Registration Dossier

Administrative data

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).
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): n-propyl propionate
- Physical state: colorless, transparent, low viscosity liquid
- Analytical purity: 100%
- Lot/batch No.: 51-535; 52-19 (15RLRX51)
- Storage condition of test material: room temperature

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:
not applicable
Effect levelsopen allclose all
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

Any other information on results incl. tables

None

Applicant's summary and conclusion

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.