Acrylaldehyde

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982-12-16 to 1982-12-30

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Acrylaldehyde

EC Number:

203-453-4

EC Name:

Acrylaldehyde

Cas Number:

107-02-8

Molecular formula:

C3H4O

IUPAC Name:

acrylaldehyde

Details on test material:

- Name of test material (as cited in study report): Acrolein
- Physical state: liquid
- Analytical purity: greater than 96 %
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: 6241
- Expiration date of the lot/batch: no data
- Stability under test conditions: at least 5 days
- Storage condition of test material: room temperature (dose preparation)
- Other: density: 0.845 g/ml at 20 °C
- Other: solubility: 16 % w/v in water (used solvent)

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratory, Wilmington, Massachusetts, USA
- Age at study initiation: 5 weeks
- Weight at study initiation: 20.3 . 24.0 g
- Fasting period before study: yes, overnight prior to dosing
- Housing: polycarbonate cages, five animals per cage, Hazelton system
- Diet (e.g. ad libitum): ad libitum, Zeigler NIH-07 pelleted diet
- Water (e.g. ad libitum): ad libitum, from an automatic watering system, untreated city water
- Acclimation period: 1 day


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 69-72
- Humidity (%): 48-65
- Air changes (per hr): 12-16 complete changes of 100% fresh air filtered through roughing filter Varicol and HEPA filters prior to introduction into the animal room
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle (lights on 7 am to 7 pm), fluorescent, automatically controlled; the lights were on due to a broken timer at two evenings

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1.10, 1.32, 1.58, and 1.90 mg/ml
- Amount of vehicle (if gavage): 10 ml
- Justification for choice of vehicle: test item is soluble in the vehicle
- Lot/batch no. (if required): N/A
- Purity: resistance greater than 10 megaohms

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION: Separate stock solutions were prepared fresh for each dose level. An appropriate volume of acrolein was placed in a 100 ml volumetric flask and the volume was adjusted to 100 ml with deionized water. Spectrophotometrically dose analysis at 10 nm was performed. The analyzed concentrations of acrolein in the dose formulations were found to be within 4% of the target dose level.

Doses:

11.0, 13.2, 15.84, and 19.0 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: during the day of dosing and twice daily therafter for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: gross necropsy on all animals that died during the test, body weight on the day of dosing, on day 7 and at death or sacrifice

Statistics:

according to D.J. Finney, Probit Analysis, 2nd Edition, University Press, Cambridge (1952)

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

13.9 mg/kg bw

95% CL:

12.9 - 15.1

Mortality:

19.00 mg/kg bw: 6/10 (3/10 within 1-6 hours, 2/10 within 18-24 hours, and 1/10 within 30-48 hours after dosing)
15.84 mg/kg bw: 8/10 (2/10 within 1-6 hours, 4/10 within 18-24 hours, 1/10 within 24-30 hours, and 1/10 within 30-48 hours after dosing)
13.20 mg/kg bw: 4/10 (2/10 within 18-24 hours, and 2/10 within 30-48 hours after dosing)
11.00 mg/kg bw: 4/10 (2/10 within 18-24 hours, and 2/10 within 24-30 hours after dosing)

Clinical signs:

Immediately following dose administration, through Day 3 post-dosing, the majority of animals at all dose levels showed signs of lethargy, squinted eyes, rough coats, hunching, and pilo erection.
The surviving animals of all dose levels showed rough coats for varying lengths of time through most of the observation period.
Blackening, followed by necrosis and breaking of the tips of the tails were found in several of the survivors with the exception of the controls.
Control animals remained healthy throughout the observation period.

Body weight:

On day 7, all levels showed reduced body weight gain compared to the controls.
At terminal sacrifice , animals dosed with 11.0, 15.84, or 19.0 mg/kg bw had increased their rate of weight gain substantially when compared to day 7. All dose levels, however, still showed reduced weight gains of -11.6% to -28.6% compared to controls.

Gross pathology:

Died animals: Most animals which died 1-3 days after dosing showed reddening of the lungs, and hemorrhagic stomachs and intestines.
Surviving animals: At terminal sacrifice, one animal dosed with 13.2 mg/kg bw (second dose level) showed reddening of the lungs. All other animals sacrificed (by CO2 asphyxiation) at the termination of the study showed minimal, non-specific lesions.

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Remarks:

Migrated information

Executive summary:

In an acute oral toxicity study (standard acute method, aquivalent or similar to OECD 401), 10 male CD1 mice were given a single oral dose of 11.0, 13.2, 15.84, and 19.0 Acrolein (at least 96 % a.i., formulated in deionized water) and observed for 15 days.

 

Oral LD₅₀ Males 13.9 mg/kg bw (95% confidence level: 1.8 - 15.1 mg/kg bw)

At the dose levels 11.0, 13.2, 15.84, and 19.0 mg/kg bw, 4/10, 4/10, 8/10, and 6/10 animals died within 48 hours post dosing, respectively. Immediately following dose administration, through Day 3 post-dosing, the majority of animals at all dose levels showed signs of lethargy, squinted eyes, rough coats, hunching, and pilo erection. All dose levels showed reduced weight gains of -11.6% to -28.6% compared to controls. Most animals which died 1-3 days after dosing showed reddening of the lungs, and hemorrhagic stomachs and intestines. At terminal sacrifice, one animal dosed with 13.2 mg/kg bw (second dose level) showed reddening of the lungs. All other animals sacrificed (by CO2 asphyxiation) at the termination of the study showed minimal, non-specific lesions.

 

Acrolein is of high toxicity based on the LD₅₀ in males.