1-(3,4-ジクロロフェニルアゾ)-3,4-ジクロロベンゼン

log Kow = 5.53

5.53

This chemical does not meet GHS hazard criteria for 100% (37 of 37) of all reports.

Not Classified

Aggregated GHS information provided per 37 reports by companies from 1 notifications to the ECHA C&L Inventory.

Danger

H227: Combustible liquid [Warning Flammable liquids]

P203, P210, P261, P264, P272, P273, P280, P302+P352, P318, P321, P332+P317, P333+P317, P362+P364, P370+P378, P391, P403, P405, and P501 (click each P-code to see the statement)

Not Classified

Germ cell mutagenicity - Category 2

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 57,000(SRC), determined from a structure estimation method(2), indicates that 3,4,3',4'-tetrachloroazobenzene is expected to be immobile in soil(SRC). Field monitoring in rice soils found that 3,4,3',4'-tetrachloroazobenzene residues remained primarily in the upper 0-10 cm soil layer(3). Volatilization of 3,4,3',4'-tetrachloroazobenzene from moist soil surfaces is possible given an estimated Henry's Law constant of 4.4X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(2), but it is not expected to be an important fate process due to strong adsorption(SRC). 3,4,3',4'-Tetrachloroazobenzene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.56X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Soil studies have found 14-CO2 evolution or mineralization of 3,4,3',4'-tetrachloroazobenzene to be only 0.04-0.20% over 42-day and 6 month incubation periods(4,5). In 6-month studies in French soils with different pHs and organic matter content, more than 93% of initial 3,4,3',4'-tetrachloroazobenzene was recovered intact in all soils(5) indicating microbiological and chemical stability(4,5). 3,3',4,4'-Tetrachloroazoxybenzene has been identified as a soil degradation product and metabolite of 3,4,3',4'-tetrachloroazobenzene(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 57,000(SRC), determined from a structure estimation method(2), indicates that 3,4,3',4'-tetrachloroazobenzene is expected to adsorb strongly to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 4.4X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 8 and 66 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column; the estimated volatilization half-life from a model pond 2 meter deep is 86 years if adsorption is considered, but only 166 days with no adsorption(4). According to a classification scheme(5), an estimated BCF of 10(SRC), from log Kow of 5.53(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). 3,4,3',4'-Tetrachloroazobenzene is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). 3,4,3',4'-Tetrachloroazobenzene contains the azo chromophore that absorbs at wavelengths >290 nm(3), and therefore may be susceptible to direct photolysis by sunlight(SRC). Azobenzene has been shown to photodegrade readily when irradiated with lamps using >290 nm light(7).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3,4,3',4'-tetrachloroazobenzene, which has an estimated vapor pressure of 1.56X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 3,4,3',4'-tetrachloroazobenzene is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 50 days(SRC), calculated from its rate constant of 3.2X10-13 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase 3,4,3',4'-tetrachloroazobenzene may be removed from the air by wet or dry deposition(SRC). 3,4,3',4'-Tetrachloroazobenzene contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of June 21, 2012: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=14047-09-7]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 3,4,3',4'-tetrachloroazobenzene can be estimated to be 57,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that 3,4,3',4'-tetrachloroazobenzene is expected to be immobile in soil. Residues of 3,4,3',4'-tetrachloroazobenzene in Arkansas rice soils remained primarily in the upper 0-10.1 cm soil layer(3).

3,4,3',4'-Tetrachloroazobenzene is not commercially manufactured but is formed as an unwanted byproduct in the manufacture of 3,4-dichloroaniline and its herbicidal derivatives propanil, linuron, and diuron. In addition, environmental contamination by 3,4,3',4'-tetrachloroazobenzene occurs from the degradation of chloranilide herbicides and the photolysis and biolysis of 3,4-dichloroaniline(1).

AEROBIC: In rice soil studies, 14-CO2 evolution during 3 and 6-month aging periods was only 0.04 and 0.13%, respectively, of applied radio-labeled 3,4,3',4'-tetrachloroazobenzene(1); mineralization of 3,4,3',4'-tetrachloroazobenzene to 14-CO2 during a 42-day growth period of rice plants was only 0.04-0.07%(1). Incubation of radio-labeled 3,4,3',4'-tetrachloroazobenzene for 6-months in French soils with different pHs and organic matter content evolved only 0.05-0.20% as 14-CO2(2); more than 93% was recovered intact in all soils(2) indicating microbiological and chemical stability(1,2).

3,3′,4,4′-Tetrachloroazobenzene

Group 2A: Probably carcinogenic to humans

Volume 117: (2019) Pentachlorophenol and Some Related Compounds

2019

2016

NB Overall evaluation upgraded to Group 2A

An estimated BCF of 10 was calculated in fish for 3,4,3',4'-tetrachloroazobenzene(SRC), using a log Kow of 5.53(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low (SRC). In a 28-day aquarium study using snails, 3,4,3',4'-tetrachloroazobenzene bioaccumulated only to maximum level of 287 ppb (whole body basis)(4).

