Acrylaldehyde

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-08-08 to 1986-10-02

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:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

4 hour exposure as required by the guideline and additional experiments with 1 h exposures

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, CAS Registry No. 107-02-8, Aldrich Chemical Co., Inc.
- Physical state: no data
- Analytical purity: The 99+% Gold Label reagent was inhibited with approximately 3% water and 200 ppm hydrochinon
- Impurities (identity and concentrations): 3 % water, 200 ppm hydrochinon
- Purity test date: no data
- Lot/batch No.: 70526 JM
- Expiration date of the lot/batch: no data
- Stability under test conditions: stable when stored at room temperature
- Storage condition of test material: refrigerator

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc., Indianapolis, IN, USA
- Age at study initiation: males 56 to 73 days, females 56 to 93 days
- Weight at study initiation: males 250 to 323 g, females 201 to 247 g
- Fasting period before study: no data
- Housing: two or three per sex in 23.5 x 20 x 18 cm stainless-steel wire-mesh cages except during exposure
- Diet: ad libitum, standard laboratory pelleted feed (Certified Rodent Chow #5002, Ralson Purina Co.)
- Water: ad libitum, municipal tap water
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 24
- Humidity (%): 36 to 60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
-- 4 hour exposure: 21 x 12.5 x 18 cm wire-mesh cages exposed in 900-liter (approximate volume) rectangular, with pyramidal top and bottom, stainless-steel and glass chamber
-- 1 hour exposure: 26 x 18.5 x 18 cm wire-mesh cages exposed in a 120-liter (approximate volume) cuboidal Plexiglas and stainless-steel chamber
- Exposure chamber volume:
-- 4 hour exposure: 900 liter (approximate volume)
-- 1 hour exposure: 120 liter (approximate volume)
- Method of holding animals in test chamber:
-- 4 hour exposure: individually
-- 1 hour exposure: five per cage
- Source and rate of air: humified air, total chamber airflow rate (l/min) for 1 hour exposure 50 to 52, for 4 hour exposure 100 or 200
- Method of conditioning air:
- System of generating particulates/aerosols: dynamically generated: Liquid acrolein was metered with a syringe pump into a heated evaporator (evaporator temperature 26 or 32 °C in 1 hour experiment and 50 or 70 °C in 4 hour experiment). The evaporator tube (6´´ in length and 1´´ in diameter) used for the 1 hour exposures was filled with glass beads. The evaporator used for the 4 hour exposures was similar in design to that described by Carpenter et al., 1975. The resultant vapor was carried to the chamber by an air stream that entered the bottom of the evaporator or the top of the evaporator. For the 31, 22, and 14 ppm 1 hour exposure groups the acrolein test material/air mixture was further diluted with humified air. The acrolein test atmosphere was generated in the exposure chamber for 55, 46, 47, 26, and 41 minutes for the 81, 31, 24, 22, and 14 ppm exposures, respectively, prior to insertion of animals in order for the test concentration to reach equilibrium.
- Method of particle size determination: not determined
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: 24 to 26 °C, relative humidity during 1 hour exposures to 14, 22, 24, 31, and 81 ppm: 43+/-0 %, 42+/-3 %, 10 +/- 3 % (no humified air used for dilution), 42+/-1 %, and 30+/-5 % (no humified air used for dilution), relative humidity during 4 hour exposures appr. 53 to 57 %


TEST ATMOSPHERE
- Brief description of analytical method used: A Perkin-Elmar Model 3920B gas chromatograph eqipped with flame ionization detector was used to monitor the acrolein vapour concentration in the chamber
- Samples taken from breathing zone: no data


VEHICLE
- no vehicle used


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not relevant, vapour exposure
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): nor relevant, vapour exposure


- Rationale for the selection of the starting concentration:
The target concentration for the first 1 hour exposure was 81 ppm, based on literature information of a 30 minutes LC50 value of 130 ppm. The target concentrations for subsequent 1 hour groups, and for the 4 hour exposure groups, was based on the observed mortality of previous acrolein exposure groups.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gas chromaography with flame ionization detector

Duration of exposure:

4 h

Remarks on duration:

additional experiments with 1 h exposure performed

Concentrations:

measured:
- 4 hour exposures: 4.8, 7.0, 9.1, and 12.1 ppm (corresponding to appr. 0.0107, 0.0156, 0.0202, and 0.0269 mg/l)
- 1 hour exposures: 14, 22, 24, 31, and 81 ppm (rounded values, corresponding to 0.0311, 0.0489, 0.0533, 0.0690, and 0.1802 mg/l)

Conversion factor according to information given in the study report: 1 mg/l = 449.518 ppm at 735 Hg and 24 °C, molecular weight of acrolein=56.06, specific gravity= 0.844
The nominal concentrations for the 12.1, 7.0, and 4.8 ppm exposures as calculated from gravimetric measurements were 0.0368, 0.0228, and 0.0160 mg/l, respectively.

