Reaction mass of 2-dodecylhexadecyl methacrylate and 2-Tetradecyloctadecyl methacrylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 29 August 2019 to 24 September 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

impurity 1

Reference substance name:

Unknown Impurities

IUPAC Name:

Unknown Impurities

impurity 2

Reference substance name:

13-Methylheptacosane

Molecular formula:

C28H58

IUPAC Name:

13-Methylheptacosane

impurity 3

Reference substance name:

Hexadecyl methacrylate

EC Number:

219-672-3

EC Name:

Hexadecyl methacrylate

Cas Number:

2495-27-4

Molecular formula:

C20H38O2

IUPAC Name:

hexadecyl methacrylate

impurity 4

Reference substance name:

Tridecyl methacrylate

EC Number:

219-671-8

EC Name:

Tridecyl methacrylate

Cas Number:

2495-25-2

Molecular formula:

C17H32O2

IUPAC Name:

tridecyl methacrylate

impurity 5

Reference substance name:

Pentadecyl methacrylate

EC Number:

228-126-3

EC Name:

Pentadecyl methacrylate

Cas Number:

6140-74-5

Molecular formula:

C19H36O2

IUPAC Name:

pentadecyl methacrylate

impurity 6

Reference substance name:

Tetradecyl methacrylate

EC Number:

219-835-9

EC Name:

Tetradecyl methacrylate

Cas Number:

2549-53-3

Molecular formula:

C18H34O2

IUPAC Name:

tetradecyl methacrylate

impurity 7

Reference substance name:

Dodecyl methacrylate

EC Number:

205-570-6

EC Name:

Dodecyl methacrylate

Cas Number:

142-90-5

Molecular formula:

C16H30O2

IUPAC Name:

dodecyl methacrylate

impurity 8

Reference substance name:

2-Decyltetradecyl methacrylate

Molecular formula:

C28H54O2

IUPAC Name:

2-Decyltetradecyl methacrylate

Constituent 1

Reference substance name:

2-Tetradecyloctadecyl methacrylate

Cas Number:

1046154-63-5

Molecular formula:

C36H70O2

IUPAC Name:

2-Tetradecyloctadecyl methacrylate

Constituent 2

Reference substance name:

2-Dodecylhexadecyl methacrylate

Cas Number:

536972-42-6

Molecular formula:

C32H62O2

IUPAC Name:

2-Dodecylhexadecyl methacrylate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Ltd
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: 158 to 170 g
- Fasting period before study: Overnight before dosing
- Housing: solid bottomed polycarbonate cages with a stainless steel mesh lid
- Diet: standard rodent diet (Teklad 2014C Diet) ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least five days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): Periodic checks were made on the number of air changes in the animal rooms.
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle: 10 mL/kg body weight
- Justification for choice of vehicle: A vehicle trial was conducted; water resulted in an offwhite, hazy emulsion which separated quickly and was therefore determined unsuitable, 1% methyl cellulose was considered to be incompatible due to the test items previous incompatibility with water, and therefore, corn oil was tested – which resulted in a clear, yellow solution and determined suitable for formulation.

Doses:

300 mg/kg bw was chosen as the starting dose.
In the absence of mortality or clear evident toxicity at a dose level of 300 mg/kg, additional testing was performed at 2,000 mg/kg bw.

No. of animals per sex per dose:

One animal at 300 mg/kg bw.
Five animals at 2,000 mg/kg bw.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cages of rats were checked at least twice daily for any mortalities. The weight of each rat was recorded on Days -1, 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of the brain, cecum, duodenum, heart, kidneys, small and large intestine, liver, lungs and bronchi, spleen, stomach, subcutaneous tissue and urinary bladder was recorded.
- Other examinations performed: Animals were observed soon after dosing and at frequent (approximately hourly) intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of any clinical signs and the time were recorded at each observation.

Results and discussion

Preliminary study:

In the absence of mortality or toxicity at 300 mg/kg bw and 2,000 mg/kg bw, definitive test was conducted at 2,000 mg/kg bw

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: There were no clinical signs of reaction to treatment throughout the study.

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Following an acute oral toxicity experiment in rats, it was determined that Reaction mass of 2-Propenoic acid, 2-methyl-, 2-dodecylhexadecyl ester and 2-Propenoic acid, 2-methyl-, 2-tetradecyloctadecyl ester was not acutely toxic via the oral route under the conditions of the study. No mortality was observed at the highest dose over a 14-day period, therefore the LD50 is concluded to be >2000 mg/kg bw. The substance does not meet the criteria for classification according to Regulation 1272/2008.

Executive summary:

The acute toxicity of Reaction mass of 2-Propenoic acid, 2-methyl-, 2-dodecylhexadecyl ester and 2-Propenoic acid, 2-methyl-, 2-tetradecyloctadecyl ester via the oral route was

evaluated during a study performed according to the OECD Testing Guideline 420. The study was GLP-compliant.

The fixed dose method was used. One female Wistar rat received by gavage a single dose of 300 mg/kg bw in corn oil. In the absence of observable toxicity at 300 mg/kg bw, an animal was treated at 2,000 mg/kg bw. Considering that no mortality or clear signs of toxicity were observed, four additional female Wistar rats were treated at 2,000 mg/kg bw.

Following exposure to the test substance, animals were observed for 14 days. There were no deaths nor clinical signs of reaction to treatment during the study. All animals were considered to have achieved satisfactory body weight gains throughout the study. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

It can be concluded that2 Reaction mass of 2-Propenoic acid, 2-methyl-, 2-dodecylhexadecyl ester and 2-Propenoic acid, 2-methyl-, 2-tetradecyloctadecyl ester has a LD50 > 2,000 mg/kg bw via the oral route.