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Description of key information

Acute oral - In a non-GLP study conducted with study methodology equivalent to OECD TG 401, Under the conditions of the study, as the oral LD50 of n-propyl propionate is in excess of 10000 mg/kg (male LD50 – 11.7 ml/kg ~ 10258.67 mg/kg and female LD50 – 12.6 ml/kg ~ 11047.80 mg/kg; conversions based on density of 0.87681 g/cc at 25 °C), 
Acute dermal - In a non-GLP study conducted with study methodology equivalent to OECD TG 402, the acute dermal LD50 value for propyl propionate was 14028.96 mg/kg (Conversion from ml/kg resulted in - 16 ml/kg - 14028.96 mg/kg)
Acute inhalation - In a non-GLP study conducted with study methodology equivalent to OECD TG 403, the lethal time LT50 of propyl propionate to male and female Spraque-Dawley rats exposed to saturated vapors over a period of 6 hours was 66 mL/l.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to OECD TG 401 and there is no mention in the report on the status of compliance with the Principles of Good Laboratory Practice (GLP).
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: assumed to be in-house
- Age at study initiation: young adults
- Weight at study initiation: 200-300 grams
- Fasting period before study: yes
- Housing: assumed to be group housed
- Diet: ad libitum, appropriate commercial diet, except during the period of fasting
- Water: municipal water, ad libitum
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Groups of Sprague Dawley rats (both sexes) were administered undiluted n-propyl propionate with a ball-end stainless steel needle.
Doses:
Males - 4.0, 8.0, 11.3 and 16 ml/kg
Females - 8.0, 11.3 and 16.0 ml/kg
No. of animals per sex per dose:
5 rats/dose, except that 2 male rats were administered undiluted n-propyl propionate 4.0 ml/kg dose group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations and body weights recorded weekly
- Necropsy of survivors performed: yes
Statistics:
LD50's and the estimated LD50 slopes were calculated by the moving average method
Preliminary study:
not applicable
Sex:
male
Dose descriptor:
LD50
Effect level:
11.7 mL/kg bw
Based on:
test mat.
95% CL:
9.6 - 14.3
Remarks on result:
other: Conversion value of 10258.67 mg/kg based on density of 0.87681 g/cc at 25 °C
Sex:
female
Dose descriptor:
LD50
Effect level:
12.6 mL/kg bw
Based on:
test mat.
95% CL:
10.7 - 14.7
Remarks on result:
other: Conversion value of 11047.80 mg/kg based on density of 0.87681 g/cc at 25 °C
Mortality:
No mortalities were noted in either sex upto 8.0 ml/kg, in the 11.3 ml/kg group - 2 males and 1 female rat were found dead and 100% mortality was noted in the 16.0 ml/kg group.
Clinical signs:
Signs of toxicity included sluggishness, an unsteady gait, lacrimation, prostration, a moribund appearance, diarrhea, red crust on the perinasal fur and staining of the periurogenital fur.
Body weight:
Weight gain was noted in all the surviving animals
Gross pathology:
Necropsy of victims revealed discolored lungs (red, pink or mottled), discolored stomachs (white, grey or dark brown), stomachs with black areas, liquid and/or gas-filled stomachs, liquid-filled intestines, discolored intestines (red, white, yellow or dark brown), intestines with black areas (in 2), mottled tan to dark red livers, mottled tan to dark red kidneys, red discharge on the periurogenital fur and bladders filled with yellow or red liquid. The only gross pathologic finding for survivors was mottled dark red kidneys (in 2).
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, as the oral LD50 of n-propyl propionate is in excess of 10000 mg/kg, hence based on the Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, n-propyl propionate will not be classified for acute oral toxicity.
Executive summary:

In this study, groups of Sprague Dawley rats (weighing between 200-300 grams) were administered undiluted n-propyl propionate by oral gavage and observed for signs of toxicity and mortality over a period of 14 days. No mortalities were noted in either sex upto 8.0 ml/kg, in the 11.3 ml/kg group - 2 males and 1 female rat were found dead and 100% mortality was noted in the 16.0 ml/kg group. Signs of toxicity included sluggishness, an unsteady gait, lacrimation, prostration, a moribund appearance, diarrhea, red crust on the perinasal fur and staining of the periurogenital fur. Weight gain was noted in all the surviving animals. Necropsy of victims revealed discolored lungs (red, pink or mottled), discolored stomachs (white, grey or dark brown), stomachs with black areas, liquid and/or gas-filled stomachs, liquid-filled intestines,  discolored intestines (red, white, yellow or dark brown), intestines with black areas (in 2), mottled tan to dark red livers, mottled tan to dark red kidneys, red discharge on the periurogenital fur and bladders filled with yellow or red liquid. The only gross pathologic finding for survivors was mottled dark red kidneys (in 2).

