Registration Dossier

Administrative data

Description of key information

"The oral LD50 values vary between 13.9-28 mg/kg bw (mouse) and 42-46 mg/kg bw (rat). When administered dermally the LD50 values in rabbits range from 164 to 1022 mg/kg bw depending on the vehicle and concentration of acrolein applied. The dermal LD50 value of undiluted acrolein is reported to amount to 562 mg/kg bw. The 4-h LC50 values are 18-150 mg acrolein vapour/m³ in the rat and 58 mg/m³ in hamsters (nature of the substance is unknown). In mice the 6-h LC50 value is 151 mg acrolein vapour/m³. Signs of toxicity after single oral administration included decrease of motor activity, lethargy, loss of reflexes and muscle tone, tremor, respiratory distress, squinted eyes, rough coats, hunching, piloerection, blackening and breaking of tail tips, reduced body weight gain, lung congestion and oedema as well as haemorrhagic stomach and intestines. There are no data on effects (other than mortality) after acute dermal administration. After inhalation exposure, signs of eye and nose irritation, mouth breathing, decreased breathing rate, body weight loss, and discoloration of lungs and liver were reported. Microscopic examination of the lungs revealed congestion, haemorrhages, fibrin deposition and necrosis." quotation from European Union Risk Assessment Report Acrylaldehyde (EU, 2001) 
Studies on sensory irritation after acute inhalation exposure are referred in Chapter 7.3.
"Assessment of the available acute toxicity data indicates that, according to the EC-classification criteria, acrolein is toxic by the oral and dermal route and very toxic after exposure by inhalation." quotation from European Union Risk Assessment Report Acrylaldehyde (EU, 2001)

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:
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
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
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
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)
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.
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.

Endpoint conclusion
Dose descriptor:
LD50
Value:
13.9 mg/kg bw

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:
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
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
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
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.
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)
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)
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)
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)
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)
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.

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.

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.

Endpoint conclusion
Dose descriptor:
LC50
Value:
18 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
164 mg/kg bw

Additional information

Acrolein has been the subject of a risk assessment carried out under Community Regulation (EEC) No 793/93 (EU, 2001). The key information on acute toxicity of acrolein as stated is a quotation taken from this EU Risk Assessment. The information on acute toxicity of acrolein given in the EU Risk Assessment correspond to the greatest extend to further assessments carried out under other international and national programmes published after finalisation of the EU Risk Assessment Report 2001 (World Health Organization, International Programme on Chemical Safety (IPCS), Concise International Chemical Assessment Document of Acrolein, CICADS 43 (WHO, 2002); United States Environmental Protection Agency, Toxicological Review of Acrolein (US-EPA, 2003); United States Agency for Toxic Substances and Desease Registry, Toxicological Profile for Acrolein (US ATSDR, 2007); United States Environmental Protection Agency, HED Risk Assessment for Reregistration Eligibility Decision (RED) Document for Acrolein (US-EPA, 2008)):

1. European Union Risk Assessment Report of Acrolein (EU, 2001)

Acute Toxicity: Oral:

"The oral LD50 values vary between 13.9-28 mg/kg (mouse) and 42-46 mg/kg bw (rat)."

"Signs of toxicity after single oral administration included decrease of motor activity, lethargy, loss of reflexes and muscle tone, tremor, respiratory distress, squinted eyes, rough coats, hunching, piloerection, blackening and breaking of tail tips, reduced body weight gain, lung congestion and oedema well as haemorrhagic stomach and intestines." quotations from EU, 2001, p 57

Acute Toxicity: Inhalation:

"The 4-h LC50 values are 18-150 mg acrolein vapour/m³ in the rat and 58 mg/m³ in hamsters (nature of the substance is unknown). In mice the 6-h LC50 value is 151 mg acrolein vapour/m³."

