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EC number: 926-809-7 | CAS number: -
- 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
Endpoint summary
Administrative data
Description of key information
A number of acute oral studies were included as part of NONS registrations. Acute oral toxicity studies were conducted on four MDI category members; A mixture of: 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea; 3-cyclohexyl-1-(4-(4-(3-octadecylureido)benzyl) phenyl)urea; 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea (PU10; A002; PU18; EC 406-530-2); 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea (R95; EC 406-370-3); N,N''-(methylenedi-4,1-phenylene) bis[N'-octyl]urea (A124; EC 445-760-8); and 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea (PU12/A123; EC 406-690-3). The results from these studies showed no evidence of acute toxicity up to the highest dose tested in any study (2000 or 5000 mg/kg test item in either cellulose or corn oil).
Additionally, as part of an updated testing program, acute oral studies were conducted on: Reaction product of MDI, Octadecylamine and Magnesium Hydroxide (PU05; EC 944-730-6); Reaction product of MDI and p-toluidine (PU07; EC 926-809-7); and Polyurea, produced by reacting diphenylmethane diisocyanate with octylamine and dodecyl amine (R03; EC 812-490-0. The results from these studies showed no evidence of acute toxicity up to the highest dose tested (2000 mg/kg body weight). Therefore, there is no evidence of a relevant intrinsic acute oral toxicity requiring classification or substance specific risk management measures.
A number of acute dermal studies were also included as part of NONS registrations. Acute dermal studies were conducted on four MDI category members: A mixture of: 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea; 3-cyclohexyl-1-(4-(4-(3-octadecylureido)benzyl) phenyl)urea; 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea (PU10; A002; PU18; EC 406-530-2);3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea (R95; EC 406-370-3);N,N''-(methylenedi-4,1-phenylene) bis[N'-octyl]urea (A124; EC 445-760-8);and3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea (PU12/A123; EC 406-690-3). The results from these studies showed no evidence of acute toxicity at the only dose tested in any study (2000 mg/kg test item). There is no evidence of a relevant intrinsic acute dermal toxicity requiring classification or substance specific risk management measures.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
- Qualifier:
- according to guideline
- Guideline:
- other: Annex V
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 10 male and 10 female rats
- Route of administration:
- oral: unspecified
- Vehicle:
- corn oil
- Doses:
- 2000 mg/kg b.w.
- No. of animals per sex per dose:
- 10 animals per sex per dose
- Control animals:
- not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- not specified
- Mortality:
- Male: 2000 mg/kg bw ; Number of animals: 10; Number of deaths: 0
Female: 2000 mg/kg bw ; Number of animals: 10; Number of deaths: 0 - Clinical signs:
- other: other: No deaths and no signs of toxicity were observed.
- Gross pathology:
- No effects on organs
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for the test item was determined to be > 2000 mg/kg b.w., the only concentration tested. No deaths and no signs of toxicity were observed.
- Executive summary:
The acute oral toxicity of the test item to Crj(CD)SD rats was determined in a limit test conducted according to international guidelines. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested. No deaths and no signs of toxicity were observed.
The study is a GLP compliant, guideline study and is acceptable with restrictions.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
- Qualifier:
- according to guideline
- Guideline:
- other: Annex V
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- Albino
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 5 male and 5 female rats
- Route of administration:
- oral: unspecified
- Vehicle:
- corn oil
- Doses:
- 2000 mg/kg b.w.
- No. of animals per sex per dose:
- 5 animals per sex per dose
- Control animals:
- not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Male: 2000 mg/kg bw ; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw ; Number of animals: 5; Number of deaths: 0 - Clinical signs:
- other: other: No deaths and no signs of toxicity were observed.
- Gross pathology:
- No treatment-related macroscopic findings were observed.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for the test item to albino Wistar rats was determined to be > 2000 mg/kg b.w., the only concentration tested. No signs of toxicity were observed, and the gross pathological examination revealed no treatment-related findings.
- Executive summary:
The acute oral toxicity of the test item to albino Wistar rats was determined in a limit test conducted according to international guidelines. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested. No signs of toxicity were observed, and the gross pathological examination revealed no treatment-related findings.
The study is a GLP compliant, guideline study and is acceptable with restrictions.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
- Qualifier:
- according to guideline
- Guideline:
- other: Annex V
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Route of administration:
- oral: unspecified
- Vehicle:
- corn oil
- Remarks:
- at 0.5 %
- Doses:
- 5000 mg/kg b.w.
