N-[2-[2-(2-methoxyethoxy)ethoxy]ethyl]-2-methyl-propan-2-amine

Endpoint summary

Description of key information

skin corrosion (OECD 431): borderline (BASF, 2018)

skin corrosion (OECD 435): corrosive category 1C (BASF, 2018)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

pH value: >11.5 (according to available product information of the sponsor)
Physical state / color: Liquid / colorless, clear
Storage conditions: Room temperature

Test system:

artificial membrane barrier model

Source species:

other: Corrositex® kit

Details on animal used as source of test system:

Corrositex: InVitro International, Irvine CA, USA

Vehicle:

unchanged (no vehicle)

Details on test system:

The objective was to assess the skin corrosion and irritation potential of 2-Propanamine, N-[2-[2-(2-methoxyethoxy)ethoxy]ethyl]-2-methyl-. By using the methods currently available a single in vitro assay is not sufficient to cover the full range of skin irritating/corrosion potential including transport classification.

The study was conducted in two steps first performing the Skin Corrosion Test (SCT). As a corrosion potential of the test substance could not be excluded, the In vitro Membrane Barrier Test (Corrositex®) was conducted subsequently

Species:

other:

Vehicle:

unchanged (no vehicle)

Controls:

other: Concurrent treatment : Negative control (NC): 10% citric acid Positive control (PC): Sodium hydroxide (solid)

Amount / concentration applied:

500 µL of the undiluted test substance were added onto the membrane disc

Duration of treatment / exposure:

one time

Observation period:

The vial was observed for three minutes for any change in the CDS.
If no color change was observed within three minutes the membraneswere observed continuously for the first ten minutes. Thereafter, the vials were observed for approximately ten minutes around the time points relevant for evaluation or until breakthrough of the test substance

Details on study design:

The experimental design of this study consisted of
- a qualification screen with the CDS (to determine if a color change can be detected)
- a categorization screen (to categorize weak acids/bases and strong acids/bases
- a definitive Corrositex® assay

Corrositex® assay

Following the acceptance of the positive control, the Corrositex® assay was performed for the test substance. Four vials containing the CDS were used for the test substance.

In addition, one vial was used for the PC, the NC and the color control (blank) each.
A membrane disc coated with the biobarrier matrix was placed into one vial containing the CDS and approximately 500 µL test substance were added onto the membrane disc. The vial was observed for three minutes for any change in the CDS.

If no color change was observed within three minutes the membranes remaining were treated with the test substance. The vials were observed continuously for the first ten minutes. Thereafter, the vials were observed for approximately ten minutes around the time points relevant for evaluation or until breakthrough of the test substance. The elapsed time between test substance application and the first change in the indicator solution (i.e. barrier penetration) was recorded.

The positive control vial was prepared as described above and contained one pellet of sodium hydroxide on top of the membrane disc. This vial was continuously monitored until breakthrough.

The negative control vial was prepared as described above and contained 500 µL 10% citric acid. This vial was observed for 60 minutes and was evaluated as “non-corrosive” if no reaction had been observed.

Irritation / corrosion parameter:

penetration time (in minutes)

Value:

63.52

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

Pretest
Qualification screen: the test substance can react with the CDS and produce a visible color change.

Categorization screen: the test substance was assigned to timescale category 1 (having a high acid/alkaline reserve)

4.1.2.2. Maintest
The times recorded:
Vial 1: 68:18 (min)
Vial 2: 62:52 (min)
Vial 3: 63:58 (min)
Vial 4: 60:20 (min)

Mean: 63:52 (min)

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

The mean breakthrough time determined in the in vitro Membrane Barrier Test (Corrositex®) was 63 minutes and 52 seconds. The breakthrough time indicates that the test substance has a weak corrosive potential and should be assigned to UN GHS skin corrosivity subcategories 1C.

Executive summary:

Based on the results observed and by applying the evaluation criteria it was concluded that 2-Propanamine, N-[2-[2-(2-methoxyethoxy)ethoxy]ethyl]-2-methyl has a weak corrosive potential and should be assigned to UN GHS skin corrosivity subcategory 1C.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

artificial membrane barrier model

Source species:

other: EpiDerm™ 200 kit

Details on animal used as source of test system:

TEST SYSTEM:
- Source: MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia

Details on test system:

The objective was to assess the skin corrosion and irritation potential of 2-Propanamine, N-[2-[2-(2-methoxyethoxy)ethoxy]ethyl]-2-methyl-. By using the methods currently available a single in vitro assay is not sufficient to cover the full range of skin irritating/corrosion potential including transport classification.

