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Updated: Jul 17, 2026

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Generation of Neurospheres from Mixed Primary Hippocampal and Cortical Neurons Isolated from E14-E16 Sprague Dawley Rat Embryo
Published on: August 31, 2019
Developmental neurotoxicity of short-chain phthalates in human neurospheres
Soontag Jung1, Yixian Quah1, Ji-Seong Jeong1
1Laboratory of Developmental and Reproductive Toxicology, Korea Institute of Toxicology, Daejeon, Republic of Korea.
Environmental Toxicology and Pharmacology
|July 15, 2026
Summary
Short-chain phthalates (SCPs) in personal care products may cause developmental neurotoxicity (DNT). These chemicals disrupt mitochondrial energy, impacting fetal neurodevelopment and raising public health concerns.
Area of Science:
- Environmental Health
- Neuroscience
- Toxicology
Background:
- Short-chain phthalates (SCPs) are common in personal care products, leading to widespread human exposure.
- Limited understanding exists regarding the developmental neurotoxicity (DNT) of SCPs, particularly concerning fetal exposure during pregnancy.
Purpose of the Study:
- To investigate the DNT of single and mixed SCPs using human neurospheres.
- To elucidate the mechanisms underlying SCP-induced neurotoxicity.
Main Methods:
- Screening of five SCPs (dimethyl-, diethyl-, dipropyl-, dibutyl-, dipentyl phthalate) for effects on neurite outgrowth in human neurospheres.
- RNA-sequencing (RNA-seq) analysis to identify affected biological pathways.
- Assessment of mitochondrial ATP production and the impact of exogenous ATP and vitamin B complex.
Main Results:
- Diethyl-, dipropyl-, and dipentyl phthalate significantly reduced neurite outgrowth.
- A mixture of these three SCPs (DEPPP) exhibited similar neurotoxic effects.
- RNA-seq revealed oxidative phosphorylation as a key affected pathway, with SCPs and DEPPP impairing mitochondrial ATP production.
- Exogenous ATP and vitamin B complex partially restored neurite outgrowth.
Conclusions:
- SCPs induce developmental neurotoxicity by disrupting mitochondrial energy metabolism.
- The findings highlight the DNT potential of SCPs, necessitating public health considerations for pregnant women and during critical neurodevelopmental periods.

