Registration Dossier
Registration Dossier
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EC number: 206-735-5 | CAS number: 371-40-4
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
The test substance is a potent inducer of methaemoglobinaemia in the rat.
The test substance is mainly metabolised by ortho-hydroxylation to 2-amino-5- fluorophenylsulphate.
Key value for chemical safety assessment
Additional information
In Eadsforth et al. two possible methods for monitoring exposure to 2,4-difluoroaniline and the test substance have been investigated by measurement of methaemoglobin content in blood and measurement of urinary metabolites. Experiments using rats dosed by the oral route as a model system showed that measurement of methaemoglobin content provides a very rapid and simple monitoring method, but is not very sensitive. Measurement of the ortho-hydroxy metabolites of the two compounds, as their benzoxazole derivatives, provides a much more sensitive, but complicated technique. Ortho-sulphate was determined as a metabolite.
Scarfe et al.(1998) evaluated the metabolic fate of the test substance using NMR-based methods after 50 and 100 mg/kg bw i.p. doses respectively to the male Sprague-Dawley rat.
The test substance was both ortho- and para-hydroxylated. The major metabolite produced by ortho-hydroxylation was 2-amino-5- fluorophenylsulphate accounting for ca. 30% of the dose. Of the dose, ca. 10% was excreted via para-hydroxylation and the resulting defluorinated metabolites were N-acetylated and excreted as sulphate (major), glucuronide (minor) and N-acetyl-cysteinyl (minor) conjugates of 4-acetamidophenol (paracetamol).
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