Studies on the Toxicological Effects of PFOA and PFOS on Rats Using Histological Observation and Chemical Analysis

As an emerging class of environmentally persistent and bioaccumulative contaminants, perfluorinated compounds (PFCs), especially perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), have been ubiquitously found in the environment. Increasing evidence shows that the accumulated levels of PFCs in animals and the human body might cause potential impairment to their health. In the present study, toxicological effects of PFOA and PFOS on male Sprague–Dawley rats were examined after 28 days of subchronic exposure. Abnormal behavior and sharp weight loss were observed in the high-dose PFOS group. Marked hepatomegaly, renal hypertrophy, and orchioncus in treated groups were in accordance with the viscera–somatic indexes of the liver, kidney, and gonad. Histopathological observation showed that relatively serious damage occurred in the liver and lung, mainly including hepatocytic hypertrophy and cytoplasmic vacuolation in the livers and congestion and thickened epithelial walls in the lungs. PFOA concentrations in main target organs were in the order of kidney > liver > lung > (heart, whole blood) > testicle > (spleen, brain), whereas the bioaccumulation order for PFOS was liver > heart > kidney > (whole blood) > lung > (testicle, spleen, brain). The highest concentration of PFOA detected in the kidney exposed to 5 mg/kg/day was 228 ± 37 μg/g and PFOS in the liver exposed to 20 mg/kg/day reached the highest level of 648 ± 17 μg/g, indicating that the liver, lung, and kidney might serve as the main target organs for PFCs. Furthermore, a dose-dependent accumulation of PFOS in various tissues was found. The accumulation levels of PFOS were universally higher than PFOA, which might explain the relative high toxicity of PFOS. The definite toxicity and high accumulation of the tested PFCs might pose a great threat to biota and human beings due to their widespread application in various fields.

[1]  J. Depierre Effects on Rodents of Perfluorofatty Acids , 2002 .

[2]  J. Giesy,et al.  Peer Reviewed: Perfluorochemical Surfactants in the Environment , 2002 .

[3]  Nathan M. Bass,et al.  Interactions of flurochemicals with rat liver fatty acid-binding protein , 2002 .

[4]  C. Lau,et al.  Prenatal window of susceptibility to perfluorooctane sulfonate-induced neonatal mortality in the Sprague-Dawley rat. , 2003, Birth defects research. Part B, Developmental and reproductive toxicology.

[5]  Zhang Ping,et al.  Determination of perfluorinated compounds in water samples by high performance liquid chromatography-electrospray tandem mass spectrometry , 2007 .

[6]  M. Rämet,et al.  Surfactant in respiratory distress syndrome and lung injury. , 2001, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[7]  K P Lee,et al.  Biochemical and morphological studies of ammonium perfluorooctanoate-induced hepatomegaly and peroxisome proliferation. , 1987, Experimental and molecular pathology.

[8]  L C Chen,et al.  Peroxisome proliferator perfluorodecanoic acid alters glutathione and related enzymes , 2001, Journal of biochemical and molecular toxicology.

[9]  T. Satoh,et al.  Differences in the induction of carboxylesterase isozymes in rat liver microsomes by perfluorinated fatty acids. , 1993, Xenobiotica; the fate of foreign compounds in biological systems.

[10]  G. W. Jepson,et al.  Subcellular Distribution and Protein Binding of Perfluorooctanoic Acid in Rat Liver and Kidney , 2005, Drug and chemical toxicology.

[11]  Harvey J Clewell,et al.  Pharmacokinetic modeling of saturable, renal resorption of perfluoroalkylacids in monkeys--probing the determinants of long plasma half-lives. , 2006, Toxicology.

[12]  M. Roberfroid,et al.  Peroxisome proliferation and modulation of rat liver carcinogenesis by 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, perfluorooctanoic acid and nafenopin. , 1990, Carcinogenesis.

[13]  C. Elcombe,et al.  Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats. , 2003, Toxicology.

[14]  S. Dzhekova-Stojkova,et al.  Peroxisome Proliferators: Their Biological and Toxicological Effects , 2001, Clinical chemistry and laboratory medicine.

[15]  A. Seacat,et al.  Interactions of fluorochemicals with rat liver fatty acid-binding protein. , 2002, Toxicology.

[16]  홀덴 데이비드윌리암,et al.  Identification of genes , 1995 .

[17]  M Roberfroid,et al.  The modulation of rat liver carcinogenesis by perfluorooctanoic acid, a peroxisome proliferator. , 1991, Toxicology and applied pharmacology.

[18]  N. Kudo,et al.  Sex hormone-regulated renal transport of perfluorooctanoic acid. , 2002, Chemico-biological interactions.

