In Vivo Characterization of the Toxicological Properties of DPhP, One of the Main Degradation Products of Aryl Phosphate Esters.

BACKGROUND: Aryl phosphate esters (APEs) are widely used and commonly present in the environment. Health hazards associated with these compounds remain largely unknown and the effects of diphenyl phosphate (DPhP), one of their most frequent derivatives, are poorly characterized. OBJECTIVE: Our aim was to investigate whether DPhP per se may represent a more relevant marker of exposure to APEs than direct assessment of their concentration and determine its potential deleterious biological effects in chronically exposed mice. METHODS: Conventional animals (FVB mice) were acutely or chronically exposed to relevant doses of DPhP or to triphenyl phosphate (TPhP), one of its main precursors. Both molecules were measured in blood and other tissues by liquid chromatography-mass spectrometry (LC-MS). Effects of chronic DPhP exposure were addressed through liver multi-omics analysis to determine the corresponding metabolic profile. Deep statistical exploration was performed to extract correlated information, guiding further physiological analyses. RESULTS: Multi-omics analysis confirmed the existence of biological effects of DPhP, even at a very low dose of 0.1mg/mL in drinking water. Chemical structural homology and pathway mapping demonstrated a clear reduction of the fatty acid catabolic processes centered on acylcarnitine and mitochondrial ß-oxidation in mice exposed to DPhP in comparison with those treated with vehicle. An interesting finding was that in mice exposed to DPhP, mRNA, expression of genes involved in lipid catabolic processes and regulated by peroxisome proliferator-activated receptor alpha (PPARα) was lower than that in vehicle-treated mice. Immunohistochemistry analysis showed a specific down-regulation of HMGCS2, a kernel target gene of PPARα. Overall, DPhP absorption disrupted body weight-gain processes. CONCLUSIONS: Our results suggest that in mice, the effects of chronic exposure to DPhP, even at a low dose, are not negligible. Fatty acid metabolism in the liver is essential for controlling fast and feast periods, with adverse consequences on the overall physiology. Therefore, the impact of DPhP on circulating fat, cardiovascular pathologies and metabolic disease incidence deserves, in light of our results, further investigations. https://doi.org/10.1289/EHP6826.

Occurrence of pharmaceuticals in WWTP effluents and their impact in a karstic rural catchment of Eastern France.

The occurrence of pharmaceuticals in freshwater ecosystems provokes increasing concern due to their potential risk to non-target organisms and to human health. Pharmaceuticals are used in both human and veterinary medicine and are essentially released into the environment via wastewater treatment plants (WWTPs) and from livestock. In this study, 31 pharmaceuticals were analyzed in effluent and surface water upstream and downstream of two WWTPs in the Loue-Doubs rural karstic catchment in Eastern France. Diclofenac (965 and 2476 ng L-1), sulfamethoxazole (655 and 1380 ng L-1) and carbamazepine (566 and 1007 ng L-1) displayed the highest levels in the effluents of both WWTPs. Diclofenac levels were also high in surface water samples 300 and 166 ng L-1 in the River Doubs and the River Loue, respectively, followed by paracetamol (273 and 158 ng L-1) and sulfamethoxazole (126 and 73 ng L-1). In both rivers, the most critical compounds were found to be the antibiotic sulfamethoxazole (risk quotient (RQ) from 23.7 to 51.1) and ofloxacine (RQ from 1.1 to 18.9), which reached levels inducing toxic effects in aquatic organisms. This study showed that WWTP effluents are the major sources of the pharmaceuticals, but raw discharges from human residences, pastures and livestock manure represent significant sources of contamination of surface water and groundwater. The aim of this study was to assist scientists and authorities in understanding occurrence and sources of pharmaceuticals in order to improve water quality management in chalk streams.