Blood-partition coefficients, mechanistic models

Mechanistic models for determining the partitioning of a pesticide between skin and blood are addressed in Sect. 4.4. In this section, blood plasma protein binding (F p) was included in the Poulin-TheU model (2000 2002a b) to calculate tissue blood partition coefficients. This procedure greatly reduces the amount of unbound pesticide in blood that is available for partitioning into adipose tissues. A laboratory method, such as the one developed by Jepson et al. (1992, 1994) and reviewed by Knaak et al. (2008), may be used to determine whether predicted values are correct. 

Knaak et al. (2008) reviewed the literature pertaining to in vitro methods for developing tissue blood partition coefficients for PBPK models. The experimental work of Jepson et al. (1992,1994) is significant. Ultrafiltration was used to develop tissue saline and tissue blood partition coefficients. No new studies of this nature were found during the preparation of this review on pyrethroids. Automated laboratory methods are still needed and must be developed to insure the partition coefficients obtained firom the use of mechanistic or QSAR models are reasonable (Payne and Kenny 2002 Rowland, personal communication). 

Tissue blood partition coefficients were developed for the parent pyrethroids and their metabolites, by using a published mechanistic model introduced by Poulin and Thiele (2002a b) and log Dpn 7 4 values. The estimated coefficients, especially those of adipose tissue, were too high and had to be corrected by using a procedure in which the proportion of parent or metabolite residues that are unbound to plasma albumin is considered, as described in the GastroPlus model (SimulationsPlus, Inc., Lancaster, CA). The literature suggested that values be adjusted by multiplying... 

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