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MEASUREMENT OF THYROID HORMONES IN THE RAT SERA CONTAINING PERFLUOROOCTANESULFONATE (PFOS)
Tanaka, S., J R. Thibodeaux, M. Eastvold, J. Bjork, D. Ehresman, R. Singh, K. Wallace, C S. Lau, AND J. L. Butenhoff. MEASUREMENT OF THYROID HORMONES IN THE RAT SERA CONTAINING PERFLUOROOCTANESULFONATE (PFOS). Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Perfluorooctanesulfonate (PFOS), a persistent and bioaccumulative acid, is widely distributed in humans and wildlife. Prior studies with PFOS (rats and monkeys) have observed decreased total and free thyroid hormones (TH) in serum without a rise in thyrotropin (TSH). Measurement of serum free TH by analog methods can result in negative bias if serum binding capacity (SBC) and serum protein-bound TH (PBTH) are reduced. We tested the hypothesis (in vivo and in vitro)that PFOS reduces SBC and PBTH, resulting in a negative bias in analog assays for free TH. In vivo, adult female rats (10/group) were given 3 daily oral doses of 5 mg/kg PFOS or vehicle. Sera and liver were harvested and flash frozen 24 hours after the last dose. Both chemiluminescent (CL) and RIA methods were used to measure serum total thyroxine (TT4), free thyroxine (FT4), and TSH. FT4 was also measured by equilibrium dialysis-RIA (ED-RIA), a reference method not subject to negative bias. Hepatic mRNA transcripts for malic enzyme (ME), ?-glycero-3-phosphate-dehydrogenase (?G3PD) (both responsive to TH), and UDP-GST-1A were quantified by RT-PCR. In vitro, rat sera were mixed with PFOS (0-100 ?g/mL) and assayed for TT4 and FT4 (CL and ED-RIA). In vivo, PFOS decreased TT4 and FT4 by CL and RIA. TSH, by CL and RIA, and FT4, by ED-RIA, were comparable to controls. ME and UDP-GST-1A transcripts were elevated 20% (p<0.05) and 38% (p<0.001), respectively, by PFOS. ?G3PD transcripts were unchanged. In vitro, TT4 was unchanged, and FT4 was positively correlated with PFOS concentration by both CL and ED-RIA up to 32% and 89% over control, respectively, at 100 ?g/mL PFOS. Thus, PFOS in serum resulted in a negative bias in analog FT4 measurements and did not reduce either FT4 by ED-RIA or the liver response to TH. These observations suggest that prior reports of reduced free TH were artifacts of the analog methods.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
REPRODUCTIVE TOXICOLOGY DIVISION
DEVELOPMENTAL BIOLOGY BRANCH