tert-butyl methacrylate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-12-20 to 1992-02-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

tert-butyl methacrylate

EC Number:

209-548-7

EC Name:

tert-butyl methacrylate

Cas Number:

585-07-9

Molecular formula:

C8H14O2

IUPAC Name:

tert-butyl 2-methylprop-2-enoate

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- batch number of test material: 1430811

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

FORM AS APPLIED IN THE TEST (if different from that of starting material)
- aerosol

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 Laboratories, Inc., Manston, Kent, UK
- Age at exposure initiation: 8 to 10 weeks
- Weight at study initiation: male rats weighed 226 to 245 g and female rats weighed 214 to 237 g
- Housing: 5 animals per cage (sexes separate) in polypropylene cages with saw dust bedding
- Diet: Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited Witham, Essex, U.K., ad libitum)
- Water: Drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 40- 68
- Air changes: approx. 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass concentric jet nebuliser (Radleys, Sawbridgeworth, Herts.) connected to a glass syringe attached to a modified infusion pump, which provided a continuous supply of test material under pressure, and to a metered compressed air supply
- Exposure chamber volume: approx. 30 L
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber '0' ring.
- Source and rate of air (airflow): Compressed air was supplied by means of a Gast 2HBB-10-P25Y oil free compressor
- Temperature, humidity, pressure in air chamber: 20 - 21°C, 27 - 42%, negative pressure
- air flow: 17 L/min, providing 34 air changes/h

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: a known amount of the chamber atmosphere was pumped through a dreschel flask containing 40 mL of methanol. After sampling, the dreschel head was flushed through with a further 10 mL of methanol to remove any deposits. This gave a 50 mL sample to be submitted for chemical analysis (spectrophotometrical analysis using an external standard technique)
- Samples taken from breathing zone: not specified
- Time needed for equilibrium of exposure concentration before animal exposure: 8 min

TEST ATMOSPHERE (if not tabulated)
Due to the volatile nature of the test material the distribution of particles was not determined. Particle size analysis was therefore not performed during the study.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

10.17 mg/L (range 9.29 - 11.07 mg/L)

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 and weighing: All animals were observed, for clinical signs, at hourly intervals during the exposure, one hour after termination of the exposure and subsequently once daily for 14 days. Any deaths or evidence of overt toxicity were recorded at each observation.
- Necropsy of survivors performed: yes
- Clinical signs including body weight

Statistics:

Not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 10.17 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities occurred

Clinical signs:

other: Wet fur was eommonly noted during the exposure period and, on removal from the ehamber additional signs of hunehed posture, piloerection, ataxia and oeeasional body tremors were noted. One female showed red/brown stains around the snout.

Body weight:

Expected body weight development was noted in all animals throughout the study.

Gross pathology:

At necropsy, abnormalities were noted on the lungs of several animals including areas that were pale, dark, raised, hardened or with a grey diseolouration. Some animals also showed dark foci. No other abnormalities were detected in animals at necropsy.

Other findings:

none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, a LC50 > 10.17 mg/L was established for rats exposed for 4 h to an aerosol.

Executive summary:

A GLP-compliant guideline study (OECD 403, EU method B2) was performed to assess the acute inhalation toxicity of the test item, by exposing a single group of 10 Sprague-Dawley strain rats (five males and five females) to an aerosol atmosphere. The animals were exposed for 4 hours using a nose only exposure system. The mean achieved atmosphere concentration was 10.17 mg/L. No mortalities were observed.Common abnormalities noted on removal from the chamber included wet fur, hunched posture, piloerection, ataxia and occasional body tremors. Signs of hunched posture and pilo-erextion were still evident 1 hour after completion of exposure but on day one and for the rest of the study all animals appeared normal. Expected body weight development was noted throughout the study. At necropsy, abnormalities were noted on the lungs of several animals including areas that were pale, dark, raised, hardened or with a grey discolouration. Some animals also showed dark foci. No abnormalities were detected in 3 animals at necropsy. No deaths occurred in a group of ten rats exposed to a mean achieved concentration of 10.17 mg/L. It was therefore considered that the acute inhalation median lethal concentration (LC50) of the test material in the Sprague-Dawley rat was greater than 10.17 mg/L.