title: Therapeutic dose as the point of departure in assessing potential health hazards from drugs in drinking water and recycled municipal wastewater.
abstract: The detection of drugs in drinking water sources has raised questions related to safety. In the absence of regulatory or other official guidance, water utilities are faced with a problem of which drugs should be monitored and the detection limits that should be required. The US FDA summarizes data required for drug approval and post marketing adverse reaction reporting. The use of these data as a means of arriving at concentrations in water where adverse health effects are minimal or non-existent was explored. The minimum therapeutic dose was assumed an appropriate point of departure. Appropriate uncertainty factors could be applied depending upon the qualitative and quantitative nature of the data that are available. Assumptions inherent in US FDA's approval of drugs for use in subsets of the population relative to the broader concerns that arise for exposures of the entire population had to be considered. Additional questions are; whether the drug under consideration is carcinogenic, carries pregnancy and lactation warnings, approval for limited vs. chronic use, exposures to multiple compounds that could act in additive or synergistic ways, and the seriousness of toxicities that are observed. Aside from these considerations, a combined uncertainty factor of 1000 appeared adequate.
authors.affiliation: MoBull Consulting, 1928 Meadows Drive North, Richland, WA 99352, USA. rjbull@earthlink.net
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bull
authors.forename: James
authors.initials: J
authors.lastname: Crook
authors.forename: Margaret
authors.initials: M
authors.lastname: Whittaker
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Cotruvo
mesh_terms: D000818:Animals; D000830:Animals, Laboratory; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004784:Environmental Monitoring; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000592:standards; D059027:Recycling / Q000379:methods* / Q000592:standards; D018570:Risk Assessment; D014865:Waste Disposal, Fluid / Q000379:methods* / Q000592:standards; D014874:Water Pollutants, Chemical / Q000009:adverse effects* / Q000032:analysis / Q000592:standards; D018508:Water Purification / Q000379:methods* / Q000592:standards; D014881:Water Supply / Q000032:analysis / Q000592:standards
chemical_list: D004364:Pharmaceutical Preparations; D014874:Water Pollutants, Chemical