[19]  J. Depierre,et al.  Effects of peroxisome proliferators on the thymus and spleen of mice , 2000, Clinical and experimental immunology.

[20]  Craig S. Criddle,et al.  Fluorinated Organics in the Biosphere , 1997 .

[21]  Kurunthachalam Kannan,et al.  Neuroendocrine effects of perfluorooctane sulfonate in rats. , 2003, Environmental health perspectives.

[22]  G. W. Jepson,et al.  Binding of perfluorooctanoic acid to rat and human plasma proteins. , 2003, Chemical research in toxicology.

[23]  D. Grandér,et al.  Reactive oxygen species and mitochondria mediate the induction of apoptosis in human hepatoma HepG2 cells by the rodent peroxisome proliferator and hepatocarcinogen, perfluorooctanoic acid. , 2001, Toxicology and applied pharmacology.

[24]  P. Hinderliter,et al.  Pharmacokinetics of perfluorooctanoate in cynomolgus monkeys. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[25]  Yoichi Kawashima,et al.  Comparison of the toxicokinetics between perfluorocarboxylic acids with different carbon chain length. , 2003, Toxicology.

[26]  J. Giesy,et al.  Perfluorochemical surfactants in the environment. , 2002, Environmental science & technology.

[27]  I. Edelman Subcellular Distribution and Mode of Action of Aldosterone , 1966 .

[28]  M. Cunningham,et al.  Effects of peroxisome proliferators on glutathione and glutathione-related enzymes in rats and hamsters. , 2001, Toxicology and applied pharmacology.

[29]  C. Lau,et al.  Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[30]  Christopher S Lau,et al.  Prenatal window of susceptibility to perfluorooctane sulfonate-induced neonatal mortality in the Sprague-Dawley rat. , 2003, Birth defects research. Part B, Developmental and reproductive toxicology.

[31]  Paul D Jones,et al.  Gene expression profiles in rat liver treated with perfluorooctanoic acid (PFOA). , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[32]  Derek C G Muir,et al.  Biological monitoring of polyfluoroalkyl substances: A review. , 2006, Environmental science & technology.

[33]  Kouji Harada,et al.  Renal clearance of perfluorooctane sulfonate and perfluorooctanoate in humans and their species-specific excretion. , 2005, Environmental research.

[34]  M. A. Mohd,et al.  Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries. , 2004, Environmental science & technology.

[35]  K. Hansen,et al.  Compound-specific, quantitative characterization of organic fluorochemicals in biological matrices. , 2001, Environmental science & technology.

[36]  K. Wallace,et al.  Perfluorooctanoate, perflourooctanesulfonate, and N-ethyl perfluorooctanesulfonamido ethanol; peroxisome proliferation and mitochondrial biogenesis. , 2002, Toxicology letters.

[37]  C. Dodia,et al.  Lysosomal-type PLA2 and turnover of alveolar DPPC. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[38]  M. Stanton,et al.  Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. II: postnatal evaluation. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[39]  O. Spydevold,et al.  The mechanism underlying the hypolipemic effect of perfluorooctanoic acid (PFOA), perfluorooctane sulphonic acid (PFOSA) and clofibric acid. , 1992, Biochimica et biophysica acta.

[40]  H. Haagsman,et al.  The Pulmonary Surfactant System: Biochemical and Clinical Aspects , 1997, Lung.

[41]  M Tanaka,et al.  The induction of peroxisome proliferation in rat liver by perfluorinated fatty acids, metabolically inert derivatives of fatty acids. , 1985, Journal of biochemistry.

[42]  Rolf Schock,et al.  On induction , 1965, Notre Dame J. Formal Log..

[43]  Derek C G Muir,et al.  Biomagnification of perfluoroalkyl compounds in the bottlenose dolphin (Tursiops truncatus) food web. , 2006, Environmental science & technology.

[44]  Wenyue Hu,et al.  Identification of genes responsive to PFOS using gene expression profiling. , 2005, Environmental toxicology and pharmacology.

[45]  C. Lau,et al.  The developmental toxicity of perfluoroalkyl acids and their derivatives. , 2004, Toxicology and applied pharmacology.

[46]  J. J. Batenburg Surfactant phospholipids: synthesis and storage. , 1992, The American journal of physiology.

[47]  J. Giesy,et al.  Global distribution of perfluorooctane sulfonate in wildlife. , 2001, Environmental science & technology.

[48]  Pekka Peura,et al.  Disposition of perfluorooctanoic acid in the rat after single and subchronic administration , 1990, Bulletin of environmental contamination and toxicology.

[49]  Roger G Perkins,et al.  The Toxicology of Perfluorooctanoate , 2004, Critical reviews in toxicology.