N'-[3-(dimethylamino)propyl]-N,N-dimethylpropane-1,3-diamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin corrosion: in vitro / ex vivo

Remarks:

In vitro Membrane Barrier Test for Skin Corrosion

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-10-22 to 2021-11-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2022

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

28 July 2015

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

N'-[3-(dimethylamino)propyl]-N,N-dimethylpropane-1,3-diamine

EC Number:

229-761-9

EC Name:

N'-[3-(dimethylamino)propyl]-N,N-dimethylpropane-1,3-diamine

Cas Number:

6711-48-4

Molecular formula:

C10H25N3

IUPAC Name:

(3-{[3-(dimethylamino)propyl]amino}propyl)dimethylamine

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch (Lot) Number: PFW210614
- Expiry date: 20 September 2023 (retest date)
- Physical Description: Clear amber liquid
- Purity/Composition: 99.0 A% by GC
- Purity/Composition correction factor: No correction factor required

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature protected from light container flushed with nitrogen

FORM AS APPLIED IN THE TEST: liquid

OTHER SPECIFICS
- Test item handling: Use amber glassware or wrap container in aluminum foil. Handle in glove box or AtmosBag (nitrogen environment). An inert gas such nitrogen blanketing is recommended.
- For each batch (lot) of test item, a reserve sample (about 0.5 gram) was collected and maintained under the appropriate storage conditions by the Test Facility.
- pH: 11.4 at a concentration of 1%
12.0 at a concentration of 10%

In vitro test system

Test system:

artificial membrane barrier model

Remarks:

Corrositex® is a test system that is composed of two components, a hydrated collagen matrix (bio-barrier) on a supporting filter membrane and CDS, an underlying aqueous solution of two pH indicator dyes.

Source species:

other: artificial bio-barrier (hydrated collagen matrix)

Justification for test system used:

Recommended test system in international guideline (OECD 435).

Vehicle:

unchanged (no vehicle)

Details on test system:

SOURCE AND COMPOSITION OF MEMBRANE BARRIER USED:
- Batch number: CT051021
- Source: InVitro International Inc., Irvin CA, USA.
- Components: Bio-barrier matrix, Bio-barrier diluent, Vials with Chemical Detection System (= CDS), Membrane discs, Compatibility test tubes, Timescale categorize test tubes with buffer A and B, Confirm reagent.

PREPARATION PROCEDURES:
- Preparation of the Bio-Barrier:
The bio-barrier diluent (10 mL) was added to the bio-barrier matrix powder (1 gram) which contained a micro stir bar. This was stirred and heated slowly to 68°C in a water bath container. The membrane discs (at room temperature) were filled with 200 µL solubilized bio-barrier matrix. The entire membrane was covered with matrix and care was taken to avoid air bubbles. Membrane disks were stored in the refrigerator set to maintain 4°C until use. The membrane discs with biobarrier were used the day after preparation.

- Test Item Compatibility Test:
Prior to performing the membrane barrier penetration study, the test item was evaluated for the compatibility with the CDS. The test item (150 µL) was added to the compatibility test tubes filled with CDS fluid. The tube was shaken to dissolve solids. In case the test item was immiscible, the vial was shaken and the color change was read at the interface after 1 minute. If the CDS solution detected a color or consistency change within 5 minutes, the test item was tested for corrosivity using the Corrositex® kit. In case the CDS solution detected no color or consistency change the membrane barrier penetration study was not performed with Corrositex®.

- Test Item Timescale Category Test:
The test item was classified into one of the two timescale categories. This category determined how the penetration response time (if one occurs) was interpreted. The two different penetration response timescales were based on the acid or alkali reserve of the chemical. The test item (150 µL) was added to both buffers A and B, shaken vigorously for 10 seconds and after 1 minute the color change was read on the chart. In case the test item was immiscible, the color change was read at the interface after another minute. Buffer A detected weak or strong acids and buffer B detected strong or weak bases. The tube was shaken vigorously for 5 seconds and the color of the solution was read on the chart confirming that the item is a timescale category 2 item.

TEMPERATURE USED DURING TREATMENT: All tests were performed at room temperature. The samples were at room temperature when applied.

