tert-butyl methacrylate

Endpoint summary

Description of key information

Acute oral toxicity: EU Method B1 (modified according to the acute toxic class method), GLP compliant, K1 rat: LD50 > 2000 mg/kg bw

Acute dermal toxicity: OECD 402, GLP compliant, K1, rat: LD50> 2000 mg/kg bw

Acute inhalation toxicity: OECD 403, GLP compliant, K1, rat: LC50> 10.17 mg/L

Studies conducted on the structural analoge nBMA support these findings.

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:

1994-01-20 to 1994-02-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1992

Deviations:

yes

Remarks:

modified according to the acute toxic class method (1992)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot number of test material: 387
- Purity: 99.9%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: refrigerator, exclusion of light
- the test substance was stable of the study period (study amendment information)

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

Species:

rat

Strain:

Wistar

Remarks:

CHBB: THOM (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Thomae GmbH, Biberach, D
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: young adult
- Weight at study initiation: 150 - 300 g (+-20% of the mean weight)
- Fasting period before study: at least 16 h
- Housing: single housing
- Historical data: not specified
- Diet: Kliba Labordiaet 343, Klingenthalmuehle AG, Kauseraugst, CH; ad libitum
- Water: municipal drinking water; ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): yes (undefined)
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: not specified

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- olive oil DAB10
- Concentration in vehicle: 10 g/ 100 mL
- Justification for choice of vehicle: poor solubility of the test substance in water

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on the pysical and chemical properties of the test substance and the composition, no pronounced acute oral toxicity was expected and a dose of 2000 mg/kg bw was tested (first in females afterwards in males).

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: several times on the day of administration, at least once each workday
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (at least once a workday), body weight (before application, weekly thereafter and at the end of the study)

Preliminary study:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality observed

Clinical signs:

other: males: no abnormalities females: abnormalities directly after exposure (hour 0); all animals showed a poor general state, piloerection, staggering; one animal showed a poor general state, apathy, and tremor; all symptoms were reversible within at least

Gross pathology:

no pathological findings observed

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this acute oral gavage study in male and female rats a LD50 > 2000 mg/kg bw was derived.

Executive summary:

A GLP conform study was performed to assess the range of mortality following oral administration of the test material as a solution in olive oil to Wistar rats. The study procedure was based on the EU method guideline B.1 and modified according to the acute toxic class method. A group of 6 fasted animals (3 males and 3 females) was given a single oral dose of 2000 mg/kg body weight. Signs of toxicity noted in the female animals comprised impaired or poor general state, dyspnoea, apathy, staggering and tremor. These symptoms are considered to be unspecific and disapperead within 2 days after exposure. The expected body weight gain has been observed in the course of the study. No mortality occurred. No abnormalities were noted at necropsy of animals sacrificed at the end of the study. Under the conditions of this study the range of mortality after oral application was found to be greater than 2000 mg/kg body weight for male and female animals.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study

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:

1991-12-20 to 1992-02-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

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

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

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

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

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

10.17 mg/L air

Physical form:

inhalation: aerosol

Quality of whole database:

GLP and guideline compliant study

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-09-14 until 2006-09-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot No.: 0481076
- Purity: 99.9%
- Known impurities: H2O 0.009 %

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

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Cr!: CD® (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Ltd, Margate, Kent, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: >= 200 g
- Housing: suspended solid-floor polypropylene cages furnished within woodflakes; single housing during exposure, group housing (up to 4/sex) during the observation period
- Historical data:
- Diet: Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK , ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 days
- Microbiological status when known
- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 25°C
- Humidity: 30 - 70 %
- Air changes: 15 air changes per hour
- Photoperiod: 12 hours of artificial light

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10 %
- Type of wrap if used: surgical gauze, semi-occluded with self-adhesie bandage

REMOVAL OF TEST SUBSTANCE
- Washing: with cotton woll moistened with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.29 mL/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

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: 0.5, 1, 2 and 4 h after dosing and daily thereafter, body weights on day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: dermal irritation according to Draize (1977)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No adverse effects noted

Mortality:

No mortality was observed.

Clinical signs:

other: There were no signs of systemic reaction to treatment. There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted.

Other findings:

none

No signs of dermal irritation were detected during the 14 post-exposure period.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test material In the rat was found to be greater than 2000 mg/kg body weight under the conditions of the present study.

Executive summary:

A GLP-compliant acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat was conducted according to OECD guideline 402 and EU method B3. A total of 10 animals (5 males and 5 females) were given a single, 24-hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs, bodyweight development, and dermal irritation were monitored during the study. All animals were subjected to gross necropsy. At each observation time point and following necropsy, there were no signs of dermal irritation or systemic toxicity. All animals showed expected gains in body weight over the study period. The acute LD50 of the test material In the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study

Additional information

Besides acute systemic toxicity studies with the test item, reliable studies using the analogous substance n-BMA (CAS 97 -88 -1) were used to assess the acute dermal and inhalative toxicity of the test item.