Under the conditions of the study, as the oral LD50 of n-propyl propionate is in excess of 10000 mg/kg (male LD50 – 11.7 ml/kg ~ 10258.67 mg/kg and female LD50 – 12.6 ml/kg ~ 11047.80 mg/kg; conversions based on density of 0.87681 g/cc at 25 °C), hence based on the Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, n-propyl propionate will not be classified for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
10 259 mg/kg bw
Quality of whole database:
Good

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to OECD TG 403 and there is no mention in the report on the status of compliance with the Principles of Good Laboratory Practice (GLP).
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: assumed to be in-house
- Age at study initiation: young adults
- Weight at study initiation: 200-300 grams
- Fasting period before study: yes
- Housing: assumed to be group housed
- Diet: ad libitum, appropriate commercial diet, except during the period of fasting
- Water: municipal water, ad libitum
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
The vapor was produced by enclosing approximately 100 g of the test material in a sealed 100 to 152-liter animal chamber for approximately 18 hours (static conditions). A mixing fan periodically agitated the chamber atmosphere to aid in distribution of the vapor. Oxygen was added, as needed, for static exposures to maintain chamber oxygen content of approximately 20%.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
6 h
Concentrations:
Saturated vapor concentration (conversion value of 14031.58 ppm or 66 mg/l, based on vapor pressure of 10.664 mm Hg at 20 °C and molecular weight of 116.16)
No. of animals per sex per dose:
5 males + 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:observed daily and body weights recorded weekly
- Necropsy of survivors performed: yes
Statistics:
LD50's and the estimated LD50 slopes were calculated by the moving average method
Preliminary study:
not applicable
Sex:
male/female
Dose descriptor:
other: LT50 (lethal time 50)
Effect level:
other: Saturated vapor concentration
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Saturated vapor concentration (conversion value of 14031.58 ppm or 66 mg/l, based on vapor pressure of 10.664 mm Hg at 20 °C and molecular weight of 116.16)
Mortality:
Exposure to a statically-generated, substantially saturated vapor produced deaths of 2 of 5 female rats within one day, while no mortality was noted in the male rats.
Clinical signs:
Hypoactivity, a reduced breathing rate and ataxia were evident during or following exposure.
Body weight:
Body weight gain was noted in all the animals
Gross pathology:
Necropsy revealed dark red lungs in the rats that died, while the survivors had no remarkable gross pathologic findings.
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study and based on the Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, n-propyl propionate will not be classified for acute inhalation toxicity.
Executive summary:

In this study, Sprague-Dawley albino rats, weighing between 200 and 300 g, were exposed to substantially saturated vapor for 6 hours. The vapor was produced by enclosing approximately 100 g of the test material in a sealed 100 to 152-liter animal chamber for approximately 18 hours (static conditions). A mixing fan periodically agitated the chamber atmosphere to aid in distribution of the vapor. Oxygen was added, as needed, for static exposures to maintain chamber oxygen content of approximately 20%.

 

Exposure to a statically-generated, substantially saturated vapor (conversion value of 14031.58 ppm or 66 mg/l, based on vapor pressure of 10.664 mm Hg at 20 °C and molecular weight of 116.16) produced deaths of 2 of 5 female rats within one day, while no mortality was noted in the male rats. Hypoactivity, a reduced breathing rate and ataxia were evident during or following exposure. Survivors recovered after one day. Under the conditions of the study and based on the Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, n-propyl propionate will not be classified for acute inhalation toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
66 000 mg/m³
Quality of whole database:
Good

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to OECD TG 402 and there is no mention in the report on the status of compliance with the Principles of Good Laboratory Practice (GLP).
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: assumed to be in-house
- Age at study initiation: young adults
- Weight at study initiation: 2.0 - 3.0 kg
- Fasting period before study: no
- Housing: assumed to be individually housed
- Diet: appropriate commercial diet, ad libitum
- Water: municipal water, ad libitum
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
New Zealand White rabbits, weighing between 2.0 and 3.0 kg, were subjected to 24 hours of contact with the test material which was retained under impervious sheeting on the clipped, intact skin of the trunk. On account of the large dose, gauze was wrapped around the trunk over the sample to prevent leakage and Vetrap Bandaging Tape was wrapped over the impervious sheeting and the animal was returned to its cage for the contact period
Duration of exposure:
24 hours
Doses:
16 ml/kg
No. of animals per sex per dose:
5 male + 5 female rabbits
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed daily and body weights recorded weekly
- Necropsy of survivors performed: yes
Statistics:
LD50's and the estimated LD50 slopes were calculated by the moving average method
Preliminary study:
not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
16 mL/kg bw
Based on:
test mat.
Remarks on result:
other: Conversion value of 14028.96 mg/kg based on density of 0.87681 g/cc at 25 °C
Mortality:
There were no mortalities noted in the animals dermally exposed to n-propyl propionate
Clinical signs:
There were no signs of systemic toxicity observed.
Body weight:
Body weight gain was noted in all the animals
Gross pathology:
Gross pathologic findings included mottled or dark red lungs. The lungs of one rabbit were light pink with dark red foci.
Other findings:
Local dermal effects included erythema, edema, necrosis, ecchymosis, fissuring, ulcerations, desquamation, alopecia and scabs.

