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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 270-109-8 | CAS number: 68411-20-1
- 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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.82 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 37.5
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 30.85 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Oral subacute repeated dose toxicity study available ( NOAEL 25 mg/kg; 28 day subacute gavage study).
Corrected human NOAEC = 30.85 mg/m³ (25 x 1/0,38 x7/5 x50/100 x 6.7/10)
A correction has to be made for workers because of their exposure only being 5 days a week instead of 7 days a week, which is a factor 7/5.
Bioavailability: animal experiment (oral) = 50% (default oral)
Bioavailability human route = 100% (default inhalation)
- AF for dose response relationship:
- 1
- Justification:
- Default value ECHA
- AF for differences in duration of exposure:
- 3
- Justification:
- *A reduced time extrapolation factors is considered appropriate for initial risk assessment because the main toxicological effects observed, hematology and spleen, are similar to effects observed with the main hydrolysis product aniline and these effects are considered to be acute effects independent of time of exposure (e.g. see DFG (Deutsche Forschungsgemeinschaft) (2010) MAK- und BAT-Werte-Liste 2010. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Mitteilung 46, Wiley-VCH, Weinheim). Based on the limited data set for Butanal, reaction products with aniline a time extrapolation factor of 3 seems appropriate.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Default value ECHA
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value ECHA
- AF for intraspecies differences:
- 5
- Justification:
- Default value ECHA
- AF for the quality of the whole database:
- 1
- Justification:
- Default value ECHA
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.64 mg/m³
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.23 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 150
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 35 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
A correction has to be made for workers because of their exposure only being 5 days a week instead of 7 days a week, which is a factor 7/5.
Bioavailability: animal experiment (oral) = 50% (default oral)
Bioavailability human route = 50% (default dermal)
25 x 7/5 = 35 [mg/kg bw]
- AF for dose response relationship:
- 1
- Justification:
- Default value ECHA
- AF for differences in duration of exposure:
- 3
- Justification:
- *A reduced time extrapolation factors is considered appropriate for initial risk assessment because the main toxicological effects observed, hematology and spleen, are similar to effects observed with the main hydrolysis product aniline and these effects are considered to be acute effects independent of time of exposure (e.g. see DFG (Deutsche Forschungsgemeinschaft) (2010) MAK- und BAT-Werte-Liste 2010. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Mitteilung 46, Wiley-VCH, Weinheim). Based on the limited data set for Butanal, reaction products with aniline a time extrapolation factor of 3 seems appropriate.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value ECHA
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value ECHA
- AF for intraspecies differences:
- 5
- Justification:
- Default value ECHA
- AF for the quality of the whole database:
- 1
- Justification:
- Guideline study
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Butanal, reaction products with aniline (CAS 68411-20-1)
DNELs (worker)
Repeated dose toxicity
A subacute gavage study in rats was evaluated for the derivation of DNELs of butanal, reaction products with aniline
Basis for delineation of the DNEL:
Study (rat study)
Repeated dose study
rat, male, female,
subacute gavage study for 28 days
rat: 0 (control), 25, 100, or 400 mg/kg/ day
Effects, NOAEL
NOAEL = 25 mg/kg bw (male + female rats)
Effects:
There was no mortality
Hematology revealed statistically significant changes in red blood parameters in both sexes at 100 mg/kg and/or 400 mg/kg.
Histopathology showed significant changes in various organs at 100 mg/kg and/or 400 mg/kg:
- Spleen: Increased extramedullary hematopoiesis
- Liver: Hepatocellular hypertrophy
- Heart: Myocardial vacuolation
- Bone marrow (femur and sternum): Increase in cellularity
- Thyroid gland: Hypertrophy/hyperplasia of follicular cell epithelia
- Kidneys: Tubular swelling/degeneration
- Adrenals: Increased vacuolation of zona fasciculata cells
Reference
Popp L
Butanal, reaction products with aniline - Subacute oral toxicity study in Wistar rats (4-weeks administration by gavage)
Bayer Pharma AG - Toxicology - 42096 Wuppertal, Germany
1.) Long-term tocixity – systemic effects (worker)
Long-term dermal route-systemic effects (worker) using default extrapolation factors:
NOAEL(rat, male) from a subacute toxicity study: 25 mg/kg bw/day
Penetration oral compared to dermal (both assumed 50%) 1
For interspecies rat vs. human: 4
For remaining interspecies differences: 2.5
For intraspecies differences in workers: 5
For extrapolation of exposure duration subacute to chronic: 3*
For reliability of dose-response: 1
For quality of whole database: 1
Overall factor: 150
Worker DNEL long-term for oral route-systemic: 0.23 mg/kg bw/day (35/ 150)
Oral subacute repeated dose toxicity study available ( NOAEL 25 mg/kg; 28 day subacute gavage study).
