Document Detail


An FDA review of sulfamethazine toxicity.
MedLine Citation:
PMID:  10620471     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently, changes have been proposed in the criteria historically used in the evaluation of the applicability to humans of some of the results obtained from the rodent carcinogenicity bioassay data. These questions center on the suitability of the rodent model for agents that exert their toxic effects via specific enzyme interactions and endocrine mechanisms which appear to be inoperative within humans. Within the U.S. Food and Drug Administration (FDA), this issue has been brought to the forefront of concern with the recent application for a New Animal Drug Application for sulfamethazine (SMZ). A panel of FDA experts from the National Center for Toxicological Research (NCTR), the Center for Veterinary Medicine (CVM), and the Center for Food Safety and Applied Nutrition has reviewed the sum of the scientific evidence available on the toxicology of SMZ. They noted that, in previous feeding studies at NCTR, high doses of SMZ were associated with significant incidences of thyroid tumors in mice and rats. The panel also notes that the tumorigenic activity of SMZ in rodents was due to its goitrogenic activity, resulting in constant stimulation of the thyroid by TSH. Humans, on the other hand, were found to be insensitive to the SMZ-like inhibition of thyroid function. Further, apart from X-irradiation and radioactive iodine, there are no other physical or chemical agents known to cause thyroid tumors in humans. Thus, the expert panel concludes that the best scientific information available indicates that elevated levels of TSH and the consequent thyroid tumors would not be produced under approved use conditions of SMZ. This conclusion is in agreement with recommendations made by three other panels, viz. the World Health Organization, the U.S. Environmental Protection Agency, and CVM, which also evaluated the public health risk of SMZ.
Authors:
L A Poirier; D R Doerge; D W Gaylor; M A Miller; R J Lorentzen; D A Casciano; F F Kadlubar; B A Schwetz
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Regulatory toxicology and pharmacology : RTP     Volume:  30     ISSN:  0273-2300     ISO Abbreviation:  Regul. Toxicol. Pharmacol.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-02-24     Completed Date:  2000-02-24     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  8214983     Medline TA:  Regul Toxicol Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  217-22     Citation Subset:  IM    
Affiliation:
Division of Molecular Epidemiology, NCTR, Jefferson, Arkansas, 72079, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Infective Agents / adverse effects,  toxicity*
Carcinogenicity Tests / methods
Carcinogens / adverse effects,  toxicity*
Humans
Sulfamethazine / adverse effects,  toxicity*
Thyroid Neoplasms / chemically induced
United States
United States Food and Drug Administration
Chemical
Reg. No./Substance:
0/Anti-Infective Agents; 0/Carcinogens; 57-68-1/Sulfamethazine

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


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