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EC number: 237-860-3 | CAS number: 14024-63-6
- 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
Key value for chemical safety assessment
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Materials and methods are well-documented.
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Materials and methods are well-documented.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston, NY, USA).
- Age at study initiation: 34 to 38 days
- Acclimation period: 2 weeks
- Housing: cage
- Light/dark: 12 h / 12 h
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Temperature: 23 to 24 °C
- Humidity: 40 to 48 % - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were analyzed approximately every 33 minutes during the exposure by a gas chromatograph equipped with a flame ionization detector.
- Duration of treatment / exposure:
- In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-pentanedione vapor, using groups containing 20 males and 20 females, with halfbeing sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period.
- Frequency of treatment:
- In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-pentanedione vapor, using groups containing 20 males and 20 females, with halfbeing sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period.
- Dose / conc.:
- 650 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 307 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 101 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 0 ppm
- Remarks:
- 14-week study
- No. of animals per sex per dose:
- 20 m, 20 f for 14-week study
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- 20 male and 20 female rats per group, with half being sacrificed at the end of exposure period and the remaining after a 4 week recovery period for the determination of the reversibility of observable effects, were exposed to nominal concentrations of 0, 101, 307 and 650 ppm test substance, respectively.
- Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: before the first exposure, preceding the second, fifih, sixth, and seventh exposures
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day of sacrifice, sacrification by methoxyflurane - Sacrifice and pathology:
- Necropsy was performed, and weights of the brain, liver, kidneys, lungs, heart, thymus, and testes were determined.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Signs of toxicity in the 650-ppm group: complete or partial eyelid closure, periocular, perinasal, and perioral encrustation, wetness around the urogenital area, hypoactivity, lack of coordination, paresis, ataxia, irregular gait, hypothermia, and emaciation
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- In the 650-ppm group all females and 10 of the 30 males dies between the second and the sixth week of exposure.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weights of the 650-ppm males were reduced throughout the 14-week exposure period, but there was considerable weight increase during the 4-week recovery period. However, final weights were still statistically significantly below those for the control males. Before death, body weights of the female rats of the 650-ppm group were considerably reduced.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- For the 650-ppm males and the 307-ppm females, the respective mean erythrocyte counts were 11 and 4% below control values. The decrease in red blood cell count was accompanied with slight increases in MCV and MCH and a mild decrease in hematocrit. The white blood cell count was increased in the 650-ppm male rats, due to an increase in lymphocytes.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Clinical chemistry detenninations which deviated from controls were an increase in urea nitrogen and alkaline phosphatase activity, and a decrease in creatinine, calcium, and aspartate aminotransferase (AST) activity in the 650-ppm males. Serum calcium was also decreased in males and females of the 307-ppm group.
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Urinalysis showed minimal alterations in males, which included low pH (6.0 vs 7.0 in controls) at 650 ppm, and slightly increased bilirubin and urobilinogen at 650 and 307 ppm.
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- After 14-weeks of 2,4-PD vapor exposure,a statistically significant decrease in most absolute organ weights was observed for the 650-ppm males, but organ weights relative to body weight had increased.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The brain lesions observed in 7 of 10 male and 18 of 20 female rats that died during the exposure regimen took the form of acute degenerative changes in the vestibular nuclei, deep cerebellar nuclei, and corpora striata.
- Neuropathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The most noticeable feature in this study was the presence of degenerative changes in the deep cerebellar and vestibular nuclei and the corpora striata in animals that died following repeated exposures to 650 ppm of 2,4-PD vapor.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The most noticeable feature in this study was the presence of degenerative changes in the deep cerebellar and vestibular nuclei and the corpora striata in animals that died following repeated exposures to 650 ppm of 2,4-PD vapor.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 101 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effect observed
- Key result
- Dose descriptor:
- LOEC
- Effect level:
- 307 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- haematology
- histopathology: non-neoplastic
- urinalysis
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 650 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- urinalysis
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 307 ppm (analytical)
- System:
- respiratory system: lower respiratory tract
- Organ:
- lungs
- Treatment related:
- yes
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 650 ppm (analytical)
- System:
- other: several organs
- Organ:
- brain
- heart
- kidney
- liver
- lungs
- testes
- Treatment related:
- yes
- Conclusions:
- The most noteworthy systemics observations in the 14-week inhalation study were the brain and thymus lesions in animals that died due to inhalation of 650 ppm of 2,4-pentanedione. Mild squamous metaplasia in the nasal mucosa was observed in the 650 ppm rats. Perhaps inflammation in the nasal mucosa is a transient response at 2,4-pentanedione concentrations of 307 ppm and higher. Rats exposed to 100 ppm of 2,4-pentanedione for 14 weeks showed no signs of irritancy or toxicity (nominal concentrations, corresponding to 413; 1,255 and 2,657 mg/m3)
It can be stated that for the inhalative repeated dose toxicity for 2,4-pentanedione for an axposure duration of 14 weeks the NOEC is 101 ppm, the LOEC is 307 ppm and the LOAEC is 650 ppm, respectively, for both male and female. - Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Based on the structural similarities, a read-across to pentane-2,4-dione is acceptable.
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Materials and methods are well-documented.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston, NY, USA).
- Age at study initiation: 34 to 38 days
- Acclimation period: 2 weeks
- Housing: cage
- Light/dark: 12 h / 12 h
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Temperature: 23 to 24 °C
- Humidity: 40 to 48 % - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were analyzed approximately every 33 minutes during the exposure by a gas chromatograph equipped with a flame ionization detector.
- Duration of treatment / exposure:
- In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-pentanedione vapor, using groups containing 20 males and 20 females, with halfbeing sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period.
- Frequency of treatment:
- In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-pentanedione vapor, using groups containing 20 males and 20 females, with halfbeing sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period.
- Dose / conc.:
- 650 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 307 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 101 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 0 ppm
- Remarks:
- 14-week study
- No. of animals per sex per dose:
- 20 m, 20 f for 14-week study
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- 20 male and 20 female rats per group, with half being sacrificed at the end of exposure period and the remaining after a 4 week recovery period for the determination of the reversibility of observable effects, were exposed to nominal concentrations of 0, 101, 307 and 650 ppm test substance, respectively.
- Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: before the first exposure, preceding the second, fifih, sixth, and seventh exposures
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day of sacrifice, sacrification by methoxyflurane - Sacrifice and pathology:
- Necropsy was performed, and weights of the brain, liver, kidneys, lungs, heart, thymus, and testes were determined.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Signs of toxicity in the 650-ppm group: complete or partial eyelid closure, periocular, perinasal, and perioral encrustation, wetness around the urogenital area, hypoactivity, lack of coordination, paresis, ataxia, irregular gait, hypothermia, and emaciation
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- In the 650-ppm group all females and 10 of the 30 males dies between the second and the sixth week of exposure.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weights of the 650-ppm males were reduced throughout the 14-week exposure period, but there was considerable weight increase during the 4-week recovery period. However, final weights were still statistically significantly below those for the control males. Before death, body weights of the female rats of the 650-ppm group were considerably reduced.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- For the 650-ppm males and the 307-ppm females, the respective mean erythrocyte counts were 11 and 4% below control values. The decrease in red blood cell count was accompanied with slight increases in MCV and MCH and a mild decrease in hematocrit. The white blood cell count was increased in the 650-ppm male rats, due to an increase in lymphocytes.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Clinical chemistry detenninations which deviated from controls were an increase in urea nitrogen and alkaline phosphatase activity, and a decrease in creatinine, calcium, and aspartate aminotransferase (AST) activity in the 650-ppm males. Serum calcium was also decreased in males and females of the 307-ppm group.
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Urinalysis showed minimal alterations in males, which included low pH (6.0 vs 7.0 in controls) at 650 ppm, and slightly increased bilirubin and urobilinogen at 650 and 307 ppm.