Corrected human NOAEC = 35 mg/kg (25 x 7/5)
A correction has to be made for workers because of their exposure only being 5 days a week instead of 7 days a week, which is a factor 7/5.
*A reduced time extrapolation factors is considered appropriate for initial risk assessment because the main toxicological effects observed, hematology and spleen, are similar to effects observed with the main hydrolysis product aniline and these effects are considered to be acute effects independent of time of exposure (e.g. see DFG (Deutsche Forschungsgemeinschaft) (2010) MAK- und BAT-Werte-Liste 2010. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Mitteilung 46, Wiley-VCH, Weinheim). Based on the limited data set for Butanal, reaction products with aniline a time extrapolation factor of 3 seems appropriate.
Worker DNEL long-term for dermal route-systemic: 0.23 mg/kg (35/ 150) mg/kg bw/day
Long-term inhalation route-systemic effects (worker):
NOAEL(rat) from a subacute oral toxicity study: 25 mg/kg bw/day
Correction of the starting point according TGD Figure R.8-3:
Corrected inhalatory NOAEC = Oral NOAEL (25 x 1/0,38 x7/5 x50/100 x 6.7/10)
=> NOAEC worker = 30.85 mg/m³
Bioavailability: animal experiment (oral) = 50% (default oral)
Bioavailability human route = 100% (default inhalation)
For interspecies differences rat vs. human: 1 (according TGD Table R.8-4. already covered by correction of starting point)
For remaining interspecies differences: 2.5
For intraspecies differences in workers: 5
For extrapolation of exposure duration subacute to chronic: 3*
For reliability of dose-response: 1
For quality of whole database: 1
Overall factor: 37.5
Worker DNEL long-term for inhalation exposure: 0.82 mg/m³ (30.85 / 37.5)
*A reduced time extrapolation factors is considered appropriate for initial risk assessment because the main toxicological effects observed, hematology and spleen, are similar to effects observed with the main hydrolysis product aniline and these effects are considered to be acute effects independent of time of exposure (e.g. see DFG (Deutsche Forschungsgemeinschaft) (2010) MAK- und BAT-Werte-Liste 2010. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Mitteilung 46, Wiley-VCH, Weinheim). Based on the limited data set for Butanal, reaction products with aniline a time extrapolation factor of 3 seems appropriate.
2.) Short-term toxicity – systemic effects (workers)
Dermal: Acute toxicity (dermal): Discriminating dose = 7940 mg/kg.
Inhalation: No acute study available. MAK: Exposure limit value of Anilin Factor 2 (peak expoure) compare to long-term exposure.
Worker DNEL short-term dermal route-systemic: No hazard identified (Discriminating dose = 7940 mg/kg)
Worker DNEL short-term for inhalation exposure: 0.29 mg/m³
Conclusion (systemic effects):
Worker DNEL long-term dermal route-systemic: 0.23 mg/kg bw/day
Worker DNEL long-term for inhalation exposure: 0.82 mg/m³
Worker DNEL short-term for dermal route-systemic: No hazard identified
Worker DNEL short-term for inhalation exposure: 1.64 mg/m³
3.) Reproductive Toxicity – systemic effects (worker)
Effects on reproductive organs in male and female rats were examined in a 4 week repeat dose toxicity study. Male and female reproductive organs and tissues were examined via gross necropsy as well as histopatholgical evaluations. Organ weight evaluations (absolute and relative) of several organs included an examination of testes, epidiymides, prostate, semical vesicle coagulation gland, ovaries, and uterus. No adverse effects on the reproductive organs examined were found.
