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EC number: 203-137-6 | CAS number: 103-71-9
- 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
Endpoint summary
Administrative data
Description of key information
No results from repeated-dose toxicity tests are available for the oral and dermal route of exposure.
For inhalation an exploratory subacute vapour inhalation study and a subacute inhalation toxicity (28-Day Study) according to OECD Guideline 412 are available.
Administration/exposure - 5d per week/ 6 hours per day for 28 days;
Type of exposure: dynamic head-nose only vapor exposure.
Result: NOAEC = 0.83 mg phenyl isocyanate/m³ air (male + female rats);
LOAEC = 2.79 mg phenyl isocyanate/m³ air (male + female rats).
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: guideline study - well documented
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Principles of method if other than guideline:
- Ten male and female rats per group were exposed nose/head only to mean analytical concentrations of 0.35, 0.83, 2.79 and 10.07 mg phenyl isocyanate/m³ for 4 weeks (6h/d, 5 exposures per week). During the study, the body weights were determined and clinical signs were recorded. At the end of the study ophthalmological examinations were performed and clinicochemical and hematological parameters were determined and a urinalysis performed. During sacrifice, gross pathological examinations of rats were made and selected organs were collected for gravimetric and histopathological examinations.
- GLP compliance:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Route of administration:
- inhalation
- Type of inhalation exposure:
- nose/head only
- Vehicle:
- air
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- 6h/d, 5d/w
- Dose / conc.:
- 0 mg/m³ air
- Dose / conc.:
- 0.35 mg/m³ air (analytical)
- Dose / conc.:
- 0.83 mg/m³ air (analytical)
- Dose / conc.:
- 2.79 mg/m³ air (analytical)
- Dose / conc.:
- 10.07 mg/m³ air (analytical)
- Dose / conc.:
- 0.2 mg/m³ air (nominal)
- Dose / conc.:
- 0.7 mg/m³ air (nominal)
- Dose / conc.:
- 2.5 mg/m³ air (nominal)
- Dose / conc.:
- 7.5 mg/m³ air (nominal)
- No. of animals per sex per dose:
- 10 male and 10 female animals/group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: no
- Positive control:
- None
- Observations and examinations performed and frequency:
- Body weights, clinical signs, rectal temperature, ophthalmological examinations, clinicochemical, hematological parameters, urinalysis.
- Sacrifice and pathology:
- Gross pathological examinations, selected organs were collected for gravimetric and histopathological examinations.
- Statistics:
- A statistical calculation of the determined parameters was conducted.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Up to 7.5 mg/m³ no findings. In the 7.5 mg/m³ group a decrease of the general condition was observed.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- In the 7.5 mg/m³ group 70% of the male rats and 50% of the female rats died intercurrent or were killed in moribund state.
- Description (incidence and severity):
- In the 2.5 mg/m³ group no toxicological relevant influence on the body weights were observed. In the 7.5 mg/kg bw group a statistical significant decrease of the body weights were seen.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 2.5 mg/m³ no findings. In the 7.5 mg/m³ group a hyperemia of the iris and a reddened ocular fundus were observed.
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 7.5 mg/m³ group the erythrocyte concentration, hematocrit and, hemoglobin and reticulocyte concentration were increased. Additional the rats revealed an increased coagulation time. the differential blood count showed an increase of the monocytes.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 7.5 mg/m³ group a statistically relevant decrease of the albumin, protein and chloride concentration of the plasma was observed, as well as an increase of the plasma ASAT (aspartate aminotransferase) and GLDH (glutamate dehydrogenase) activity. Additional the bilirubin and sodium concentrations were increased.
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Urine was more acidic in the 7.5 mg/m³ group.
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- In the 7.5 mg/m³ a decrease of the reflexes were observed.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 7.5 mg/m³ group, the weights of liver, thymus, testis/ovaries and spleen were decreased, the liver weights were increased. No findings in the 2.5 mg/m³ group.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 7.5 mg/m³ group, lungs was dark red discoloured, congestion of the cerebral blood vessels, dark spleen and decreased thymus. No findings in the 2.5 mg/m³ group.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- <= 2.79 mg/m³: no findings
2.79 mg/m³: histopathological alterations in the nasal septum (hyperplasia)
10.07 mg/³: metaplasia of the epithelium (nasal septum, larynx, trachea, stem bronchus), increased number of alveolar macrophages and swollen septum (lung), proliferating connective tissue, perivascular infiltration of round cells and accumulation of mucus (lobar bronchus). - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 0.83 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 2.79 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
- histopathology: non-neoplastic
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 2.79 mg/m³ air (analytical)
- System:
- other: respiratory tract
- Organ:
- lungs
- nasal cavity
- trachea
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
- Conclusions:
- At a concentration <= 2.79 mg/m³ no mortality and no clinical signs were seen. Starting with 2.79 mg/m³ histopathological alterations in the nasal septum (hyperplasia) were evident. At a concentration of 10.07 mg/m³ 5/10 females and 7/10 males died. An elevated temperature, decreased body weights, changed haematological and clinical biochemistry parameters, decreased organ weights (liver, thymus, gonads, spleen), increased lung weight, metaplasia of the epithelium (nasal septum, larynx, trachea, stem bronchus), increased number of alveolar macrophages and swollen septum (lung), proliferating connective tissue, perivascular infiltration of round cells and accumulation of mucus (lobar bronchus) were observed.
