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A SHORT-TERM DOSING MODEL FOR DETECTING THE EFFECTS OF ENVIRONMENTAL CONTAMINANTS ON THYROID HORMONES IN THE RAT: EFFECTS OF PESTICIDES.
Citation:
Hedge, J M., D. G. Ross, M J. DeVito, AND K M. Crofton. A SHORT-TERM DOSING MODEL FOR DETECTING THE EFFECTS OF ENVIRONMENTAL CONTAMINANTS ON THYROID HORMONES IN THE RAT: EFFECTS OF PESTICIDES. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
Recently, a short-term rat dosing model has been developed to examine the effects of environmental mixtures on thyroid homeostasis (TH). Prototypic chemicals such as dioxins, polychlorinated biphenyls and polybrominated diphenyl ethers have been tested and shown to adversely impact both neurological development and TH, primarily by up regulating catabolism of thyroid hormones by liver enzymes. Current efforts examined the effects of select pesticides in this model. Female Long Evans rats (28 days old) were orally dosed for four consecutive days with the dithiocarbamate fungicide mancozeb (MAN) or the herbicide pronamide (PRO) (0, 3.9, 7.8, 15.6, 31.25, 62.5, 125, 250, 500, 1000 mg/kg/day), or the dithiocarbamate fungicide Thiram (THI) (0, 6.25, 12.5, 25, 50, 100, 200, 400, 800 mg/kg/day). Serum and liver samples were collected 24 hrs after the last dose. Triiodothyronine (T3) and thyroxine (T4) were measured via radioimmunoassays. Hepatic ethoxy-resorufin-O-deethylase ( EROD), pentoxy-resorufin-O-deethylase (PROD), and uridinediphosphate-glucuronsyltransferase (UDPGT), were determined in hepatic microsomal fractions. Liver-to-body weight ratios (LBR) increased for PRO at doses >125 mg/kg/day, MAN at >500 mg/kg/day, and THI at >400 mg/kg/day. PRO, MAN and THI all produced similar dose-related decreases in T4, with estimated ED50s of approximately 250 mg/kg/day. Potencies for decreases in T3 were THI > PRO > MAN. Maximal suppression of T3 and T4 was ~50% and 80% at the highest doses, respectively. Neither MAN or THI caused changes in EROD or PROD. These data suggest that this rodent dosing model is sensitive to short-term pertubations in thyroid hormones caused by these pesticides. This abstract does not necessarily reflect the policy of the USEPA.