As the NOAEL for fertility (400 mg/kg bw/day) is higher than the NOAEL for repeated dose toxicity (25 mg/kg bw/day), the derivation of a separate DNEL for fertility is not necessary, because the DNEL for repeated dose toxicity covers fertility.
No study is available for developmental toxicity / teratogenicity. A study is planned for conducting an OECD 421 screening study.
4. Irritation/corrosion to the skin and eyes
The test material was not irritating to the eyes and skin of rabbits, therefore a classification for skin and eye irritation is not justified.
5. Sensitization
In a LLNA , butanal, reaction products with aniline was a weak dermal sensitizer.
Butanal, reaction products with aniline is sensitizing and not irritating to the skin and eyes. Therefore a DNEL for local dermal effects is not applicable.
For local dermal effects butanal, reaction products with aniline should be allocated to the moderate hazard band.
For local inhalation effects butanal, reaction products with aniline no hazard identified ( Not classified for skin irritation).
Conclusion (systemic and local effects - worker):
Route of exposure DNEL; local effect DNEL; systemic effect
Dermal (long term) moderate hazard band 0.23 mg/kg/day
Dermal (short term) moderate hazard band No hazard identified
Inhalation (long term) No hazard identified 0.82 mg/m³/day
Inhalation (short term) No hazard identified 1.64 mg/m³
References:
• Popp L, Butanal, reaction products with aniline - Subacute oral toxicity study in Wistar rats (4-weeks administration by gavage), Bayer Pharma AG - Toxicology - 42096 Wuppertal, Germany
• Mihail F, Vulkacit 576 - Untersuchung zur Haut- und Schleimhautvertraeglichkeit, Bayer - Institut fuer Toxikologie, Wuppertal-Elberfeld, Germany
• Leidenfrost P, Butanal, reaction products with aniline - Local lymph node assay in mice (LLNA/IMS), draft, Bayer Pharma AG - Toxicology - 42096 Wuppertal, Germany
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.145 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Dose descriptor starting point:
- NOAEL
- Value:
- 25 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 10.87 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Oral subacute repeated dose toxicity study available ( NOAEL 25 mg/kg; 28 day subacute gavage study).
Corrected human NOAEC = 10.87 mg/m³ (25 x 1/1,15 x 50/100)
Bioavailability: animal experiment (oral) = 50% (default oral)
Bioavailability human route = 100% (default inhalation)
- AF for dose response relationship:
- 1
- Justification:
- Default value ECHA
- AF for differences in duration of exposure:
- 3
- Justification:
- *A reduced time extrapolation factors is considered appropriate for initial risk assessment because the main toxicological effects observed, hematology and spleen, are similar to effects observed with the main hydrolysis product aniline and these effects are considered to be acute effects independent of time of exposure (e.g. see DFG (Deutsche Forschungsgemeinschaft) (2010) MAK- und BAT-Werte-Liste 2010. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Mitteilung 46, Wiley-VCH, Weinheim). Based on the limited data set for Butanal, reaction products with aniline a time extrapolation factor of 3 seems appropriate.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Default value ECHA
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value ECHA
- AF for intraspecies differences:
- 10
- Justification:
- Default value ECHA
- AF for the quality of the whole database:
- 1
- Justification:
- Guideline study
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.29 mg/m³
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.083 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 25 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Default value ECHA
- AF for differences in duration of exposure:
- 3
- Justification:
- *A reduced time extrapolation factors is considered appropriate for initial risk assessment because the main toxicological effects observed, hematology and spleen, are similar to effects observed with the main hydrolysis product aniline and these effects are considered to be acute effects independent of time of exposure (e.g. see DFG (Deutsche Forschungsgemeinschaft) (2010) MAK- und BAT-Werte-Liste 2010. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Mitteilung 46, Wiley-VCH, Weinheim). Based on the limited data set for Butanal, reaction products with aniline a time extrapolation factor of 3 seems appropriate.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value ECHA
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value ECHA
- AF for intraspecies differences:
- 10
- Justification:
- Default value ECHA
- AF for the quality of the whole database:
- 1
- Justification:
- Guideline study.