The effects observed in the respiratory system are mainly caused by irritation/corrosion. Therefore according to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified. - Executive summary:
Ten male and female rats per group were exposed nose/head only to mean analytical concentrations of 0.35, 0.83, 2.79 and 10.07 mg phenyl isocyanate for 4 weeks (6h/d, 5 exposures per week). During the study, the body weights were determined and clinical signs were recorded. At the end of the study ophthalmological examinations was performed and clinicochemical and hematological parameters were determined and an urinalysis performed. During sacrifice, gross pathological examinations of rats were made and selected organs were collected for gravimetric and histopathological examinations.
The NOAEL = 0.83 mg phenyl isocyanate/m³ air is based on the most sensitive parameter (hyperplasia of goblet cells in the turbinalia area).
Reference
<= 2.79 mg/m³: no mortality, no clinical signs; 2.79 mg/m³: histopathological alterations in the nasal septum (hyperplasia) 10.07 mg/³: 5/10 (females) and 7/10 (males) died, elevated temperature, decreased body weights, changed haematological and clinical biochemistry parameters, decreased organ weights (liver, thymus, gonads, spleen), increased lung weight, metaplasia of the epithelium (nasal septum, larynx, trachea, stem bronchus), increased number of alveolar macrophages and swollen septum (lung), proliferating connective tissue, perivascular infiltration of round cells and accumulation of mucus (lobar bronchus).
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- GLP guideline study
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: guideline study - well documented
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Principles of method if other than guideline:
- Ten male and female rats per group were exposed nose/head only to mean analytical concentrations of 0.35, 0.83, 2.79 and 10.07 mg phenyl isocyanate/m³ for 4 weeks (6h/d, 5 exposures per week). During the study, the body weights were determined and clinical signs were recorded. At the end of the study ophthalmological examinations were performed and clinicochemical and hematological parameters were determined and a urinalysis performed. During sacrifice, gross pathological examinations of rats were made and selected organs were collected for gravimetric and histopathological examinations.
- GLP compliance:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Route of administration:
- inhalation
- Type of inhalation exposure:
- nose/head only
- Vehicle:
- air
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- 6h/d, 5d/w
- Dose / conc.:
- 0 mg/m³ air
- Dose / conc.:
- 0.35 mg/m³ air (analytical)
- Dose / conc.:
- 0.83 mg/m³ air (analytical)
- Dose / conc.:
- 2.79 mg/m³ air (analytical)
- Dose / conc.:
- 10.07 mg/m³ air (analytical)
- Dose / conc.:
- 0.2 mg/m³ air (nominal)
- Dose / conc.:
- 0.7 mg/m³ air (nominal)
- Dose / conc.:
- 2.5 mg/m³ air (nominal)
- Dose / conc.:
- 7.5 mg/m³ air (nominal)
- No. of animals per sex per dose:
- 10 male and 10 female animals/group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: no
- Positive control:
- None
- Observations and examinations performed and frequency:
- Body weights, clinical signs, rectal temperature, ophthalmological examinations, clinicochemical, hematological parameters, urinalysis.
- Sacrifice and pathology:
- Gross pathological examinations, selected organs were collected for gravimetric and histopathological examinations.
- Statistics:
- A statistical calculation of the determined parameters was conducted.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Up to 7.5 mg/m³ no findings. In the 7.5 mg/m³ group a decrease of the general condition was observed.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- In the 7.5 mg/m³ group 70% of the male rats and 50% of the female rats died intercurrent or were killed in moribund state.
- Description (incidence and severity):
- In the 2.5 mg/m³ group no toxicological relevant influence on the body weights were observed. In the 7.5 mg/kg bw group a statistical significant decrease of the body weights were seen.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 2.5 mg/m³ no findings. In the 7.5 mg/m³ group a hyperemia of the iris and a reddened ocular fundus were observed.
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 7.5 mg/m³ group the erythrocyte concentration, hematocrit and, hemoglobin and reticulocyte concentration were increased. Additional the rats revealed an increased coagulation time. the differential blood count showed an increase of the monocytes.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 7.5 mg/m³ group a statistically relevant decrease of the albumin, protein and chloride concentration of the plasma was observed, as well as an increase of the plasma ASAT (aspartate aminotransferase) and GLDH (glutamate dehydrogenase) activity. Additional the bilirubin and sodium concentrations were increased.
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Urine was more acidic in the 7.5 mg/m³ group.
