Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Corrositex
Deviations:
no
Principles of method if other than guideline:
The Corrositex® (InVitro International, Placentia, CA) test is a standardized and reproducible method that can be employed to determine the potential corrosivity and the Packing Group classification of specified categories of chemical compounds under the hazardous materials transportation regulations administered by the U.S. Department of Transportation (DOT) and international dangerous goods codes. The Corrositex® test predicts1,2 the in vivo corrosive potential of a chemical compound or mixture by using as an endpoint the amount of time it takes for a chemical to permeate or destroy a synthetic biobarrier. A color change in a proprietary liquid Chemical Detection System (CDS) is used to indicate that the chemical has passed through the biobarrier.

Procedure
The Corrositex® test is a three step procedure. First, the test article was qualified to ensure that it was compatible with the Corrositex® system, and then it was categorized according to pH to determine cut-off times. Finally, it was classified based on the mean time the test article took to penetrate the biobarriers

Qualification
150 μl of the test article were added to the CDS reagent in a Qualify vial, and the vial was observed for any notable color change. An observable color change indicates that the test article is compatible with the Corrositex® system.

GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
(2-hydroxy-1,1-dimethylethyl)ammonium toluene-4-sulphonate
EC Number:
269-537-8
EC Name:
(2-hydroxy-1,1-dimethylethyl)ammonium toluene-4-sulphonate
Cas Number:
68298-05-5
Molecular formula:
C7H8O3S.C4H11NO
IUPAC Name:
1-hydroxy-2-methylpropan-2-aminium 4-methylbenzene-1-sulfonate
Constituent 2
Chemical structure
Reference substance name:
Butan-1-ol
EC Number:
200-751-6
EC Name:
Butan-1-ol
Cas Number:
71-36-3
Molecular formula:
C4H10O
IUPAC Name:
1-Butanol
Constituent 3
Chemical structure
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
water
Test material form:
liquid

In vitro test system

Test system:
artificial membrane barrier model
Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
NA
Duration of post-treatment incubation (if applicable):
NA
Number of replicates:
3

Test system

Type of coverage:
other: Not applicable
Preparation of test site:
other: Not applicable
Vehicle:
other: Not applicable
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
See section Details on study design
Duration of treatment / exposure:
See section Details on study design
Observation period:
See section Details on study design
Number of animals:
Not applicable
Details on study design:
Test sample preparation: 100 μl of the test article were added to 900 μl of tissue culture water and vortexed to yield a 10% solution (clear colorless liquid). The test article was also used as received.

Categorization:
Next, the test article was categorized, which determined cut-off times for the Packing Group designations. A 10% formulation of the test article was prepared and its pH was measured. If the pH of the 10% formulation was > 7.0, 150 μl of the neat test article were added to Tube A. The pH of Tube A was then measured, and if it was < 5.0, the test article was assigned to Category 1, and if it was > 5.0, the test article was assigned to Category 2. If the pH of the 10% formulation was > 7.0, 150 μl of the neat test article were added to Tube B. The pH of Tube B was measured, and if the final pH was < 9.0, the test article was Category 1, and if it was > 9.0, the test article was Category 2 .

Classification:
Finally, the test article was classified by adding 500 μl of the test article to four test vials containing biobarriers to determine the Packing Group. If the test article mixture permeates or destroys the biobarrier, it will come in contact with the CDS reagent in the vial and induce a color change similar to that observed in the Qualify tube. The amount of time required for the test article to permeate or destroy each biobarrier was recorded and the mean time of the four replicates is used to designate the United Nations (U.N.) Packing Group classification . Classifications are as follows: Packing Group I (severe corrosivity), Packing Group II (moderate corrosivity), Packing Group III (mild corrosivity), or Non-Corrosive. A Positive Control was performed using 1.0 N Sodium Hydroxide. The result for the Positive Control is considered valid if it falls within the range of the MB Research historical mean ± 2 standard deviations. A Negative Control was performed using 1% Citric Acid; the result is considered valid if the breakthrough time is greater than 60 minutes.

Results and discussion

In vitro

Resultsopen allclose all
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
1
Value:
70.5
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
2
Value:
70.33
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
3
Value:
70.17
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
4
Value:
70
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Test article (Catalyst 1786B) is classified as non-corrosive based on results of the Corrositex study. Based on this result, also propan-1-ol,2-amino-2-methyl-, 4-methylbenzenesulphonate is considered non-corrosive.
Executive summary:

Test article Catalyst 1786B was analyzed using Corrositex test method to determine its dermal corrosivity potential.

The results of this study indicated that the test article was compatible with the Corrositex system. The results obtained from the evaluation of 4 replicate tests demonstrated that a mean time of > 70.25 minutes was required to penetrate the biobarriers. These lead to the classification of this test article as a Non-Corrosive material (t>60 min). Based on this result, also propan-1-ol,2-amino-2-methyl-, 4-methylbenzenesulphonate is considered non-corrosive.