Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 212-298-1 | CAS number: 778-94-9
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: HJ/T 154-2004, 408 Sub-Chronic (90-Day) Oral Toxicity Test in Rodents
- Version / remarks:
- Second edition, 2013
- GLP compliance:
- yes
- Remarks:
- The test complied with the Principles of Good Laboratory Practices (GLP) of the Certification and Accreditation Administration of the People’s Republic of China (2013 revised edition).
- Limit test:
- no
Test material
- Reference substance name:
- 2-nitro-4-(trifluoromethyl)benzonitrile
- EC Number:
- 212-298-1
- EC Name:
- 2-nitro-4-(trifluoromethyl)benzonitrile
- Cas Number:
- 778-94-9
- Molecular formula:
- C8H3F3N2O2
- IUPAC Name:
- 2-nitro-4-(trifluoromethyl)benzonitrile
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- SPF grade
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 10 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 27 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 70 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- control and high-dose groups: 16 (additional 6 animals each for recovery group examinations)
low- and mid-dose groups: 10 - Control animals:
- yes, concurrent vehicle
- Positive control:
- no
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In the exposure period at days 3, 24, 31, 38, 45, 52, 59, 66, 73, 80, and 87, mean body weights for male rats in the high-dose group were reduced compared to the control group and presented a significant or extremely significant statistical difference (P ≤ 0.05, P ≤ 0.01, P ≤ 0.001). In the exposure period at day 80, mean body weight for male rats in the medium-dose group was reduced compared to the control group and the difference was significant (P ≤ 0.05). In the exposure period at days 3, 24, 31, and 66, weight gain for male rats in the high-dose group was reduced compared to the control group, and presented an extremely significant or significant statistical difference (P ≤ 0.001, P ≤ 0.01). In the exposure period at day 3, weight gain for male rats in the medium-dose group was reduced compared to the control group, and the difference was extremely significant (P ≤ 0.001). In the exposure period at day 45, weight gain for female rats in the high-dose group was elevated compared to the control group, and the difference was significant (P ≤ 0.05, P ≤ 0.01).
In the exposure period and the recovery period, for the remaining male and female animals in all dose groups, body weights and weight gain in all weeks did not present statistical differences compared to the control group.
The above changes did not present an obvious dose-response relationship and it can be concluded that they were not toxicologically significant. - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- In the exposure period at days 3, 45, 59, 73, 80, and 87, mean change in food intake for male rats in the high-dose group was lower than in the control group and presented an extremely significant or significant statistical difference (P ≤ 0.001, P ≤ 0.01, P ≤ 0.05). In the exposure period at days 45, 59, 66, 73, 80, and 87 mean change in food intake for male rats in the medium-dose group was lower than in the control group and presented an extremely significant or significant statistical difference (P ≤ 0.001, P ≤ 0.01, P ≤ 0.05). In the exposure period at days 59 and 87 mean change in food intake for male rats in the low-dose group was lower than in the control group and presented a significant or extremely significant statistical difference (P ≤ 0.01, P ≤ 0.001). In the exposure period at days 3, 45, and 73, mean change in food intake for female rats in the high-dose group was lower than in the control group and the difference was significant (P ≤ 0.05). In the exposure period at day 10 mean change in food intake for female rats in the high-dose group was higher than in the control group and the difference was extremely significant (P ≤ 0.001). In the exposure period at days 10 and 66, mean change in food intake for female rats in the medium-dose group was higher than in the control group and the difference was significant (P ≤ 0.01, P ≤ 0.05). In the exposure period at days 10, 17, and 66 mean change in food intake for female rats in the low-dose group was higher than in the control group and the difference was significant (P ≤ 0.05, P ≤ 0.01).
In the exposure period and the recovery period, food intake quantities for male and female animals of all other dose groups did not present a statistical difference compared to the control group.
The above changes did not present an obvious dose-response relationship and it can be concluded that they were not toxicologically significant. - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At the end of the exposure period, haemoglobin concentration, total white blood cells, and lymphocytes in male rats in the high-dose group were reduced compared to the control group and the differences were significant (P ≤ 0.01, P ≤ 0.05). At the end of the exposure period, haemoglobin concentration in male rats in the medium-dose group was reduced compared to the control group, and the difference was significant (P ≤ 0.01). At the end of the exposure period total red blood cells, haemoglobin concentration, and haematocrit in female rats in the high-dose group were reduced compared to the control group and the difference was significant (P ≤ 0.05).