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- After 14-weeks of 2,4-PD vapor exposure,a statistically significant decrease in most absolute organ weights was observed for the 650-ppm males, but organ weights relative to body weight had increased.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The brain lesions observed in 7 of 10 male and 18 of 20 female rats that died during the exposure regimen took the form of acute degenerative changes in the vestibular nuclei, deep cerebellar nuclei, and corpora striata.
- Neuropathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The most noticeable feature in this study was the presence of degenerative changes in the deep cerebellar and vestibular nuclei and the corpora striata in animals that died following repeated exposures to 650 ppm of 2,4-PD vapor.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The most noticeable feature in this study was the presence of degenerative changes in the deep cerebellar and vestibular nuclei and the corpora striata in animals that died following repeated exposures to 650 ppm of 2,4-PD vapor.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 101 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effect observed
- Key result
- Dose descriptor:
- LOEC
- Effect level:
- 307 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- haematology
- histopathology: non-neoplastic
- urinalysis
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 650 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- urinalysis
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 307 ppm (analytical)
- System:
- respiratory system: lower respiratory tract
- Organ:
- lungs
- Treatment related:
- yes
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 650 ppm (analytical)
- System:
- other: several organs
- Organ:
- brain
- heart
- kidney
- liver
- lungs
- testes
- Treatment related:
- yes
- Conclusions:
- A 14-week inhalation study in rats is available for the read-across substance, 2,4-pentanedione. The most noteworthy systemics observations in the 14-week inhalation study were the brain and thymus lesions in animals that died due to inhalation of 650 ppm of 2,4-pentanedione. Mild squamous metaplasia in the nasal mucosa was observed in the 650 ppm rats. Perhaps inflammation in the nasal mucosa is a transient response at 2,4-pentanedione concentrations of 307 ppm and higher. Rats exposed to 100 ppm of 2,4-pentanedione for 14 weeks showed no signs of irritancy or toxicity (nominal concentrations, corresponding to 413; 1,255 and 2,657 mg/m3)
It can be stated that for the inhalative repeated dose toxicity for 2,4-pentanedione for an axposure duration of 14 weeks the NOEC is 101 ppm, the LOEC is 307 ppm and the LOAEC is 650 ppm, respectively, for both male and female.
By molecular weight correction the following values can be stated for bis(oentane-2,4-dionato)zinc: NOEC = 545 mg/m3; LOEC = 1657 mg/m3; LOAEC = 3507 mg/m3 - Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Materials and methods are well-documented.
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Materials and methods are well-documented.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston, NY, USA).
- Age at study initiation: 34 to 38 days
- Acclimation period: 2 weeks
- Housing: cage
- Light/dark: 12 h / 12 h
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Temperature: 23 to 24 °C
- Humidity: 40 to 48 % - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were analyzed approximately every 33 minutes during the exposure by a gas chromatograph equipped with a flame ionization detector.
- Duration of treatment / exposure:
- For the 9-day study, four groups, each containing 10 male and 10 female rats, were exposed for 6 hr/day to 3 dilferent target concentrations (805, 418 and 197 ppm) of 2,4-pentanedione vapor and one air control atmosphere.
- Frequency of treatment:
- For the 9-day study, four groups, each containing 10 male and 10 female rats, were exposed for 6 hr/day to 3 dilferent target concentrations (805, 418 and 197 ppm) of 2,4-pentanedione vapor and one air control atmosphere.
- Dose / conc.:
- 805 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 418 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 197 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 0 ppm
- Remarks:
- 9-day study
- No. of animals per sex per dose:
- 10 m, 10 f for 9-day study
- Control animals:
- yes, concurrent no treatment
- Positive control:
- no
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
- Time schedule for examinations: before the first exposure, preceding the second, fifih, sixth, and seventh exposures
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day of sacrifice, sacrification by methoxyflurane - Sacrifice and pathology:
- Necropsy was performed, and weights of the brain, liver, kidneys, lungs, heart, thymus, and testes were determined.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- signs of irritancy to eyes
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- For male and female test animals, a decrease in body weight was observed during the exposure period of the 805-ppm group.
