pfas.clearance

<p>If the chemical- and species-specific TK half-life ($t_{1/2}$) and volume of 
distribution ($V_{d}$) are known, a whole-body plasma clearance rate can be 
calculated as: $$Cl_{tot} = ln(1/2) / t_{1/2} * V_{d}$$
The first term involving the natural logarithm of 1/2 converts half-life (h) 
into an elimination rate (1/h) so that $Cl_{tot}$ has units of 
L/kg bodyweight/h. 
Dawson et al. (2023) reported a table of in vivo PFAS $t_{1/2}$ data for multiple 
species across eleven PFAS. Most of the measured data are for rodents. These
 data result from a series of reviews of the literature by 
Lau et al. (most recently Fenton et al. 2021) that were further revised for
Dawson et al. (2023).
Dawson et al. (2023) Supplemental Information S2.5 compiled $V_{d}$
values that 
were used here for calculating total clearance. A dataset of 
literature-derived values of $V_{d}$ was compiled starting from 
Pizzurro et al. (2019) Table 2, which compiled 38 observations spanning 
five PFAS chemicals, four species, and both sexes from various literature 
sources. To these we added 24 calculated $V_{d}$ observations in rat for three 
chemicals across a range of doses and routes from Huang et al. (2019). 
Further values for $V_{d}$ were collected from the peer-review literature 
(Dzierlenga et al. 2020; Lau et al. 2020; Lou et al. 2009; Tatum-Gibbs et al. 2011).
 The total data set includes 128 values for $V_{d}$ from 8 PFAS chemicals 
across 4 species. 
A $Cl_{tot}$ was calculated using the above equation for every chemical- and 
species-specific half-life reported in the
 Dawson et al. (2023) supplemental materials. For chemicals without
 species- and compound-specific measurements for $V_{d}$ we used the median
 in vivo measured PFAS Vd of 0.205 L/kg BW.</p>

data

Pre-made models that can be rapidly tailored to various chemicals
and species using chemical-specific in vitro data and physiological
information. These tools allow incorporation of chemical
toxicokinetics ("TK") and in vitro-in vivo extrapolation ("IVIVE")
into bioinformatics, as described by Pearce et al. (2017)
(<doi:10.18637/jss.v079.i04>). Chemical-specific
in vitro data characterizing toxicokinetics have been obtained
from relatively high-throughput experiments.   The
chemical-independent ("generic") physiologically-based ("PBTK") and empirical
(for example, one compartment) "TK" models included here can be
parameterized with in vitro data or in silico predictions which are
provided for thousands of chemicals, multiple exposure routes,
and various species. High throughput toxicokinetics ("HTTK") is the
combination of in vitro data and generic models. We establish the
expected accuracy of HTTK for chemicals without in vivo data
through statistical evaluation of HTTK predictions for chemicals
where in vivo data do exist. The models are systems of ordinary
differential equations that are developed in MCSim and solved
using compiled (C-based) code for speed. A Monte Carlo sampler is
included for simulating human biological variability
(Ring et al., 2017 <doi:10.1016/j.envint.2017.06.004>)
and propagating parameter uncertainty
(Wambaugh et al., 2019 <doi:10.1093/toxsci/kfz205>).
Empirically calibrated methods are included for predicting
tissue:plasma partition coefficients and volume of distribution
(Pearce et al., 2017 <doi:10.1007/s10928-017-9548-7>).
These functions and data provide a set of tools for using IVIVE to
convert concentrations from high-throughput screening experiments
(for example, Tox21, ToxCast) to real-world exposures via reverse
dosimetry (also known as "RTK")
(Wetmore et al., 2015 <doi:10.1093/toxsci/kfv171>).

Column Name	Description
DTXSID	CompTox Chemicals Dashboard substance identifier
Species	Species for which the clearance was calculated
Sex	Sex for which the clearance was calculated
HalfLifeHours	Half-life in hours
HlReference	Reference(s) for half-life
VdLpkgbw	Volume of distribution in L/kg body weight
VdReference	Reference for volume of distribution
Kelimph	Elimination rate in 1/hour
ClLphpkgbw	Total clearance in L/h/kg body weight

pfas.clearance: Interspecies In vivo Clearance Data for PFAS

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