 

Acute oral toxicity

Key study:

A GLP conform study was performed to assess the range of mortality following oral administration of the test substance applied as a solution in olive oil to Wistar rats (reliabilty 1; 1994). The study procedure was based on the EU method guideline B.1 and modified according to the acute toxic class method. A group of 6 fasted animals (3 males and 3 females) was given a single oral dose of 2000 mg/kg body weight. Signs of toxicity noted in the female animals comprised impaired or poor general state, dyspnoea, apathy, staggering and tremor. These symptoms are considered to be unspecific. The animals appeared normal 1 or 5 days after application.

The expected body weight gain has been observed in the course of the study.

No mortality occurred. No abnormalities were noted at necropsy of animals sacrificed at the end of the study. Under the conditions of this study the range of mortality after oral application was found to be greater than 2000 mg/kg body weight for male and female animals.

 

Supporting study:

An acute oral toxicity study (acute toxic calls method) with the test material in the Sprague-Dawley CD strain rat was conducted according to OECD guideline 423 and EU method B1 tris (GLP, reliability 1; 2006). A total of 6 female animals were treated with the test material at a dose level of 2000 mg/kg body weight. The test material was administered orally undiluted. Clinical signs were monitored during the study. All animals were subjected to goss necroscopy. No mortalitiy occurred. At each observation time point and following necropsy, there were no signs of systemic toxicity. All animals showed expected gains in bodyweight over the study period. The acute LD50 of the test material in the female Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bw.

 

Acute dermal toxicity

Key study:

An acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat was conducted according to OECD guideline 402 and EU method B3 (GLP, reliability 1; 2006). A total of 10 animals (5 males and 5 females) were given a single, 24-hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. At each observation time point and following necropsy, there were no signs of dermal irritation or systemic toxicity. All animals showed expected gains in body weight over the study period. The acute LD50 of the test material In the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bw.

 

Supporting study (read-across):

In an OECD 402 and GLP conform study (reliability 1, 1993), a single dose of the structural analoge was applied to the shaved, intact skin of 5 male and 5 female New Zealand White rabbits at a dosage of 2000 mg/kg of body weight. The application site was occluded for 24 hours. The rabbits were observed for 14 days following application. No rabbits died within 14 days after dosing. No to severe erythema and no to severe edema were observed in the treated rabbits during the study. Superficial necrosis was observed in 1 rabbit on day 4 after application of the test substance and in most other rabbits by day 12 after application. Two rabbits also exhibited necrosis during the study. No target organ was identified at necropsy. Under the conditions of this test, the acute dermal LD50 for n-butyl methacrylate was >= 2000 mg/kg of body weight.

 

Acute inhalation toxicity

Acute inhalation toxicity studies with the test item and with a analogous substance are availabale.

 

Key study:

A study was performed to assess the acute inhalation toxicity of the test item, by exposing a single group of ten 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 test was conducted in accordance to OECD guideline 403 and EU Method B2 (GLP, reliability 1; 1992). 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 one hour after completion of exposure but on day one and for the rest of the study all animals appeared normal. Expected bodyweight 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 three 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.

 

Supporting studies (read-across):

In an OECD 403 and GLP conform study with acceptable restriction (no macroscopic observation at sacrifice), six groups of five male and five female Sprague-Dawley rats each were exposed for a single, 4-hour period to atmospheres containing the structural analoge substance as vapour in air (reliability 2,1993).

Aerosol concentrations were determined by gravimetric analysis and vapour concentrations were determined by gas chromatography. During a 14-day recovery period, rats were weighed and observed for clinical signs of toxicity. Rats were exposed to 14, 18, 24, 27, 29, or 36 mg/L of the test substance and the aerosol MMADs were 4.5, 6.0, 3.9, 6.7, 8.0 or 8.3 µm, respectively. Deaths occurred following exposure to concentrations of 29 mg/L (6/10 animals) and 36 mg/L (3/10 animals). Some important effects of exposure included slight to severe weight loss and signs of respiratory tract irritation. Surviving rats had an overall weight gain by the end of the recovery period. Under the conditions of this study, it was not possible to calculate the LC50. The approximate lethal concentration was 29 mg/L.

In an non-GLP inhalation study (reliability 2, 2002) in F344 rats, using specialist histopathology techniques to study the nasal tissues, the structural analogue as a vapour did not produce lesions in the olfactory region of the nasal cavity following exposure at 200 ppm corresponding to ca. 1.18 mg/L for 6 h.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result, the substance is not considered to be classified for acute oral, dermal, and inhalative toxicity under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.