- 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:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The hematology results indicated a mild (approximately 20% above control value) leukocytosis for rats of the 805-ppm group, which was mainly the result of an increase in lymphocytes.
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Due to the decrease in body weight gain at 805 ppm, the weights of several organs (brain, liver, kidney, Jung, and thymus) were lower tban those of the controls. However, relative weights of most of these organs from the 805-ppm group were higher than control values, indicating that body weight decrease was more marked than decreases in absolute organ weights.
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- exposure-related inflammation of nasal mucosa at the 805-ppm group
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 197 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effect observed
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 805 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- haematology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 805 ppm (analytical)
- System:
- other: several organs
- Organ:
- brain
- kidney
- liver
- lungs
- Treatment related:
- yes
- Conclusions:
- It can be stated that for the inhalative repeated dose toxicity for 2,4-pentanedione for an axposure duration of 9 days the NOEC is 197 ppm and the LOAEC is 805 ppm, respectively, for both male and female.
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Based on the structural similarities, a read-across to pentane-2,4-dione is acceptable.
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Materials and methods are well-documented.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston, NY, USA).
- Age at study initiation: 34 to 38 days
- Acclimation period: 2 weeks
- Housing: cage
- Light/dark: 12 h / 12 h
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Temperature: 23 to 24 °C
- Humidity: 40 to 48 % - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were analyzed approximately every 33 minutes during the exposure by a gas chromatograph equipped with a flame ionization detector.
- Duration of treatment / exposure:
- For the 9-day study, four groups, each containing 10 male and 10 female rats, were exposed for 6 hr/day to 3 dilferent target concentrations (805, 418 and 197 ppm) of 2,4-pentanedione vapor and one air control atmosphere.
- Frequency of treatment:
- For the 9-day study, four groups, each containing 10 male and 10 female rats, were exposed for 6 hr/day to 3 dilferent target concentrations (805, 418 and 197 ppm) of 2,4-pentanedione vapor and one air control atmosphere.
- Dose / conc.:
- 805 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 418 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 197 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 0 ppm
- Remarks:
- 9-day study
- No. of animals per sex per dose:
- 10 m, 10 f for 9-day study
- Control animals:
- yes, concurrent no treatment
- Positive control:
- no
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
- Time schedule for examinations: before the first exposure, preceding the second, fifih, sixth, and seventh exposures
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day of sacrifice, sacrification by methoxyflurane - Sacrifice and pathology:
- Necropsy was performed, and weights of the brain, liver, kidneys, lungs, heart, thymus, and testes were determined.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- signs of irritancy to eyes
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- For male and female test animals, a decrease in body weight was observed during the exposure period of the 805-ppm group.
- 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:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The hematology results indicated a mild (approximately 20% above control value) leukocytosis for rats of the 805-ppm group, which was mainly the result of an increase in lymphocytes.
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Due to the decrease in body weight gain at 805 ppm, the weights of several organs (brain, liver, kidney, Jung, and thymus) were lower tban those of the controls. However, relative weights of most of these organs from the 805-ppm group were higher than control values, indicating that body weight decrease was more marked than decreases in absolute organ weights.
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- exposure-related inflammation of nasal mucosa at the 805-ppm group
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 197 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effect observed
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 805 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- haematology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 805 ppm (analytical)
- System:
- other: several organs
- Organ:
- brain
- kidney
- liver
- lungs
- Treatment related:
- yes
- Conclusions:
- It can be stated that for the inhalative repeated dose toxicity for 2,4-pentanedione for an axposure duration of 9 days the NOEC is 197 ppm and the LOAEC is 805 ppm, respectively, for both male and female.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 545 mg/m³
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- It can be stated that for the inhalative repeated dose toxicity for 2,4-pentanedione for an axposure duration of 14 weeks the NOEC is 101 ppm (413 mg/m³), the LOEC is 307 ppm (1255 mg/m³) and the LOAEC is 650 ppm (2657 mg/m³), respectively, for both male and female.
