Disposition of perfluorodecanoic acid in male and female rats

Heuvel, John P. Vanden; Kuslikis, Benedict I.; Rafelghem, Marc J. Van; Peterson, Richard E.

doi:10.1016/0041-008x(91)90308-2

Cited by 66 publications

(46 citation statements)

References 14 publications

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“…The observed uniqueness of PFC(A) physical properties is in the properties of the anionic species, not the neutral species. Thus, the agreement between observed tissue-water distributions and the standard BCF model applied to PFCAs could have been anticipated from recent experimental results that are consistent with the neutral species binding with proteins [31,43,52], and with earlier speculation to the same effect [43,53]. The D SW calculated by Equation 2 with an assumed typical sediment solids density of 2.4 kg/L [54,55] allowed the direct comparison of model results with all measured sediment-water distributions reported by Higgins and Luthy [37] in consistent units of L/kg.…”

Section: Resultssupporting

confidence: 80%

Equilibrium modeling: A pathway to understanding observed perfluorocarboxylic and perfluorosulfonic acid behavior

Webster

Ellis

2011

Enviro Toxic and Chemistry

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Equilibrium distribution models of hydrophobic neutral partitioning of the perfluorinated carboxylic and sulfonic acids were shown, without the need for any physical chemical properties, to successfully predict the sediment-water distribution (D(SW) ) directly from independently measured equilibrium tissue distributions known as the bioconcentration factor (BCF). The constant of proportionality required by the models successfully predicted the correlation between the biotic and abiotic distributions of both sets of chemicals, thus demonstrating the applicability of the assumptions inherent in the models, that is, hydrophobically driven partitioning of the neutral species, and thus the applicability of the models themselves. Colloquially speaking, the models are thus validated as applicable to these chemicals. Subsequent application of the standard equilibrium models showed order of magnitude agreement for 83% of measured BCF values and 88% of measured D(SW) for the perfluorinated carboxylic acids, confirming the physical chemical properties used. The applicability of the models to perfluorooctane sulfonic acid (PFOSA) was shown by the successful prediction of D(SW) from BCF. Therefore, the measured D(SW) and BCF could be used to calculate the octanol-water distribution, D(OW) , and hence the corresponding pK(a):K(OW) solution set, thus providing independent experimentally based estimates of these properties. For both the perfluorinated carboxylic and sulfonic acids, the existing standard equilibrium models are shown to be applicable.

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Section: Resultssupporting

confidence: 80%

Equilibrium modeling: A pathway to understanding observed perfluorocarboxylic and perfluorosulfonic acid behavior

Webster

Ellis

2011

Enviro Toxic and Chemistry

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“…The relatively high concentrations of PFAs in rainbow trout kidney may simply reflect the high perfusion of blood, and do not automatically indicate that urinary elimination is a significant depuration route. For example, despite high kidney concentrations of PFDA in exposed rats, the primary mode of depuration was feces, with only minor excretion in urine [27].…”

Section: Resultsmentioning

confidence: 99%

Bioconcentration and tissue distribution of perfluorinated acids in rainbow trout (Oncorhynchus mykiss)

Martin

Mabury

Solomon

et al. 2003

Enviro Toxic and Chemistry

795

335

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Rainbow trout (Oncorhynchus mykiss) were exposed simultaneously to a homologous series of perfluoroalkyl carboxylates and sulfonates in a flow-through system to determine compound-specific tissue distribution and bioconcentration parameters for perfluorinated acids (PFAs). In general, PFAs accumulated to the greatest extent in blood > kidney > liver > gall bladder. Carboxylates and sulfonates with perfluoroalkyl chain lengths shorter than seven and six carbons, respectively, could not be detected in most tissues and were considered to have insignificant bioconcentration factors (BCFs). For detectable PFAs, carcass BCFs increased with increasing length of the perfluoroalkyl chain, ranging from 4.0 to 23,000, based on wet weight concentrations. Carboxylate carcass BCFs increased by a factor of eight for each additional carbon in the perfluoroalkyl chain between 8 and 12 carbons, but this relationship deviated from linearity for the longest PFA tested, possibly because of decreased gill permeability. In general, half-lives (3.9-28 d) and uptake rates (0.053-1.700 L/kg/d) also increased with increasing length of the perfluoroalkyl chain in all tissues. Sulfonates had greater BCFs, half-lives, and rates of uptake than the corresponding carboxylate of equal perfluoroalkyl chain length, indicating that hydrophobicity, as predicted by the critical micelle concentration, is not the only determinant of PFA bioaccumulation potential and that the acid function must be considered.

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“…These results suggest that the whole body elimination of PFUA in rats, as well as other PFCAs, is slow. There are some reports indicating that PFCAs are secreted in bile and undergo extensive reabsorption from the gastrointestinal tract (Kudo et al, 2001;Vanden Heuvel et al, 1991a, 1991breviewed in ATSDR, 2009). In general, PFCAs with longer carbon chains (C4-C10) have a longer halflife (Hirata-Koizumi et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Repeated dose and reproductive/developmental toxicity of perfluoroundecanoic acid in rats

Takahashi¹,

Ishida

Hirata-Koizumi³

et al. 2014

J. Toxicol. Sci.

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-Perfluoroalkyl acids (PFAAs) are environmental contaminants that have received attention because of their possible effects on wildlife and human health. In order to obtain initial risk information on the toxicity of perfluoroundecanoic acid (PFUA), we conducted a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD test guideline 422). PFUA was administered by gavage to rats at 0 (vehicle: corn oil), 0.1, 0.3 or 1.0 mg/kg/day. At 1.0 mg/kg/day, body weight gain was inhibited in both sexes, and there was a decrease in fibrinogen in both sexes and shortening of the activated partial thromboplastin time in males. An increase in blood urea nitrogen and a decrease in total protein in both sexes and increases in alkaline phosphatase and alanine transaminase and a decrease in albumin in males were observed at 1.0 mg/kg/day. Liver weight was increased in males at 0.3 mg/kg/day and above and in females at 1.0 mg/kg/day, and this change was observed after a recovery period. In both sexes, centrilobular hypertrophy of hepatocytes was observed at 0.3 mg/kg/day and above and focal necrosis was observed at 1.0 mg/kg/day. In reproductive/developmental toxicity, body weight of pups at birth was lowered and body weight gain at 4 days after birth was inhibited at 1.0 mg/kg/day, while no dose-related changes were found in the other parameters. Based on these findings, the no observed adverse effect levels (NOAELs) for the repeated dose and reproductive/developmental toxicity were considered to be 0.1 mg/kg/day and 0.3 mg/kg/day, respectively.

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Disposition of perfluorodecanoic acid in male and female rats

Cited by 66 publications

References 14 publications

Equilibrium modeling: A pathway to understanding observed perfluorocarboxylic and perfluorosulfonic acid behavior

Equilibrium modeling: A pathway to understanding observed perfluorocarboxylic and perfluorosulfonic acid behavior

Bioconcentration and tissue distribution of perfluorinated acids in rainbow trout (Oncorhynchus mykiss)

Repeated dose and reproductive/developmental toxicity of perfluoroundecanoic acid in rats

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