Citronellol, a rose-scented compound commonly found in cosmetics and household products, has long been considered safe. However, a Korean research team has, for the first time, identified its potential to cause neurotoxicity when excessively exposed.
A collaborative research team led by Dr. Myung Ae Bae at the Korea Research Institute of Chemical Technology (KRICT) and Professors Hae-Chul Park and Suhyun Kim at Korea University has discovered that high concentrations of citronellol can trigger neurological and behavioral toxicity. The study, published in the Journal of Hazardous Materials (Impact Factor: 12.2), employed multiple experimental models across species and used advanced metabolomic profiling to reveal this novel toxicity mechanism.
Citronellol is a naturally occurring fragrance compound derived from plants such as rose, geranium, and citronella. While it has been widely used in products for its floral scent and calming effect, this study revealed that excessive exposure can negatively affect the nervous system.
To ensure the reliability of their findings, the researchers employed four distinct biological models: zebrafish, mice, human brain organoids, and a blood-brain barrier (BBB) organ-on-chip system. The neurotoxic effects of citronellol were evaluated across these systems to confirm cross-species relevance.
In animal models, the team observed that citronellol could penetrate the BBB and accumulate in the brain. This accumulation led to increased generation of reactive oxygen species (ROS) and activation of inflammatory signaling pathways. Both phenomena are known contributors to impaired neurological and behavioral function. The researchers also noted damage to the BBB and the infiltration of immune cells into brain tissue, further exacerbating neuroinflammation.
A key discovery of the study was the alteration of kynurenine metabolism. Kynurenine, a metabolite derived from tryptophan, can be converted into either kynurenic acid, a neuroprotective compound, or 3-hydroxykynurenine (3-HK), which is neurotoxic. The researchers found that citronellol exposure shifted this balance toward the production of 3-HK, thereby enhancing neurotoxic risk.
Notably, zebrafish behavioral tests revealed signs of anxiety and abnormal locomotor activity following exposure to citronellol (2, 4, and 8 mg/L). This included reduced phototactic behavior and increased thigmotaxis, common indicators of stress or neurobehavioral disorders in aquatic models.
Beyond animal testing, the study confirmed similar toxicity mechanisms in human-relevant models. Brain organoids derived from human stem cells and BBB chips both showed evidence of citronellol-induced neurotoxicity and inflammation, suggesting potential risks in humans.
Currently, citronellol is listed by the Korea Ministry of Food and Drug Safety as a potential allergen that must be labeled on cosmetics exceeding certain concentrations, in line with EU regulations. However, its potential neurotoxic effects under high-exposure conditions have not been previously studied.
"This is a representative success case demonstrating the utility of next-generation human-mimicking platforms such as zebrafish and organoids," the researchers said. Dr. Lee Young-Kuk, President of KRICT, commented, "Through follow-up studies, we plan to use this biomimetic platform to advance human safety assessments and contribute to public health."