The study was conducted in two steps first performing the Skin Corrosion Test (SCT). As a corrosion potential of the test substance could not be excluded, the In vitro Membrane Barrier Test (Corrositex®) was conducted subsequently

Control samples:

other: CONTROLS The Skin Corrosion Test (SCT): Negative control (NC): Deionized water Positive control (PC): 8-N potassium hydroxide solution MTT reduction control (KC): Deionized water or test substance

Amount/concentration applied:

Fifty microliters (50 µL) undiluted liquid test substance were applied

Duration of treatment / exposure:

The tissues were washed with PBS to remove residual test material 3 minutes or 1 hour after start of the application treatmen

Duration of post-treatment incubation (if applicable):

Rinsed tissues were kept in 24-well plates (holding plates) at room temperature on assay medium until all tissues per application time were dosed and rinsed. The assay medium was then replaced by MTT solution and tissues were incubated for 3 hours

Number of replicates:

Two tissues per exposure time (3 minutes at room temperature or 1 hour in the incubator as a rule) and test group (test material, negative control and positive control)

Details on study design:

From the day of arrival in the laboratory, tissues were kept in the refrigerator. At least 1 hour, but not more than 1.5 hours before test substance application, tissues were transferred to 6-well plates with 0.9 mL assay medium and preconditioned in the incubator at 37°C. The pre-incubation medium was replaced by fresh medium immediately before application.

Two tissues per exposure time (3 minutes at room temperature or 1 hour in the incubator as a rule) and test group (test material, negative control and positive control; 12 tissues per test) were used. In addition, two killed control tissues per exposure time were treated with the test substance and the NC, respectively, to detect direct MTT reduction.

Fifty microliters (50 µL) undiluted liquid test substance were applied by using a pipette.

Control tissues were concurrently treated with 50 µL deionized water (NC, NC KC) or with 50 µL 8 N potassium hydroxide (PC) or test substance (KC).

The tissues were washed with PBS to remove residual test material 3 minutes or 1 hour after start of the application treatment.

Rinsed tissues were kept in 24-well plates (holding plates) at room temperature on assay medium until all tissues per application time were dosed and rinsed. The assay medium was then replaced by MTT solution and tissues were incubated for 3 hours.

After incubation, the tissues were washed with PBS to stop the MTT incubation. The formazan that was metabolically produced by the tissues was extracted by incubation of the tissues in isopropanol. The optical density at a wavelength of 570 nm (OD570) of the extracts was spectrophotometrically determined. Blank values were established of 4 microtiter wells filled with isopropanol for each microtiter plate

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3 minutes

Value:

61.9

Negative controls validity:

valid

Positive controls validity:

valid

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

1 hour

Value:

10.2

Negative controls validity:

valid

Positive controls validity:

valid

Interpretation of results:

other:

Conclusions:

The final mean viability of the tissues treated with the test substance determined after an exposure period of 3 minutes was 61.9%, and it was 10.2% after an exposure period of 1 hour.
The borderline result of the skin corrosion test (SCT) after an exposure period of 1 hour does not clearly allow the evaluation of the skin corrosion potential. Thus, further testing in the In vitro Membrane Barrier Test (Corrositex®) was conducted to clarify the result for transport classification.

Executive summary:

The borderline result of the skin corrosion test (SCT) after an exposure period of 1 hour does not clearly allow the evaluation of the skin corrosion potential.Thus,further testing in the In vitro Membrane Barrier Test (Corrositex^®) was conducted to clarify the result for transport classification

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The objective was to assess the skin corrosion and irritation potential of 2-Propanamine, N-[2-[2-(2-methoxyethoxy)ethoxy]ethyl]-2-methyl-. By using the methods currently available a single in vitro assay is not sufficient to cover the full range of skin irritating/corrosion potential including transport classification.

The study was conducted in two steps first performing theSkin Corrosion Test (SCT). As a corrosion potential of the test substance could not be excluded, the In vitro Membrane Barrier Test (Corrositex^®) was conducted subsequently.

The mean breakthrough time determined in the In vitro Membrane Barrier Test (Corrositex^®) was 63 minutes and 52 seconds. The breakthrough time indicates that the test substance has a weak corrosive potential and should be assigned to UN GHS skin corrosivity subcategories 1C or UN Transport Packing Group III.

Based on the results observed and by applying the evaluation criteria it was concluded that 2-Propanamine, N-[2-[2-(2-methoxyethoxy)ethoxy]ethyl]-2-methyl-shows a corrosive potential in the EpiDerm™in vitro skin irritation and corrosion test strategy including transport classification under the test conditions chosen.

 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance should be assigned to UN GHS skin corrosivity subcategories 1C under Regulation (EC) No 1272/2008 or UN Transport Packing Group III.