The Henry's Law constant for 3,4,3',4'-tetrachloroazobenzene is estimated as 4.4X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 3,4,3',4'-tetrachloroazobenzene is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 8 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 66 days(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond 2 meter deep is 86 years if adsorption is considered, but only 166 days with no adsorption(3). 3,4,3',4'-Tetrachloroazobenzene's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may occur, but it is not expected to be an important fate process due to adsorption(SRC). 3,4,3',4'-Tetrachloroazobenzene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.56X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(1).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The toxicity of 3,3',4,4'-tetrachloroazobenzene (TCAB) was evaluated in 13-week gavage studies in male and female F344/N rats and B6C3F1 mice. In addition to histopathology, evaluations included clinical chemistry, hematology, thyroid hormone analyses, and reproductive parameters. Groups of 10 rats and 10 mice of each sex were exposed to TCAB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg for 5 days a week for 13 weeks. In the rat studies, the major effects for both males and females included a 10% decrease in terminal body weight at 30 mg/kg/day, an increase in hematopoietic cell proliferation in the spleen at 10 and 30 mg/kg/day, and a responsive anemia at 10 and 30 mg/kg/day. A 15 to 30% decrease in platelet counts and a 20 to 40% decrease in thymus weights was observed at 10 and 30 mg/kg/day. An increase in liver weight up to 15% was found at 3 mg/kg/day and higher doses in males and at 10 and 30 mg/kg/day in females, respectively. An increase in spleen weights up to 15% was observed at 10 and 30 mg/kg/day in males and at 30 mg/kg/day in females. A marked decrease in circulating total thyroxine (TT4) was found in both males and females at all dose levels tested. TT4 could hardly be detected at 10 and 30 mg TCAB/kg/day. In addition, hyperplasia of the forestomach was increased at 3 mg/kg/day and higher doses in males and at 30 mg/kg/day in females. In the mouse studies, an increase in liver and spleen weight was observed up to approximately 25% in both males and females at 10 and 30 mg/kg/day. Hyperplasia of the forestomach was observed at 1 mg/kg/day and higher doses in both males and females. In males, a 30% decrease in thymus weights at 30 mg/kg/day and a 60% decrease in epididymal sperm density at 3 and 30 mg/kg/day was observed. Also in males, centrilobular hypertrophy of hepatocytes and an increase in hematopoietic cell proliferation in the spleen was observed at 3 mg/kg/day and higher doses. ...

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ B6C3F1 mice chronically exposed to 3,3',4,4'-tetrachloroazobenzene (TCAB), a contaminant of dichloroaniline-derived herbicides, developed a number of neoplastic and nonneoplastic lesions, including carcinoma of the urinary tract. Groups of fifty male and fifty female B6C3F1 mice were exposed by gavage to TCAB at dose levels of 0, 3, 10, and 30 mg/kg five days a week for two years. Control animals received corn oil:acetone (99:1) vehicle. Decreased survival of male mice in the mid-dose group and of male and female mice in the high-dose groups was related mainly to the occurrence of urethral transitional cell (urothelial) carcinoma and resulting urinary obstruction. Increased urethral transitional cell carcinomas were seen in all treated male groups in a dose-related manner as well as in the females treated with 30 mg/kg TCAB. Administration of TCAB was also associated with increased transitional cell hyperplasia of the urethra. Most nonneoplastic lesions of the urogenital tract were considered secondary to local invasion and urinary obstruction by the urethral transitional cell carcinomas. The mechanism of tumor induction is uncertain, but the high frequency of tumors in the proximal urethra of male mice suggests that the neoplasms result from the exposure of a susceptible population of urothelial cells to a carcinogenic metabolite of TCAB.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The toxicity of 3,3',4,4'-tetrachloroazobenzene (TCAB) and 3,3',4,4'-tetrachloroazoxybenzene (TCAOB) to chick embryos was examined. TCAB or TCAOB was dissolved in corn oil and injected into the air cell of fertile chicken eggs. The time of injection had a major effect on embryo mortality as eggs injected with TCAB or TCAOB on the fourth day of incubation had a higher incidence of embryo mortality than eggs injected on days 11-13. Both TCAB and TCAOB were more toxic than all other chemicals that have been tested in the chick embryo with the exception of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Comparing the potency of the two compounds, TCAOB was more potent than TCAB in the chick embryo with an estimated LD50 of 12 ng and 44 ng respectively. Rump edema was the major abnormality observed in embryos treated with either TCAB or TCAOB. Other malformations included altered feather pattern and lack of down, hemorrhage, external viscera, reduced body size, failure to withdraw the yolk sac, beak malformation, dilation of blood vessels, and monomicropthalmia. The results of this investigation suggest that both TCAB and TCAOB are teratogenic in the chick embryo.

