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Risk assessment of parabens in a transcriptomics-based in vitro test.

Florian Seidel1, Franziska Kappenberg2, Susann Fayyaz3

  • 1Leibniz Research Centre for Working Environment and Human Factors at the Technical University of Dortmund (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany.

Chemico-Biological Interactions
|September 10, 2023
PubMed
Summary
This summary is machine-generated.

This study found that ethylparaben and other parabens show toxicity and gene expression changes only at concentrations far exceeding human exposure levels. These findings suggest no additional animal studies are needed to assess ethylparaben

Keywords:
Alternative testing strategiesDevelopmental and reproductive toxicityGene expressionIn vitro testInduced pluripotent stem cellsParabensToxicogenomicsTranscriptomics

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Area of Science:

  • Toxicology
  • Cosmetic Science
  • Developmental Biology

Background:

  • Parabens are widely used preservatives in cosmetics, drugs, and food.
  • Most parabens were banned in 2009 and 2014, leaving methyl-, ethyl-, propyl-, and butylparabens.
  • Ethylparaben lacks developmental and reproductive toxicity (DART) testing, prompting debate on further animal studies.

Purpose of the Study:

  • To compare the in vitro toxicity of four approved parabens: methyl-, ethyl-, propyl-, and butylparaben.
  • To assess whether ethylparaben warrants additional in vivo DART studies.

Main Methods:

  • Utilized a human induced pluripotent stem cell (iPSC)-based in vitro test.
  • Exposed iPSCs to parabens during neuroectodermal differentiation.
  • Determined EC50 values for cytotoxicity and analyzed genome-wide gene expression changes.

Main Results:

  • Cytotoxicity increased with alkyl chain length: EC50 values ranged from 906 μM (methyl-) to 63 μM (butyl-).
  • Significant gene expression changes (differentially expressed genes - DEG) occurred only at or near cytotoxic concentrations.
  • Ethylparaben showed no cytotoxicity or DEG at concentrations 1670-fold higher than reported human biomonitoring levels.

Conclusions:

  • Ethylparaben's toxicity and gene expression alterations occur at concentrations significantly higher than human exposure.
  • Toxicity correlates with alkyl chain length, and gene expression changes are linked to cytotoxic levels.
  • In vitro data do not suggest that in vivo DART studies with ethylparaben would yield different results compared to methyl- or propylparaben.