(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-amine

Skin irritation / corrosion

Administrative data

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-amine

EC Number:

700-140-9

Cas Number:

752984-24-0

Molecular formula:

C11H15N

IUPAC Name:

(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-amine

Specific details on test material used for the study:

Name of test substance: 1H-Inden-1-amine, 2,3-dihydro-2,6-dimethyl-, (1R,2S)-
Test substance No.: 19/0201-1
Batch identification: B6943 v. 10.04.2019
CAS No.: 752984-24-0
Content: 99.9 area-% (96.6 area-% trans isomer, 3.3 area-% cis diastereomer)
Identity: Confirmed (for details see Final Report, Study code: 19L00134)
Homogeneity: The test substance was homogeneous by visual inspection.
Storage stability: Expiry date: 09 Apr 2021
The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.

In vitro test system

Test system:

artificial membrane barrier model

Justification for test system used:

The Corrositex® assay is a standardized in vitro corrosion test. The Corrositex® assay kit is available commercially from InVitro International. The Corrositex® bio barrier membrane is a test system consisting of a reconstituted collagen matrix. The assay is based on the time that the test substance requires to penetrate through the Corrositex® bio barrier membrane and produce a change in the Chemical Detection System (CDS). The Corrositex® assay is used to determine the corrosive potential of test substances. The assay is limited to testing materials that cause detectable pH changes in the CDS.

Vehicle:

unchanged (no vehicle)

Details on test system:

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 (blank) control each. A membrane disc coated with the bio barrier matrix was placed into one vial containing the CDS. 500 μL undiluted test substance were added onto the membrane disc. An electronic time clock was started with the application. The vial was observed for three minutes for any change in the CDS. If no color change was observed within three minutes, the remaining membranes were treated with the test substance. An electronic time clock was started with each application. 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 occurred. The elapsed time between test substance application and the first change in the indicator solution (i.e. barrier penetration) was recorded.

The Corrositex® assay was accepted if the breakthrough time for the positive control substance was in the historic control range (mean ± 2-3x standard deviations, see chapter 4.3.). The expected breakthrough time of the concurrent positive control (Sodium Hydroxide solid) should be between 8 - 16 min. In order to demonstrate the functional integrity of the membrane barrier, the acceptance criterium for the negative control was not to induce membrance breakthrough within a 60-minute observation period.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

500 µL

Duration of treatment / exposure:

up to 60 min

Number of replicates:

5

Results and discussion

In vitro

Results

Results 1

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

first experiment vial #1

Value:

3.37

Results 2

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

first experiment vial #2

Value:

> 60

Remarks on result:

other: no breakthrough

Results 3

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

first experiment vial #3

Value:

> 60

Remarks on result:

other: no breakthrough

Results 4

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

first experiment vial #4

Value:

3.06

Results 5

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

first experiment vial #5

Value:

> 60

Remarks on result:

other: no breakthrough

Results 6

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

first experiment: Positive Control (PC)

Value:

14.49

Results 7

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

first experiment: Negative Control (NC)

Value:

> 60

Remarks on result:

other: no breakthrough

Results 8

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

second experiment vial #1

Value:

20.09

Results 9

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

second experiment vial #2

Value:

1.56

Results 10

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

second experiment vial #3

Value:

6.12

Results 11

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

second experiment vial #4

Value:

9.38

Results 12

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

second experiment: Positive Control (PC)

Value:

10.39

Results 13

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

second experiment: Negative Control (NC)

Remarks on result:

other: no breakthrough

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

Based on the inconclusive result observed and by applying the evaluation criteria the potential of 1H-Inden-1-amine, 2,3-dihydro-2,6-dimethyl-, (1R,2S)- to cause dermal corrosion cannot be assessed in the Corrositex® assay and it cannot be excluded that
the test substance has a corrosive potential. For final assignment of a risk phase at present, results from another study would be needed.

Executive summary:

The Corrositex® assay was conducted in order to assess the potential of 1H-Inden-1-amine, 2,3-dihydro-2,6-dimethyl-, (1R,2S)- to cause dermal corrosion by a single topical application of 500 μL test substance to the Corrositex® bio barrier membrane. The Corrositex® bio barrier membrane is a test system consisting of a reconstituted collagen matrix. The assay is based on the time that the test substance requires to penetrate through the Corrositex® bio barrier membrane and produce a change in the Chemical Detection System (CDS).

In addition to the test substance, a positive and a negative control were run in the assay. The Corrositex® assay showed the following results: The qualification screen demonstrated that the test substance is able to react with the CDS and produce a visible color change. Therefore, the membrane barrier test method was determined to be suitable for the evaluation of the corrosive potential of the test substance. A timescale category test was carried out to distinguish between weak and strong acids or bases. The test substance was assigned to timescale category 2 (having a low acid/alkaline reserve).

In the main test, five Corrositex® bio barrier membranes were treated with the undiluted test substance. Two CDS showed a minimal reddish discoloration on the surface shortly after test substance application, while the other two CDS did not show any discoloration within the 60-minute observation period. A fifth CDS first used for color comparison and then applied additionally to the four CDS with test substance did not show any discoloration within the 60-minute observation period either. Due to the nontypical observations without concrete breakthrough, no conclusive result could be determined. The negative control, 10% citric acid monohydrate, did not produce any reaction within 60 minutes after application. Sodium hydroxide (solid) applied as positive control showed a reaction time of 14 minutes and 49 seconds after application and was assigned accordingly Thus, the controls fulfill the acceptance criteria and demonstrate the validity of the assays.

A second test run was performed for clarification. In the second test run, four Corrositex® bio barrier membranes were treated with the undiluted test substance. All of the CDS showed a minimal reddish discoloration on the surface shortly after test substance application. Due to the recurrent nontypical observations without concrete breakthrough, no conclusive result could be determined in the second test run as well. The negative control, 10% citric acid monohydrate, did not produce any reaction within 60 minutes after application. Sodium hydroxide (solid) applied as positive control showed a reaction time of 10 minutes and 39 seconds after application and was assigned accordingly. Thus, the controls fulfill the acceptance criteria and demonstrate the validity of the assays. Based on the inconclusive results observed and by applying the evaluation criteria, the potential of 1H-Inden-1-amine, 2,3-dihydro-2,6-dimethyl-, (1R,2S)- to cause dermal corrosion can not be assessed in the Corrositex® assay and it can not be excluded that the test substance has a corrosive potential.

For final assignment of a risk phase at present, results from another study would be needed.