Reaction mass of 2-hydroxy-N-(2-(2-hydroxyethoxy)ethyl)-N-(2-hydroxyethyl)-N-methylethan-1-amininium hydroxide and 2-hydroxy-N,N-bis(2-hydroxyethyl)-N-methylethanaminium hydroxide

Skin irritation / corrosion

Administrative data

Endpoint:

skin corrosion: in vitro / ex vivo

Remarks:

In vitro membrane barrier

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-02-11

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)

Principles of method if other than guideline:

The Corrositex test predicts the in vivo corrosive potential of a chemical compound or mixture by using as an endpoint the time it takes for the chemical to permeate through or destroy a synthetic biobarrier.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Tris(2-hydroxyethyl)methylammonium hydroxide

EC Number:

251-624-7

EC Name:

Tris(2-hydroxyethyl)methylammonium hydroxide

Cas Number:

33667-48-0

Molecular formula:

C7H18NO3.HO

IUPAC Name:

2-hydroxy-N,N-bis(2-hydroxyethyl)-N-methylethanaminium hydroxide

Constituent 2

Reference substance name:

2-hydroxy-N-(2-(2-hydroxyethoxy)ethyl)-N-(2-hydroxyethyl)-N-methylethan-1-amininium hydroxide

Molecular formula:

C9H22NO4.HO

IUPAC Name:

2-hydroxy-N-(2-(2-hydroxyethoxy)ethyl)-N-(2-hydroxyethyl)-N-methylethan-1-amininium hydroxide

impurity 1

Reference substance name:

2,2'-methyliminodiethanol

EC Number:

203-312-7

EC Name:

2,2'-methyliminodiethanol

Cas Number:

105-59-9

Molecular formula:

C5H13NO2

IUPAC Name:

2,2'-(methylimino)diethanol

impurity 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Dihydrogenoxide

Test material form:

liquid

Remarks:

brown viscous liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Identification: THEMAH
- CAS number: 33667-48-0
- Physical state/appearance: translucent, homogenous liquid
- Source and lot/batch No.of test material: not specified
- Expiration date of the lot/batch: Not specified
- Purity: Not specified
- pH: 12.35

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was used as supplied.

In vitro test system

Test system:

artificial membrane barrier model

Source species:

other: synthetic biobarriers

Details on animal used as source of test system:

Not applicable

Justification for test system used:

The Corrositex(R) test is an internationally accepted validated test method for skin corrosion according to GHS classifications. The test is a standardized, as well as reproducible method that can be employed to determine the potential corrosivity and determine the Packing Group classification of specified categories of chemical compounds under the hazardous materials transportation regulations administered by the US Department of Transportation and international dangerous goods codes. The Corrositex test predicts the in vivo corrosive potential of a chemical compounds or mixture by using as an endpoint the time it takes for the chemical to permeate through or destroy a synthetic biobarrier. When the chemical has passed through this biobarrier, a visual change is produced in a proprietary Chemical Detection system (CDS).
Occasionally, due to the limitation of the Membrane Barrier Test Method, when the test sample was not causing a detectable change in the step 1, Chemical Compatibility Test, the sample is not suitable for a standard Membrane Barrier Test Method to determine the penetration (breakthrough) time. In the database for which in vivo data were available, when an aqueous chemical with a pH in the range of 4.5 to 8.5 often do not qualify for testing, however, 85% of non-qualifying chemicals tested in this pH range were non-corrosive in animal tests.

Details on test system:

The Corrositex® test is performed in three steps.
1/ First, a Chemical Compatibility Test is done to insure that the test sample and the Chemical Detection System (CDS) reagent are compatible. This is achieved by placing either 150 µl of a liquid or 100 mg of a solid into an aliquot of the CDS reagent and observing it for the presence of any detectable change. If a physical or color change is observed, the sample is judged to be compatible with the detection solution and the remainder of the test is performed.
2/ The second step, Chemical Timescale Category Test, utilizes appropriate indicator solutions to permit categorization of the test sample as either a Category 1 or Category 2 material. Category 1 materials are typically strong acids/bases, while Category 2 materials are typically weak acids/bases
3/ The third step, Membrane Barrier Test Method, is performed by applying 500 µl of a liquid or 500 mg of a solid test sample to the biobarrier. When the chemical permeates through or destroys the full thickness of this biobarrier, it comes into contact with the CDS which then undergoes a simple color change. This color change is visually observed and the time required for the color change to occur is recorded.
The time required to destroy the biobarrier is recorded for four sample replicates and the mean of these replicates is utilized to designate the UN Packing Group classification as I (severe corrosivity), II (moderate corrosivity), III (mild corrosivity), or Non-corrosive (NC). Positive and negative controls are analyzed concurrently to confirm the test’s validity.

Amount/concentration applied:

150µl of test substance (in step 1 the Chemical Compatibility Test)
500 µl of the test substance (in step 3 Membrane Barrier Test Method)

Results and discussion

In vitro

Results

Results 1

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

1

Value:

23.7

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Results 2

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

2

Value:

27.35

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Results 3

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

3

Value:

25.78

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Results 4

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

4

Value:

27.52

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Results 5

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

mean +/- sd

Value:

26.09

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Remarks on result:

other: 26.09+/-1.77

Any other information on results incl. tables

Summary of Corrositex Test Results

	Corrositex Time (minutes)
Sample:  E-Grade® THEMAH	Replicate #1:  23.70
Conc. Tested:  Neat	Replicate #2:  27.35
pH(10%) :  12.35	Replicate #3:  25.78
Compatibility Test: Qualify	Replicate #4:  27.52
Corrositex Category:  1	Mean +/- SD:    26.09 ± 1.7
UN Packing Group:  PG II GHS Skin Corrosion Category: GHS 1B

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

A single sample was analyzed by the Corrositex(R) method to determine its corrosive potential and GHS and U.N. Packing Group designations. The results of this study indicated that the sample was compatible with the Corrositex(R) system and was classified as a Category 1 material. The results obtained from the evaluation of four replicate samples were highly reproducible, demonstrating that a mean time of 26.09 ± 1.77 minutes required to destroy the synthetic biobarriers. These findings lead to the designation of this sample as a UN Packing Group II/GHS 1B.