1,2-Dichlor-4-nitrobenzol

log Kow = 3.12

3.12

1.4558 at 167 °F (NTP, 1992) - Denser than water; will sink

1.4558 at 75 °C/4 °C

Density (at 15 °C): 1.56 g/cm³

Needles from alcohol

SOLID

less than 0.1 mg/mL at 74.3 °F (NTP, 1992)

Soluble in ether, alcohol; slightly soluble in carbon tetrachloride

In water, 121 mg/L at 20 °C

Solubility in water: none

255 °F (NTP, 1992)

124 °C

124 °C

491 to 493 °F at 760 mmHg (NTP, 1992)

255-256 °C

255 °C

109 °F (NTP, 1992)

43 °C

Has both a stable and labile form. The stable alpha-form has a melting point of 42-43 °C and beta-form is a liquid which changes to the alpha-form at 15 °C

39-41 °C

6.63 (NTP, 1992) - Heavier than air; will sink (Relative to Air)

6.63

Relative vapor density (air = 1): 6.6

0.01 [mmHg]

1.03X10-2 mm Hg at 25 °C

Vapor pressure, Pa at 25 °C: 2

Warning

H302 (97.9%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P272, P273, P280, P301+P317, P302+P352, P305+P351+P338, P321, P330, P333+P317, P337+P317, P362+P364, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 47 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

Chemical: Benzene, 1,2-dichloro-4-nitro-

TP - indicates a substance that is the subject of a proposed TSCA section 4 test rule.

Status: Active Update: 20-12-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/12146

1,2-Dichloro-4-nitrobenzene: Does not have an individual approval but may be used under an appropriate group standard

This chemical is combustible. (NTP, 1992)

Combustible. Gives off irritating or toxic fumes (or gases) in a fire. Finely dispersed particles form explosive mixtures in air.

A skin and eye irritant; May cause effects on the blood; [ICSC] May cause liver damage; [CAMEO] Causes methemoglobinemia in high-dose animals experiments; Methemoglobinemia also reported in exposed workers; Dermal LD50 (rats) >2000 mg/kg; Oral LDLo (rabbits) = 950 mg/kg; [HSDB] An eye irritant; Can be absorbed through skin; May cause skin sensitization; May induce methemoglobinemia; Effects in high-dose animal studies include cyanosis; [MSDSonline] No evidence of skin sensitization; [INCHEM: SIDS] Danger of cutaneous absorption; Could be carcinogenic for man but not conclusive because of insufficient data; [MAK]

Organisation for Economic Cooperation and Development; Screening Information Data Set for 1,2-Dichloro-4-nitrobenzene, CAS # 99-54-7 (2003). A compliation of the chemical properties, toxicity and pharmacokinetics of 1,2-dichloro-4-nitrobenzene used for the initial assesment of the test compound. Includes an IUCLID dataset updated in 2004 as an appendix.

European Chemicals Bureau; IUCLID Dataset, 1,2-Dichloro-4-Nitrobenzene (CAS # 99-54-7) (2000 CD-ROM edition). Available from the Database Query page at: http://ecb.jrc.it/esis/esis.php as of July 5, 2007. A report on the ecotoxicity, toxicity, and pharmacokinetics of 1,2-dichlor-4-nitrobenzene.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 3,4-Dichloronitrobenzene is included on this list.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329.

Fires involving this compound can be controlled using a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Use powder, water spray, foam, carbon dioxide.

Fresh air, rest.

Rinse and then wash skin with water and soap.

Rinse with plenty of water (remove contact lenses if easily possible).

Rinse mouth.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure 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, aquatic, and plant life; and conformance with environmental and public health regulations.

The following wastewater treatment technologies have been investigated for nitrobenzene: Activated carbon and stripping. /Nitrobenzene/

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into sealable containers. If appropriate, moisten first to prevent dusting. Do NOT let this chemical enter the environment.

LC50 Leuciscus idus /(Ide)/ 3.1 mg/L for 48 hr /Conditions of bioassay not specified in source examined/

LC50 Leuciscus idus /(Ide)/ 5.6 mg/L for 96 hr /Conditions of bioassay not specified in source examined/

LC50 Leusiscus Idus melanotus /golden orfe/ 5.2 mg/L for 96 hr /Static bioassay/

LC50 Oryzias latipes /Japanese medaka/ 7 mg/L for 48 hr/ Static bioassay

TERRESTRIAL FATE: Based on a classification scheme(1), measured Koc values of 390 to 393(2,3), indicate that 3,4-dichloronitrobenzene is expected to have moderate mobility in soil(SRC). Volatilization of 3,4-dichloronitrobenzene from moist soil surfaces is expected to be an important fate process(SRC) given a Henry's Law constant of 8.07X10-6 atm-cu m/mole(4). 3,4-Dichloronitrobenzene is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.03X10-2 mm Hg(5). Lack of biodegradation of 3,4-dichloronitrobenzene incubated in an aquifer slurry over an unspecified time frame(6) suggests that biodegradation is not an important environmental fate process in soil(SRC). However, under anaerobic conditions using a river sediment, a half-life of 2.4 days has been reported(7).