By molecular weight correction the following values can be stated for bis(oentane-2,4-dionato)zinc: NOEC = 545 mg/m3; LOEC = 1657 mg/m3; LOAEC = 3507 mg/m3
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Materials and methods are well-documented.
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Materials and methods are well-documented.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston, NY, USA).
- Age at study initiation: 34 to 38 days
- Acclimation period: 2 weeks
- Housing: cage
- Light/dark: 12 h / 12 h
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Temperature: 23 to 24 °C
- Humidity: 40 to 48 % - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were analyzed approximately every 33 minutes during the exposure by a gas chromatograph equipped with a flame ionization detector.
- Duration of treatment / exposure:
- In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-pentanedione vapor, using groups containing 20 males and 20 females, with halfbeing sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period.
- Frequency of treatment:
- In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-pentanedione vapor, using groups containing 20 males and 20 females, with halfbeing sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period.
- Dose / conc.:
- 650 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 307 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 101 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 0 ppm
- Remarks:
- 14-week study
- No. of animals per sex per dose:
- 20 m, 20 f for 14-week study
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- 20 male and 20 female rats per group, with half being sacrificed at the end of exposure period and the remaining after a 4 week recovery period for the determination of the reversibility of observable effects, were exposed to nominal concentrations of 0, 101, 307 and 650 ppm test substance, respectively.
- Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: before the first exposure, preceding the second, fifih, sixth, and seventh exposures
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day of sacrifice, sacrification by methoxyflurane - Sacrifice and pathology:
- Necropsy was performed, and weights of the brain, liver, kidneys, lungs, heart, thymus, and testes were determined.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Signs of toxicity in the 650-ppm group: complete or partial eyelid closure, periocular, perinasal, and perioral encrustation, wetness around the urogenital area, hypoactivity, lack of coordination, paresis, ataxia, irregular gait, hypothermia, and emaciation
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- In the 650-ppm group all females and 10 of the 30 males dies between the second and the sixth week of exposure.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weights of the 650-ppm males were reduced throughout the 14-week exposure period, but there was considerable weight increase during the 4-week recovery period. However, final weights were still statistically significantly below those for the control males. Before death, body weights of the female rats of the 650-ppm group were considerably reduced.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- For the 650-ppm males and the 307-ppm females, the respective mean erythrocyte counts were 11 and 4% below control values. The decrease in red blood cell count was accompanied with slight increases in MCV and MCH and a mild decrease in hematocrit. The white blood cell count was increased in the 650-ppm male rats, due to an increase in lymphocytes.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Clinical chemistry detenninations which deviated from controls were an increase in urea nitrogen and alkaline phosphatase activity, and a decrease in creatinine, calcium, and aspartate aminotransferase (AST) activity in the 650-ppm males. Serum calcium was also decreased in males and females of the 307-ppm group.
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Urinalysis showed minimal alterations in males, which included low pH (6.0 vs 7.0 in controls) at 650 ppm, and slightly increased bilirubin and urobilinogen at 650 and 307 ppm.
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- After 14-weeks of 2,4-PD vapor exposure,a statistically significant decrease in most absolute organ weights was observed for the 650-ppm males, but organ weights relative to body weight had increased.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The brain lesions observed in 7 of 10 male and 18 of 20 female rats that died during the exposure regimen took the form of acute degenerative changes in the vestibular nuclei, deep cerebellar nuclei, and corpora striata.
- Neuropathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The most noticeable feature in this study was the presence of degenerative changes in the deep cerebellar and vestibular nuclei and the corpora striata in animals that died following repeated exposures to 650 ppm of 2,4-PD vapor.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The most noticeable feature in this study was the presence of degenerative changes in the deep cerebellar and vestibular nuclei and the corpora striata in animals that died following repeated exposures to 650 ppm of 2,4-PD vapor.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 101 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effect observed
- Key result
- Dose descriptor:
- LOEC
- Effect level:
- 307 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- haematology
- histopathology: non-neoplastic
- urinalysis
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 650 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- urinalysis
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 307 ppm (analytical)
- System:
- respiratory system: lower respiratory tract
- Organ:
- lungs
- Treatment related:
- yes
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 650 ppm (analytical)
- System:
- other: several organs
- Organ:
- brain
- heart
- kidney
- liver
- lungs
- testes
- Treatment related:
- yes
- Conclusions:
- The most noteworthy systemics observations in the 14-week inhalation study were the brain and thymus lesions in animals that died due to inhalation of 650 ppm of 2,4-pentanedione. Mild squamous metaplasia in the nasal mucosa was observed in the 650 ppm rats. Perhaps inflammation in the nasal mucosa is a transient response at 2,4-pentanedione concentrations of 307 ppm and higher. Rats exposed to 100 ppm of 2,4-pentanedione for 14 weeks showed no signs of irritancy or toxicity (nominal concentrations, corresponding to 413; 1,255 and 2,657 mg/m3)
It can be stated that for the inhalative repeated dose toxicity for 2,4-pentanedione for an axposure duration of 14 weeks the NOEC is 101 ppm, the LOEC is 307 ppm and the LOAEC is 650 ppm, respectively, for both male and female. - Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Based on the structural similarities, a read-across to pentane-2,4-dione is acceptable.
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Materials and methods are well-documented.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston, NY, USA).
- Age at study initiation: 34 to 38 days
- Acclimation period: 2 weeks
- Housing: cage
- Light/dark: 12 h / 12 h
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Temperature: 23 to 24 °C
- Humidity: 40 to 48 % - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were analyzed approximately every 33 minutes during the exposure by a gas chromatograph equipped with a flame ionization detector.
- Duration of treatment / exposure:
- In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-pentanedione vapor, using groups containing 20 males and 20 females, with halfbeing sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period.
- Frequency of treatment:
- In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-pentanedione vapor, using groups containing 20 males and 20 females, with halfbeing sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period.
- Dose / conc.:
- 650 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 307 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 101 ppm
- Remarks:
- 14-week study
- Dose / conc.:
- 0 ppm
- Remarks:
- 14-week study
- No. of animals per sex per dose:
- 20 m, 20 f for 14-week study
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- 20 male and 20 female rats per group, with half being sacrificed at the end of exposure period and the remaining after a 4 week recovery period for the determination of the reversibility of observable effects, were exposed to nominal concentrations of 0, 101, 307 and 650 ppm test substance, respectively.
- Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: before the first exposure, preceding the second, fifih, sixth, and seventh exposures
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day of sacrifice, sacrification by methoxyflurane - Sacrifice and pathology:
- Necropsy was performed, and weights of the brain, liver, kidneys, lungs, heart, thymus, and testes were determined.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Signs of toxicity in the 650-ppm group: complete or partial eyelid closure, periocular, perinasal, and perioral encrustation, wetness around the urogenital area, hypoactivity, lack of coordination, paresis, ataxia, irregular gait, hypothermia, and emaciation
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- In the 650-ppm group all females and 10 of the 30 males dies between the second and the sixth week of exposure.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weights of the 650-ppm males were reduced throughout the 14-week exposure period, but there was considerable weight increase during the 4-week recovery period. However, final weights were still statistically significantly below those for the control males. Before death, body weights of the female rats of the 650-ppm group were considerably reduced.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- For the 650-ppm males and the 307-ppm females, the respective mean erythrocyte counts were 11 and 4% below control values. The decrease in red blood cell count was accompanied with slight increases in MCV and MCH and a mild decrease in hematocrit. The white blood cell count was increased in the 650-ppm male rats, due to an increase in lymphocytes.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Clinical chemistry detenninations which deviated from controls were an increase in urea nitrogen and alkaline phosphatase activity, and a decrease in creatinine, calcium, and aspartate aminotransferase (AST) activity in the 650-ppm males. Serum calcium was also decreased in males and females of the 307-ppm group.
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Urinalysis showed minimal alterations in males, which included low pH (6.0 vs 7.0 in controls) at 650 ppm, and slightly increased bilirubin and urobilinogen at 650 and 307 ppm.
