pfas.clearance {httk} | R Documentation |
Interspecies In vivo Clearance Data for PFAS
Description
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.
Usage
pfas.clearance
Format
data.frame
Details
The data.frame contains the following columns:
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 |
References
Dawson DE, Lau C, Pradeep P, Sayre RR, Judson RS, Tornero-Velez R, Wambaugh JF (2023). “A machine learning model to estimate toxicokinetic half-lives of per-and polyfluoro-alkyl substances (PFAS) in multiple species.” Toxics, 11(2), 98.
Fenton SE, Ducatman A, Boobis A, DeWitt JC, Lau C, Ng C, Smith JS, Roberts SM (2021). “Per-and polyfluoroalkyl substance toxicity and human health review: Current state of knowledge and strategies for informing future research.” Environmental toxicology and chemistry, 40(3), 606–630.
Pizzurro DM, Seeley M, Kerper LE, Beck BD (2019). “Interspecies differences in perfluoroalkyl substances (PFAS) toxicokinetics and application to health-based criteria.” Regulatory Toxicology and Pharmacology, 106, 239–250.
Huang MC, Dzierlenga AL, Robinson VG, Waidyanatha S, DeVito MJ, Eifrid MA, Granville CA, Gibbs ST, Blystone CR (2019). “Toxicokinetics of perfluorobutane sulfonate (PFBS), perfluorohexane-1-sulphonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in male and female Hsd: Sprague Dawley SD rats after intravenous and gavage administration.” Toxicology reports, 6, 645–655.
Dzierlenga AL, Robinson VG, Waidyanatha S, DeVito MJ, Eifrid MA, Gibbs ST, Granville CA, Blystone CR (2020). “Toxicokinetics of perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) in male and female Hsd: Sprague dawley SD rats following intravenous or gavage administration.” Xenobiotica, 50(6), 722–732.
Lau C, Rumpler J, Das KP, Wood CR, Schmid JE, Strynar MJ, Wambaugh JF (2020). “Pharmacokinetic profile of Perfluorobutane Sulfonate and activation of hepatic nuclear receptor target genes in mice.” Toxicology, 441, 152522.
Lou I, Wambaugh JF, Lau C, Hanson RG, Lindstrom AB, Strynar MJ, Zehr RD, Setzer RW, Barton HA (2009). “Modeling single and repeated dose pharmacokinetics of PFOA in mice.” Toxicological Sciences, 107(2), 331–341.
Tatum-Gibbs K, Wambaugh JF, Das KP, Zehr RD, Strynar MJ, Lindstrom AB, Delinsky A, Lau C (2011). “Comparative pharmacokinetics of perfluorononanoic acid in rat and mouse.” Toxicology, 281(1-3), 48–55.