2005 Fiscal Year Final Research Report Summary
Studies on toxicokinetics of perfluoroaklyltelomer alcohol in experimental animals and its application to the estimation of accumulation in humans
| Project/Area Number |
15510060
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | Josai University |
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Principal Investigator |
KUDO Naomi Josai University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 講師 (10161647)
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| Project Period (FY) |
2003 – 2005
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| Keywords | 8-2 fluorotelomer alcohol / perfluorooctanoic acid / metabolism / Peroxisome proliferation / oleic acid formation |
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| Research Abstract |
In this study, toxicokinetics of 1H,1H,2H,2H-perfluorodecanol (8-2 fluorotelomer alcohol) and the effects of this chemical were estimated in mice and rats.
1)Toxicokinetics_of 8-2_fluorotelomer_alcohol_in_mice_and_rats
8-2 Fluorotelomer alcohol that had been arally administered to mice was found in stomach, intestine and thereafter in feces but not in urine. Serum abd tissue concentrations of 8-2 fluorotelomer alcohol were low. The concentration of 8-2 fluorotelomer alcohol was the highest in adipose tissue immediately after the administration and thereafter decreased. A few metabolites were detected transiently in the serum of mice. Perfluorooctanoic acid (PFOA) was also detected in the liver and serum after the administration and its concentration gradually increased. The same results were obtained with rats. The results indicated that 8-2 fluorotelomer alcohol hardly absorbed in intestine and once incotporaed, quickly metabolized to PFOA and acclumulated in the liver and serum in rats and mice.
2)Effects_of_repeated_administration_of_8-2_fluorotelomer_alcohol_in_mice
Feeding of 8-2 fluorotelomer alcohol for 28 days induced reduction of triglyceride in the serum and Peroxisome proliferation and increse in the proportion of oleic acid in the liver of mice. These effects were also obsereved in the mice administered with PFOA. PFOA was accumulated in time- and dose- dependent manners in the serum and liver of mice.
3)Mechanism_for_in_creased_oleic_acid_in_the_liver
The administration of 8-2 fluorotelomer alcohol induced the enzymes stearoyl-CoA desaturae and palmitoyl-CoA chain elongase that are involved in oleic acid formation in the liver of mice and rats. The induction is thought to be due to transcriptional activation of these enzymes in these animals.
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