- No. of animals per sex per dose:
- 5 animals per sex per dose
- Control animals:
- not specified
- Details on study design:
- The total dose of 5000 mg/kg was given as two doses of 2500 mg/kg administered within a 24 hour period.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 5 000 mg/kg bw
- Based on:
- not specified
- Mortality:
- Male: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0 - Clinical signs:
- other: other: Signs of toxicity related to dose levels: No clear toxicologically significant effects were seen.
- Gross pathology:
- Effects on organs: None.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for the test item was determined to be > 5000 mg/kg b.w. No signs of toxicity were observed, and the gross pathological examination revealed no effects on organs.
- Executive summary:
The acute oral toxicity of the test item to male and female Wistar rats was determined in a study conducted according to EU Annex V guidelines. The test item was administered to 5 male and 5 female rats, with the 5000 mg/kg/b.w. dose administered as two doses of 2500 mg/kg/b.w. in a 24 hour period. The LD50 was determined to be > 5000 mg/kg b.w. No signs of toxicity were observed, and the gross pathological examination revealed no effects on organs.
The study is a GLP compliant, guideline experimental study and is acceptable with restrictions.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 (Acute Toxicity (Oral))
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 6 male and 3 female rats
- Route of administration:
- oral: unspecified
- Vehicle:
- methylcellulose
- Remarks:
- at 0.5 %
- Doses:
- 200 and 2000 mg/kg b.w.
- No. of animals per sex per dose:
- 3 animals per sex per dose
- Control animals:
- not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- not specified
- Mortality:
- Male: 200 mg/kg bw ; Number of animals: 3; Number of deaths: 0
Male: 2000 mg/kg bw ; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw ; Number of animals: 3; Number of deaths: 0 - Clinical signs:
- other: other: At doses of 200 and 2000 mg / kg, no clinical signs and no mortality were observed in the animals.
- Gross pathology:
- No apparent abnormality is observed on macroscopic examination of the main organs of animals sacrificed at the end of the study.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for the test item was determined to be > 2000 mg/kg b.w. No signs of toxicity were observed, no effects on body weight were observed and the gross pathological examination revealed no treatment-related findings.
- Executive summary:
The acute oral toxicity of the test item to Sprague-Dawley rats was determined in a study conducted according to OECD 423 and EU method B.1 guidelines. The LD50 was determined to be > 2000 mg/kg b.w. No signs of toxicity or effects on body weight were observed, and the gross pathological examination revealed no treatment-related findings.
The study is a GLP compliant, guideline experimental study and is acceptable with restrictions.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 02/11/2021 - 14/10/2022
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
- Version / remarks:
- 2001
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 (Acute Toxicity (Oral))
- Version / remarks:
- 2008
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- fixed dose procedure
- Limit test:
- no
- Species:
- rat
- Strain:
- other:
- Remarks:
- Crl:WI(Han)
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 10 weeks old
- Weight at study initiation: 151 to 200 grams
- Fasting period before study: Period of fasting from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing.
- Housing: Animals housed in groups of 6 in cages
- Diet: 5LF2 EU Rodent Diet 14% provided ad libitum
- Water: Water provided ad libitum
- Acclimation period: 7 to 15 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 40 to 70 %
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- DOSE VOLUME APPLIED: 10 mL/kg
- Doses:
- Sighting study: 300 and 2000 mg/kg
Main study: 2000 mg/kg - No. of animals per sex per dose:
- Sighting study: 1
Main study: 4 - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All animals were observed at the beginning and the end of the working day for signs of ill health or overt toxicity. - Preliminary study:
- No deaths observed.
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Mortality:
- No mortality observed.
- Clinical signs:
- other: other: other: Piloerection was noted in the animal treated at 300 mg/kg, developing from 2 hours after dosing and lasting up to 3 hours after dosing. No clinical signs were seen in animals treated at 2000 mg/kg.
- Body weight:
- other body weight observations
- Gross pathology:
- No abnormalities were noted at necropsy.
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- The acute oral toxicity of the test item was tested and the oral LD50 was determined to exceed 2000 mg/kg body weight.
