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EC number: 202-764-2 | CAS number: 99-54-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
In a study according to OECD Guideline 407 male and female Sprague-Dawley rats received 0, 4, 20, 100 mg/kg bw/d dissolved in sesame oil by gavage for 28 days. The NOAEL was 4 mg/kg bw/d based on changes in red blood cell parameters, on hemolytic anemia with microscopic changes in the spleen and increase in relative liver weights in the next higher dose and increase in relative spleen weight at 100 mg/kg bw/d (Hoechst AG 1993).
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study, GLP
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: approximately 6 week
- Housing: in groups of 5 animals
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- other: sesame oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
the test compound was suspended homogenousely in the vehicle by means of a magnetic stirrer
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 0 - 2 % (w/v)
- Amount of vehicle (if gavage): 5 ml/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- the determination of the concentration was performed by photometrical detection after HPLC seperation on a reversed phase column
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- once per day
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 4 mg/kg bw/day (nominal)
- Dose / conc.:
- 20 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5 animals/sex/dose group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on preliminary dose range finding study
- Positive control:
- not relevant
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: at the start of the study and then twice weekly throughout the study
FOOD CONSUMPTION
twice weekly
WATER CONSUMPTION
once weekly
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: weekly
HAEMATOLOGY: Yes
At the termination of the study, hematological examinations were performed on all animals without previous withdrawl of food. Blood samples were taken from the retrobarbital venous plexus in narcosis. In order to prevent systematic errors, blood sampling was conducted in a randomized order.
hematological parameters:
erythrocytes, hemoglobin, hematocritm mean cellular volumd (MCV), Mean cellular hemoglobin (MCH), Mean cellular hemoglobin concentration(MCHC), Leucocyte count, thrombocyte count, differential leucocyte count, and red cell morphology, reticulocyte count, Heinz bodies, coagulation time
CLINICAL CHEMISTRY: Yes
After blood sampling for hematology the animals were killed by cutting of the vena cava cranialis in deep narcosis and exanguinated. In order to prevent systematic errors, exanguination was conducted in a randomized order.
Parameters:
sodium, potassium, inorganic phosphorus, uric acid, bilirubin total, creatinene, serum-glucose, urea-nitrogen, calcium, chloride, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, total protein, albumin
URINALYSIS: Yes
urinalysis was performed on all animals a few days before termination of the study. for this purpose, the urine was collected by using metabolism cages (Overnight from day 26 to day 27)
Parameters:
appearance, colour, pH-value, hemoglobin, protein, glucose, ketone bodies, bilirubin, urobilinogen, specific weight, sediment, volume
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: weekly
- Sacrifice and pathology:
GROSS PATHOLOGY: Yes
After exanguination all animals were necropsied and checked for macroscopically visible abnormalities. The autopsy included macroscopic examination of the skin, orifices, eyes, teeth, oral mucosa and internal organs.
organ weights (calculation of organ to body weight ratio): heart, lung, liver, kidneys, spleen, ovaries, testes, epididymides, adrenals, brain, thymus
HISTOPATHOLOGY: Yes
Heart, liver, kidneys, adrenals, spleen, lung, brain, thymus, ovaries, testes, epididymides, trachea, stomach, jejunum, colon, urinary bladder, uterus, prostata, seminal vesicles, skeletal muscles, N. ischiadicus, femur with bone marrow, spinal cord (cervical, thoracal and lumbal), lymph nodes (dervical, and iliacal)- Other examinations:
- no further data
- Statistics:
- ---One way analyses of variance with sequentially rejective multiple comparison
---One way analyses of variance based on ranks with equentially rejective multiple comparison
---Trend Test analyses for non-neoplastic lesions (ARMITAGE) - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 100 mg-group, m/f: irregular respiration, stilted gain
>= 20 mg/kg bw/day, m/f: increased salivation - Mortality:
- mortality observed, treatment-related
- Description (incidence):
- No death occurred throughout the study
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- all groups: body weight gain was not impaired
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- food consumption unaffected
