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EC number: 221-717-7 | CAS number: 3209-22-1
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well-documented study publication which meets basic scientific principles.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 994
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- 1,2-dichloro-3-nitrobenzene
- EC Number:
- 221-717-7
- EC Name:
- 1,2-dichloro-3-nitrobenzene
- Cas Number:
- 3209-22-1
- Molecular formula:
- C6H3Cl2NO2
- IUPAC Name:
- 1,2-dichloro-3-nitrobenzene
- Details on test material:
- test substance purity: 99.15%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on oral exposure:
- admnistration period: male 44 days, females from day 14 before mating to day 3 of lactation.
- Duration of treatment / exposure:
- admnistration period: male 44 days, females from day 14 before mating to day 3 of lactation; terminal kill: male day 45; females: day 4 of lactation.
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 1, 5, 100 mg/kg bw
Basis:
- No. of animals per sex per dose:
- five per dose and sex
- Control animals:
- yes, concurrent vehicle
Results and discussion
Results of examinations
- Details on results:
- 1,2-dichloro-3-nitrobenze induced toxic effects in liver and kidney and induced hemolytic anemia in treated rats. Liver and kidney weights were increased and splenic hemosiderosis occured. Hepatocellular swelling and hyaline droplets in the renal convoluted tubular epithelium were observed in males given 25 mg/kg or more. Elevations in urine protein, serum Na, total protein and total cholesterol, and decreases in blood urea nitrogen and body weight gain were noted in males given 100 mg/kg. The females given 25 mg/kg or more exhibited similar pathological changes in the liver, kidney and spleen. The change in the kidney was characterized by vacuolated tubular epithelium.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 5 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects
- Dose descriptor:
- LOAEL
- Effect level:
- 25 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: males and females: decreased body weights, increased liver and kidney weights, hepatocellular swelling, hemosiderosis (males), hyaline droplets in proximal tubular epithelium (males), vacuolated tubular epithelium of the kidney (females)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
The parental males receiving doses of 1 or 5 mg/kg exhibited no effects related to the test substance. In the 25 mg/kg dose group, liver and kidney weights were increased, and splenic hemosiderosis occurred. Histologically, hepatocellular swelling and hyaline droplets in the renal convoluted tubular epithelium were observed. In addition, to these changes, overt regeneration was found in the renal tubules of the 100 mg/kg dose group. Elevations of urine protein, serum sodium, total protein and total cholesterol, and decreases of blood urea nitrogen and body weight gain were found. Hemolytic anemia was revealed in the 100 mg/kg dose group as indicated by decrease of hemoglobin and hematocrit values, and increased reticulocyte counts. Parental females also exhibited pathological changes in the liver, kidney and spleen at doses of 25 mg/kg or more. The change in female kidneys was characterized by vacuolated tubular epithelium. Incidence of athropic thymus was increased in the 100 mg/kg dose group when compared with the control group. There were no notable alterations in general conditions, and no fatalities among any of the dosage groups. Food consumption of the 100 mg/kg males and females was decreased on the first day of the treatment but showed no significant difference from control values thereafter. NOAEL: 5 mg/kg/day.
