Registration Dossier

Administrative data

Description of key information

Acute oral toxicity
Two independent studies conducted with the test substance revealed that the LD50 value is above 2000 mg/kg bw. No systemic effects and severe local effects were noted in the studies conducted.
Acute dermal toxicity
Tests conducted with the test substance and and analogous substance revealed that the LD50 value is above 2000 mg/kg bw. No systemic effects or severe local effects were noted in the studies conducted.
Acute inhalation toxicity
Tests conducted with the test substance revealed an LC50 value above 10.17 mg/L. Two studies conducted on the structural analoge nBMA support this finding.

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:
other: GLP and guideline compliant study
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
modified according to the acute toxic class method
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: WISTAR / CHBB: THOM (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. Thomae GmbH, Biberach, D
- 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
- Diet: Kliba Labordiaet 343, Klingenthalmuehle AG, Kauseraugst, CH
- Water: municipal drinking water, regularly assayed
- 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
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
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
Statistics:
not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortality observed.
Clinical signs:
males: no abnormalities.
females: impaired or poor general state, dyspnoea, apathy, staggering, tremor, piloerection; reversible within at least 2 day.
Body weight:
The expected body weight was observed.
mean males: day 0: 189 g; day 7: 255 g; day 13: 286 g
mean females: day 0: 180 g; day 7: 198 g; day 13: 210 g
Gross pathology:
no pathological findings observed.
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:
other: GLP and guideline compliant study.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Manston, Kent, UK
- Age at exposure initiation: eight to ten weeks
- Weight at study initiation: male rats weighed 226 to 245 grams and female rats weighed 214 to 237 grams
- Housing: five animlas 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: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 40- 68
- Air changes: 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE
The test material was aerosolised using a glass concentric jet nebuliser (Radleys, Sawbridgeworth, Herts.) located at the top of the exposure chamber. The nebuliser was 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.Compressed air was passed through a water trap and respiratory quality filters which removed particulate material above 0.005 µm before it was introduced to the nebuliser.
The cylindrical exposure chamber has a volume of approximately 30 litres. The concentration within the exposure chamber was controlled by adjusting the rate of the infusion pump and the air flow rate through the chamber. The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system.

EXPOSURE PROCEDURE
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. Only the noses of the animals were exposed to the test atmosphere. A single group of ten rats (five males and five females) was exposed to an atmosphere of the test material for aperiod of four hours. A target concentration of 5 mg/L was used for the exposure.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
10.17 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
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. At the end of the 14 day observation period, the animals were killed by intravenous overdose of sodium pentobarbitone. All animals were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.
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 commonly noted during the exposure period and, on removal from the chamber additional signs of hunehed posture, piloerection, ataxia and oeeasional body tremors were noted. One female showed red/brown stains around the snout. One hour after co
Body weight:
Expected bodyweight 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
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
10.17 mg/m³
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:
other: Scientifically valid study according to GLP and current OECD guideline.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
, adopted 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd, Margate, Kent, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: >= 200 g
- Housing: suspended solid-floor polypropylene cages furnished withn woodflakes
- Diet: Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK , ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 5 days

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 AND VEHICLE
The test substance was administered at a dose level of 2000 mg/kg bw at a treatment volume of 2.26 mL/kg bw.

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
10 animals: 5 males, 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 0.5, 1, 2 and 4 h hours after dosing and daily thereafter, body weights were recorded on day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
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:
There were no signs of systemic reaction to treatment.
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweitgh over the study period.
Gross pathology:
No abnormalities were noted.
Other findings:
none
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 oral, 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 tert-Butyl methacrylate (purity: 99.9 weight-%), applied as a solution in olive oil to Wistar rats (BASF AG, 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. 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. 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, a single dose of the structural analoge n-butyl methacrylate 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 (Sarver, 1993). 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 n-butyl methacrylate (n-BMA) were 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 four hoursusing a nose only exposure system. The test was conducted in accordance to OECD guideline 403 and EU Method B2. 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:

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, four-hour period to atmospheres containing the structural analoge substance nBMA as vapour in air (Kelly DP, 1993).

Aerosol concentrations were determined by gravimetric analysis and vapor 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 nBMA 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 nBMA at 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 for nBMA was 29 mg/L.

In an inhalation study (Jones, 2002) in F344 rats, using specialist histopathology techniques to study the nasal tissues, n-butyl methacrylate 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 hrs.


Justification for selection of acute toxicity – oral endpoint
Most reliable study

Justification for selection of acute toxicity – inhalation endpoint
Most reliable study

Justification for selection of acute toxicity – dermal endpoint
Most reliable study

Justification for classification or non-classification

Based on data available on the test item and the read-across test substance, the test item is not classified for acute toxicity according to the criteria of Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP).