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Administrative data

Description of key information

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).

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Referenceopen allclose all

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.
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

Referenceopen allclose all

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.
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