- Executive summary:
The acute oral toxicity of the test item was determined in an OECD 420 and EU Method B1 bis Acute Toxicity (Oral) guideline study. The test item was tested at 2000 mg/kg formulation in corn oil, orally by gavage using a metal canula. Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. All animals were observed at the beginning and the end of the working day for signs of ill health or overt toxicity. Additionally the animal body weights were determined on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
In a preliminary study, one adult female rat was dosed at 300 mg/kg test item and one adult female rate was dosed at 2000 mg/kg test item, and no mortalities, effects on body weight or adverse findings during necropsy were observed, therefore four further female rats were dosed with 2000 mg/kg test item. No deaths or signs of systematic toxicity or adverse findings during necropsy were observed during the main study and the test animals achieved the expected weight gains during the study. The acute oral median lethal dose (LD50) of the test item was estimated to be greater than 2000 mg/kg body weight.
The study is a GLP compliant guideline experimental study and is acceptable without restrictions for assessment of this endpoint.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 06/10/2021 - 14/10/2022
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
- Version / remarks:
- 2001
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 (Acute Toxicity (Oral))
- Version / remarks:
- 2008
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- fixed dose procedure
- Limit test:
- no
- Species:
- rat
- Strain:
- other:
- Remarks:
- Crl:WI(Han)
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 10 weeks old
- Weight at study initiation: 166 to 184 grams
- Fasting period before study: Period of fasting from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing.
- Housing: Animals housed in groups of 6 in cages
- Diet: 5LF2 EU Rodent Diet 14% provided ad libitum
- Water: Water provided ad libitum
- Acclimation period: 7 to 15 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 40 to 70 %
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- DOSE VOLUME APPLIED: 10 mL/kg
- Doses:
- Sighting study: 300 and 2000 mg/kg
Main study: 2000 mg/kg - No. of animals per sex per dose:
- Sighting study: 1
Main study: 4 - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All animals were observed at the beginning and the end of the working day for signs of ill health or overt toxicity. - Preliminary study:
- No deaths observed.
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Mortality:
- No mortality observed.
- Clinical signs:
- other: other: other: Piloerection
- Body weight:
- other body weight observations
- Gross pathology:
- No abnormalities were noted at necropsy.
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- The acute oral toxicity of the test item was tested and the oral LD50 was determined to exceed 2000 mg/kg body weight.
- Executive summary:
The acute oral toxicity of the test item was determined in an OECD 420 and EU Method B1 bis Acute Toxicity (Oral) guideline study. The test item was tested at 2000 mg/kg formulation in corn oil, orally by gavage using a metal canula. Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. All animals were observed at the beginning and the end of the working day for signs of ill health or overt toxicity. Additionally the animal body weights were determined on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
In a preliminary study, one adult female rat was dosed at 300 mg/kg test item and one adult female rate was dosed at 2000 mg/kg test item, and no mortalities, effects on body weight or adverse findings during necropsy were observed, therefore four further female rats were dosed with 2000 mg/kg test item. No deaths or signs of systematic toxicity or adverse findings during necropsy were observed during the study. Piloerection was noted in four animals treated at 2000 mg/kg from 1 hour after dosing and lasted up to 4 hours after dosing. The test animals all gained weight during the first and second weeks of the observation period, except for the animal treated at 300 mg/kg, which showed slight body weight loss during the second week of the observation period. The acute oral median lethal dose (LD50) of the test item was estimated to be greater than 2000 mg/kg body weight.
The study is a GLP compliant guideline experimental study and is acceptable without restrictions for assessment of this endpoint.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 24/05/2021 - 30/06/2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
- Version / remarks:
- 2001
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 (Acute Toxicity (Oral))
- Version / remarks:
- 2008
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- fixed dose procedure
- Limit test:
- no
- Species:
- rat
- Strain:
- other:
- Remarks:
- Crl:WI(Han)
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 10 weeks old
- Weight at study initiation: 150 to 185 grams
- Fasting period before study: Period of fasting from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing.
- Housing: Animals housed in groups of 6 in cages
- Diet: 5LF2 EU Rodent Diet 14% provided ad libitum
- Water: Water provided ad libitum
- Acclimation period: 14 to 22 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 40 to 70 %
- Air changes (per hr): 15 per hr
- Photoperiod (hrs dark / hrs light): 12 hrs light / 12 hrs dark - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- DOSE VOLUME APPLIED: 10 mL/kg
- Doses:
- Sighting study: 300 and 2000 mg/kg
Main study: 2000 mg/kg - No. of animals per sex per dose:
- Sighting study: 1
Main study: 4 - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All animals were observed at the beginning and the end of the working day for signs of ill health or overt toxicity. - Preliminary study:
- No deaths observed.
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Mortality:
- No mortality observed.
