P-nitrochlorobenzene is a light yellow crystalline solid. Density 1.520 g / cm3. Melting point 83°C. Sweet odor. Very toxic by inhalation, ingestion, and skin absorption.
颜色/状态：
Monoclinic prisms
气味：
Sweet odor
蒸汽密度：
5.44 (NTP, 1992) (Relative to Air)
蒸汽压力：
2.19X10-2 mm Hg at 25 °C
亨利常数：
4.89e-06 atm-m3/mole
分解：
...WHEN HEATED TO DECOMPOSITION IT EMITS VERYY TOXIC FUMES OF /NITROGEN OXIDES AND HYDROGEN CHLORIDE./
粘度：
1.07X10-3 Pa-s at 356.65 deg K
汽化热：
6.21X10+7 J/Kmol at 356.65 deg K
表面张力：
3.71X10-2 N/m at 356.65 deg K
电离电位：
9.96 eV
折光率：
MAX ABSORPTION (METHANOL): 270.5 NM (LOG E= 4.03); SADTLER REF NUMBER: 4683 (IR, PRISM); 435 (IR, GRATING); INDEX OF REFRACTION: 1.5376 AT 100 °C/ALPHA
The major urinary metabolites were conjugated (glucuronide or sulfate) forms of nitrochlorophenol and N-acetylcysteine conjugate of nitrobenzene. Minor metabolites included aminochlorophenol and N-acetylated aminochlorophenol. Para-chloroaniline has also been identified as a metabolite in the urine of rabbits following oral administration of PNCB.
The metabolism of radiolabeled monochloronitrobenzene isomers was compared in isolated hepatocytes and hepatic subcellular fractions from male Fischer-344 rats. ... 4-Chloronitrobenzene was metabolized to 4-chloroacetanilide, 4-chloroaniline, and S-(4-nitrophenyl)glutathione in approximately equal amounts (10-15% of the added substrate in 90 min). Studies with hepatic microsomes showed that reduction of the chloronitrobenzenes to chloroanilines was inhibited by SKF 525-A, metyrapone, and carbon monoxide, suggesting that cytochrome P-450 played a role in the reaction...
Urinary metabolites from human subjects acutely poisoned with p-chloro-nitrobenzene were identified with GLC-mass spectrometry. Eight substances /were identified/, namely, a very large amount of N-acetyl-S-(4-nitrophenyl)-cysteine, relatively large quantities of p-chloroaniline, 2-chloro-5-nitrophenol and p-chloroformanilide produced by pyrolysis of a substance originating from p-chloro-nitrobenzene, small amounts of 2-amino-5-chlorophenol and 2,4-dichloroaniline, and traces of p-chloroacetanilide and 4-chloro-2-hydroxyacetanilide, were detected in urine samples. All of the absorbed p-chloro-nitrobenzene was metabolized prior to excretion, as the parent cmpd was not found in the urine.
1-Chloro-4-nitrobenzene is rapidly absorbed via skin, gastrointestinal tract or respiratory tract and distributed in the tissue predominantly in fat, blood cells, skeletal muscles, liver and kidney. Most of the substance was excreted with the urine followed by excretion with feces. 1-Chloro-4-nitrobenzene undergoes three major types of transformation in vivo in mammals: nitro-group reduction, displacement of the chloride in glutathione conjugation, and ring hydroxylation. From accidental exposure of workers to 1-chloro-4-nitrophenol, large amounts of 2-chloro-5- nitrophenol, N-acetyl-S-(4-nitrophenyl)-L-cysteine, 4-chloroaniline and 4-chloroformanilide were identified. The oral LD50 for 1-chloro-4-nitrobenzene in male rats is 294 or 694 mg/kg bw and in female rats 565 or 664 mg/kg bw. Cyanotic appearance was the predominant symptom. The ... LC50 level could not be reached up to 16100 mg/cu m during a 4-hrs exposure against vapor and microcrystalline particles. The LD50 (dermal) for male rats is 750 mg/kg bw and for female rats 1722 mg/kg bw; the LD50 for male rabbits is 3550 mg/kg bw and for female rabbits 2510 mg/kg bw after acute dermal application. Cyanotic appearance was the predominant symptom. For the evaluation of acute toxicity it has to be taken into account that 1-chloro-4-nitrobenzene is a methemoglobin forming chemical. Experience with human exposure: all available reports relate to mixed exposure, frequently in combination with 1-chloro-2-nitrobenzene and/or nitrobenzene. A critical aspect in this context is that 1-chloro-4-nitrobenzene is rapidly absorbed via skin and the respiratory tract. The signs of acute intoxication include methaemoglobinaemia, vomiting, headache and in severe cases collapse. The available study-reports on skin irritation have deficiencies with regard to the description of the results, nevertheless, 1-chloro-4-nitrobenzene is judged to be slightly irritating to the skin (intact or scarificed) of rabbits ... Due to the limited and poor quality information available regarding skin sensitization it cannot be concluded whether or not the chemical has a sensitizing activity. The repeated dose toxicity via inhalation has been examined in rats for a period of 4 weeks and 13 weeks. In both studies, NOAECs were not achieved, the LOAECs were 5 mg/cu m (4 week-study) and 1.5 ppm (9.81 mg/vu m, 13 week-study), respectively, based on methemoglobinemia (3 % and 4 %, respectively) as the most sensitive effect. ... The repeated dose toxicity via inhalation for a period of 13 weeks in mice revealed a NOAEC for histopathologic injury of 6 ppm (39.24 mg/cu m). As target organs liver, kidney (rat only), spleen and blood were identified in both species. Similarly, repeated dose toxicity by oral administration in rats ... revealed changes predominantly consistent with methemoglobinemia. ... 