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.


[Package httk version 2.7.0 Index]