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- >=20 mg/kg bw/day(m/f): slightly increased water intake (not significant, not dose dependent)
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 4 mg/kg bw/day:
male: significant decrease in erythrocyte counts (6.98 10E12/l versus 7.63 10E12/L [historical control: 6.34-8.95 10E/L])
20 mg/kg bw/day:
male: significant decrease in erythrocyte counts (6.87 10E12/L versus 7.63 10E12/L of concurrent control) and haematocrit (0.42 UNITY versus 0.46 UNITY of control)
female: significant increase in MCV (62 10E-15L versus 58 10E-15L)
100 mg/kg bw/day:
male: decrease in erythrocyte values (6.34 10E12/L versus 7.63 10E12/L of control), decrease in haematocrit (0.42/0.39 UNITY versus 0.46/0.41 UNITY of control), decrease in haemoglobin (140/131 g/L versus 149/138 g/L of control), increase in MCV values 67/66 10E-15L versus 60/58 10E-15L of control), reticulocyte counts (0.077/0.080 UNITY versus 0.011/0.008 UNITY of control) - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- male: significant increase in sodium- and chlorid-ions when compared to concurrent control, which were, however, within the historical control values of this strain:
control//4/20/100 mg/kg bw/day//historical control range:
Sodium: 135//139/142//142//132-149 mmol/L, Chlorid: 98// 101/102/102//95-106 mmol/L
20 mg/kg bw:
increase in alk. phosphatase (f: 261 U/L versus 175 U/L of control)
100 mg/kg bw/day:
increase in urea values (m/f: 8.44/8.17 mmol/L versus 5.62/6.80 mmol/L of control) )m [indicative for an impaired kidney function; however, no histopathological correlates were found]
increase in ALAT(GPT) (m: 54 U/L versus 44 U/L), increase in alk. phosphatase (f: 267 U/L versus 175 U/L of control) - Endocrine findings:
- not examined
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- dark yellow discolouration of urine: male: from 20 mg/kg bw/day onwards; female: at 100 mg/kg bw/day;
pH-Value: female: at 100 mg-group significantly decreased: pH=5.4 versus pH=6.1 (control) - Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- absolut organ weights not affected, rel. organ weights:
20 mg/kg bw
increased relative liver weight (m: 4.545 % versus 4.036 % of control)
100 mg/kg bw/day
increase in rel. liver weight (m/f: 4.571/4815 % versus 4.036/3.926 % of control)
increased rel. spleen weight (m/f: 0.321/0.330 % versus 0.189/0.234 % of control) - Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 100 mg/kg bw, spleen: 5/5 m and 5/5 f dark discoloration spleen
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- m(grading)-f(grading), low, mid, high dose versus control:
congestion
low: 0/5(0) - 0/5(0), mid: 3/5(slight) - 5/5(slight), high: 5/5(moderate) - 5/5(moderate) versus contr.: 0/5 - 0/5
increased extramedullary haematopoiesis:
low: 2/5(minimal) - 2/5(minimal), mid: 5/5(minimal) - 5/5(slight), high: 5/5(slight) - 5/5(slight) versus contr.: 3/5(minimal) - 0/5
increase in haemosiderosis:
low: 0/5 - 5/5(slight), mid: 5/5(minimal) - 5/5(marked), high: 5/5(moderate) -5/5(marked) versus contr.: 0/5 - 5/5(mild) - Histopathological findings: neoplastic:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 4 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: based on changes in red blood cell parameters, on hemolytic anemia with microscopic changes in the spleen and increase in relative liver weights in the next higher dose and increase in relative spleen weight at 100 mg/kg bw/d
- Critical effects observed:
- not specified
- Conclusions:
- The NOAEL was 4 mg/kg bw/d based on changes in red blood cell parameters, on hemolytic anemia with microscopic changes in the spleen.
- Executive summary:
In a study according to OECD Guideline 407 male and female Sprague-Dawley rats received 0, 4, 20, 100 mg/kg bw/d dissolved in sesame oil by gavage for 28 days. The NOAEL was 4 mg/kg bw/d based on changes in red blood cell parameters, on hemolytic anemia with microscopic changes in the spleen and increase in relative liver weights in the next higher dose and increase in relative spleen weight at 100 mg/kg bw/d (Hoechst AG 1993).
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 4 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
1,2-Dichloro-4-nitrobenzene shall be registrated according to Regulation (EC) 1907/2008 (REACH) Article 18 (transported isolated intermediate) and no studies are required according to REACH Annex VII.
Justification for classification or non-classification
1,2-Dichloro-4-nitrobenzene shall be registrated according to Regulation (EC) 1907/2008 (REACH) Article 18 (transported isolated intermediate, > 1000 tpa) and no studies are required according to REACH Annex VII.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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