Untargeted metabolomics reveals potential health risks associated with chronic exposure to environmentally relevant concentrations of 2-Phenylphenol

Chronic exposure to endocrine-disrupting chemicals through foods of aquatic origin, at levels that are commonly found in the environment, can affect metabolic health and lead to metabolic diseases. One such chemical is 2phenylphenol (2-PP), a suspected endocrine disruptor that is used extensively in agriculture and industry, and has become a widespread pollutant in aquatic environments. This study evaluated the risk of exposure to 2-PP through foods of aquatic origin from Vembanad Lake, using a Target Hazard Quotient (THQ) and an untargeted metabolomics approach. The study found that 2-PP content was higher in samples from areas with intense industrial, tourism, and agricultural activities. The average concentration of 2-PP in fish, crustaceans, and mollusks from the Vembanad estuary ranged from 0.012 to 0.017 mg/kg. The mean concentration of 2-PP was used to assess the THQ of exposure to the coastal population. The results showed that the THQ value was <1, indicating a low to moderate health risk for both adults and children. Furthermore, an untargeted metabolomics approach using HPLC-Q-Orbitrap MS was used to study the metabolome changes associated with chronic exposure to 2-PP (at the environmentally relevant concentration) over 60 days in the Wistar albino rat model. The findings indicated significant alterations in the phospholipid, fatty acid, sterol lipid, and amino acid profiles, suggesting that chronic exposure to 2-PP at environmentally relevant concentrations could affect purine, phenylalanine, tyrosine, and cholesterol metabolism.