AQUATIC FATE: Based on a classification scheme(1), measured Koc values of 390 to 393 in silt loams(2,3), indicate that 3,4-dichloronitrobenzene is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon a Henry's Law constant of 8.07X10-6 atm-cu m/mole(5). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 6 days and 51 days, respectively(SRC). According to a classification scheme(6), a BCF values ranging from 104 to 130(7,8) suggest the potential for bioconcentration in aquatic organisms is high(SRC). Lack of biodegradation of 3,4-dichloronitrobenzene incubated in an aquifer slurry over an unspecified time frame(9) suggests that biodegradation is not an important environmental fate process in water(SRC). However, under anaerobic conditions using a river sediment, a half-life of 2.4 days has been reported(10).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3,4-dichloronitrobenzene, which has a /an estimated vapor pressure of 1.03X10-2 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 3,4-dichloronitrobenzene 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 321 days(SRC), calculated from its rate constant of 5.0X10-14 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). 3,4-Dichloronitrobenzene contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

Human Health: 1,2-Dichloro-4-nitrobenzene is absorbed from the gastro-intestinal tract and although there are some species differences in experimental animals from the available data it can be concluded that 1,2-dichloro-4-nitrobenzene is excreted mainly via urine in the form of the mercapturic acid derivative N-acetyl-S-(2-chloro-4-nitrophenyl)-Lcysteine. ... Based on the results of the acute dermal toxicity study with rats the LD50 is > 2000 mg/kg bw. From studies with rabbits no LD50 could be derived, the lowest Lethal Dose Level (LDLo) was 950 mg/kg bw. The acute oral toxicity in rats ranges from 625 to 950 mg/kg bw. 1,2-Dichloro-4- nitrobenzene causes the formation of methemoglobin. ... 1,2-Dichloro-4-nitrobenzene gave no skin irritation effects when tested for 4 hours under semiocclusive conditions ... and showed slightly irritating effects, which disappeared within 72 hours under occlusive conditions ... 1,2-Dichloro-4-nitrobenzene is slightly irritating to the eyes /but/ ... was not found to induce dermal sensitization ... . In addition, 1,2-dichloro-4-nitrobenzene was not found to induce dermal sensitization in humans in a limited study. The main targets identified in animal studies after repeated oral administration as well as after inhalation exposure are the hematological system and in addition the kidneys after oral application and the liver after inhalation. From a 28- day oral study ... a NOAEL of 4 mg/kg bw/day was derived. The NOAEL following subchronic inhalation exposure study of limited validity (limited documentation) was 0.4 mg/cu m (4 hours per day). Changes in hematological parameters (e.g. methemoglobinaemia, Heinz bodies) are the main target in the only available report on exposure of workers. As these findings relate to mixed exposures they cannot be clearly attributed to 1,2-dichloro-4-nitrobenzene, but would be plausible, because they were also observed in animal experiments. In the recent open literature reports of human poisoning could not be identified. 1,2-Dichloro-4-nitrobenzene exhibits mutagenic activity in Salmonella typhimurium but not in the HPRT test in Chinese Hamster Ovary (CHO) cells. 1,2-Dichloro-4-nitrobenzene induced chromosomal aberrations in V79 cells with metabolic activation only at the highest concentration, which was cytotoxic. In insects (Drosophila melanogaster) 1,2-dichloro-4-nitrobenzene revealed no mutagenic activity in the SLRL-test after application over 3 days with slight increased toxicity, but revealed mutagenic activity following a single ip injection of a clearly toxic dose. 1,2-Dichloro-4-nitrobenzene showed no clastogenic activity in vivo in a chromosomal aberrations test with rats. Overall in non-toxic doses, there was no evidence for genotoxicity in vivo under the conditions tested. Studies dealing specifically with toxicity to reproduction were not identified. The subacute study with 1,2-dichloro-4- nitrobenzene yielded no damage of the reproductive organs in rats despite clear systemic toxicity up to the maximum tolerated dose of 100 mg/kg bw. 1,2-Dichloro-4-nitrobenzene commercial grade (85% 1,2-dichloro-4-nitrobenzene and 15% 1,2-dichloro-3- nitrobenzene) caused effects on development at maternally toxic doses probably due to methemoglobinemia in dams and fetuses. A significant dose-response trend for variations (dilated ureters) was seen in the fetuses of the >= 30 mg/kg bw/day-groups and significant reduced body weight gain of dams at dose levels of 30 mg/kg bw/day on gd 6-10 with an even stronger effect at 100 mg/kg bw/day. Thus, 10 mg/kg bw/day was determined as the NOAEL for maternal and developmental toxicity. Environment: ... Concerning the acute toxicity of 1.2-dichloro-4-nitrobenzene towards aquatic species reliable experimental results of tests with fish, Daphnia, and algae are available. The acute toxicity determined for fish (Leuciscus idus) was of 3.1 mg/L (48 hr LC50) ... and Daphnia (Daphnia magna) of 3 mg/L (24 hr-EC50) ... . In the growth inhibition test with algae (Scenedesmus obliquus) the value 5.8 mg/L was achieved after 48 hr (48 hr-ErC50)... . For the algae Chlorella fusca a value of 0.32 mg/L was found after 24 hr (24 hr-ErC50). In a chronic (21 d) study with Daphnia magna a NOEC of 0.025 mg/L was determined for the most sensitive endpoint reproduction rate. An ErC10 > 0.1 mg/L was reported for the algae Scenedesmus subspicatus after 48 hours. For terrestrial organisms the lowest measured 6d-EC50 was 27 mg/L for the plant Phaseolus aureus. Applying an assessment factor of 50 to the lowest available chronic value of 25 ug/L (21d reproduction in D. magna), a PNECaqua of 0.5 ug/lL is obtained.

