title: Assessment of the health risks related to the presence of drug residues in water for human consumption: application to carbamazepine.
abstract: Pharmaceutical residues have been detected at low (usually ng/L) concentrations in drinking water sources. The detection of drugs in water intended for human consumption (WIHC) has raised questions of safety. In the absence of regulatory or other official guidance, water utilities are faced with a problem of which pharmaceutical residues should be monitored and the toxicological limits that should be required. In this essay, we define an approach for the assessment of health risks related to chemicals found in drinking water. We use the examples of carbamazepine and its main metabolite 10,11-epoxycarbamazepine to demonstrate our approach, which involves application of the following algorithm: (1) when there is human or animal toxicity data, a toxicity reference value (TRV) can be calculated; (2) when this is not applicable, an attempt should be made to derive the TRV using known information about the minimum therapeutic dose (MTD); and (3) when no applicable data is available, at all, a threshold of toxicological concern (TTC) should be estimated. In the case of carbamazepine, where relevant toxicological data exists, we derived a TRV, based on the known minimum therapeutic dose (MTD). For carbamazepine's metabolite 10,11-epoxycarbamazepine, there is no toxicological data, so we applied the TTC approach. Using this approach, and combining our estimates with what is known about these chemicals' margin of exposure (MOE), suggests that there is likely to be no appreciable risk to human health exposure to carbamazepine or its major metabolite, even given the inevitable uncertainties in exposure scenarios.
authors.affiliation: Département de Toxicologie, DEMEB, Agence Française de Sécurité Sanitaire des Produits de Santé (Afssaps), 143/147 Bd Anatole France, F-93285 Saint-Denis, France. Paul.houeto@afssaps.sante.fr
authors.forename: Paul
authors.initials: P
authors.lastname: Houeto
authors.forename: Aude
authors.initials: A
authors.lastname: Carton
authors.forename: Michel
authors.initials: M
authors.lastname: Guerbet
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Mauclaire
authors.forename: Chantal
authors.initials: C
authors.lastname: Gatignol
authors.forename: Philippe
authors.initials: P
authors.lastname: Lechat
authors.forename: Dominique
authors.initials: D
authors.lastname: Masset
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000032:analysis / Q000633:toxicity*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000032:analysis / Q000633:toxicity*; D004285:Dogs; D004784:Environmental Monitoring; D006801:Humans; D051379:Mice; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*; D014881:Water Supply / Q000032:analysis
chemical_list: D000927:Anticonvulsants; D014874:Water Pollutants, Chemical; D002220:Carbamazepine; C012227:carbamazepine epoxide