Document Detail


A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat.
MedLine Citation:
PMID:  16626768     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prolonged treatment with high doses of Pyrethrins results in thyroid gland tumors in the rat. To elucidate the mode of action for tumor formation, the effect of Pyrethrins on rat thyroid gland, thyroid hormone levels and hepatic thyroxine UDPglucuronosyltransferase activity was investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42 days and for 42 days followed by 42 days of reversal. As a positive control, rats were also fed diets containing 1200-1558 ppm sodium Phenobarbital (NaPB) for 7 and 14 days. The treatment of male rats with 8000 ppm Pyrethrins, female rats with 3000 and 8000 ppm Pyrethrins and both sexes with NaPB resulted in increased thyroid gland weights, which were associated with follicular cell hypertrophy. Thyroid follicular cell replicative DNA synthesis was increased by treatment with Pyrethrins and NaPB for 7 and/or 14 days. Treatment with Pyrethrins and NaPB increased hepatic microsomal thyroxine UDPglucuronosyltransferase activity and serum thyroid stimulating hormone levels (TSH), but reduced serum levels of either thyroxine (T4) and/or triiodothyronine (T3). The effects of Pyrethrins in female rats were dose-dependent, with 100 ppm being a no-effect level, and on cessation of treatment were essentially reversible in both sexes. The concordance between the effects of Pyrethrins and NaPB suggests that the mode of action for Pyrethrins-induced rat thyroid gland tumors is similar to that of some other non-genotoxic inducers of hepatic xenobiotic metabolism.
Authors:
John M Finch; Thomas G Osimitz; Karl L Gabriel; Tom Martin; Wendy J Henderson; Charles C Capen; William H Butler; Brian G Lake
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-04-19
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  214     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-24     Completed Date:  2006-08-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  253-62     Citation Subset:  IM    
Affiliation:
Inveresk Research, Tranent EH33 2NE, Scotland.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Cell Proliferation / drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Glucuronosyltransferase / metabolism
Insecticides / toxicity*
Male
Microsomes, Liver / drug effects,  metabolism,  pathology
Organ Size / drug effects
Phenobarbital / pharmacology
Pyrethrins / toxicity*
Rats
Rats, Sprague-Dawley
Sex Factors
Thyroid Gland / drug effects*,  metabolism,  pathology
Thyroid Hormones / blood,  metabolism*
Thyroid Neoplasms / chemically induced*,  metabolism,  pathology
Chemical
Reg. No./Substance:
0/Insecticides; 0/Pyrethrins; 0/Thyroid Hormones; 50-06-6/Phenobarbital; EC 2.4.1.-/thyroxine-UDP-glucuronosyltransferase; EC 2.4.1.17/Glucuronosyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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