4-chloroaniline

Endpoint summary

Additional information

p-Chloroanilineis metabolized completely by Chlorella fusca rubra mostly to water-soluble products. 4 wk after application, 28% of the radioactivity was recovered from algae and 35% from aqueous medium. Metabolites isolated were p,p'-dichloroazoxybenzene and p,p'-chloroazobenzene from algae and p-chloro-formanilide and p-chloroanilide from nutrient medium.
Reference:AnagnostopoulosE et al; Chemosphere 7 (4): 351-7 (1978)

 

 

Microsomal fraction of germinated pea seeds oxidized 4-chloroaniline (4-CA) primarily to 4-chloronitrosobenzene, although (4-chlorophenyl)hydroxylamine was also a major product at high substrate concn. The enzyme-catalyzed oxidation of (4-chlorophenyl)hydroxylamine was faster than that for 4-chloroaniline. Oxidation of 4-chloroaniline was dependent on hydrogen peroxide & would not proceed when O2 & nicotinamide adenine dinucleotide phosphate reductase were substituted for hydrogen peroxide. Further slow oxidation of 4-chloronitrosobenzene to 4-chloronitrobenzene was an enzymatic process that was also dependent on hydrogen peroxide.
Reference:Corbett MD, Corbett BR; J Agric Food Chem 31 (6): 1276-82 (1983)

 

 

4-Chloroaniline undergoes N-oxidation in ram seminal vesicle microsomal preparations supplemented with arachidonic acid to yield N-(4-chlorophenyl)-hydroxyamine of the amine substrate to the same organic solvent extractable products, suggesting that the hydroperoxides activity of prostaglandin synthase is responsible for the co-oxidation. Analysis of the reaction mixtures by ESR spectrometry reveals the formation of a radical intermediate bearing the characteristics of a strongly immobilized nitroxide.
Reference:Golly I, Hlavica P; Biochem J 226 (3): 803-10 (1985)

 

 

PCA is rapidly metabolized. The main metabolic pathways of PCA are as follows: a) C-hydroxylation in the ortho position to yield 2-amino-5-chlorophenol followed by sulfate conjugation to 2-amino-5-chlorophenyl sulfate, which is excreted per se or after N-acetylation to N-acetyl-2-amino-5-chlorophenyl sulfate; b) N-acetylation to 4-chloroacetanilide (found mainly in blood), which is further transformed to 4-chloroglycolanilide and then to 4-chlorooxanilic acid (found in the urine); or c) N-oxidation to 4-chlorophenylhydroxylamine and further to 4-chloronitrosobenzene (in erythrocytes).
Reference:International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 48: 4-Chloroaniline (2003). Available from, as ofFebruary 22, 2005: http://www.inchem.org/pages/cicads.html

 

 

From a case of acute PCA poisoning in humans (no details of exposure/dose /or possible impurity of 2,4-dichloroaniline/), PCA (0.5% free, 62% total), 2-amino-5-chlorophenol (36%), and 2,4-dichloroaniline (1.7%; not reported in other studies), all in free and conjugated form, were detected (using HPLC) as excretory products in the urine. The biphasic elimination of the metabolites 2-amino-5-chlorophenol and 2,4-dichloroaniline was faster (half-lives of 1.7 hr for both metabolites in the first phase [T1] and 3.3 and 3.8 hr for the two metabolites, respectively, in the second phase [T2]) than that of PCA (all forms: half-lives T1 2.4 hr, T2 4.5 hr). PCA and 2-amino-5-chlorophenol were still detectable in the urine on days 3 and 4.
Reference:International Programme on Chemical Safety's Concise International Chemical Assessment Documents. Number 48: 4-Chloroaniline (2003). Available from, as ofFebruary 22, 2005: http://www.inchem.org/pages/cicads.html