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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Allyl methacrylate
EC Number:
202-473-0
EC Name:
Allyl methacrylate
Cas Number:
96-05-9
Molecular formula:
C7H10O2
IUPAC Name:
prop-2-en-1-yl 2-methylprop-2-enoate
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, England
- Age at study initiation: approximately 7 and 8 weeks old, respectively
- Housing: by sex in groups of 5
- Diet: free access to a measured excess amount of food (SDS rat and mouse diet (RMI))
- Water: free access to tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 22.5
- Humidity (%): 36 - 64
- Air changes (per hr): 15

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus / Method of holding animals in test chamber: The snout-only exposure chambers used for the exposures were of cylindrical form. The internal surfaces of the chamber have a chemically resistant coating. The rats were held for exposure in moulded polycarbonate restraining tubes, which were attached at evenly spaced ports in the cylindrical section of the chamber and were designed to allow only the snout to project into the chamber: Each rat was restrained in a forward position by an adjustable toamed plastic stopper which also provided a seal for the tube. The conditioned test atmosphere entered through a port at the top centre of the chamber and passed out through a port below the level of rats. Each chamber was positioned in a large cabinet equipped with an exhausting through an absolute filter.
- Source and rate of air: A pre-heated supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 12 litres/min - measured at the generator outlet tube.
- Method of conditioning air: The resultant test vapour was passed through a glass column containing glass wool in order to remove any condensate.
- System of generating particulates/aerosols: by evaporation of the test substance from a fritted glass disc with a countercurrent of air; the air supply to the vaporiser was warmed by passage through a stainless steel coil immersed in water maintained at 35 - 40°C in a water bath, as an aid to evaporation; the test substance was supplied to the generator from a syringe driven at a constant rate by a syringe pump; the compressed air supply to the generator was dried, filtered and oil free;
- Temperature, humidity, pressure in air chamber: The chamber exhaust was calibrated at the point of attachment to the exposure chamber and was adjusted to produce a slightly negative chamber pressure. The temperature and humidity were recorded at the start of exposure and then at 30-minute intervals during the 4-hour exposure: mean temperature: 20.1 - 20.8°C; mean humiditiy: 33 - 38%; the mean relative humidity of test atmospheres was marginally lower than the control valve and was considered not to have affected the outcome of the study. The mean chamber air temperature was similar for the control and test atmospheres;

TEST ATMOSPHERE
- Brief description of analytical method used: At least five air samples were taken from the chamber during each exposure in order to detemine the concentration of the test substance in air (analyzed by HPLC). Samples were obtained following equilibration and then approximately at hourly intervals. An additional sample was taken during the exposure of Group 2 (Sample 2) in order to ensure satisfactory generation of the test atmosphere.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Mean chamber concentration: 0, 1.02 and 2.13 mg/L (198 and 414 ppm); the nominal concentrations were 3.18 and 1.49 mg/L; the mean chamber concentrations of allyl methacrylate were approximately 67 % and 68 % of the nominal concentrations; such differences are considered likely to be associated with condensation of the test substance in the exposure system;
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, food consumption, water consumption, the lungs (including the Iarynx and trachea) were removed, dissected clear of surrounding tissue, weighed and the weights recorded;
Statistics:
no data

Results and discussion

Preliminary study:
no data
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1.47 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: LC50 (4- hour) for allyl methacrylate is between 1.02 and 2.13 mg/L (198 and 414 ppm) in air and may be considered equivalent to 1.47 mg/L (278 ppm), the geometric mean of these two concentrations.
Mortality:
Group 1 (control): 0/5 (males), 0/5 (females);
Group 2 (2.13 mg/L): 5/5 (males), 5/5 (females);
Group 3 (1.02 mg/L): 0/5 (males), 0/5 (females);

All deaths occurred within 1 day of exposure.
Clinical signs:
other: During exposure: Exaggerated breathing was first noted in test rats at 15 and 30 minutes into exposure for Groups 2 and 3, respectively. A decreased breathing rate was evident in all Group 3 test rats from 2 hours into exposure. Observation period: Gaspin
Body weight:
Bodyweight losses were recorded for all Group 2 decedents prior to necropsy. A mean bodyweight loss was evident for Group 3 rats during the 4-day period following exposure. Thereafter, a general bodyweight gain was evident for Group 3 rats for Days 4 to 7 of the observation period. The mean bodyweight gain of Group 3 rats during the second week of the observation period was similar to or greater than control values for males and females respectively.
Gross pathology:
Decedents (Group 2): The lungs of a proportion of decedents were minimally/moderately congested. A clear or white frothy discharge from the trachea was evident in a proportion of decedents. Gas-filled stomachs and intestines were noted in all decedents and a decedent male respectively. External findings noted prior to necropsy included crusty brown staining around snout and jaws, clear discharge from snout, wet fur (snout/jaws) and fur soiled with excreta.
Rats surviving the 14-day observation period: There were no treatment-related findings.
Lung weights:
Decedents (Group 2): The lung weights of female decedents were higher than similarly treated rats surviving the 14-day observation period.
Rats surviving the 14-day observation period: There were no treatment-related effects.
External findings of fur soiled with excreta and matted fur in the urino-genital region were noted for a Group 3 female prior to necropsy.
Other findings:
A reduction in the food consumption of Group 3 rats was evident during the first week following exposure. There were no treatment-related effects in water consumption.

Any other information on results incl. tables

The 'mortality curve' (mortality plotted against chamber concentration) in this investigation was relatively steep, with no unscheduled deaths following exposure at 1.02 mg/l and 100% mortality at 2.13 mg/l. Exposure of further groups was therefore considered unnecessary.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category II
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
The 4 hour LC50 value for allyl methacrylates in rats (male and female) was 1,47 mg/l air.
Executive summary:

In an acute inhalation toxicity study according to OECD 403 the LC50 (4-hour) for allyl methacrylate is between 1.02 and 2.13 mg/l (198 and 414 ppm) in air and may be considered equivalent to 1.47 mg/l (278 ppm), the geometric mean of these two concentrations.