Comment on “Estimating the Bioconcentration Factors of Hydrophobic Organic Compounds from Biotransformation Rates Using Rainbow Trout Hepatocytes” by Trowell et al. in AECT
In their recent paper, Trowell et al. performed an in vitro in vivo extrapolation (IVIVE) of metabolic rate constants to better assess bioconcentration in fish. I had difficulties reproducing the formulas that are used and putting them in context and would like to ask for clarifications.
It appears that the extrapolation formula presented is not equivalent to the extrapolation formula that was published by the same group a few months ago (Lee et al. 2017). A discussion of this discrepancy would be helpful. In fact, both variants differ from the approach by Nichols et al. (2013), which has so far widely been used in IVIVE for fish. This discrepancy to the Nichols approach remains if one removes the flow limitation in the Nichols approach and if one ignores the different approaches to estimate unbound fractions. Again, a discussion would be helpful.
Another multiplication with the cell density of hepatocytes is performed in Eq. 3 (in addition to the multiplication with the same factor in Eq. 2). It does not seem to be plausible that the square of the hepatocyte cell density should be required when extrapolating from the in vitro rate constant, kd, to the in vivo rate constant by combining Eqs. 2 and 3 in the paper.
- Nichols JW, Huggett DB, Arnot JA, Fitzsimmons PN, Cowan-Ellsberry CE (2013) Toward improved models for predicting bioconcentration of well-metabolized compounds by rainbow trout using measured rates of in vitro intrinsic clearance. Environ Toxicol Chem 32:1611–1622Google Scholar