- Body weight:
- other body weight observations
- Gross pathology:
- No abnormalities were noted at necropsy.
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- The acute oral toxicity of the test item was tested and the oral LD50 was determined to exceed 2000 mg/kg body weight.
- Executive summary:
The acute oral toxicity of the test item was determined in an OECD 420 and EU Method B1 bis Acute Toxicity (Oral) guideline study. The test item was tested at 2000 mg/kg formulation in corn oil, orally by gavage using a metal canula. Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. All animals were observed at the beginning and the end of the working day for signs of ill health or overt toxicity. Additionally the animal body weights were determined on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
In a preliminary study, one adult female rat was dosed at 300 mg/kg test item and one adult female rat 2000 mg/kg test item, and no mortalities, effects on body weight or adverse findings during necropsy were observed, therefore four further female rats were dosed with 2000 mg/kg test item. In the main study, no deaths or signs of systematic toxicity or adverse findings during necropsy were observed during the study and the test animals achieved the expected weight gains during the study. The acute oral median lethal dose (LD50) of the test item was estimated to be greater than 2000 mg/kg body weight.
The study is a GLP compliant guideline experimental study and is acceptable without restrictions for assessment of this endpoint.
Referenceopen allclose all
Table 1 Mortality Data
Dose Level (mg/kg) | Mortality Ratio |
300 | 0/1 |
2000 | 0/5 |
Table 2 Clinical Signs Following Treatment
Dose level: 300 mg/kg
Animal Number | Clinical Sign | Sign Noted after Dosing on Day 1 (hours) | Sign noted on Day: | |||||||||||||
Imm | 1/4 | 1/2 | 1 | 2 | 3 | 4 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 to 15 | ||
784 | Piloerection | + | + |
Key:
Imm: Immediately post-dose
+: Sign present (if no entry sign absent)
Dose Level: 2000 mg/kg
Clincal Sign | Animal Number | ||||
785 | 786 | 787 | 788 | 789 | |
No observations | X | X | X | X | X |
Key:
X: No clincal signs seen throughout the observation period
Table 3 Individual Body Weights and Weekly Increments
Dose Level (mg/kg) | Animal Number | Body Weight (g) at: | Increment (g) | |||||
Day -1 | Day 1 | Day 4 | Day 8 | Day 15 | Day 1 to 8 | Day 8 to 15 | ||
300 | 784 | 163 | 151 | 168 | 176 | 193 | 25 | 17 |
2000 | 785 | 214 | 200 | 219 | 231 | 248 | 31 | 17 |
786 | 190 | 173 | 195 | 203 | 219 | 30 | 16 | |
787 | 202 | 186 | 199 | 203 | 213 | 17 | 10 | |
788 | 177 | 163 | 177 | 184 | 194 | 21 | 10 | |
789 | 173 | 160 | 173 | 175 | 186 | 15 | 11 |
Table 4 Necropsy Findings
Dose Level: 300 mg/kg
Animal Number | Time and Manner of Death (Day) | Necropsy Comments |
784 | 15T | No macroscopic changes |
Dose Level: 200 mg/kg
Animal Number | Time and Manner of Death (Day) | Necropsy Comments |
785 | 15T | No macroscopic changes |
786 | 15T | No macroscopic changes |
787 | 15T | No macroscopic changes |
788 | 15T | No macroscopic changes |
789 | 15T | No macroscopic changes |
T Animal killed by exsanguination under deep inhalation anaesthesia at completion of observation period
Table 1 Mortality Data
Dose Level (mg/kg) | Mortality Ratio |
300 | 0/1 |
2000 | 0/5 |
Table 2 Clinical Signs Following Treatment
Dose Level: 300 mg/kg
Clinical Sign | Animal Number |
790 | |
No observations | X |
Key:
X No clinical signs seen throughout the observation period
Dose Level: 2000 mg/kg
Animal Number | Clinical Sign | Sign Noted after Dosing on Day 1 (hours) | Sign Noted on Day: | |||||||||||||
Imm. | 1/4 | 1/2 | 1 | 2 | 3 | 4 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 to 15 | ||
791 | Piloerection | |||||||||||||||
792 | Piloerection | + | + | + | + | |||||||||||
793 | Piloerection | + | + | + | + | |||||||||||
794 | Piloerection | + | + | + | ||||||||||||
795 | Piloerection | + | + |
Key:
Imm. Immediately post-dose