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- After 14-weeks of 2,4-PD vapor exposure,a statistically significant decrease in most absolute organ weights was observed for the 650-ppm males, but organ weights relative to body weight had increased.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The brain lesions observed in 7 of 10 male and 18 of 20 female rats that died during the exposure regimen took the form of acute degenerative changes in the vestibular nuclei, deep cerebellar nuclei, and corpora striata.
- Neuropathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The most noticeable feature in this study was the presence of degenerative changes in the deep cerebellar and vestibular nuclei and the corpora striata in animals that died following repeated exposures to 650 ppm of 2,4-PD vapor.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The most noticeable feature in this study was the presence of degenerative changes in the deep cerebellar and vestibular nuclei and the corpora striata in animals that died following repeated exposures to 650 ppm of 2,4-PD vapor.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 101 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effect observed
- Key result
- Dose descriptor:
- LOEC
- Effect level:
- 307 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- haematology
- histopathology: non-neoplastic
- urinalysis
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 650 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- urinalysis
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 307 ppm (analytical)
- System:
- respiratory system: lower respiratory tract
- Organ:
- lungs
- Treatment related:
- yes
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 650 ppm (analytical)
- System:
- other: several organs
- Organ:
- brain
- heart
- kidney
- liver
- lungs
- testes
- Treatment related:
- yes
- Conclusions:
- A 14-week inhalation study in rats is available for the read-across substance, 2,4-pentanedione. The most noteworthy systemics observations in the 14-week inhalation study were the brain and thymus lesions in animals that died due to inhalation of 650 ppm of 2,4-pentanedione. Mild squamous metaplasia in the nasal mucosa was observed in the 650 ppm rats. Perhaps inflammation in the nasal mucosa is a transient response at 2,4-pentanedione concentrations of 307 ppm and higher. Rats exposed to 100 ppm of 2,4-pentanedione for 14 weeks showed no signs of irritancy or toxicity (nominal concentrations, corresponding to 413; 1,255 and 2,657 mg/m3)
It can be stated that for the inhalative repeated dose toxicity for 2,4-pentanedione for an axposure duration of 14 weeks the NOEC is 101 ppm, the LOEC is 307 ppm and the LOAEC is 650 ppm, respectively, for both male and female.
By molecular weight correction the following values can be stated for bis(oentane-2,4-dionato)zinc: NOEC = 545 mg/m3; LOEC = 1657 mg/m3; LOAEC = 3507 mg/m3 - Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Materials and methods are well-documented.
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Materials and methods are well-documented.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston, NY, USA).
- Age at study initiation: 34 to 38 days
- Acclimation period: 2 weeks
- Housing: cage
- Light/dark: 12 h / 12 h
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Temperature: 23 to 24 °C
- Humidity: 40 to 48 % - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were analyzed approximately every 33 minutes during the exposure by a gas chromatograph equipped with a flame ionization detector.
- Duration of treatment / exposure:
- For the 9-day study, four groups, each containing 10 male and 10 female rats, were exposed for 6 hr/day to 3 dilferent target concentrations (805, 418 and 197 ppm) of 2,4-pentanedione vapor and one air control atmosphere.
- Frequency of treatment:
- For the 9-day study, four groups, each containing 10 male and 10 female rats, were exposed for 6 hr/day to 3 dilferent target concentrations (805, 418 and 197 ppm) of 2,4-pentanedione vapor and one air control atmosphere.
- Dose / conc.:
- 805 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 418 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 197 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 0 ppm
- Remarks:
- 9-day study
- No. of animals per sex per dose:
- 10 m, 10 f for 9-day study
- Control animals:
- yes, concurrent no treatment
- Positive control:
- no
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
- Time schedule for examinations: before the first exposure, preceding the second, fifih, sixth, and seventh exposures
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day of sacrifice, sacrification by methoxyflurane - Sacrifice and pathology:
- Necropsy was performed, and weights of the brain, liver, kidneys, lungs, heart, thymus, and testes were determined.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- signs of irritancy to eyes
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- For male and female test animals, a decrease in body weight was observed during the exposure period of the 805-ppm group.