"After inhalation exposure, signs of eye and nose irritation, mouth breathing, decreased breathing rate, body weight loss, and discoloration of lungs and liver were reported. Microscopic examination of the lungs revealed congestion, haemorrhages, fibrin deposition and necrosis."

"One- and/or three-day exposures of rats resulted in cell proliferation at the lowest concentration levels examined i.e. 0.2 - 0.25 ppm (0.47-0.58 mg/m³) acrolein and higher, and slight but treatment-related histopathological changes in the respiratory/transitional but not in the olfactory epithelium of the nose of rats exposed to 0.25 ppm (0.58 mg/m³) and higher." quotations from EU, 2001, p 57 and p 66

Studies on sensory irritation after acute inhalation exposure are referred in Chapter 7.3.

Acute Toxicity: Dermal:

"When administered dermally LD50-values in rabbits range from 164 to 1022 mg/kg bw depending on the vehicle and concentration of acrolein applied. The dermal LD50 value of undiluted acrolein is reported to amount to 562 mg/kg bw." "There are no data on effects (other than mortality) after acute dermal administration." quotations from EU, 2001, p 57

Acute Toxicity: Other Routes:

"Male SD rats, given a single intravenous injection at 0.5 or 1 mmol/kg bw of the 1:1 acrolein- GSH adduct, developed nephrotoxicity characterized by glycosuria, proteinuria, elevation in serum urea nitrogen, and gross and histopathologic changes of the kidneys. The nephrotoxicity was inhibited by acivicin, a gamma- glutamyltranspeptidase inhibitor, indicating that the 1:1 acrolein- GSH adduct requires processing through the first step of the renal mercapturic acid synthesis pathway to be activated to a toxic species. Rats given iv 0.1 mmol of the adduct per kg bw once did not show any signs of nephrotoxicity (Horvath et al., 1992)." "It is noted that doses of 0.1, 0.5 and 1 mmol of the 1:1 acrolein-GSH adduct represent 14, 28 and 56 mg acrolein per kg bw, respectively. These dose levels are extremely high in relation to the reported LD50- and LC50-values of acrolein." quotations from EU, 2001, p 57

2. Agreement with further International Reports and Studies Published after Finalisation of the EU Risk Assessment Report 2001

No substantial deviations in characterisation of these intrinsic properties have been found in the EU Risk Assessment Report 2001 to WHO, 2002; US-EPA, 2003, US ATSDR, 2007 and US-EPA, 2008.

Due to the large number of available studies on the acute toxicity of acrolein and a slightly deviating selection of studies referred in the individual international reports, the reported range of LD50values and LC50 values deviate to some extent between the reports. Furthermore, the focus of the different international reports are non-identically, therefore the way of data preparation and elaborateness are different, especially in US-EPA, 2003, US ATSDR, 2007 and US-EPA, 2008 in comparison to the EU Risk Assessment Report 2001. However, within the individual reports the judgement on acute toxicity does not substantially deviate.

3. Substantial Disagreements in Comparison to further International Reports to European Union Risk Assessment Report 2001

None

4. Additional Aspects in further International Reports

US ATSDR, 2007: In the US ATSDR (2007) two limited publications on observations in humans after exposure to acrolein are referred: Gosselin et al. (1979) and Champeix et al. (1966). These two studies are supporting studies to the information given in EU, 2001.

Gosselin et al. (1979) "described the cases of 2- and 4-year-old boys exposed for 2 hours to acrolein-containing smoke from an overheated fryer. The 2-year-old boy died 24 hours later of asphyxia. The data from this case report must be considered qualitative only, since smoke components other than acrolein may have contributed to the injury." quotation from US ATSDR, 2007, p 20

Champeix et al. (1966) reported a case of a 36-year-old male who was accidentally exposed to unknown concentrations of acrolein vapours in the workplace for < 1 day (duration assumed). Observed symptoms included high fever, dyspnea, coughing, foamy expectoration, and cyanosis. Eighteen months after the exposure, the chronic pneumopathy and dyspnea persisted, although no information was reported regarding any pre-existing pulmonary conditions or possible lifestyle factors (i.e., smoking) that may have impacted the diagnosis." quotation from US ATSDR, 2007, p 35

