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

Endpoint summary

Description of key information

Skin corrosion/irritation: A key, reliable in vitro skin corrosion test was performed (according to OECD guideline 435), and demonstrated the substance to be classified as skin corrosive category 1B.

Eye irritation: No study was performed as the substance is classified as corrosive to the skin (cat 1B). Moreover, the substance has a pH 13.9 > 11.5.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

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

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.

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)

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

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

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

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

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

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

the study does not need to be conducted because the substance is a strong acid (pH <= 2.0) or base (pH => 11.5) and the available information indicates that it should be classified as serious eye damage (Category 1)

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin corrosion/irritation

A sample was evaluated with the Corrositex(R) test method to determine its corrosive potential and to designate its Packing Group classification. The mean Corrositex time was demonstrated to be 26.09 +/-1.77 minutes. The substance is considered corrosive to the skin and to be classified as skin corrosive category 1B, according to CLP regulation.

Eye irritation

No study was performed as the substance is demonstrated to be corrosive to the skin, and classified as such. Moreover, the substance has a pH value higher than 11.5.

Justification for classification or non-classification

The test substance is classified as skin corrosive category 1B and serious eye damage category 1 according to the criteria described in the CLP Regulation 1272/2008.