+ Sign present (if no entry is made the sign is absent)
Table 3 Individual Body Weights and Weekly Increments
Dose Level (mg/kg) |
Animal Number | Body weight (g) at: | Increment (g) | |||||
Day -1 | Day 1 | Day 4 | Day 8 | Day 15 | Day 1 to 8 | Day 8 to 15 | ||
300 | 790 | 194 | 183 | 202 | 204 | 203 | 21 | -1 |
2000 | 791 | 171 | 166 | 179 | 187 | 202 | 21 | 15 |
792 | 203 | 184 | 203 | 210 | 218 | 26 | 8 | |
793 | 188 | 181 | 200 | 201 | 210 | 20 | 9 | |
794 | 183 | 169 | 188 | 193 | 194 | 24 | 1 | |
795 | 190 | 180 | 198 | 204 | 212 | 24 | 8 |
A minus symbol [-] indicates body weight loss
Table 4 Necropsy Findings
Dose Level: 300 mg/kg
Animal Number | Time and Manner of Death (Day) | Necropsy Comments |
790 | 15T | No macroscopic changes |
Dose Level: 2000 mg/kg
Animal Number | Time and Manner of Death (Day) | Necropsy Comments |
791 | 15T | No macroscopic changes |
792 | 15T | No macroscopic changes |
793 | 15T | No macroscopic changes |
794 | 15T | No macroscopic changes |
795 | 15T | No macroscopic changes |
T Animal killed by exsanguination under deep inhalation anaesthesia at completion of observation period
Table 1 Mortality Data
Dose Level (mg/kg) | Mortality Ratio |
300 | 0/1 |
2000 | 0/5 |
Table 2 Clinical Signs Following Treatment
Dose Level: 300 mg/kg
Clinical Sign | Animal Number |
421 | |
No observations | X |
Key:
X No clinical signs seen throughout the observation period
Dose Level: 2000 mg/kg
Clinical Sign | Animal Number | ||||
422 | 423 | 424 | 425 | 426 | |
No observations | X | X | X | X | X |
Key:
X No clinical signs seen throughout the observation period
Table 3 Individual Body Weights and Weekly Increments
Dose Level (mg/kg) |
Animal Number | Body weight (g) at: | Increment (g) | |||||
Day -1 | Day 1 | Day 4 | Day 8 | Day 15 | Day 1 to 8 | Day 8 to 15 | ||
300 | 421 | 176 | 163 | 184 | 190 | 205 | 27 | 15 |
2000 | 422 | 166 | 159 | 172 | 178 | 194 | 19 | 16 |
423 | 173 | 163 | 180 | 185 | 195 | 22 | 10 | |
424 | 172 | 163 | 186 | 198 | 203 | 35 | 5 | |
425 | 194 | 185 | 200 | 212 | 222 | 27 | 10 | |
426 | 162 | 150 | 169 | 174 | 183 | 24 | 9 |
Table 4 Necropsy Findings
Dose Level: 300 mg/kg
Animal Number | Time and Manner of Death (Day) | Necropsy Comments |
421 | 15T | No macroscopic changes |
Dose Level: 2000 mg/kg
Animal Number | Time and Manner of Death (Day) | Necropsy Comments |
422 | 15T | No macroscopic changes |
423 | 15T | No macroscopic changes |
424 | 15T | No macroscopic changes |
425 | 15T | No macroscopic changes |
426 | 15T | No macroscopic changes |
T Animal killed by exsanguination under deep inhalation anaesthesia at completion of observation period
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- > 2 000 mg/kg bw
- Quality of whole database:
- NONS data evaluated for the MDI category have been conducted following standard guidelines and have been previously submitted for regulatory purposes; and therefore they are deemed acceptable for evaluation. Data from the updated testing program are guideline, GLP studies.
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
- Qualifier:
- according to guideline
- Guideline:
- other: Annex V
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- not specified
- Sex:
- male/female
- Type of coverage:
- occlusive
- Vehicle:
- corn oil
- Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg b.w.
- No. of animals per sex per dose:
- 5 male and 5 female per dose
- Control animals:
- not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- not specified
- Mortality:
- Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0 - Clinical signs:
- other: other: No deaths or signs of toxicity were observed.
- Gross pathology:
- No treatment-related effects on organs were observed
- Other findings:
- Signs of toxicity (local): At the site of treatment, spots with crusts were noted in 2 females on day 8 and 1 female on day 15
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for the acute dermal exposure of rats to the test item was determined to be > 2000 mg/kg b.w., the only concentration tested.