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.083 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 25 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Default value ECHA
- AF for differences in duration of exposure:
- 3
- Justification:
- *A reduced time extrapolation factors is considered appropriate for initial risk assessment because the main toxicological effects observed, hematology and spleen, are similar to effects observed with the main hydrolysis product aniline and these effects are considered to be acute effects independent of time of exposure (e.g. see DFG (Deutsche Forschungsgemeinschaft) (2010) MAK- und BAT-Werte-Liste 2010. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Mitteilung 46, Wiley-VCH, Weinheim). Based on the limited data set for Butanal, reaction products with aniline a time extrapolation factor of 3 seems appropriate.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value ECHA
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value ECHA
- AF for intraspecies differences:
- 10
- Justification:
- Default value ECHA
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
Butanal, reaction products with aniline (CAS 68411-20-1)
DNELs (general population)
Repeated dose toxicity
A subacute gavage study in rats was evaluated for the derivation of DNELs of butanal, reaction products with aniline
Basis for delineation of the DNEL:
Study (rat study)
Repeated dose study
rat, male, female,
subacute gavage study for 28 days
rat: 0 (control), 25, 100, or 400 mg/kg/ day
Effects, NOAEL
NOAEL = 25 mg/kg bw (male + female rats)
Effects:
There was no mortality
Hematology revealed statistically significant changes in red blood parameters in both sexes at 100 mg/kg and/or 400 mg/kg.
Histopathology showed significant changes in various organs at 100 mg/kg and/or 400 mg/kg:
- Spleen: Increased extramedullary hematopoiesis
- Liver: Hepatocellular hypertrophy
- Heart: Myocardial vacuolation
- Bone marrow (femur and sternum): Increase in cellularity
- Thyroid gland: Hypertrophy/hyperplasia of follicular cell epithelia
- Kidneys: Tubular swelling/degeneration
- Adrenals: Increased vacuolation of zona fasciculata cells
Reference
Popp L
Butanal, reaction products with aniline - Subacute oral toxicity study in Wistar rats (4-weeks administration by gavage)
Bayer Pharma AG - Toxicology - 42096 Wuppertal, Germany
1.) Long-term tocixity – systemic effects (general population)
Long-term oral route-systemic effects (general population) using default extrapolation factors:
NOAEL(rat, male) from a subacute toxicity study: 25 mg/kg bw/day
Penetration oral compared to dermal (both assumed 50%) 1
For interspecies rat vs. human: 4
For remaining interspecies differences: 2.5
For intraspecies differences in general population: 10
For extrapolation of exposure duration subacute to chronic: 3*
For reliability of dose-response: 1
For quality of whole database: 1
Overall factor: 300
DNEL long-term for oral route-systemic: 0.083 mg/kg bw/day
*A reduced time extrapolation factors is considered appropriate for initial risk assessment because the main toxicological effects observed, hematology and spleen, are similar to effects observed with the main hydrolysis product aniline and these effects are considered to be acute effects independent of time of exposure (e.g. see DFG (Deutsche Forschungsgemeinschaft) (2010) MAK- und BAT-Werte-Liste 2010. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Mitteilung 46, Wiley-VCH, Weinheim). Based on the limited data set for Butanal, reaction products with aniline a time extrapolation factor of 3 seems appropriate.