Mean measured concentrations including +/-standard deviation:
- 4 hour exposures: 4.8+/- 0.2, 7.0+/-0.2, 9.1+/-1.4, and 12.1+/-0.4 ppm
- 1 hour exposures: 14.5+/-6.9, 22.3+/-4.6, 23.6+/-1.4, 31.2+/-2.5, and 80.8+/-1.0 ppm

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: prior to exposure and on postexposure days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: Necropsy on death animals

Statistics:

The LC50 was determined by either the moving average method of Thompson (1947) or Finney´s (1964) probit analysis. The probit analysis method was used when assumptions for the moving averagesmethod could not be met.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

8.3 ppm

95% CL:

7 - 9.9

Exp. duration:

4 h

Remarks on result:

other: appr. 0.018 mg/L (95% C.I. 0.0156 to 0.022)

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

8.8 ppm

95% CL:

7 - 11

Exp. duration:

4 h

Remarks on result:

other: appr. 0.0196 mg/L (95% C.I. 0.0156 to 0.024)

Effect levels 3

Sex:

male

Dose descriptor:

LC50

Effect level:

7.4 ppm

95% CL:

5.9 - 9.3

Exp. duration:

4 h

Remarks on result:

other: appr. 0.016 mg/l (95% C.I. 0.013 to 0.021)

Effect levels 4

Sex:

male/female

Dose descriptor:

LC50

Effect level:

26 ppm

95% CL:

24 - 27

Exp. duration:

1 h

Remarks on result:

other: appr. 0.0578 mg/L (95% C.I. 0.0534 to 0.0601)

Effect levels 5

Sex:

female

Dose descriptor:

LC50

Effect level:

24 ppm

95% CL:

20 - 30

Exp. duration:

1 h

Remarks on result:

other: appr. 0.0534 mg/L (95% C.I. 0.0445 to 0.0667)

Effect levels 6

Sex:

male

Dose descriptor:

LC50

Effect level:

26 ppm

95% CL:

23 - 28

Exp. duration:

1 h

Remarks on result:

other: appr. 0.0578 mg/L (95% C.I. 0.0511 to 0.0622)

Mortality:

Mortalities were observed in all exposure groups with the exception of the 14 ppm (1 hour exposure) and the 4.8 ppm (4 hour exposure) group. Most deaths occured following exposure and through postexposure day 6.

Clinical signs:

other: Clinical signs were observed in all exposure groups and included lacrimation, periocular, perinasal, and perioral wetness and encrustation, unkempt fur, respiratory difficulties (mouth breathing, audible respiration, decreased respiration rate), hypoactiv

Body weight:

A loss of body weight or a depression in the body weight gain was observed for all exposure groups during the first week of the postexposure period, and for some animals in the 24 and 22 (1 hour exposures) and 12.1, 9.1, and 7.0 (4 hour exposures) ppm groups during the second week postexposure.

Gross pathology:

Macroscopic lesions were found only in animals which died and included perinasal and perioral encrustation, mottled discoloration of the lungs and liver, clear fluid in trachea and the thoracic cavity, red discoloration of the submandibular lymph nodes, gas-filled stomach and intestines, and opaque cloudy eyes.

Any other information on results incl. tables

Mortalities:

- 4 hour exposure

-- females: in exposure groups 4.8, 7.0, 9.1, and 12.1 ppm: 0/5, 0/5, 4/5 (deaths postexposure days 2 (3 animals) and 13), 3/5 (deaths postexposure day 2), respectively

-- males: in exposure groups 4.8, 7.0, 9.1, and 12.1 ppm: 0/5, 3/5 (deaths postexposure days 1 (2 animals) and 5), 3/5 (deaths postexposure days 1 and 2 (2 animals)), 5/5 (deaths postexposure days 1 (2 animals), 2 (2 animals) and 3), respectively

- 1 hour exposure

-- females: in exposure groups 14, 22, 24, 31, and 81 ppm: 0/5, 1/5 (death postexposure day 2), 1/5 (death postexposure day 1), 5/5 (deaths postexposure days 1, 2 (2 animals), 4 and 6), 5/5 (deaths postexposure days 0 (2 animals died within 4 hours following exposure), 2 (2 animals) and 3)

-- males: in exposure groups 14, 22, 24, 31, and 81 ppm: 0/5, 0/5, 2/5 (death postexposure day 3), 5/5 (deaths postexposure days 0 (2 animals died within 4 hours following exposure) and 2 (3 animals), 5/5 (deaths postexposure days 0 (4animals died within 4 hours following exposure) and 3)

Clinical signs:

Clinical signs observed during exposure included lacrimation, perinasal, and perioral wetness and mouth breathing. Clinical signs observed following exposure or during the first week postexposure included perinasal, and perioral wetness and encrustation, unkempt fur, respiratory difficulties (mouth breathing, audible respiration, decreased respiration rate), hypoactivity. An additional sign observed following exposure for the 4.8 ppm (4 hours) exposure group was gas-filled distended stomachs. In general, signs of respiratory distress and hypoactivity were observed during exposure and for 1 to 6 days postexposure. THe only sign of respiratory distress observed for the 14 ppm (1 hour) groups was perinasal wetness. The only sign observed during the second week postexposure included perinasal and periocular encrustation and unkempf fur.