At the end of the recovery period, total red blood cells in male rats in the high-dose group were reduced compared to the control group and the difference was significant (P ≤ 0.05). At the end of the recovery period, mean corpuscular volume and mean corpuscular haemoglobin in male rats in the high-dose group were elevated compared to the control group, and the differences were significant (P ≤ 0.01, P ≤ 0.05). At the end of the exposure period, prothrombin time in female rats in the high-dose group and the low-dose group were reduced compared to the control group and the differences were significant (P ≤ 0.01, P ≤ 0.05). There was no obvious clinical significance.
At the end of the recovery period, prothrombin time in male rats in the high-dose group was elevated compared to the control group, and the difference was significant (P ≤ 0.05).
The above changes exhibited no obvious dose-response relationship and it can be concluded that they were not toxicologically significant. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At the end of the exposure period, creatinine in male rats in the high-dose group was reduced compared to the control group and the difference was significant (P ≤ 0.05). At the end of the exposure period, albumin in male rats in the high-dose group was elevated compared to the control group and the difference was significant (P ≤ 0.05). At the end of the exposure period, total protein and globulin in female rats in the high-dose group were elevated compared to the control group, and the differences were significant (P ≤ 0.05, P ≤ 0.01). At the end of the exposure period total protein and globulin in female rats in the medium-dose group were elevated compared to the control group, and the difference was significant (P ≤ 0.05). At the end of the exposure period urea in female rats in the low-dose group was reduced compared to the control group, and the difference was significant (P ≤ 0.05). At the end of the recovery period, urea and creatinine in male rats in the high-dose group were reduced compared to the control group, and the differences were significant (P ≤ 0.01, P ≤ 0.05). At the end of the recovery period, potassium in male rats in the high-dose group was elevated compared to the control group, and the difference was significant (P ≤ 0.05).
The above changes exhibited no obvious dose-response relationship and it can be concluded that they were not toxicologically significant. - Endocrine findings:
- not examined
- Urinalysis findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At the end of the exposure period and the recovery period, pH in female rats in the high-dose group was elevated compared to the control group, and the difference was significant (P ≤ 0.05).
Other test results at the end of the exposure period and the end of the recovery period did not present statistical differences compared to the control group.
The above changes did not present an obvious dose-response relationship and it can be concluded that they were not toxicologically significant. - Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- At the end of the exposure period, in male rats in the high-dose group absolute body weight was reduced compared to the control group, and the difference was extremely significant (P ≤ 0.001). At the end of the exposure period, in male rats in the high-dose group the liver weight was elevated compared to the control group, and the difference was significant (P ≤ 0.05). At the end of the exposure period, in male rats in the low-, medium-, and high-dose groups the thymus gland was reduced compared to the control group, which presented extremely significant or significant statistical differences (P ≤ 0.001, P ≤ 0.05). At the end of the exposure period, in male rats in the medium- and high-dose groups, liver-body ratios were elevated compared to the control group, and the difference was extremely significant (P ≤ 0.001). At the end of the exposure period, in male rats in the high-dose group heart- and kidney-body ratios were elevated compared to the control group, which presented significant or extremely significant statistical differences (P ≤ 0.05, P ≤ 0.001). At the end of the exposure period, in male rats in the low- and high-dose groups, thymus-body ratios were reduced compared to the control group, which presented extremely significant or significant statistical differences (P ≤ 0.001, P ≤ 0.01). At the end of the exposure period, in male rats in the high-dose group, the liver-brain ratio was elevated compared to the control group and the difference was extremely significant (P ≤ 0.001). At the end of the exposure period, in male rats in the low- and high-dose groups, thymus-brain ratios were reduced compared to the control group and the difference was extremely significant (P ≤ 0.001).