- 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:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The hematology results indicated a mild (approximately 20% above control value) leukocytosis for rats of the 805-ppm group, which was mainly the result of an increase in lymphocytes.
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Due to the decrease in body weight gain at 805 ppm, the weights of several organs (brain, liver, kidney, Jung, and thymus) were lower tban those of the controls. However, relative weights of most of these organs from the 805-ppm group were higher than control values, indicating that body weight decrease was more marked than decreases in absolute organ weights.
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- exposure-related inflammation of nasal mucosa at the 805-ppm group
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 197 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effect observed
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 805 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- haematology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 805 ppm (analytical)
- System:
- other: several organs
- Organ:
- brain
- kidney
- liver
- lungs
- Treatment related:
- yes
- Conclusions:
- It can be stated that for the inhalative repeated dose toxicity for 2,4-pentanedione for an axposure duration of 9 days the NOEC is 197 ppm and the LOAEC is 805 ppm, respectively, for both male and female.
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Based on the structural similarities, a read-across to pentane-2,4-dione is acceptable.
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Materials and methods are well-documented.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. (Kingston, NY, USA).
- Age at study initiation: 34 to 38 days
- Acclimation period: 2 weeks
- Housing: cage
- Light/dark: 12 h / 12 h
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Temperature: 23 to 24 °C
- Humidity: 40 to 48 % - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were analyzed approximately every 33 minutes during the exposure by a gas chromatograph equipped with a flame ionization detector.
- Duration of treatment / exposure:
- For the 9-day study, four groups, each containing 10 male and 10 female rats, were exposed for 6 hr/day to 3 dilferent target concentrations (805, 418 and 197 ppm) of 2,4-pentanedione vapor and one air control atmosphere.
- Frequency of treatment:
- For the 9-day study, four groups, each containing 10 male and 10 female rats, were exposed for 6 hr/day to 3 dilferent target concentrations (805, 418 and 197 ppm) of 2,4-pentanedione vapor and one air control atmosphere.
- Dose / conc.:
- 805 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 418 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 197 ppm
- Remarks:
- 9-day study
- Dose / conc.:
- 0 ppm
- Remarks:
- 9-day study
- No. of animals per sex per dose:
- 10 m, 10 f for 9-day study
- Control animals:
- yes, concurrent no treatment
- Positive control:
- no
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
- Time schedule for examinations: before the first exposure, preceding the second, fifih, sixth, and seventh exposures
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day of sacrifice, sacrification by methoxyflurane - Sacrifice and pathology:
- Necropsy was performed, and weights of the brain, liver, kidneys, lungs, heart, thymus, and testes were determined.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- signs of irritancy to eyes
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- For male and female test animals, a decrease in body weight was observed during the exposure period of the 805-ppm group.
- 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:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The hematology results indicated a mild (approximately 20% above control value) leukocytosis for rats of the 805-ppm group, which was mainly the result of an increase in lymphocytes.
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Due to the decrease in body weight gain at 805 ppm, the weights of several organs (brain, liver, kidney, Jung, and thymus) were lower tban those of the controls. However, relative weights of most of these organs from the 805-ppm group were higher than control values, indicating that body weight decrease was more marked than decreases in absolute organ weights.
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- exposure-related inflammation of nasal mucosa at the 805-ppm group
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 197 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effect observed
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 805 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- haematology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 805 ppm (analytical)
- System:
- other: several organs
- Organ:
- brain
- kidney
- liver
- lungs
- Treatment related:
- yes
- Conclusions:
- It can be stated that for the inhalative repeated dose toxicity for 2,4-pentanedione for an axposure duration of 9 days the NOEC is 197 ppm and the LOAEC is 805 ppm, respectively, for both male and female.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEC
- 1 255 mg/m³
- Study duration:
- subchronic
- Species:
- rat
Additional information
Justification for classification or non-classification
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