/AQUATIC SPECIES/ In a reproduction (21 d) study with Daphnia magna performed in a semistatic system in closed vessels /the authors/ found a NOEC of 0.025 mg/L for the most sensitive endpoint reproduction rate. The stability of the test substance concentration was confirmed by analytical monitoring.

Cough.

Redness.

An experimentally determined mean Koc value of 393 for 3,4-dichloronitrobenzene was reported using 4 silt loam soils(1). A log Koc value of 2.62 was reported following adsorption studies using sediment from the Yangste River in China(2), corresponding to a Koc of 390(SRC). According to a classification scheme(3), these Koc values suggest that 3,4-dichloronitrobenzene is expected to have moderate mobility in soil. Using a modified organo montmorillonite clay from Jiangning Jinagsu Province, China, a log Koc of 3.76 was determined(3), corresponding to a Koc of 5,754(SRC).

3,4-Dichloronitrobenzene (CAS# 99-54-7) was evaluated for acute oral toxicity. The test substance was administered orally to 10 rats (sex and species not specified) at a dose range of 200-3200 mg/kg body weight. Signs of toxicity included weakness (moderate to very weak), labored respiration, cyanosis, dark eyes, and prostration. Time of death was between 45 minutes and 2 days. The approximate LD50 was determined to be between 1600 and 3200 mg/kg b.w. The test substance was determined to be slightly toxic.

3,4-Dichloronitrobenzene (CAS# 99-54-7) was evaluated for acute intraperitoneal toxicity. The test substance was administered intraperitoneally to 10 rats (sex and species not specified) at a dose range of 200-3200 mg/kg body weight. Signs of toxicity included weakness (moderate to very weak), labored respiration, cyanosis, dark eyes, and prostration. Time of death was between 2 hours and 1 day. The approximate LD50 was determined to be between 400 mg/kg b.w. The test substance was determined to be moderately toxic.

3,4-Dichloronitrobenzene (CAS# 99-54-7) was evaluated for acute oral toxicity. The test substance was administered orally to 10 mice (sex and species not specified) at a dose range of 200-3200 mg/kg body weight. Clinical signs included weakness (normal to very weak), decreased activity, slow respiration, cyanosis, dark eyes, slight tremor, prostration, and yellow-orange urine. Time of death was 1 day. The approximate LD50 was determined to be between 800-1600 mg/kg b.w. The test substance was determined to be slightly toxic.

3,4-Dichloronitrobenzene (CAS# 99-54-7) was evaluated for acute intraperitoneal toxicity. The test substance was administered intraperitoneally to 10 mice (sex and species not specified) at a dose range of 200-3200 mg/kg body weight. Clinical signs included weakness (normal to very weak), decreased activity, slow respiration, cyanosis, dark eyes, slight tremor, prostration, and yellow-orange urine. Time of death was between 4-1/2 hours and 1 day. The approximate LD50 was determined to be between 400-800 mg/kg b.w. The test substance was determined to be moderately toxic.