/ALTERNATIVE and IN VITRO TESTS/ 3,3',4,4'-Tetrachloroazobenzene (TCAB) and 3,3',4, 4'-tetrachloroazoxybenzene (TCAOB) are dioxin-like chemicals that were investigated for toxicity. ... As part of the comprehensive toxicological investigation of these chemicals, peripheral blood smears from mice treated 5 days per week for 13 weeks with 0.1-30mg/kg/day TCAB or TCAOB were analyzed for the frequency of micronucleated (MN) normochromatic erythrocytes (NCE). Both chemicals produced significant increases in MN-NCE in male and female mice. In contrast to these positive results in subchronic exposure studies, no significant increases were seen in acute bone marrow MN tests in male mice administered three daily injections of 50-200mg/kg/day TCAB and TCAOB. ...

The rate constant for the vapor-phase reaction of 3,4,3',4'-tetrachloroazobenzene with photochemically-produced hydroxyl radicals has been estimated as 3.2X10-13 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 50 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 3,4,3',4'-Tetrachloroazobenzene contains the azo chromophore that absorbs at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Laboratory irradiation of azobenzene in cyclohexane solution (via mercury vapor lamps, >290 nm) required about 100 hr of irradiation to achieve complete decomposition(3); initial photodecomposition products were identified as phenylazo, phenylazomethylene and aniline radicals(3). 3,4,3',4'-Tetrachloroazobenzene is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2).

Occupational exposure to 3,4,3',4'-tetrachloroazobenzene may occur through dermal contact with this compound at workplaces where 3,4,3',4'-tetrachloroazobenzene is produced or used(SRC). Occupational exposure to 3,3',4,4'-tetrachloroazobenzene has been reported in various manufacturing plants producing 3,4-dichloroaniline or herbicides derived from 3,4-dichloroaniline(1). Monitoring data indicate that human exposure to 3,4,3',4'-tetrachloroazobenzene may occur in rice fields and other locations treated with herbicides containing 3,4,3',4'-tetrachloroazobenzene as an impurity(1,2). Because 3,4-dichloroaniline is used as a precursor to dyes and, to a limited extent, as a heat transfer fluid in addition to its use in the manufacture of herbicides, 3,4,3',4'-tetrachloroazobenzene might be present in products other than herbicides(1).

After intravenous administration, the disappearance of (14C) 3,3',4,4'-Tetrachloroazobenzene (TCAB) from blood was monitored, and the pharmacokinetic profile was consistent with a two-compartment model. Pharmacokinetic parameters reveal that the compound is readily cleared from the blood with a half-life of 4.0 hr, clearance of 12.3 mL/min/kg, and an apparent volume of distribution of 4.3 liters/kg.

The metabolism of 3,3',4,4'-tetrachloroazobenzene (TCAB), an important environmental and occupational toxicant, by rat liver microsomes has been examined in a NADPH-generating system. The metabolic pathways were delineated by the combined use of high pressure liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). The rate of (14C)TCAB metabolism using induced microsomes was found to be 381 +/- 59 pmol/min/mg microsomal protein. Approximately 13% of the radioactivity from the (14C)TCAB substrate was covalently bound to the macromolecular pellet at the end of a 2 hr incubation period. In addition, three distinct TCAB metabolites were isolated from the organic extracts and subsequently identified. Experiments with carbon monoxide, 2-diethylaminoethyl 2,2-diphenylvalerate hydrochloride (SKF 525-A), and control (uninduced) microsomes indicated the participation of the cytochrome P-450-dependent monooxygenases. ...

Following intravenous administration of (14C)3,3',4,4'-Tetrachloroazobenzene (TCAB) (3.2 mg/kg), ... TCAB metabolites in urine were identified using LC/MS. The major metabolites were sulfate ester conjugates of hydroxylated mono- or dichloroaniline derivatives. Some of these metabolites were also acetylated.

3,3',4,4'-Tetrachloroazobenzene (TCAB) is a contaminant generated during the synthesis of 3,4-dichloroaniline and 3,4-dichloroaniline-derived pesticides. TCAB is isosteric to 2,3,7,8-tetrachlorodibenzo-p-dioxin and has been shown to bind to the Ah receptor. Following oral administration of (14C)TCAB (3.2 and 32 mg/kg), 39-45% of the dosed radioactivity was excreted into the urine and 53-56% was recovered in the feces within 48 hr. Less than 6% of the dosed radioactivity remained in the tissues examined at 96 hr. After intravenous administration (3.2 mg/kg), 33% of the dose was excreted in the bile during 6 hr. ... The absolute oral bioavailability was determined to be 30%. The extensive azo reduction of TCAB decreases its systemic absorption after oral administration and thereby limits the amount of parent compound available to interact with the Ah receptor and decreases the Ah receptor-mediated toxicity.