METHOD OF DETECTION
- Indicator solution: CDS fluid
- Dye(s) used: not specified
- Chemical or electrochemical detection system: Changes in the CDS may be color changes (red, orange or lightening) and flaking or precipitation.

METHOD OF APPLICATION:
A disc was placed on a vial with CDS fluid. The test item (500 µL) was applied on top of the matrix within two minutes after the disc was placed on the CDS fluid. One disc was exposed to 500 µL citric acid (10%, negative control) and one disc was exposed to 110 ± 15 mg of the positive control sodium hydroxide. The test item and controls were evenly distributed. Each vial was at least monitored for the first 5 minutes and 5 minutes before and after each packing cut-off time. The time of a change in the CDS fluid was recorded. Changes in the CDS may be color changes (red, orange or lightening) and flaking or precipitation. The elapsed time between application and penetration of the membrane was determined.

NUMBER OF REPLICATES: The test was performed on a total of 4 membrane discs with bio-barrier matrix together with a negative and positive control.

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be corrosive to skin if 3 and 30 minutes elapsed between application of the test substance to the membrane barrier and barrier penetration.
- The test substance is considered to be non-corrosive to skin if the penetration response time > 60 minutes.
- Justification for the selection of the cut-off point(s): not indicated

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Classified as a timescale 1 compound
- Amount(s) applied (volume or weight with unit): 500 µL (undiluted), directly on top of the bio-barrier matrix

NEGATIVE CONTROL
- 10% citric acid (Merck, Nottingham, United kingdom; CAS number 5949-29-1; batch number 1.00244.100; purity ≥ 99%).
- Amount(s) applied (volume or weight): Approximately 500 µL was applied, directly on top of the biobarrier.

POSITIVE CONTROL
- Sodium hydroxide (GHS corrosive subcategory 1B; category obtained from OECD 435) as it is (Merck, Nottingham, United kingdom; CAS number 1310-73-2; batch number B1835898 027: purity ≥ 99%).
- Amount(s) applied (volume or weight): 110 ± 15 mg was applied, directly on top of the biobarrier.

Duration of treatment / exposure:

not indicated

Number of replicates:

four

Results and discussion

In vitro

Results

Irritation / corrosion parameter:

penetration time (in minutes)

Remarks:

Mean

Value:

84

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

ACCEPTABILITY CRITERIA

The in vitro membrane barrier test is considered acceptable if it meets the following criteria:

The negative control citric acid (10%) should be non-corrosive (category obtained from OECD 435) and have a penetration response time > 60 minutes.
The positive control time falls within ± two standard deviations of the positive control historical mean breakthrough time.
The breakthrough time of the positive control sodium hydroxide (as it is) should be between the 3 and 30 minutes (GHS corrosive subcategory 1B; category obtained from OECD 435).

All results presented in the tables of the report are calculated using values as per the raw data rounding procedure and may not be exactly reproduced from the individual data presented.

Any other information on results incl. tables

Test Item Compatibility Test
The test item was evaluated for the compatibility with the CDS. Because a color change (to red) was observed after 1 minute, the test item was compatible with the Corrositex® test system.

Test Item Timescale Category Test
The test item was classified into one of the two timescale categories. The timescale category test showed that the test item is a timescale 1 item (after one minute tube B showed a color change into purple). Since there appeared a color change after 1 minute, the addition of the confirm reagent to tube B was not performed.

 

Membrane barrier penetration test

Since the test item is a timescale 1 test item and showed a mean penetration time of 84 minutes, the test item is classified in UN packing group III (= GHS 1C).

The test passed all acceptance criteria:

1. The negative control citric acid (10%) showed a mean penetration time of >60 minutes (110 minutes) and was therefore non-corrosive.


2. The positive control sodium hydroxide (as it is) breakthrough time (20 minutes) falls within within ± two standard deviations of the positive control historical mean breakthrough time (Appendix 5).


3. The positive control sodium hydroxide (as it is) showed a mean penetration time of
   20 minutes and was therefore classified as UN packing group II (=GSH 1B).

 

Overall it was concluded that the test system functioned properly.

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

In conclusion, the test substance is classified as UN packing group III (= GHS 1C) in the Corrositex® assay under the experimental conditions described in this report.