Disposition of perfluorooctanoic acid in the rat after single and subchronic administration

Ylinen, Markku; Kojo, Anneli; Hanhijärvi, H; Peura, Pekka

doi:10.1007/bf01702360

Cited by 59 publications

(39 citation statements)

References 13 publications

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“…[17][18][19] The discrepancy may be due to species difference based on the difference in the molecules responsible for binding, transport, storage of PFOA although the molecules responsible for PFOA toxicokinetics have not been fully elucidated. 28) It is also possible that even in the same species, biological half-life is different if the amount of PFOA exposed to animals is quite different.…”

Section: Discussionmentioning

confidence: 99%

Tissue Distribution and Hepatic Subcellular Distribution of Perfluorooctanoic Acid at Low Dose Are Different from Those at High Dose in Rats

Kudo

Sakai

Mitsumoto

et al. 2007

Biological & Pharmaceutical Bulletin

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Perfluoroalkyl chemicals have been used since the 1950s in a wide variety of industrial and consumer products. Among them, perfluofooctanoic acid (PFOA) was used primarily in an ammonium salt form as an emulsifier in the production of fluoropolymers, such as poly(tetrafluoroethylene) and poly(vinylidine fluoride).1) These polymers have been used in various consumers and industrial products, such as water-repellants for leather paper and textiles. The toxicity of PFOA has been characterized in numerous studies with various species.2) Early studies have shown that organic fluorine accumulated in the serum of occupationally exposed people.3) Resent studies have revealed that PFOA and pefluorooctanesulfonic acid have been found in water, [4][5][6] sediment, 7) wildlife 8-10) and human. [11][12][13][14][15] These findings suggest that general population is exposed to such perfluorochemicals which have globally spread at very low levels.PFOA is thought to remain in humans for long time by the study that has estimated PFOA half-life for 9 retirees from chemical plant to be 4.37 years on the average. 16) On the other hand, several studies that have been carried out on the fate of PFOA in experimental animals including rats have shown that biological half-life of PFOA in male rats was calculated to be 105 h after an intraperitoneal administration at the dose of 50 mg/kg, 17) 9 d after an intraperitoneal administration at a dose of 4 mg/kg, 18) and 6.8 d after an intravenous administration at a dose of 20 mg/kg, 19) respectively. In the studies using experimental animals, PFOA has been shown to be mainly distributed to the liver and serum/plasma, and easily excreted into urine. [18][19][20] The reason for such species difference in half-life of PFOA between humans and experimental animals may be due to the differences in the proteins responsible for distribution, binding and transport of PFOA. Alternative explanation is that the concentrations of PFOA used for the calculation of half-life of PFOA were quite different between humans and the experimental animals. In fact, serum concentrations of PFOA were shown be 11.7 mg/ml 24 h after an intraperitoneal administration at a dose of 4 mg/kg 18) and 61.5 mg/ml 24 h after an intravenous injection at a dose of 20 mg, 19) respectively, while serum samples of human that have been used for the calculation of half-life contained PFOA at the concentrations of 0.06-1.84 mg/ml.16) To date, however, toxicokinetic study has not been performed at the serum concentrations of PFOA corresponding to the levels in serum of humans.In the view of toxicological aspects, it is important to know the toxicokinetic data of PFOA at very low serum concentrations. In the present study, we demonstrated that tissue distribution of PFOA at very low dose is markedly different from those at high doses in experimental animals. MATERIALS AND METHODSMaterials PFOA was purchased from Sigma Aldrich Japan (Tokyo, Japan Faculty of Pharmaceutical Sciences, Josai University; 1-1 Keyakidai, Sakado, Saitama 350-0295,...

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Section: Discussionmentioning

confidence: 99%

Tissue Distribution and Hepatic Subcellular Distribution of Perfluorooctanoic Acid at Low Dose Are Different from Those at High Dose in Rats

Kudo

Sakai

Mitsumoto

et al. 2007

Biological & Pharmaceutical Bulletin

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“…The combined properties of rapid absorption and poor elimination could contribute to the bioaccumulation of PFOA or PFOS. It has been determined that the accumulation of PFOA in tissues of rodents, as well as PFOS, is principally in liver, kidney, and blood Ylinen et al 1990). …”