Table: absolute and relative organ weights of parental male and female rats
Sex | Dose (mg/kg) | 0 | 1 | 5 | 25 | 100 |
Males | Number of animals | 10 | 10 | 10 | 10 | 10 |
Final body weight (g) | 543 ± 43 | 506 ± 15 | 515 ± 24 | 496 ± 28* | 481 ± 31** | |
Liver (g) | 17.76 ± 2.88 | 16.23 ± 1.34 | 17.00± 2.02 | 19.71 ± 2.35 | 21.64 ± 2.27** | |
Liver (g%) | 3.30 ±0.30 | 3.21 ± 0.23 | 3.36 ± 0.27 | 3.96 ± 0.29** | 4.49 ± 0.26** | |
kidneys (g) | 3.54 ± 0.34 | 3.35 ± 0.22 | 3.49 ± 0.26 | 3.75 ± 0.42 | 4.11 ± 0.51** | |
kidneys (g%) | 0.66 ± 0.07 | 0.66 ± 0.05 | 0.69 ± 0.07 | 0.76 ± 0.08* | 0.85 ± 0.10** | |
Thymus (g) | 0.41 ± 0.11 | 0.44 ± 0.07 | 0.37 ± 0.07 | 0.38 ± 0.06 | 0.38 ± 0.10 | |
Thymus (g%) | 0.08±0.02 | 0.09± 0.01 | 0.07±0.01 | 0.08± 0.01 | 0.08±0.02 | |
Testes (g) | 3.28 ± 0.23 | 3.30± 0.17 | 3.40±0.24 | 3.47± 0.29 | 3.39±0.32 | |
Testes (g%) | 0.62±0.07 | 0.65± 0.03 | 0.68±0.06 | 0.70± 0.08* | 0.70±0.05** | |
Epididymides (g) | 1.33±0.09 | 1.35± 0.07 | 1.35±0.07 | 1.35± 0.11 | 1.37±0.12 | |
Epididymides (g%) | 0.25 ±0.03 | 0.27± 0.01 | 0.27±0.02 | 0.27± 0.03 | 0.29±0.03** | |
Females | Number of animals | 8 | 7 | 9 | 8 | 8 |
Final body weight (g) | 348 ± 30 | 355 ± 31 | 360 ± 21 | 354 ± 12 | 342 ±20 | |
Liver (g) | 13.86 ± 0.80 | 15.00± 1.11 | 15.30±0.62 | 17.27± 0.65* | 20.52±2.24** | |
Liver (g%) | 4.00 ± 0.22 | 4.23 ± 0.31 | 4.26 ±0.18 | 4.89± 0.10 | 5.99±0.42** | |
Kidneys (g) | 2.00 ± 0.11 | 2.20± 0.20 | 2.19±0.25 | 2.30± 0.25 | 2.46±0.19** | |
Kidneys (g%) | 0.58 ±0.03 | 0.62±0.04 | 0.61±0.06 | 0.65± 0.06 | 0.72± 0.06** | |
Thymus (g%) | 0.07 ±0.03 | 0.06± 0.02 | 0.08±0.02 | 0.06± 0.01 | 0.04±0.02 | |
Thymus (g) | 0.24±0.12 | 0.20± 0.07 | 0.28±0.09 | 0.20± 0.04 | 0.15±0.05 |
* significantly different from control at 5% level of probability
** significantly different from control at 1% level of probability
Table: Incidence of histopathological findings in parental male rats
Males | Findings | ||||||
Dose | 0 | 1 | 5 | 25 | 100 | ||
Organ | Animals examined | 10 | 10 | 10 | 10 | 10 | |
Liver | Hepatocellular swelling | + | 0 | 0 | 0 | 7 | 7 |
Hepatocellular swelling | ++ | 0 | 0 | 0 | 0 | 3 | |
Total | 0 | 0 | 0 | 7** | 10** | ||
Hepatocellullar fatty change | + | 3 | 1 | 0 | 0 | 0 | |
Focal necrosis | + | 0 | 0 | 0 | 0 | 0 | |
Kidneys | Hyaline droplets in proximal tubular epithelium | + | 0 | 0 | 0 | 4 | 0 |
Hyaline droplets in proximal tubular epithelium | ++ | 0 | 0 | 0 | 3 | 9 | |
Hyaline droplets in proximal tubular epithelium | +++ | 0 | 0 | 0 | 0 | 1 | |
Total | 0 | 0 | 0 | 7** | 10** | ||
Eosinophilic bodies in proximal tubule | + | 3 | 3 | 2 | 2 | 4 | |
Eosinophilic bodies in proximal tubule | ++ | 2 | 1 | 1 | 4 | 1 | |
+++ | 0 | 0 | 0 | 0 | 1 | ||
Total | 5 | 4 | 3 | 6 | 6 | ||
Tubular casts | + | 0 | 0 | 0 | 0 | 2 | |
Tubular atrophy and regeneration | + | 2 | 0 | 0 | 4 | 4 | |
Tubular atrophy and regeneration | ++ | 0 | 0 | 0 | 0 | 3 | |
Tubular atrophy and regeneration | +++ | 0 | 0 | 0 | 0 | 1 | |
Total | 0 | 0 | 0 | 4 | 8** | ||
Fibrotic foci | + | 0 | 0 | 0 | 0 | 0 | |
Tubular mineralization | + | 0 | 0 | 0 | 0 | 0 | |
Spleen | Increased extramedullary hematopoiesis | + | 0 | 0 | 0 | 0 | 2 |