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, as the dermal LD50 of n-propyl propionate is in excess of 14000 mg/kg, hence based on the Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, n-propyl propionate will not be classified for acute dermal toxicity.
Executive summary:

In this study, New Zealand White rabbits, weighing between 2.0 and 3.0 kg, were subjected to 24 hours of contact with the test material which was retained under impervious sheeting on the clipped, intact skin of the trunk. On account of the large dose, gauze was wrapped around the trunk over the sample to prevent leakage and Vetrap Bandaging Tape was wrapped over the impervious sheeting and the animal was returned to its cage for the contact period. After the contact period, excess fluid was removed to diminish ingestion. Observations for skin reaction were made at one hour, 7 days and 14 days after the contact period.

 

By the percutaneous route, none of 5 male and none of 5 female rabbits died from 16.0 ml/kg. Local dermal effects included erythema, edema, necrosis, ecchymosis, fissuring, ulcerations, desquamation, alopecia and scabs. There were no signs of systemic toxicity observed. Gross pathologic findings included mottled or dark red lungs. The lungs of one rabbit were light pink with dark red foci. Under the conditions of the study, as the dermal LD50 of n-propyl propionate is in excess of 14000 mg/kg, hence based on the Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, n-propyl propionate will not be classified for acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
14 029 mg/kg bw
Quality of whole database:
Good

Additional information

Acute oral -

In a non-GLP study conducted with study methodology equivalent to OECD TG 401. No mortalities were noted in either sex upto 8.0 ml/kg, in the 11.3 ml/kg group - 2 males and 1 female rat were found dead and 100% mortality was noted in the 16.0 ml/kg group. Under the conditions of the study, as the oral LD50 of n-propyl propionate is in excess of 10000 mg/kg (male LD50 – 11.7 ml/kg ~ 10258.67 mg/kg and female LD50 – 12.6 ml/kg ~ 11047.80 mg/kg; conversions based on density of 0.87681 g/cc at 25 °C), Using the read-across approach, there are four studies available for butyl propionate and one study for pentyl propionate, The acute oral LD50 values for butyl propionate ranged between > 5000 to < 19786.3 mg/kg, while the acute oral LD50 value for propyl propionate was in excess of 10000 mg/kg. the acute oral LD50 value of pentyl propionate to male and female Sprague Dawley rats was > 16 ml/kg (Conversion from ml/kg to mg/kg resulted in - 16 ml/kg - 13920 mg/kg (based on density of 0.87)).

Acute dermal -

In a non-GLP study conducted with study methodology equivalent to OECD TG 402, the acute dermal LD50 value for propyl propionate was 14028.96 mg/kg (Conversion from ml/kg to mg/kg resulted in - 16 ml/kg – 14028.96 mg/kg (based on density of 0.87681)).

Using the read-across approach, there are three studies available (two rabbit studies and one rat study) for butyl propionate and one rabbit study for propyl propionate, The acute dermal LD50 values (rabbit) for butyl propionate was 14008 mg/kg (Conversion from ml/kg to mg/kg resulted in - 16 ml/kg - 14008 mg/kg (based on density of 0.8755)) and the LD50 value for rat was > 2000 mg/kg, while the acute dermal LD50 value of pentyl propionate to male and female New Zealand rabbits was > 16 ml/kg (Conversion from ml/kg to mg/kg resulted in - 16 ml/kg - 13920 mg/kg (based on density of 0.87)).

Acute inhalation -

In a non-GLP study conducted with study methodology equivalent to OECD TG 403, and the lethal time LT50 of propyl propionate to male and female Sprague Dawley rats exposed to saturated vapors over a period of 6 hours was > 14031.58 ppm or 66 mg/l.

Using the read-across approach, there are two studies available for butyl propionate and one study for propyl propionate. The acute inhalation LC50 of butyl propionate to male and female Sprague Dawley and male Wistar rats exposed to saturate vapors over a minimum for a period of 6 hours was 23.78 mg/l or 4473.68 ppm (based on conversion). The acute inhalation LC50 value of pentyl propionate to male and female Sprague Dawley rats exposed to saturated vapors over a period of 6 hours was > 10070 mg/m3 or 10.07 mg/l (based on conversion). This was the highest concentration atainable and produced no lethality.


Justification for selection of acute toxicity – oral endpoint
The study methodology followed was equivalent or similar to OECD TG 401

Justification for selection of acute toxicity – inhalation endpoint
The study methodology followed was equivalent or similar to OECD TG 403. The effect level was LT50

Justification for selection of acute toxicity – dermal endpoint
The study methodology followed was equivalent or similar to OECD TG 402

Justification for classification or non-classification

Based on the acute oral, dermal and inhalation LD/LC50 values noted andbased on the Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, propyl propionate will not be classified foracute toxicity via oral, dermal and inhalation routes of exposure.