At the end of the exposure period, in female rats in the medium- and high-dose groups, the liver weight was elevated compared to the control group, and the difference was extremely significant (P ≤ 0.001). At the end of the exposure period, in female rats in the low-dose group, the ovaries were reduced compared to the control group and the difference was significant (P ≤ 0.01). At the end of the exposure period, in female rats in the medium- and high-dose groups, the liver-body ratios were elevated compared to the control group, presenting significant or extremely significant statistical differences (P ≤ 0.05, P ≤ 0.001). At the end of the exposure period, in female rats in the low-dose group, the ovary-body ratio was reduced compared to the control group, the difference was significant (P ≤ 0.01). At the end of the exposure period, in female rats in the medium- and high-dose groups, liver-brain ratios were elevated compared to the control group and the difference was extremely significant (P ≤ 0.001). At the end of the exposure period, in female rats in the low-dose group, the ovary-brain ratio was reduced compared to the control group, and the difference was extremely significant (P ≤ 0.001).
At the end of the recovery period, in male rats in the high-dose group, the heart was elevated compared to the control group, and the difference was significant (P ≤ 0.05). At the end of the recovery period, in male rats in the high-dose group, the thymus and adrenal glands were reduced compared to the control group, and the difference was significant (P ≤ 0.05). At the end of the recovery period, in male rats in the high-dose group, the heart-body and kidney-body ratios were elevated compared to the control group, and the difference was significant (P ≤ 0.05). At the end of the recovery period, in male rats in the high-dose group, the thymus-body ratio was reduced compared to the control group, and the difference was significant (P ≤ 0.05). At the end of the recovery period, in male rats in the high-dose group, the heart-brain ratio was elevated compared to the control group, and the difference was significant (P ≤ 0.05). At the end of the recovery period, in male rats in the high-dose group, the thymus-brain ratio was reduced compared to the control group, and the difference was significant (P ≤ 0.01).
At the end of the recovery period, in female rats in the high-dose group, the brain and the ovaries were reduced compared to the control group, and the difference was significant (P ≤ 0.05). At the end of the recovery period, in female rats in the high-dose group, the brain-body and the ovary-body ratios were reduced compared to the control group, and the differences were significant (P ≤ 0.05, P ≤ 0.01). At the end of the recovery period, in female rats in the high-dose group, the ovary-brain ratio was reduced compared to the control group, and the difference was significant (P ≤ 0.05).
The organ weight results illustrated that, at the end of the exposure period, in male rats in the high-dose group, the liver’s absolute organ weight, organ-body ratio, and organ-brain ratio were higher than in the control group, presenting a statistical difference and showing an upward trend as dose increased. It was judged that this was possibly related to the test sample. At the end of the exposure period, in female rats in the medium- and high-dose groups, the liver’s absolute organ weight, organ-body ratio, and organ-brain ratio were higher than in the control group, presenting a statistical difference and showing an upward trend as dose increased. It was judged that this was possibly related to the test sample. At the end of the recovery period, in male and female rats in the high-dose group, the liver’s absolute organ weight, organ-body ratio, and organ-brain ratio recovered and did not present statistical significances. - Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- End of exposure period: One male rat in the control group exhibited enlarged submandibular lymph nodes; another male rat in the control group exhibited missing right testis and missing right epididymis; a third male rat in the control group exhibited small left testis and small left epididymis; one male rat in the medium-dose group exhibited small left testis and small left epididymis; another male rat in the medium-dose group exhibited centrilobular nodules of the liver; one female rat in the low-dose group exhibited enlarged uterus. There were no abnormalities in the remaining animals.
End of recovery period: No abnormalities were seen in any of the animals. - Neuropathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At the end of both the exposure and recovery period, there were no statistical significance in lesions occurring in all organs and they were spontaneous or occasional changes in SD rats at this age.
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- food consumption and compound intake
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- organ weights and organ / body weight ratios
Target system / organ toxicity
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 25 mg/kg bw/day (actual dose received)
- System:
- hepatobiliary
- Organ:
- liver
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- no
Applicant's summary and conclusion
- Conclusions:
- Based on the results of the 2-nitro-4-(trifluoromethyl)benzonitrile 90-day repeated oral exposure test in rats, it can be concluded that, based on statistical results of mean change in food intake for male rats, the NOAEL in male rats was 10 mg/kg bw/day. Based on statistical results of liver weight in female rats, it was determined that NOAEL in female rats was 10 mg/kg bw/day.
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.