Body Weights:

A loss of body weight or a depression in body weight gain was observed for both sexes during the first week of the postexposure period for all exposure groups. During the second week postexposure body weight gains were observed for all males with the exception of those in the 24 ( 1 hour exposure) and 9.1 (4 hour exposure) ppm exposure groups. Mean body weight gains were observed during the second postexposure week for females in the 14, 22, and 24 ppm 1 -hour exposure groups and in the 4.8, 7.0, and 12.1 ppm 4 -hour exposure groups. However, a further loss of body weight was observed for one female rat in the 22 (1 hour exposure) and 12.1 (4 hour exposure) ppm groups. In addition, a depression in body weight gain was observed for females in the 7.0 ppm exposure group relative to females of comparable age in the 4.8 ppm exposure group.

Necropsy:

Gross lesions were observed in animals which died and included perinasal and perioral encrustation, mottled discoloration of the lungs and liver, cleear fluid in the trachea and thoracic cavity, red discoloration of the submandibular lymph nodes, gas-filled stomach and intestines, opaque or cloudy eyes, and subdural hemorrage.

No macroscopic lesions were observed in rats sacrificed after the 14 -day recovery period.

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Remarks:

Migrated information

Executive summary:

In an acute inhalation toxicity study equivalent or similar to OECD Guideline 403, groups of 5 young male and female adult Sprague-Dawley rats were exposed by inhalation route to acrolein (> 99% a.i.) for 4 hours or 1 hour to whole body at concentrations of  4.8, 7.0, 9.1, and 12.1 ppm (corresponding to appr. 0.0107, 0.0156, 0.0202, and 0.0269 mg/l) in the 4-hour exposure experiment and to 14, 22, 24, 31, and 81 ppm (rounded values, corresponding to 0.0311, 0.0489, 0.0533, 0.0690, and 0.1802 mg/l) in the 1-hour experiment .  Animals then were observed for 14 days.

 

4 -hour LC₅₀ Males = 7.4 ppm (95% C.I. 5.9 to 9.3), corresponding to appr. 0.016 mg/l (95% C.I. 0.013 to 0.021)

4 -hour LC₅₀ Females = 8.8 ppm (95% C.I. 7.0 to 11.0), corresponding to appr. 0.0196 mg/L (95% C.I. 0.0156 to 0.024)

4 -hour LC₅₀ Combined = 8.3 ppm (95% C.I. 7.0 to 9.9), corresponding to appr. 0.018 mg/L (95% C.I. 0.0156 to 0.022)

       

1 -hour LC₅₀ Males = 26 ppm (95% C.I. 23 to 28), corresponding to appr. 0.0578 mg/L (95% C.I. 0.0511 to 0.0622)

1 -hour LC₅₀ Females = 24 ppm (95% C.I. 20 to 30), corresponding to appr. 0.0534 mg/L (95% C.I. 0.0445 to 0.0667)

1 -hour LC₅₀ Combined = 26 ppm (95% C.I. 24 to 27), corresponding to appr. 0.0578 mg/L (95% C.I. 0.0534 to 0.0601)

(Conversion factor used: 1 mg/l = 449.518 ppm at 735 mm Hg and 24 °C as given by the study authors)

Mortalities were observed in all exposure groups with the exception of the 14 ppm (1 hour exposure) and the 4.8 ppm (4 hour exposure) group. Most deaths occured following exposure and through postexposure day 6.

Clinical signs were observed in all exposure groups and included lacrimation, periocular, perinasal, and perioral wetness and encrustation, unkempt fur, respiratory difficulties (mouth breathing, audible respiration, decreased respiration rate), hypoactivity, distended stomachs, and a loss of body weight or a depression in the body weight gain.

Macroscopic lesions were found only in animals which died and included perinasal and perioral encrustation, mottled discoloration of the lungs and liver, clear fluid in trachea and the thoracic cavity, red discoloration of the submandibular lymph nodes, gas-filled stomach and intestines, and opaque cloudy eyes.

Acrolein is classified as being of High Toxicity based on 4 -hour LC₅₀ values of 7.4 and 8.8 ppm in male and female rats, respectively.