Evidence map›Paper›PMID 37642336›Full record

ArticleEnvironmental science & technology2023

Urine Excretion, Organ Distribution, and Placental Transfer of 6PPD and 6PPD-Quinone in Mice and Potential Developmental Toxicity through Nuclear Receptor Pathways.

Haoqi Nina Zhao, Sydney P Thomas, Mark J Zylka, Pieter C Dorrestein, Wenxin Hu

Open access · greenAbstract read
In one paragraph

Article in Environmental science & technology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
14.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 93 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. 6PPD and 6PPD-Q Induce Mitochondrial Dysfunction inInternational journal of molecular sciences · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Toxicity of ubiquitous tire rubber antiozonantBiochemistry and biophysics reports · 2025
    Article
  14. Article
  15. Identifying environmental chemicals impacting neurodevelopment using a random mixture-based screening approach.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  16. Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish- and mammalian-based assays.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Haoqi Nina ZhaoSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, United States.ORCID 0000-0003-3908-630X
Sydney P ThomasSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, United States.ORCID 0000-0001-8261-1195
Mark J ZylkaUniversity of North Carolina Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Pieter C DorresteinSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, United States.
Wenxin HuUniversity of North Carolina Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
University of California San Diego · USUniversity of North Carolina at Chapel Hill · US

Funding

Environmental-use chemicals that target pathways linked to autism and other neurodevelopmental disordersR35ES028366 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Mark J. Zylka · 2019 to 2026
$6.8M
NIEHS NIH HHS R35 ES028366
6 · The paper itself

Abstract

The rubber antioxidant 6PPD has gained significant attention due to its highly toxic transformation product, 6PPD-quinone (6PPDQ). Despite their detection in urines of pregnant women, the placental transfer and developmental toxicity of 6PPD and 6PPDQ are unknown. Here, we treated C57Bl/6 mice with 4 mg/kg 6PPD or 6PPDQ to investigate their urine excretion and placental transfer. Female and male mice exhibited sex difference in excretion profiles of 6PPD and 6PPDQ. Urine concentrations of 6PPDQ were one order of magnitude lower than those of 6PPD, suggesting lower excretion and higher bioaccumulation of 6PPDQ. In pregnant mice treated with 6PPD or 6PPDQ from embryonic day 11.5 to 15.5, 6PPDQ showed ∼1.5-8 times higher concentrations than 6PPD in placenta, embryo body, and embryo brain, suggesting higher placental transfer of 6PPDQ. Using in vitro dual-luciferase reporter assays, we revealed that 6PPDQ activated the human retinoic acid receptor α (RARα) and retinoid X receptor α (RXRα) at concentrations as low as 0.3 μM, which was ∼10-fold higher than the concentrations detected in human urines. 6PPD activated the RXRα at concentrations as low as 1.2 μM. These results demonstrate the exposure risks of 6PPD and 6PPDQ during pregnancy and emphasize the need for further toxicological and epidemiological investigations.

Indexed as

BenzoquinonesEmbryonic DevelopmentPhenylenediaminesAnimalsFemaleHEK293 CellsHumansMaleMiceMice, Inbred C57BLPlacentaPregnancyRetinoic Acid Receptor alphaRetinoid X Receptor alphaSex FactorsTissue DistributionBenzoquinonesN-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamineN-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinonePhenylenediaminesRetinoic Acid Receptor alphaRetinoid X Receptor alpha6PPD6PPDQblood−brain barrierplacental transferRARαRXRαurine excretion

Identifiers

PMID37642336
PMCPMC11648498
OpenAlexW4386245353

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.