2-tert-butylaminoethyl methacrylate

Endpoint summary

Description of key information

There is a Klimisch 1 acute oral toxicity study on 2-tert-butylaminoethyl methacrylate available.  Dermal and inhalation acute toxicity tests are not available and due to the corrosive properties of 2-tert-butylaminoethyl methacrylate it is not considered scientifically justified to carry out these studies.

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:

January to March 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study to OECD guideline with sufficient details on the study and the test substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals

The animals used in this study are Sprague-Dawley strain rats ICO: OFA SD (IOPS Caw) supplied by Iffa Credo (69210 Arbresle. France).

Upon arrival at C. I. T., the animals are acclimated to local conditions for a minimum period of 5 days, during which they are observed daily.

On the first day of treatment, the young adult animals were of an age of approximately 6 weeks and an average weight of 186 ± 6 g for males and 148 ± 6 g for females. They are individually identified by holes or slots in their ears.

Environment
During the period of acclimation and during the study, the animals were kept in a conventional airconditioned animal room.
Conditions were maintained at:

Temperature 22 ± 3 ° C
Humidity 50 ± 20% relative humidity
Light cycle 12 hours of light/12 hours of darkness

The non-recycled air, was filtered through absolute filters
.
The animals are housed with 4 to 7 animals of the same sex during the acclimation period and 5 of the same sex during the study. Animals are housed in a sterilisable polycarbonate cage (dimensions 48 x 27 x 20 cm) equipped with a stainless steel lid forming a food hopper and a
water bottle (500 ml).

Animals were housed on sifted saw dust (Societe Parisienne of Sawdust, 95100 Argenteuil, France). The analysis for potential residues and major contaminants is performed
regularly (Municipal and Regional Laboratory of Rouen, 76000 Rouen,
France).

The animals were fed with Rat and Mice diet A04 Reference C "(UAR 91360 Villemoisson-sur-Orge, France) presented as standardized pellets, provided ad libitum throughout the
duration of the study (except for the period of fasting prior to treatment). The analysis of the food and the result for the main contaminants (pesticides, heavy metals, mycotoxins, etc ...)
are given by the supplier with each batch.

Drinking water was filtered with a 0.22 micron membrane (Millipore Corporation, 78140 Velizy, France) was provided ad libitum during the study. It was dispensed in bottles. Bacteriological and chemical analyzes and the main contaminants are performed regularly
(Municipal and Regional Laboratory of Rouen, 76000 Rouen, France).
There was no information available to the Study Director 1 indicating the presence in food or drinking water for any contaminants a level sufficient to adversely affect the conduct of the study.

Route of administration:

oral: gavage

Vehicle:

other: None or 0.5% methyl cellulose in water

Details on oral exposure:

Before the day of treatment, the animals are fasted only provided with water for about 18 hours before administration. The food was returned 4 hours after treatment.

In a first test, the test substance was administered undiluted to a group of 10 animals (5 males and 5 females) at a dose of 2000 mg / kg in a volume taking into account the density of the test substance d = 0.92.

Mortality being greater than 50%, a preliminary study was performed with a reduced number of animals to find approximately the scale of doses administered for the determination of the LD 50.

The next phase of the study included four groups of five males and two groups of five females.

The dose levels for the males being 500, 800, 1300 and 2000mg/kg at a dose volume of 10mg/kg of the suspension. For the female just 800 and 1300mg/kg were administered.

Administration of the test substance

The doing suspensions were administered using an 18G stainless steel 2 inch gavage.

Doses:

In a first test, the test substance was administered undiluted to a group of 10 animals (5 males and 5 females) at a dose of 2000 mg / kg in a volume taking into account the density of the test substance d = 0.92.

For the second phase of the experiment the dose levels for the males were 500, 800, 1300 and 2000mg/kg at a dose volume of 10mg/kg of the suspension. For the female just 800 and 1300mg/kg were administered

No. of animals per sex per dose:

In a first test, the test substance was administered undiluted to a group of 10 animals (5 males and 5 females).

The second test included four groups of five males and two groups of five females.

Control animals:

no

Details on study design:

TREATMENT

Before the day of treatment, the animals are fasted only provided with water for about 18 hours before administration. The food was returned 4 hours after treatment.

In a first test, the test substance was administered undiluted to a group of 10 animals (5 males and 5 females) at a dose of 2000 mg / kg in a volume taking into account the density of the test substance d = 0.92.

Mortality being greater than 50%, a preliminary study was performed with a reduced number of animals to find approximately the scale of doses administered for the determination of the LD 50.

The next phase of the study included four groups of five males and two groups of five females.

