic plasticizers, not heavy metals — paper is ingested as out-of-core-scope methodology reference per the precedent set by lea2018-dinp-endocrine-disruption.md (DINP weight-of-evidence) and aurisano2022-mouthing-exposure-childrens-products.md (mouthing-migration model).
  • Brand-firewall compliance. Authors did NOT name the specific diaper brands sampled (Section 2.1, p. 2: “diapers of the same brand and style used by babies in the last week were obtained from the baby’s parents or guardian” — no brand list). Comparison data in Table 2 reference other studies’ country-level summaries (Japan, US, China, six-country) without naming brands. No brand-attribution risk.
  • Sample-size stratification. Authors report n = 21 ≤ 0.5 y, n = 10 > 0.5-1.0 y, n = 35 ≥ 1.0 y in Table 1 (Frequency column). Table 4 daily-intake age groups are 0-0.5 y (n = 21), > 0.5-1.0 y (n = 10), > 1.0-2.0 y (n = 20), > 2.0 y (n = 15). The 20 + 15 = 35 in the > 1 y strata reconciles the Table 1 ≥ 1 y category. Table 1 reports sex breakdown 53 male / 13 female only at the overall level — sex × age cross-tab not provided.
  • Median diaper-change frequencies. Table 1 reports mean ± SD: 10.3 ± 1.3, 5.2 ± 1.4, 2.4 ± 0.7 per day for ≤ 0.5, 0.5-1.0, ≥ 1.0 y respectively. The overall row “5.33 ± 3.69” and “Median (Range) 3 (1-13)” applies to the whole n = 66 cohort.
  • Permeation rates. The introduction cites permeation rates ”~ 2 µg/cm²/h for DEP, ~ 0.1 µg/cm²/h for DnBP, only ~ 0.0002 µg/cm²/h for DEHP” with attribution [17] (likely Hopf et al. 2024 per the reference list, ref 17). Verified against Section 1, p. 2 of the PDF.
  • Author author-list and affiliations. Lai X and Zhu J are listed as co-first authors (dagger note on p. 1 of the published article); Li W and Zhao T are co-corresponding (asterisks). All authors affiliated with Guangzhou Women and Children’s Medical Center / Guangdong Medical University or with Guangdong University of Technology (Institute of Environmental Health and Pollution Control).
  • Funding. National Natural Science Foundation of China grants 82103814, 82202011; Guangdong Basic and Applied Basic Research Foundation 2022A1515012576; Guangzhou Municipal Science and Technology Project 202201011840, 202201011221, 2024A04J3929, 2024A04J3925, 2025A04J5228; and the Research Fund for Clinical Doctor of Guangzhou Women and Children’s Medical Center. Public-funded; no industry conflicts declared.
  • License. MDPI Toxics is open access under Creative Commons Attribution (CC BY 4.0) license per the front-page copyright notice: “This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).”
  • Audit subagent (2026-05-17) flagged the bullet sub-heading “mEP composition share by sub-group” as a mislabel — the figures are ΣmPAEs composition shares per PDF p. 5 §3.2. Verified against PDF: the values (mEHP 41.5%, mnBP 29.8%, mEP 20.2%, miBP 8.5%) describe ΣmPAEs composition, not mEP. Applied: bullet sub-heading rewritten to “ΣmPAEs composition by metabolite”.
  • Audit subagent (2026-05-17) flagged products/diapers-and-components as not present in the taxonomy snapshot. Verified against live wiki: wiki/products/diapers-and-components.md exists as an HMTc Cat 9 Row 7 scaffold (literature_scope: thin, splits_locked: false, frontmatter dated 2026-05-17). Snapshot-staleness false positive — taxonomy snapshot used by the audit subagent has not yet been refreshed to include the diaper scaffold. Wiki page retains the routing destination.

Ingest log

  • 2026-05-17 fresh ingest (Claude Opus 4.7, autonomous v2.0 manual-fetch skill, daemon tick): NEW path. Three identity checks against wiki/sources/ returned no hits: DOI 10.3390/toxics13030218 not present; raw_handle MFK_infants-dermal-exposure-to-phthalates-from-disposa not present; cite-key stem lai2025 not present. PDF SHA-256 3a4b48c9a92214b7d1a3e0ba16da8937b157e226ca915de5de8ca49a3472f736. Paper measures phthalates only — zero heavy metals — ingested as methodology / out-of-core-scope reference per the lea2018 and aurisano2022 precedents. Routed to [[products/diapers-and-components]] (HMTc Cat 9 Row 7 scaffold) for discoverability as a diaper-paper but metals: [] correctly reflects no metal occurrence data.

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