Hemosiderosis | + | 0 | 0 | 0 | 4* | 8** | |
Table: Incidence of histopathological findings in parental female rats
females | Findings | ||||||
Dose | 0 | 1 | 5 | 25 | 100 | ||
Organ | Animals examined | 10 | 10 | 10 | 10 | 10 | |
Liver | Hepatocellular swelling | + | 0 | 0 | 0 | 10 | 0 |
Hepatocellular swelling | ++ | 0 | 0 | 0 | 0 | 10 | |
Total | 0 | 0 | 0 | 10** | 10** | ||
Hepatocellullar fatty change | + | 0 | 0 | 0 | 0 | 0 | |
Focal necrosis | + | 0 | 0 | 0 | 0 | 1 | |
Kidneys | Tubular epithelial vacuolation | + | 0 | 0 | 0 | 1 | 3 |
Tubular epithelial vacuolation | ++ | 0 | 0 | 0 | 1 | 3 | |
Tubular epithelial vacuolation | +++ | 0 | 0 | 0 | 0 | 1 | |
Total | 0 | 0 | 0 | 2 | 7** | ||
Tubular atrophy and regeneration | + | 0 | 0 | 1 | 0 | 1 | |
Tubular atrophy and regeneration | ++ | 0 | 0 | 0 | 0 | 0 | |
Tubular atrophy and regeneration | 0 | 0 | 0 | 0 | 0 | ||
Total | 0 | 0 | 1 | 0 | 1 | ||
Fibrotic foci | + | 0 | 1 | 0 | 0 | 0 | |
Tubular mineralization | + | 1 | 0 | 0 | 0 | 0 | |
Spleen | Hemosiderosis | + | 0 | 0 | 0 | 1 | 5** |
* significantly different from control at 5% level of probability ** significantly different from control at 1% level of probability
* significantly different from control at 5% level of probability
** significantly different from control at 1% level of probability
Applicant's summary and conclusion
- Executive summary:
In a repeated dose and reproductive/developmental toxicity Screening Test (OECD TG 422) 1,2-dichloro-3-nitrobenzene was administered (oral gavage) to male and female Crj:CD (SD) rats. The rats were treated with 0 (vehicle)1, 5, 25 and 100 mg/kg bw/day test substance. The parental males receiving doses of 1 or 5 mg/kg exhibited no effects related to the test substance. In the 25 mg/kg dose group, liver and kidney weights were increased, and splenic hemosiderosis occurred. Histologically, hepatocellular swelling and hyaline droplets in the renal convoluted tubular epithelium were observed. In addition, to these changes, overt regeneration was found in the renal tubules of the 100 mg/kg dose group. Elevations of urine protein, serum sodium, total protein and total cholesterol, and decreases of blood urea nitrogen and body weight gain were found. Hemolytic anemia was revealed in the 100 mg/kg dose group as indicated by decrease of hemoglobin and hematocrit values, and increased reticulocyte counts. Parental females also exhibited pathological changes in the liver, kidney and spleen at doses of 25 mg/kg or more. The change in female kidneys was characterized by vacuolated tubular epithelium. Incidence of atrophic thymus was increased in the 100 mg/kg dose group when compared with the control group. There were no notable alterations in general conditions, and no fatalities among any of the dosage groups. Food consumption of the 100 mg/kg males and females was decreased on the first day of the treatment but showed no significant difference from control values thereafter.
Based on these findings the authors suggested a NOAEL of 5 mg/kg bw/day (Ministry of Health and Welfare Japan 1994).
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