Energy of exothermic decomposition in range 210-400 °C was measured as 0.633 kJ/g by /diffential scanning calorimetry/, and T(ait24) was determined as 200 °C by adiabatic Dewar tests, with an apparent energy of activation of 124 kJ/mol.
Yields para-chloro-n-hydroxyaniline in rabbit. Yields para-aminophenol in rabbits. Yields para-chloroaniline-n-beta-dextro-glucuronide in rabbit. Yields 2-amino-5-chlorophenol in rabbits. Yields 3-amino-7-chlorophenoxazin-2-one in rabbits. /from table/
p-Chloroaniline is 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.
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.
The amines undergo a process of metabolism within the organism and real active agents are the metabolites, some of which induce methemaglobinemia while others are carcinogenic. These metabolites generally take the form of hydroxylamines, changing to aminophenols as a form of detoxification. /Amines/
IDENTIFICATION: 4-Chloroaniline (PCA) is a colorless to slightly amber-colored crystalline solid with a mild aromatic odor. The chemical is soluble in water and in common organic solvents. PCA is used as an intermediate in the production of a number of products, including agricultural chemicals, azo dyes and pigments, cosmetics, and pharmaceutical products. HUMAN EXPOSURE: In humans, hemoglobin adducts are detectable as early as 30 min after accidental exposure, with a maximum level at 3 hr. Slow acetylating individuals have a higher potency to form hemoglobin adducts compared with fast acetylators. Excretion in humans occurs primarily via the urine, with PCA and its conjugates appearing as early as 30 min after exposure. Excretion takes place mainly during the first 24 h and is almost complete within 72 h. Data on occupational exposure of humans to PCA are mostly from a few older reports of severe intoxications after accidental exposure to PCA during production. Symptoms include increased methemoglobin and sulfhemoglobin levels, cyanosis, the development of anemia, and changes due to anoxia. PCA has a strong tendency to form hemoglobin adducts, and their determination can be used in biomonitoring of employees exposed to 4-chloroaniline in the workplace. There are reports of severe methemoglobinemia in neonates from neonatal intensive care units in two countries where premature babies were exposed to PCA as a breakdown product of chlorohexidine; the chlorohexidine, which had been inadvertently used in the humidifying fluid, broke down to PCA upon heating in a new type of incubator. Three neonates in one report (14.5-43.5% methemoglobin) and 33 of 415 neonates in another report (6.5-45.5% methemoglobin during the 8-month screening period) were found to be methemoglobin positive. A prospective clinical study showed that immaturity, severe illness, time exposed to PCA, and low concentrations of NADH reductase probably contributed to the condition. ANIMAL STUDIES: PCA is rapidly absorbed and 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 as is 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). Reactive metabolites of PCA bind covalently to hemoglobin and to proteins of liver and kidney. Excretion in animals occurs primarily via the urine, with PCA and its conjugates appearing as early as 30 min after exposure. Excretion takes place mainly during the first 24 hr and is almost complete within 72 hr. The prominent toxic effect is methemoglobin formation. PCA is a more potent and faster methemoglobin inducer than aniline. PCA also exhibits a nephrotoxic and hepatotoxic potential. PCA was found to be non-irritating to rabbit skin and slightly irritating to rabbit eyes. A weak sensitizing potential was demonstrated with several test systems. Repeated exposure to PCA leads to cyanosis and methemoglobinemia, followed by effects in blood, liver, spleen, and kidneys, manifested as changes in hematological parameters, splenomegaly, and moderate to heavy hemosiderosis in spleen, liver, and kidney, partially accompanied by extramedullary hematopoiesis. These effects occur secondary to excessive compound-induced hemolysis and are consistent with a regenerative anemia. PCA is carcinogenic in male rats, with the induction of unusual and rare tumors of the spleen (fibrosarcomas and osteosarcomas), which is typical for aniline and related substances. In female rats, the precancerous stages of the spleen tumors are increased in frequency. Increased incidences of pheochromocytoma of the adrenal gland in male and female rats may have been related to PCA administration. There was some evidence of carcinogenicity in male mice, indicated by hepatocellular tumors and hemangiosarcoma. PCA shows transforming activity in cell transformation assays. A variety of in vitro genotoxicity tests Salmonella mutagenicity test, mouse lymphoma assay, chromosomal aberration test, induction of sister chromatid exchange indicate that PCA is possibly genotoxic, although results are sometimes conflicting. Due to lack of data, it is impossible to make any conclusion about PCA's in vivo genotoxicity. No studies are available on reproductive toxicity. From valid test results available on the toxicity of PCA to various aquatic organisms, PCA can be classified as moderately to highly toxic in the aquatic compartment. Therefore, a possible risk to aquatic organisms, particularly benthic species, cannot be completely ruled out, particularly in waters where significant amounts of particulate matter inhibit rapid photomineralization. Experiments with Daphnia magna revealed significantly reduced toxicity with increasing concentrations of dissolved humic materials in the medium, possibly caused by reduced bioavailability of PCA from adsorption to dissolved humic materials.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
癌症分类：B2组可能的人类致癌物
Cancer Classification: Group B2 Probable Human Carcinogen
Evaluation: There is inadequate evidence in humans for the carcinogenicty of para-chloroaniline. There is sufficient evidence in experimental animals for the carcinogenicity of para-chloroaniline. OVERALL EVALUATION: Group 2B: para-Chloroaniline is possibly carcinogenic to humans.
Tomato uptake of 4-chloroaniline from soil increased in direct proportion with amount present in soil. Compound was mostly root-localized, but translocation to stem increased with increasing concentration. In carrots, roots accumulated only slightly more chloroaniline than green parts. 4-Chloroaniline was also taken up by wheat and barley.
Oats took up and translocated 1.4% of soil-bound (14)C-4-chloroaniline within 6 wk; uptake from solution was 1.7-2.3%. Labeled compound was added to soil at 1 ppm. There were only slight differences in results between 2 soil types (humus-rich gley and parabrown soils) studied.
In male /Fischer 344/ rats administered (14)C-labelled compound (5 mCi/mmol (0.04 mCi/mg) (radiochemical purity unspecified)) at 0.3-30 mg/kg bw by gavage in 0.01 N hydrochloric acid, 75-85% of the dose was excreted in urine and 8-12% in feces by 24 hr; only 4% was excreted as unchanged amine in urine, 2.5% in bile and 1% in feces. At seven days, appreciable radiolabel was still present in blood cells, accounting for 1-2% of the dose. After an intravenous dose of 3.0 mg/kg bw in ethanol:propylene glycol:water (1:1:8), 60% of the dose was excreted in urine after 4 hr, 25% was excreted in bile after 6 hr, and 90% was eliminated in urine and feces by 8 hr. Initial levels in tissues were highest in muscle >fat >skin >liver >blood... .