1-Chloro-4-nitrobenzene induced reverse mutations in bacteria. It was not mutagenic in mammalian cells in vitro (HPRT test) and in insects in vivo. A mouse lymphoma assay was positive. In vitro it induced chromosomal aberrations and sister chromatid exchanges at high doses; no UDS in rat hepatocytes was reported. The chemical induced micronuclei in mouse bone marrow in vivo at a toxic dose. In rat bone marrow it did not induce chromosomal aberrations in vivo. An in vivo SCE test was weakly positive in bone marrow cells of Chinese hamsters. DNA strand breaks were observed in liver, kidney and brain of mice. 1-Chloro-4-nitrobenzene is consequently capable of expressing mutagenic activity in vivo with low potency. A combined chronic toxicity/carcinogenicity study ... with 1-chloro-4-nitrobenzene in rats produced an increased incidence in interstitial cell tumours of the testes which were within the range of the historical control data and evaluated as not compound related. ... In another rat study ... reported in brief, no tumors were found. In the available study with mice ... reported in brief, vascular tumors (localization not specified) were found. ... Overall, taking into consideration the results of the genotoxicity tests and the limitations in the available long term studies, a carcinogenic potential cannot be ruled out. Toxicity to reproduction of 1-chloro-4-nitrobenzene has been examined in rats and mice by oral administration. In a two generation study with rats ... no impairment of fertility was observed up to 5 mg/kg bw (high dose group), nevertheless, at this dose histopathological effects in testes were observed. But the evaluation of the effect on the male reproductive tract is limited because the testes in the low and mid dose group were not examined histopathologically. Therefore a NOAEL (male reproductive organ toxicity) was not established. ... In mice a study was performed using the NTP continuous breeding protocol. The NOAEL (fertility) is 125 mg/kg bw/day, the LOAEL (offspring general toxicity) is 62.5 mg/kg bw/day. The NOAEL (adult general toxicity) is 125 mg/kg bw/day, but full evaluation is not possible because evaluation of the animals of the two lower groups were very limited. Two subchronic inhalation studies with rats and mice with histopathologic evaluations on reproductive organs are available. There was evidence of decreased spermatogenesis (24 ppm) and decrease in average estrous cycle length in rats exposed to 1-chloro-4-nitrobenzene (6 ppm and above). In female mice an increase in estrous cycle length was noted at the highest exposure group (24 ppm). Developmental toxicity of 1-chloro-4-nitrobenzene has been examined in rats and rabbits by oral administration ... a NOAEL for maternal toxicity was not achieved, the LOAEL(maternal toxicity) is 5 mg/kg bw/day; the NOAEL (developmental toxicity) is 15 mg/kg bw/day. The study with rabbits suffered from methodology deficiencies. Due to high mortality rate at the highest dose level, only two doses could be evaluated: the LOAEL (maternal toxicity) is 5 mg/kg bw/day and the LOAEL (developmental toxicity) is 5 mg/kg bw/day. Thus, in both species developmental toxicity occurred in the presence of maternal toxicity. There are indications of immunotoxic potency following single and repeated applications of 1-chloro-4- nitrobenzene. Concerning the toxicity of 1-chloro-4-nitrobenzene towards aquatic species reliable experimental results of tests with fish, daphnia, and algae are available. The acute toxicity determined for fish (Brachydanio rerio) was of 14.36 mg/L (96 hr LC50) and 2 mg/L (48 hr) for Leuciscus idus and for daphnia (Daphnia magna) of 2.7 mg/L (48 hr-EC50). In the growth rate tests with algae (Scenedesmus subspicatus) the values 4.9 mg/L (48 hr-ErC10) and 16 mg/L (48 hr- ErC50) were achieved while for Chlorella pyrenoidosa an effect value of 4.9 mg/L (96 hr-EC50) was found. The prolonged toxicity to fish (Brachydanio rerio) for the endpoint sub-lethal effects (feeding, malposition) was evaluated through a 14 days test and a NOEC value of 1.53 mg/l was determined. Two chronic tests with Daphnia (Daphnia magna) are available that were performed with analytical monitoring of the test substance concentration. In one test a 21 d-EC10 of 0.103 mg/L (effective concentration) was observed for the endpoint reproduction rate. The second test resulted in a 21d-NOEC of 0.19 mg/L (effective concentration) for the same endpoint. Calculating the geometric mean of these two values gives a NOEC of 0.14 mg/Ll. A PNECaqua = 2.8 g/L is derived from this value, using an assessment factor of 50.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of chloronitrobenzenes. There is inadequate evidence in experimental animals for the carcinogenicity of chloronitrobenzenes. Overall evaluation: Chloronitrobenzenes are not classifiable as to their carcinogenicity to humans (Group 3). /Chloronitrobenzenes/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A3; 已确认的动物致癌物，对人类的相关性未知。
A3; Confirmed animal carcinogen with unknown relevance to humans.
