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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992
Reference Type:
secondary source
Title:
document ID 86-9300000070
Author:
TSCATS
Year:
1992
Bibliographic source:
Microfiche OTS0543436
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
only 3 male rats used
GLP compliance:
yes
Remarks:
Bushy Run Research Center
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): propionaldehyde
- Physical state: liquid
- Analytical purity: approx. 99.77%
- Impurities (identity and concentrations): n-propanol: 0.01%, 2-methyl butyraldehyde: 0.02%, valeraldehyde: 0.06%, propionic acid: 0.07%, propionaldehyde dimers: 0.03%, propionaldehyde trimers: 0.01%, all other: approx. 0.03%
- 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: Harlan Sprague Dawley, Inc. (Indianapolis, IN, USA)
- Age at study initiation: female: 6-11 weeks, male: 6-8 weeks
- Weight at study initiation: female: 220-240 g, male: 195-215 g
- Fasting period before study: 18 hours
- Housing: up to 5 per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3 - 25
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: varied by changing the concentration of the test substance in the dosing dilutions and maintaining a constant dose volume.

MAXIMUM DOSE VOLUME APPLIED: 1ml of dose / 100g of rat body weight

DOSAGE PREPARATION: each dosing mixture was prepared just prior to administration by diluting the appropriate amount of propionaldehyde with distilled water. All dilutions were mixed for approximately 2 to 3 minutes on a magnetic stirrer.
Doses:
2000, 1410, 1000 mg/kg b.w.
No. of animals per sex per dose:
3 male with 2000 mg/kg,
15 female: 5 per dose
(3 male for preliminary tests)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on the first day of the test and twice a day thereafter (except on weekends or holidays when they were examined for death alone); weights were recorded on the day of dosing and at 7 and 14 days after dosing and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
1 690 mg/kg bw
Based on:
test mat.
95% CL:
> 1 440 - < 1 990
Sex:
male
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 2 of 3 dead
Mortality:
2/3 male rats at 2000mg/kg b.w. by day 2 after application
5/5 female rats at 2000mg/kg b.w. by day 1 after application
0/5 female rats at 1410 mg/kg b.w.
0/5 female rats at 1000 mg/kg b.w.
Clinical signs:
male rats: Marked unsteady gait at 2 min, prostration, marked labored breathing at 3 min; marked sluggishness, lacrimation at 30 min. Partial recovery at 30 min but followed by death at day 1 or 2, if not followed by death recovery at day 2. In 2 of 3 rats red crust on perinasal fur at day 1.
female rats: 2000mg/kg b.w.: Marked sluggishness at 2 min (5/5), prostration (5/5), marked labored breathing at 3 min (5/5), marked unsteady gait (4/5), gray eys at 45 min (1/5), lacrimation at 2.5 hr (4/5), partial recovery at 45 min but followed by death at 1 day (4/5).
female rats: 1410mg/kg b.w.: marked unsteady gait at 2 min. (5/5), prostration (5/5), marked labored breathing at 3 min (5/5), lacrimation at 45 min (1/5), red crust on perinasal fur at day 1 (5/5), red crust at periocular fur (1/5), moderate to large amount of blood in urine (2/5), emaciation at day 6 (1/5), marked sluggishness at 45 min (4/5), partial recovery at 45 min (5/5) or at 1.25h (1/5), recovery at day 2 (4/5) and at day 10 (1/5)
female rats: 1000mg/kg b.w.: Sluggishness (3/5), labored breathing at 2 min (5/5), recovery at 1 hour (5/5)
Body weight:
male: day 0: 247 ± 22.5 g; day 7: 287g; day 14: 320 g
female: 2000 mg/kg b.w.: day 0: 223 ± 3.2g
female: 1410 mg/kg b.w.: day 0: 218 ± 6.2 g; day 7: 224 ± 21.8 g; day 14: 238 ± 14.2 g
female: 1000 mg/kg b.w.: day 0: 228 ± 8.3 g ; day 7: 243 ± 7.4 g; day 14: 257 ± 13.6 g
Gross pathology:
male rats: #1: Lunges mottled dark red, liver mottled dark maroon, stomach gray (glandular portion), intestines red (hamorraged), moderate amount of blood in urine. #2: Lungs with multiple, red pinpoint foci. #3: Lungs mottled red; stomach (glandular portion) dark red and purple hemorrhaged), intestine dark brown (possibly necrotic), kidneys mottled tan, moderate amount of blood in urine.
female rats: 2000mg/kg b.w.: Lungs light red to red (5/5), small amount of foam present in trachea (3/5), glandular portion of stomach red and purple (hemorrhaged; 3/5), upper portion of intestines black (necrotic;4/5), liver dark marron (1/5).
female rats: 1410mg/kg b.w.: Glandular portion of stomach light tan with a thickened texture (possibly ulcerated; 1/5), non-glandular portion of stomach enlarged (1/5).
female rats: 1000mg/kg b.w.: Lungs with red foci (1/5), lungs mottled red and pink (2/5), liver anomaly (1/5), pinworms in colon (1/5)

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the experiment conditions chosen, the peroral LD50 for propionaldehyd, expressed in terms of test substance as received, was 1690 mg/kg b.w. for female rats. There was no marked difference between genders.