5. Additional Information in Newer Studies, not Included in the European Union Risk Assessment Report 2001 or further Cited International Reports

None substantial

The following information is taken into account for hazard / risk assessment:

The oral LD50 values vary between 13.9-28 mg/kg bw (mouse) and 42-46 mg/kg bw (rat). When administered dermally the LD50 values in rabbits range from 164 to 1022 mg/kg bw depending on the vehicle and concentration of acrolein applied. The dermal LD50 value of undiluted acrolein is reported to amount to 562 mg/kg bw. The 4-h LC50 values are 18-150 mg acrolein vapour/m³ in the rat and 58 mg/m³ in hamsters (nature of the substance is unknown). In mice the 6-h LC50 value is 151 mg acrolein vapour/m³. Signs of toxicity after single oral administration included decrease of motor activity, lethargy, loss of reflexes and muscle tone, tremor, respiratory distress, squinted eyes, rough coats, hunching, piloerection, blackening and breaking of tail tips, reduced body weight gain, lung congestion and oedema as well as haemorrhagic stomach and intestines. There are no data on effects (other than mortality) after acute dermal administration. After inhalation exposure, signs of eye and nose irritation, mouth breathing, decreased breathing rate, body weight loss, and discoloration of lungs and liver were reported. Microscopic examination of the lungs revealed congestion, haemorrhages, fibrin deposition and necrosis.

Assessment of the available acute toxicity data indicates that, according to the EC-classification criteria, acrolein is toxic by the oral and dermal route and very toxic after exposure by inhalation.


Justification for selection of acute toxicity – oral endpoint
Key study; see also European Union Risk Assessment Report of Acrolein (EU, 2001)

Justification for selection of acute toxicity – inhalation endpoint
Key study; see also European Union Risk Assessment Report of Acrolein (EU, 2001)

Justification for selection of acute toxicity – dermal endpoint
see European Union Risk Assessment Report of Acrolein (EU, 2001)

Justification for classification or non-classification

Legally binding harmonised classification as given in REGULATION (EC) No 1272/2008 Annex VI

Table 3.1 (CLP):

Acute tox. 2*      H330

Acute tox. 3*      H311

Acute tox. 3*      H301

 

Table 3.2 (Annex I of Directive 67/548/EEC):

T+; R26

T; R24/25

 

Re-classification of minimum classification:

However, the inhalative 4-h LC50 values are 18-150 mg acrolein vapour/m³ (0.018 -0.15 mg/l) in the rat and 58 mg/m³ (0.058 mg/l) in hamsters (nature of the substance is unknown). In mice the 6-h LC50 value is 151 mg acrolein vapour/m³ (0.151 mg/l). These acute vapour toxicity estimates (ATE) are </= 0.5 mg/l. The oral LD50 values are 42-46 mg/kg bw in the rat and 13.9-28 mg/kg bw in mice. These acute oral toxicity estimates (ATE) are > 5 and < 50 mg/kg bw. Therefore, in deviation to the classification as given in REGULATION (EC) No 1272/2008 Annex VI Table 3.1 (GHS), acrolein should be classified:

Acute tox. 1      H330 for inhalative exposure route

Acute tox. 2      H300 for oral exposure route

Acute tox. 3      H311 for dermal exposure route (remaining in acute tox 3 after re-classification)

 

In addition to classification for inhalation toxicity, according to Annex I No. 3.1.2.3.3 (CLP) the test substance acrolein should be classified as:

EUH071      Corrosive to the respiratory tract

The mechanism of toxicity of acrolein is corrosive. Microscopic examination of the lungs revealed congestion, haemorrhages, fibrin deposition and necrosis (EU, 2001).