Elimination of PNCB or its metabolites was essentially complete (95.5%) within 72 hours after a single oral dose of approximately 200 mg/kg to male rats.
The effect of dose on the dermal absorption of 2-chloronitrobenzene and 4-chloronitrobenzene was studied in rats. (14)C labeled 2-chloronitrobenzene or 4-chloronitrobenzene was applied to the shaved backs of male Fischer 344 rats at an application rates equivalent to doses of 0, 0.65, 6.5 or 65 mg/kg. Urine and feces samples were collected for 24, 48 or 72 hr and assayed for (14)C activity. Exhaled volatiles were collected in ethanol traps and analyzed. After 72 hr, the rats were /sacrificed/ and their skin removed and analyzed for (14)C activity. Approx 21-27% and 43 to 45% of the 2-chloronitrobenzene and 4-chloronitrobenzene doses, respectively, were eliminated in the urine over 72 hr. Approx 11 to 15% of the 2-chloronitrobenzene dose and 5 to 12% of the 4-chloronitrobenzene dose were excreted over 72 hr. Fecal excretion of 4-chloronitrobenzene showed a dose related incr which was statistically significant only when comparing the 65 mg/kg dose with the 0.65 mg/kg dose. Approx 27 to 32% of 2-chloronitrobenzene derived radioactivity and 13 to 15% of the 4-chloronitrobenzene derived (14)C activity were recovered in the ethanol traps. The amt of collected radioactivity did not depend on dose and consisted of unchanged 2-chloronitrobenzene or 4-chloronitrobenzene. ... An analysis of all (14)C data indicated that the dermal absorption of 2-chloronitrobenzene ... was linear over the entire dose range. Dermal absorption of 4-chloronitrobenzene was linear only after application of 0.65 and 6.5 mg/kg. /Results indicate/ that under the experimental conditions used at least 33 to 40% and 51 to 62% of the applied 2-chloronitrobenzene and 4-chloronitrobenzene doses, respectively, are absorbed from the skin of rats. ... Dermal absorption of 2-chloronitrobenzene is linear over the dose range 0.65 mg/kg to 65 mg/kg. Dermal absorption of 4-chloronitrobenzene is essentially unaffected by dose.
p-chloronitrobenzene was studied in male Sprague-Dawley rats injected ip with 0, 30, 100, or 333 mg/kg p-nitrochlorobenzene. Blood and urine samples were collected periodically from 1 to 169 hr after dosing. Plasma p-nitrochlorobenzene concn were determined at these times. The urine samples were analyzed for p-nitrochlorobenzene metabolites. The plasma concentrations of p-chloronitrobenzene following injection with the 30 and 100 mg/kg doses decreased linearly with time. The decrease following 333 mg/kg p-chloronitrobenzene was nonlinear. The mean residence time of p-chloronitrobenzene, determined from the first normal moment, increased with increasing dose. Systemic p-chloronitrobenzene clearance, defined as the ratio of the dose to the area under the plasma concn time curve, decreased with increasing p-chlorobenzene dose. The observations indicated that clearance of p-chloronitrobenzene from the plasma was nonlinear. N-acetyl-5-(4-nitrophenyl)-L-cysteine was the major urinary metabolite accounting for approx 30% of each administered p-chloronitrobenzene dose and 50% of the total metabolite concn. The rate constants for estimation of each p-chloronitrobenzene metabolite decr with increasing dose and were larger than those for production of the metabolites. The elimination rate of N-acetyl-S-(4-nitrophenyl)-L-cysteine, however, was proportional to p-chloronitrobenzene.
In rats, following oral dosing at least 78 % and following dermal application at least 62 % of the applied compound were absorbed. 72 hours after oral uptake of the compound up to 74 % of the dose was excreted with the urine and up to 12 % with the feces. After dermal application 45 % of the dose was excreted in the urine and 12 % in the feces within 72 hrs (up to 30 % of the dose was recovered in the protective device and ethanol trap (collects volatiles)). In both application routes, it was shown that at very high doses the initial urinary excretion rate is delayed and the initial fecal excretion is markedly depressed. These observations at high doses may reflect the reabsorption from greater biliary excretion rates suggesting involvement of the enterohepatic cycle, but there are no signs of accumulation of 1-chloro-4-nitrobenzene or one of its metabolites. 24 hours post oral application the highest concentrations of the compound were found in the fat, followed by blood cells, skeletal muscles , liver and kidney. At 72 hours greatest concentration was found in the blood cells followed by fat, skeletal muscles and liver.