The dose levels for the males being 500, 800, 1300 and 2000mg/kg at a dose volume of 10mg/kg of the suspension. For the female just 800 and 1300mg/kg were administered.

Administration of the test substance

The doing suspensions were administered using an 18G stainless steel 2 inch gavage.

Clinical Investigations

The animals were observed frequently during the hours after administration of the test substance. It was then performed at least once daily for 14 days to record if the clinical signs
reversible or irreversible.

Mortality

Checking for deaths was done frequently performed during the hours after administration of the test substance and at least 2 times a day for the 14 days of observation. The time of death was noted individually in days or hours from the time of administration of the test substance.

Body weights

The animals were weighed individually just before the administration of test substance, then on days 5, 8 and 5. The changes in the animals bodyweights were compared with a reference curve established at CIT from untreated animals with the same initial weight.

Pathology

Dead animals in the test were given a post mortem examination. Then on the15th day, the surviving animals were sacrificed by inhalation of an excess of C02 and examined post mortem. After opening the abdominal and thoracic cavities, a macroscopic examination of the major organs is carried out: the digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and other organs with abnormalities. Organs presenting macroscopic lesions were preserved in an appropriate fixative (10% formalin). No histological examination was performed.

Statistics:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 800 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no statistical analysis

Mortality:

There were no mortalities at 500 mg/kg in males and 800 mg/kg in both males and females. When dose at 2000 mg/kg (undiluted) 4 out of five males and all five females died. Mortalities in the males at 2000 mg/kg using the suspension in 0.5% methyl cellulose were three of the five rats.

Details are provided in the table below.

Clinical signs:

other: The following clinical signs were observed after the administration of test substance: Hypokinesia was seen at 500 mg / kg and 800 mg / kg Hypokinesia and sedation with an associated piloerection were seen after 4 hours and dyspnea on day 3 at a dose

Gross pathology:

The post mortem examination of animals found dead on day 1 (doses of 1300 and 2000 mg / kg)
found the presence of an abnormally reddish coloration to the stomach and intestines. In animals found dead on day 5 there were no detectable abnormality.

The autopsy of animals sacrificed at the end of study did not find any abnormalities

Mortality by sex separately or combined is presented below:

			Cumulative	Mortality
Sex	Dose mg/kg	Volume ml/kg	Day 1	Day 2	Day5	Day 15	% mortality
Males	500	10	0	0	0	0	0
	800	10	0	0	0	0	0
	1300	10	1	1	1	1	20
	2000	10	2	2	3	3	60
	2000	2.18	4	4	4	4	80
Females	800	10	0	0	0	0	0
	1300	10	0	0	0	0	0
	2000	2.18	5	5	5	5	100
Males &	800	10	0	0	0	0	0
Females	1300	10	1	1	1	1	10
combined	2000	2.18	9	9	9	9	90

 

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this experiment the LD 50 of the MATBAE administered orally in rats was higher than 800 mg / kg (0% death) and lower than 2000 mg / kg (60% death). The toxicity of the test substance in females is comparable to that of males.

This results in a classification of Category 4 for acute oral toxicity by the EU CLP(GHS) criteria.

Executive summary:

The acute toxicity of MATBAE was assessed in rats in accordance with the Guideline No. 401 (OECD - February 24, 1987) for oral acute toxicty and according to the rules of Good Laboratory Practice (O.C.D.E. - May 12, 1981).

Materials and Methods

In a first test, the test substance was administered orally as is to a group of 10 Sprague-Dawley rats (5 males and 5 females) at a dose of 2000 mg / kg in a volume taking into account the density of the test substance = 0.92.

In a second experiment, the test substance was administered at doses of 500, 800, 1300 and 2000 mg / kg to 4 groups of 5 males and at doses of 800 and 1300 mg / kg to groups of 5 females. The test substances suspended in 0.5% methylcellulose and was administered in volume of 10 ml / kg.

All animals were starved over night before treatment. Mortality, the general behavior and the general condition and the weight gain in the surviving animals were followed for a period of 14 days after the administration one of the Test substance. A pathological examination was performed on each animal find dead or sacrificed at the end of study.

Results

After administration of the test substance as the mortality is 90% at the 2000 mg / kg. After administration of the test substance in suspension, mortality in males, were respectively 0%, 0%, 20% and 60% to Doses of 500, 800, 1300 and 2000 mg / kg and is in females of 0%, 0% at doses of 800 and 1300 mg / kg. The death of animals is essentially recorded between 1 hour and 4 hours after treatment.

