Data derived Extrapolation Factors for developmental toxicity: A preliminary research case study with perfluorooctanoate (PFOA)

Publication date: Available online 16 August 2019Source: Regulatory Toxicology and PharmacologyAuthor(s): Michael L. Dourson, Bernard Gadagbui, Chijioke Onyema, Patricia M. McGinnis, Raymond G. YorkAbstractGuidelines of the United States Environmental Protection Agency (EPA, 1991) and the International Programme on Chemical Safety (IPCS, 2005) suggest two different default positions for dosimetric extrapolation from experimental animals to humans when the dosimetry of the critical effect is not known. The default position of EPA (1991) for developmental toxicity is to use peak concentration (or Cmax) for this dosimetric extrapolation. In contrast, IPCS (2005, page 39) states its default position for dosimetric choice in the absence of data is to use the area under the curve (or AUC). The choice of the appropriate dose metric is important in the development of either a Chemical Specific Adjustment Factor (CSAF) of IPCS (2005) or a Data Derived Extrapolation Factor (DDEF) of EPA (2014). This research shows the derivation of a DDEF for developmental toxicity for perfluorooctanoate (PFOA), a chemical of current interest. Here, identification of the appropriate dosimetric adjustment from a review of developmental effects identified by EPA (2016) is attempted. Although some of these effects appear to be related to Cmax, most appear to be related to the average concentration or its AUC, but only during the critical period of development for a particular effect. A comparison was made...
Source: Regulatory Toxicology and Pharmacology - Category: Toxicology Source Type: research