mentioning

confidence: 99%

Excretion of PFOA and PFOS in Male Rats During a Subchronic Exposure

Cui

Liao

Zhou

et al. 2009

Arch Environ Contam Toxicol

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Perfluorinated compounds (PFCs), a class of synthetic surfactants that are widely used, have become global environmental contaminants because of their high persistence and bioaccumulation. An increasing number of studies have described the pharmacokinetics of PFCs following in vivo exposure, however, few papers have focused on the excretion of these compounds during a period of consecutive exposure. In this study, the excretions of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in male Sprague-Dawley rats gavaged consecutively for 28 days were investigated and compared. The faster elimination rate in urine compared to feces indicated that urinary excretion is the primary clearance route in rats for either PFOA or PFOS. During the first 24 h after administration of PFOA (5 and 20 mg/ kg body weight/day), about 24.7-29.6% of the oral dose was excreted through urine and feces, while for PFOS, the excretion amounts were only 2.6-2.8% of the total gavaged doses (5 and 20 mg/kg body weight/day). The excretion rates of both PFCs increased with increasing exposure doses. The higher elimination rate of PFOA through excretion indicated its lower accumulation in rats, thus inducing possible lower toxicities compared to PFOS.

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“…In-vitro-Tests lassen vermuten, dass Sulfhydrylgruppen von Proteinen an der Bindung beteiligt sind ( Van den Heuvel et al 1992). In der Leber von Affen (Butenhoff et al 2002;Griffith und Long 1980) wird PFOA bei gleicher Konzentration im Serum (50 mg/L) deutlich weniger stark angereichert als bei männlichen Ratten (Ylinen et al 1990). Bei Nagern wurde nachgewiesen, dass PFOA auch in die Muttermilch und über die Placenta in den Embryo und die Amnionflüssigkeit übergeht (EPA 2005).…”

Section: Metabolismus Und Toxikokinetikunclassified

“…Die Halbwertszeit von PFOA ist beim Menschen wesentlich länger als bei Nagern (männliche Ratten 4,4-9 Tage, weibliche Ratten 3-24 Stunden) (Hanhijärvi et al 1982;Van den Heuvel et al 1991;Ylinen et al 1990) Biegel et al 2001;Cook et al 1992;Griffith und Long 1980;Haughom und Spydevold 1992;Kennedy 1987;Kennedy et al 1986;Liu et al 1996;Perkins et al 2004). Darüber hinaus werden durch APFO bei Ratten -wahrscheinlich über einen nicht genotoxischen MechanismusLeberadenome, Leydigzelltumoren sowie Azinartumoren des Pankreas hervorgerufen und wahrscheinlich auch Fibroadenome der Mamma (3M Corporation 1987; Biegel et al 2001;EPA 2005;Kennedy et al 2004).…”

Section: Metabolismus Und Toxikokinetikunclassified

“…Diese Dosis entspricht einer Konzentration von 7 mg PFOA/L Serum. Für Affen liegt kein entsprechender NOAEL vor, für diese Tierspezies lässt sich jedoch über die aus verschiedenen Studien an Ratten und Affen (Butenhoff et al 2002;Griffith und Long 1980;Ylinen et al 1990) gewonnenen Beziehungen Dosis/Serumkonzentration, Serumkonzentration/Leberkonzentration, Leberkonzentration/relative Lebergewichtszunahme und Serumkonzentration/relative Lebergewichtszunahme ein NAEL ableiten. Dieser liegt unter der Annahme einer linearen Kinetik bei einer Konzentration von 0,57 mg PFOA/kg Leber, der wiederum eine Serumkonzentration von 7 mg PFOA/L entspricht.…”

Section: Metabolismus Und Toxikokinetikunclassified

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Perfluoroctansäure und ihre anorganischen Salze [BAT Value Documentation in German language, 2007]

Rettenmeier¹

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Biologische Arbeitsstoff‐Toleranz‐Werte (BAT‐Werte), Expositionsäquivalente für krebserzeugende Arbeitsstoffe (EKA) und Biologische Leitwerte (BLW) , 14. Lieferung, Ausgabe 2007 Der Artikel enthält folgende Kapitel: Metabolismus und Toxikokinetik Kritische Toxizität Belastung und Beanspruchung Auswahl der Indikatoren Untersuchungsmethoden Hintergrundbelastung Evaluierung des BAT‐Wertes Interpretation der Untersuchungsdaten

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Disposition of perfluorooctanoic acid in the rat after single and subchronic administration

Cited by 59 publications

References 13 publications

Tissue Distribution and Hepatic Subcellular Distribution of Perfluorooctanoic Acid at Low Dose Are Different from Those at High Dose in Rats

Tissue Distribution and Hepatic Subcellular Distribution of Perfluorooctanoic Acid at Low Dose Are Different from Those at High Dose in Rats

Excretion of PFOA and PFOS in Male Rats During a Subchronic Exposure

Perfluoroctansäure und ihre anorganischen Salze [BAT Value Documentation in German language, 2007]

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