For more TSCA Test Submissions (Complete) data for 3,4-DICHLORONITROBENZENE (14 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ In a study with 10 female subjects the single dermal application of a 10 % solution of 1,2-dichloro- 4-nitrobenzene in acetone followed by a challenge with a 10 or 0.01 - 1 % solution in acetone on day 28 and 49 caused no skin sensitization.

/BIOMONITORING/ 3,4-Dichloronitrobenzene, like other nitro and amino aromatics, is responsible for methemoglobin formation in humans. Levels of 10 mg/L of 3,4-dichloronitrobenzene metabolites in human urine may be considered to be warning levels of overexposure.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 3,4-Dichloronitrobenzene is included on this list.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329.

YIELDS S-(2-CHLORO-4-NITROPHENYL)GLUTATHIONE IN RAT & RABBIT; YIELDS 3,4-DICHLOROANILINE IN RABBIT. /FROM TABLE/

FOLLOWING ORAL ADMINISTRATION OF 3,4-DICHLORONITROBENZENE TO PIGEONS, ANALYSIS OF EXCREMENT SHOWED THAT DCNB IS MAINLY METABOLIZED BY REDUCTION OF THE NITRO GROUP WITH VERY LITTLE FORMATION OF MERCAPTURIC ACID.

WHEN THE DRUG METABOLIZING POTENTIALS OF LUNG AND LIVER WERE COMPARED OF 4 TRANSFERASE, THE ACTIVITIES IN THE LUNG WERE GENERALLY LESS THAN THE ACTIVITIES IN THE LIVER. THE ACTIVITY OF GLUTATHIONE S-ARYLTRANSFERASE TOWARD 1,2-DICHLORO-4-NITROBENZENE IN THE LUNG WAS APPROXIMATELY 20% THAT IN THE LIVER.

Observed that rat liver contains an enzyme that catalyzes the conjugation of glutathione and 3,4-dichloronitrobenzene with loss of the nitro group.

Female rats were dosed by oral intubation with 3,4-dichloronitrobenzene at 500 mg/kg. Six hr after dosing, liver glutathione had decreased to 56% of controls. Blood glutathione although increased by 18%, was not considered to be significantly changed. The effect on liver glutathione was related to formation of mercapturic acid during metabolism.

In rats about 19 % (range 4 - 29 %) of the applied dose (approx. 350 mg/kg bw via gavage) was excreted as mercapturic acid via urine within 24 hrs. In a second trial the animals were dosed with approximately 250 or 350 mg/kg bw and the maximum rate for excretion of mercapturic acid via urine 2 - 6 days after dosing was given with approx 2 or 4 mg/kg bw/hr, resp.

In rabbits dosed orally with 400 mg/kg bw via gavage most of the applied dose was excreted via urine within 72 hrs as mercapturic acid derivative N-acetyl-S-(2-chloro-4-nitrophenyl)-L-cysteine (approx. 45 %) followed by conjugates of amino dichlorophenols (approx 13 % as glucuronide and approx. 12 % as sulfate ester)and 3,4-dichloroaniline (approx. 22 %).

Used to make herbicides, insecticides, and dyes; [HSDB]

CHEM INTERMEDIATE FOR HERBICIDES (EG, PROPANIL) AND INSECTICIDES & DYE INTERMEDIATES

Iron reduction of 1,2-dichloro-4-nitrobenzene yields 3,4-dichloroaniline, an important agrochemical intermediate. Amination produces 2-chloro-4-nitroaniline, which is an important diazo component and intermediate.

(1977) 1.19X10+6 GRAMS (PRINCPL CUSTMS DISTS)

(1978) 2.05X10+7 GRAMS (PRINCPL CUSTMS DISTS)

(1977) PROBABLY GREATER THAN 4.54X10+6 GRAMS

(1979) PROBABLY GREATER THAN 2.27X10+6 GRAMS

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#4889]

This chemical is listed as a High Production Volume (HPV) (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Nitration of 1,2-dichlorobenzene with mixed acid at 35 - 60 °C results in a mixture of 3-nitro (10 %) and 4-nitro (90 %) isomers, which are separated by crystallization. A more expensive process (two stages from chlorobenzene) is based on chlorination of molten 4-chloronitrobenzene (90 - 100 °C) by a process similar to that used for 3-chloronitrobenzene production. Chlorination has the advantage of giving a pure product, but it cannot be used if the isomeric 1,2-dichloro-3-nitrobenzene is also required.

CHLORINATION OF P-NITROCHLOROBENZENE; NITRATION OF O-DICHLOROBENZENE