Human health risk assessment of carbamazepine in surface waters of North America and Europe

A human health risk assessment was carried out for environmental exposures to carbamazepine (CBZ) and its major human metabolites, carbamazepine diol (CBZ-DiOH) and carbamazepine N-glucuronide (CBZ-N-Glu). Carbamazepine is an active pharmaceutical ingredient (API) used worldwide as a medicine for treating epileptic seizures and trigeminal neuralgia. Carbamazepine tends to be detected in surface water more frequently, and at relatively higher concentrations, than most other APIs. Predicted no effect levels (PNECs) for CBZ and its major human metabolites were developed for surface waters to be protective of human health from environmental exposures from drinking water and fish consumption. These PNECs were compared to both measured (MEC) and predicted (PEC) environmental concentrations for North America and Europe. PECs were calculated using the geo-referenced models PhATE for North America and GREAT-ER for Europe. The combined PNEC for drinking water and fish consumption for CBZ is 226,000ng/L. Ninetieth percentile MECs ranged from 150 to 220ng/L, while 90th percentile PECs ranged from 333 to 658ng/L. Calculated margins of safety (MOS) therefore range from 340 to 1500. MOS for the major metabolites are significantly higher. This assessment indicates that CBZ and its major metabolites have high MOS (>>1) and thus should have no appreciable risk to human health through environmental exposures based on available human data.