A frying pan with a PFAS-based coating. This image is not directly related to the article. [Getty Images Bank]
A frying pan with a PFAS-based coating. This image is not directly related to the article. [Getty Images Bank]

A substance developed to replace per- and polyfluoroalkyl substances — the synthetic chemicals known as PFAS, or "forever chemicals" for their resistance to natural decomposition — may itself inhibit brain growth, new research suggests.

Researchers at the Korea Institute of Toxicology's Convergence Toxicology Research Center, led by Dr. Ka Min-han, used cerebral organoids — miniature brain-like structures grown from human stem cells — to identify the developmental neurotoxicity of GenX, one of the most widely used PFAS alternatives.

PFAS are used in nonstick cookware coatings, waterproof clothing and semiconductor manufacturing. Their strong carbon-fluorine bonds resist environmental breakdown, causing them to accumulate as persistent pollutants. GenX was developed as a replacement for perfluorooctanoic acid, one of the most common PFAS compounds. Primarily released from manufacturing facilities, GenX contaminates rivers, groundwater, soil and the atmosphere, and can enter the human body indirectly through contaminated drinking water and the consumption of affected agricultural and aquatic products. Until now, the scientific basis for assessing its safety in humans had been insufficient.

When the researchers continuously exposed cerebral organoids to GenX, the organoids shrank by up to 35%. The team also observed suppressed proliferation of neural progenitor cells and reduced generation of neurons and astrocytes. Both excitatory and inhibitory synapses decreased, and multielectrode array analysis showed a marked reduction in the spontaneous electrical activity and synchronization of neurons — indicating that normal neural network formation and function were simultaneously impaired.

The Korea Institute of Toxicology research team behind the study. From left: senior researcher Lee Byeong-seok, senior researcher Lee Yeong-ju, Dr. Ka Min-han and senior researcher Hyeon Seong-ae. [Korea Institute of Toxicology]
The Korea Institute of Toxicology research team behind the study. From left: senior researcher Lee Byeong-seok, senior researcher Lee Yeong-ju, Dr. Ka Min-han and senior researcher Hyeon Seong-ae. [Korea Institute of Toxicology]

The team uncovered GenX's toxic mechanism through results that defied their initial expectations. They had first assumed the organoids' reduced size was caused by cell death, but apoptosis analysis showed no significant difference. Detailed examination of ventricular zone structures and neural rosettes then revealed that GenX does not kill cells outright — rather, it suppresses the brain's growth process itself. Subsequent electrophysiological analysis confirmed a reduction in neural signaling, demonstrating that the structural changes translated into actual functional decline.

The study evaluated developmental neurotoxicity from multiple angles using human-derived cerebral organoids instead of animal testing, highlighting the potential of next-generation alternative testing methods known as New Approach Methodologies, or NAMs. The findings also show that PFAS substitutes can carry their own hazards, and are expected to serve as a scientific basis for future chemical safety assessments and the development of international testing guidelines.

"This research is a case study in multilayered evaluation of developmental neurotoxicity using a human-derived organoid platform," said Dr. Hyeon Seong-ae. "We will continue our research to build a standardized testing framework that can be used internationally, enabling faster and more accurate safety assessments of new chemical substances."

The findings were published in Materials Today Bio, an international journal in the field of materials science.


nbgkoo@heraldcorp.com