- Executive summary:
The acute dermal toxicity of the test item was determined in a guideline limit test with male and female wistar rats at a dose level of 2000 mg/kg b.w. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested. No deaths or effects on organs were observed. At the site of treatment, spots with crusts were noted in 2 females on day 8 and 1 female on day 15. The test item does not meet the GHS criteria and is not classified.
The study is a GLP compliant, guideline study suitable for use for assessment of this endpoint, with restrictions.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
- Qualifier:
- according to guideline
- Guideline:
- other: Annex V
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Type of coverage:
- occlusive
- Vehicle:
- corn oil
- Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg b.w.
- No. of animals per sex per dose:
- 5 male and 5 female per dose
- Control animals:
- not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0 - Clinical signs:
- other: other: No deaths or signs of toxicity were observed. Slight erythema was observed at the site of application in one female on day 2.
- Gross pathology:
- No treatment-related macroscopic findings were observed
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for the acute dermal exposure of Wistar rats to the test item was determined to be > 2000 mg/kg b.w., the only concentration tested.
- Executive summary:
The acute dermal toxicity of the test item was determined in a guideline limit test with male and female Wistar rats at a dose level of 2000 mg/kg b.w. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested. No deaths, gross pathological findings or signs of toxicity were observed, except slight erythema at the site of application in one female on day 2. Therefore, the test item does not meet the GHS criteria and is not classified.
The study is a GLP compliant, guideline study suitable for use for assessment of this endpoint with restrictions.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
- Qualifier:
- according to guideline
- Guideline:
- other: Annex V
- Version / remarks:
- Version not reported
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Type of coverage:
- occlusive
- Vehicle:
- corn oil
- Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg b.w.
- No. of animals per sex per dose:
- 5 male and 5 female per dose
- Control animals:
- not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- not specified
- Mortality:
- Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0 - Clinical signs:
- other: other: Lethargy was noted in 1 male and 1 female during the treatment period.
- Gross pathology:
- No treatment-related effects on organs were observed.
- Other findings:
- Signs of toxicity (local): Slight erythema of treated skin was noted in one male on days 5 and 8 and scaliness in 1 male on day 5.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for the acute dermal exposure of rats to the test item was determined to be > 2000 mg/kg b.w., the only concentration tested.
- Executive summary:
The acute dermal toxicity of the test item was determined in a limit test conducted at a dose of 2000 mg/kg b.w., with male and female Wistar rats, according to EU Annex V guidelines. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested.
No deaths and effects on organs were observed. Lethargy was noted in 1 male and 1 female during the treatment period. Slight erythema of treated skin was noted in one male on days 5 and 8 and scaliness in 1 male on day 5. The test item does not meet the GHS criteria and is not classified.
The study is a GLP compliant, guideline experimental study and is suitable for use for assessment of this endpoint with restrictions.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Remarks:
- The substance was moistened with reverse osmosis purified water.
- Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg b.w.
- No. of animals per sex per dose:
- 5 male and 5 female per dose
- Control animals:
- not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- not specified
- Mortality:
- Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0 - Clinical signs:
- other: other: No clinical signs were observed.
- Gross pathology:
- No treatment-related effects on organs were observed
- Other findings:
- Signs of toxicity (local): No skin reaction is observed. A white coloring of the skin, due to the substance, could mask a very slight erythema and is noted in all the animals at day 2 only.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 for the acute dermal exposure of the test item was determined to be > 2000 mg/kg b.w., the only concentration tested.
- Executive summary:
The acute dermal toxicity of the test item was determined in a guideline limit test with male and female Sprague-Dawley rats at 2000 mg/kg b.w. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested. No deaths and no effects on organs were observed. A slower body weight gain or a slight decrease in body weight is noted in 2/5 females between days 1 and 8 and in 1/5 females between days 8 and 15. The body weight gain of other animals is similar to that of historical control animals. No local skin reaction was observed, however a white colouring of the skin, due to the substance, could mask a very slight erythema is noted in all the animals at day 2 only. The test item does not meet the GHS criteria and is not classified.
The study is a GLP compliant, guideline experimental study and is suitable for use for assessment of this endpoint with restrictions.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- All studies evaluated for the MDI category have been conducted following standard guidelines and have been previously submitted for regulatory purposes; and therefore they are deemed acceptable for evaluation.
Additional information
Justification for classification or non-classification
The oral and dermal LD50 values are greater than 2000 mg/kg bw in all studies conducted on the MDI category; therefore, the existing data supports the justification for non-classification.
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