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Mechanism of nitrofen teratogenesis.
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MedLine Citation:
PMID:  3830099     Owner:  NLM     Status:  MEDLINE    
Nitrofen (2,4-dichloro-4'-nitrodiphenyl ether) is an herbicide with potent teratogenic activity in rats. When administered at doses as low as 0.15 mg/kg/day during organogenesis, abnormal development of the heart, kidneys, diaphragm, and lung occurs. The specific pattern of visceral malformations produced in the absence of overt maternal toxicity or embryolethality/cytotoxicity suggest that the compound perturbs processes unique or highly selective for embryonic differentiation. Despite findings of metabolic activation to mutagenic intermediates and carcinogenic activity in adult rodents, several lines of evidence indicate that teratogenicity is not based on mutagenic insult to the embryo. Rather, evidence is accumulating that nitrofen exerts a teratogenic effect via alterations in thyroid hormone status. The premature and pharmacologic exposure of the embryo to a nitrofen-derived thyromimetic challenge is believed to be the cause of abnormal morphogenesis of the heart, lungs, kidneys, and diaphragm. The parent compound itself could directly bind to embryonic nuclear receptors for T3, leading to altered differentiation of target organs. Alternatively, increased availability and placental transport of free thyroid hormones in the maternal compartment could be the source of thyromimetic challenge to the embryo. Overall, these studies indicate that, in the case of nitrofen, the mode of teratogenic activity is uniquely different from the mode of adult toxicity.
J M Manson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Environmental health perspectives     Volume:  70     ISSN:  0091-6765     ISO Abbreviation:  Environ. Health Perspect.     Publication Date:  1986 Dec 
Date Detail:
Created Date:  1987-05-18     Completed Date:  1987-05-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0330411     Medline TA:  Environ Health Perspect     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  137-47     Citation Subset:  IM    
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MeSH Terms
Abnormalities, Drug-Induced / pathology
Herbicides / toxicity*
Maternal-Fetal Exchange
Phenyl Ethers / metabolism,  toxicity*
Tissue Distribution
Reg. No./Substance:
0/Herbicides; 0/Phenyl Ethers; 0/Teratogens; 1836-75-5/nitrofen

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

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Journal Information
Journal ID (nlm-ta): Environ Health Perspect
ISSN: 0091-6765
Article Information
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Print publication date: Month: 12 Year: 1986
Volume: 70First Page: 137 Last Page: 147
ID: 1474278
PubMed Id: 3830099

Mechanism of nitrofen teratogenesis.
J M Manson

Article Categories:
  • Research Article

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