The observed clinical signs include a decrease in spontaneous activity for 24 hours at a dose of 500 mg / kg for 48 hours with the 800 mg / kg dose, for 6 days at doses of 1300 and 2000 mg / kg. Symptoms of difficulty breathing and piloerection were occasionally observed at doses of 1300 and 2000 mg / kg

Thebody weight gainof surviving animals was normal at doses of 500and 800mg/kgthroughout the durationof the study. A slight reduction in weight gain at1300mg /kg and more significantly at2000mg /kg was observed between days 1 and5. with subsequent normal bodyweight recovery on days 8 to 15.

The autopsy of dead animals found dead on day 1(dosesof 1300and 2000mg /kg) showed the presence of an abnormally reddish coloration levelof the stomach and intestines. In animals found dead on day 5 (dose2000 mg / kg of the test substance suspended) noabnormalities were detectable.The autopsy in all animals sacrificed at the end ofthe study showed macroscopically visible abnormalities.

Conclusion

Under the conditions of this experiment the LD 50 of the MATBAE administered orally in rats was higher than 800mg /kg (0%death) and lower than 2000mg /kg (60%death).The toxicity of the test substance in females is comparable to that of males.

 

This results in a classification of Category 4 for acute oral toxicity by the EU CLP(GHS) criteria.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 400 mg/kg bw

Quality of whole database:

This acute oral toxicity study is considered to be adequate for classification and labeling purposes, the test substance was clearly specified as MATBAE the abbreviation of the name in French for 2-tert-butylaminoethyl methacrylate.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are Klimisch 1 studies available on the 2-tert-butylaminoethyl methacrylateavailable for acute oral and toxicity allowing for classification for acute oral toxicity. This shows only moderate acute oral toxicity between 800 and <2000 mg/kg a mean value of 1400 mg/kg has been calculated  Dermal and acute inhalation toxicity tests are not available and due to the corrosive properties of 2-tert-butylaminoethyl methacrylate it is not considered scientifically justified to carry out these studies due to the technical difficulties and animal welfare considerations. Due to the corrosive and sensitizing properties of 2-tert-butylaminoethyl methacrylate to the skin, an acute toxicity classification would have not changes the occupational handling of this product. As it is a monomer it will be handled in substantially closed systems so inhalation exposure would be expected to be well controlled.

Justification for selection of acute toxicity – oral endpoint

There is a Klimisch validity 1, GLP oral LD50 study available for 2-tert-butylaminoethyl methacrylate CAS No 3775-90-4 carried to a protocol equivalent to OECD401. The oral LD50 was considered to be between 800 mg/kg bodyweight where there were no deaths in males or females and 2000 mg/kg bodyweight where all five females and four of five males died i.e. 90%mortality.  A mean value of 1400mg/kg will be used.  Therefore 2-tert-butylaminoethyl methacrylate is classified for acute oral toxicity at Category 4 as the oral LD50 is between 300 and <2000 mg/kg bodyweight by the criteria of EU CLP (GHS).

Justification for selection of acute toxicity – inhalation endpoint

2-tert-butylaminoethyl methacrylate is corrosive to skin and eyes and therefore would be at least a severe irritant to the respiratory tract.  Data is available for acute oral exposure which indicates only moderate acute toxicity.  Therefore it is not scientifically justified to do acute inhalation studies due to animal welfare considerations from exposure to a corrosive chemical and this is not expected to result in any change in the occupational handling of this monomer

Justification for selection of acute toxicity – dermal endpoint

2-tert-butylaminoethyl methacrylate is corrosive to skin and it is a skin sensitiser, therefore exposure to skin contact has to be carefully controlled.  Data is available for acute oral exposure which indicates only moderate acute toxicity.  Therefore due to the corrosive nature of this substance it is not scientifically justified to carry out an acute dermal toxicity study to avoid unnecessary suffering of the animals.  Also a classification for acute dermal toxicity would not change the occupational handling of the substance.

Justification for classification or non-classification

The oral LD50 for 2-tert-butylaminoethyl methacrylate is ca. 1400 mg/kg bodyweight, calculated based on no deaths in ten rats at 800 mg/kg bodyweight and 9 out of ten rats dying at 2000 mg/kg bodyweight. This results in a classification of Category 4 for acute oral toxicity based on the EU CLP criteria.  No classification is possible for inhalation or dermal contact due to the lack of test data. Due to the corrosive and sensitizing properties of 2-tert-butylaminoethyl methacrylate to the skin, an acute toxicity classification would have not changes the occupational handling of this product. As it is a monomer it will be handled in substantially closed systems so inhalation exposure would be expected to be well controlled. Therefore the lack of classification for these routes of exposure is acceptable.