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- In the 7.5 mg/m³ a decrease of the reflexes were observed.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 7.5 mg/m³ group, the weights of liver, thymus, testis/ovaries and spleen were decreased, the liver weights were increased. No findings in the 2.5 mg/m³ group.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the 7.5 mg/m³ group, lungs was dark red discoloured, congestion of the cerebral blood vessels, dark spleen and decreased thymus. No findings in the 2.5 mg/m³ group.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- <= 2.79 mg/m³: no findings
2.79 mg/m³: histopathological alterations in the nasal septum (hyperplasia)
10.07 mg/³: metaplasia of the epithelium (nasal septum, larynx, trachea, stem bronchus), increased number of alveolar macrophages and swollen septum (lung), proliferating connective tissue, perivascular infiltration of round cells and accumulation of mucus (lobar bronchus). - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 0.83 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 2.79 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
- histopathology: non-neoplastic
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 2.79 mg/m³ air (analytical)
- System:
- other: respiratory tract
- Organ:
- lungs
- nasal cavity
- trachea
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
- Conclusions:
- At a concentration <= 2.79 mg/m³ no mortality and no clinical signs were seen. Starting with 2.79 mg/m³ histopathological alterations in the nasal septum (hyperplasia) were evident. At a concentration of 10.07 mg/m³ 5/10 females and 7/10 males died. An elevated temperature, decreased body weights, changed haematological and clinical biochemistry parameters, decreased organ weights (liver, thymus, gonads, spleen), increased lung weight, metaplasia of the epithelium (nasal septum, larynx, trachea, stem bronchus), increased number of alveolar macrophages and swollen septum (lung), proliferating connective tissue, perivascular infiltration of round cells and accumulation of mucus (lobar bronchus) were observed.
The effects observed in the respiratory system are mainly caused by irritation/corrosion. Therefore according to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified. - Executive summary:
Ten male and female rats per group were exposed nose/head only to mean analytical concentrations of 0.35, 0.83, 2.79 and 10.07 mg phenyl isocyanate for 4 weeks (6h/d, 5 exposures per week). During the study, the body weights were determined and clinical signs were recorded. At the end of the study ophthalmological examinations was performed and clinicochemical and hematological parameters were determined and an urinalysis performed. During sacrifice, gross pathological examinations of rats were made and selected organs were collected for gravimetric and histopathological examinations.
The NOAEL = 0.83 mg phenyl isocyanate/m³ air is based on the most sensitive parameter (hyperplasia of goblet cells in the turbinalia area).
Reference
<= 2.79 mg/m³: no mortality, no clinical signs; 2.79 mg/m³: histopathological alterations in the nasal septum (hyperplasia) 10.07 mg/³: 5/10 (females) and 7/10 (males) died, elevated temperature, decreased body weights, changed haematological and clinical biochemistry parameters, decreased organ weights (liver, thymus, gonads, spleen), increased lung weight, metaplasia of the epithelium (nasal septum, larynx, trachea, stem bronchus), increased number of alveolar macrophages and swollen septum (lung), proliferating connective tissue, perivascular infiltration of round cells and accumulation of mucus (lobar bronchus).
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 0.83 mg/m³
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- GLP guideline study
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Mode of Action Analysis / Human Relevance Framework
The effects observed in the respiratory system are mainly caused by irritation/corrosion.
Additional information
No results from repeated-dose toxicity tests are available for the oral and dermal route of exposure.
An exploratory subacute vapour inhalation study (0, 0.12, 0.57 or 3.14 mg/m³ phenyl isocyanate for 6 hours per day for 5 days) with male rats demonstrated that rats exposed to 0.12 or 0.57 mg/m³ exhibited no symptoms. Until 3.14 mg/m³ no toxicological relevant changes of body weight were evident. The animals exposed to 3.14 mg/m³ phenyl isocyanate had a discharging nose, body weight gain was normal, organ weight of heart, lung and liver normal, an increased protein- LDH- and gamma-GT content in the lung lavage 2 -3 days after termination of exposure was found, no deviation at 28th/29th day.
From these examinations it is concluded, that only animals exposed to 3.14 mg/m³ showed signs of an irritation of the upper (discharge of the nose) and the lower (increased gGT content) respiratory tract. A concentration of 0.57 mg phenyl isocyanate/m³ was tolerated without adverse effects.
In a subacute inhalation study ten male and female rats per group were exposed nose/head only to mean analytical concentrations of 0.35, 0.83, 2.79 and 10.07 mg phenyl isocyanate/m³ for 4 weeks (6h/d, 5 exposures per week). On the basis of the most sensitive parameter (hyperplasia of goblet cells in the turbinalia area) 0.83 mg/m³ phenyl isocyanate were regarded as the no-adverse-effect-level.
Justification for classification or non-classification
In a subacute inhalation repeated dose toxicity study were male rats were exposed to phenyl isocyanate for 4 weeks (6h/d, 5 exposures per week a NOAEC = 0.83 mg phenyl isocyanate/m³ air and a LOAEC = 2.79 mg phenyl isocyanate/m³ air in male + female rats) were found. The effects observed in the respiratory system are mainly caused by irritation/corrosion. Therefore according to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.
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