DNEL long-term for oral and dermal route-systemic: 0.083 mg/kg bw/day
Long-term inhalation route-systemic effects (general population):
NOAEL(rat) from a subacute oral toxicity study: 25 mg/kg bw/day
Correction of the starting point according TGD Figure R.8-3:
Corrected inhalatory NOAEC = Oral NOAEL (25 x 1/1,15 x 50/100) mg/m³
=> NOAEC general population = 10.87 mg/m³
Bioavailability: animal experiment (oral) = 50% (default oral)
Bioavailability human route = 100% (default inhalation)
For interspecies differences rat vs. human: 1 (according TGD Table R.8-4. already covered by correction of starting point)
For remaining interspecies differences: 2.5
For intraspecies differences in general population: 10
For extrapolation of exposure duration subacute to chronic: 3*
For reliability of dose-response: 1
For quality of whole database: 1
Overall factor: 75
DNEL long-term for inhalation exposure: 0.145 mg/m³ (10.87 / 75)
*A reduced time extrapolation factors is considered appropriate for initial risk assessment because the main toxicological effects observed, hematology and spleen, are similar to effects observed with the main hydrolysis product aniline and these effects are considered to be acute effects independent of time of exposure (e.g. see DFG (Deutsche Forschungsgemeinschaft) (2010) MAK- und BAT-Werte-Liste 2010. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Mitteilung 46, Wiley-VCH, Weinheim). Based on the limited data set for Butanal, reaction products with aniline a time extrapolation factor of 3 seems appropriate.
2.) Short-term toxicity – systemic effects (general population)
General population DNEL short-term for oral route-systemic: No hazard identified
General population DNEL short-term for dermal route-systemic: No hazard identified
General population DNEL short-term for inhalation exposure: 0.29 mg/m³
Conclusion (systemic effects):
General population DNEL long-term for oral route-systemic: 0.083 mg/kg bw/day
General population DNEL long-term for dermal route-systemic: 0.083 mg/kg bw/day
General population DNEL long-term for inhalation exposure: 0.145 mg/m³
General population DNEL short-term for oral route-systemic: No hazard identified
General population DNEL short-term for dermal route-systemic: No hazard identified
General population DNEL short-term for inhalation exposure: 0.29 mg/m³
3.) Reproductive Toxicity – systemic effects (general population)
Effects on reproductive organs in male and female rats were examined in a 4 week repeat dose toxicity study. Male and female reproductive organs and tissues were examined via gross necropsy as well as histopatholgical evaluations. Organ weight evaluations (absolute and relative) of several organs included an examination of testes, epidiymides, prostate, semical vesicle coagulation gland, ovaries, and uterus. No adverse effects on the reproductive organs examined were found.
As the NOAEL for fertility (400 mg/kg bw/day) is higher than the NOAEL for repeated dose toxicity (25 mg/kg bw/day), the derivation of a separate DNEL for fertility is not necessary, because the DNEL for repeated dose toxicity covers fertility.
No study is available for developmental toxicity / teratogenicity. A study is planned for conducting an OECD 421 screening study.
4. Irritation/corrosion to the skin and eyes
The test material was not irritating to the eyes and skin of rabbits, therefore a classification for skin and eye irritation is not justified.
5. Sensitization
In a LLNA , butanal, reaction products with aniline was a weak dermal sensitizer.
Butanal, reaction products with aniline is sensitizing and not irritating to the skin and eyes. Therefore a DNEL for local dermal effects is not applicable.
For local dermal effects butanal, reaction products with aniline should be allocated to the moderate hazard band.
For local inhalation effects butanal, reaction products with aniline no hazard identified ( Not classified for skin irritation).
Conclusion (systemic and local effects – general population):
Route of exposure DNEL; local effect DNEL; systemic effect
Oral (long term) not required 0.083 mg/kg/day
Oral (short term) not required No hazard identified ( LD50 > 3830 mg/kg bw)
Dermal (long term) moderate hazard band 0.083 mg/kg/day
Dermal (short term) moderate hazard band No hazard identified ( Discriminating dose = 7940 mg/kg)
Inhalation (long term) No hazard identified 0.145 mg/m³/day
Inhalation (short term) No hazard identified 0.29 mg/m³
References:
• Popp L, Butanal, reaction products with aniline - Subacute oral toxicity study in Wistar rats (4-weeks administration by gavage), Bayer Pharma AG - Toxicology - 42096 Wuppertal, Germany
• Mihail F, Vulkacit 576 - Untersuchung zur Haut- und Schleimhautvertraeglichkeit, Bayer - Institut fuer Toxikologie, Wuppertal-Elberfeld, Germany
• Leidenfrost P, Butanal, reaction products with aniline - Local lymph node assay in mice (LLNA/IMS), draft, Bayer Pharma AG - Toxicology - 42096 Wuppertal, Germany
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.