N-Nitrosophenacetin: Its Synthesis, Characterization, Mutagenicity, and Teratogenicity

Reaction of phenacetin (CAS: 62-44-2; p-aceto-phenetidide) with nitrous fumes (N2O3) in glacial acetic acid at 0–5°C yields N-nitrosophenacetin (NP), 2-nitrophenacetin, N-nitroso-2-nitrophenacetin (NNP), and other compounds. Both NP and NNP are fairly stable at low temperature (−30° C) but extremely...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 1984-04, Vol.72 (4), p.863-869
Main Authors: Lin, Jen-Kun, Yen, Jong-Young, Chang, Han-Wei, Lin-Shiau, Shoei-Yn
Format: Article
Language:English
Subjects:
Abnormalities, Drug-Induced - embryology
Animals
Biological and medical sciences
Chemical mutagenesis
Chemical Phenomena
Chemistry
Chick Embryo
Diethylnitrosamine - toxicity
Dimethylnitrosamine - toxicity
Lethal Dose 50
Medical sciences
Methylnitronitrosoguanidine - toxicity
Methylnitrosourea - toxicity
Mutagenicity Tests
Mutagens - toxicity
Nitrosamines - analysis
Nitrosamines - chemical synthesis
Nitrosamines - toxicity
Rats
Rats, Inbred Strains
Spectrophotometry
Teratogens - toxicity
Toxicology
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Summary:Reaction of phenacetin (CAS: 62-44-2; p-aceto-phenetidide) with nitrous fumes (N2O3) in glacial acetic acid at 0–5°C yields N-nitrosophenacetin (NP), 2-nitrophenacetin, N-nitroso-2-nitrophenacetin (NNP), and other compounds. Both NP and NNP are fairly stable at low temperature (−30° C) but extremely labile at ambient temperature. NP (median lethal dose to Sprague-Dawley rat: 21 mg/kg body wt) is 80 times more toxic than its parent compound phenacetin and is directly mutagenic to bacterial cells including Salmonella typhimurium and Sarcina lutea. The mutagenicity of NP is comparable to that of N-methyl-N′-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7; 1-methyl-3-nitro-1-nitrosoguanidine] and requires no microsomal metabolic activation. The teratogenic potential of NP was studied in White Leghorn chick embryos given a single dose of 5–15 μg/egg on day 6 of incubation. A low incidence of exencephaly and eyelid defect and a high incidence of feather and claw malformations were found in the treated group; no such malformed embryos were found in the control group. The teratogenicity of NP was found to be weaker than that of MNNG, but stronger than that of N-methyl-N-nitrosourea (CAS: 684-93-5), dimethylnitrosamine (CAS: 62-75-9; N-nitrosodimethylamine), and diethylnitrosamine (CAS: 15-18-5; N-nitrosodiethylamine).
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/72.4.863