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Administrative data

Description of key information

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.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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:
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. certificate)
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
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.
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
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: 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:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
GLP compliance:
yes (incl. certificate)
Species:
cattle
Strain:
not specified
Details on test animals or tissues and environmental conditions:
The bovine eyes, in a Hanks’ Balanced Salt Solution (HBSS) with penicillin-streptomycin, were received from Spear Products on 29 Oct 2015 and transported to MB Research in a refrigerated container.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
Three bovine corneas per group were dosed with 0.75 ml of Catalyst 1786B,
Batch# 1776194, Minimal Essential Media (MEM) (negative control), or 100% Ethanol (positive control). Following a 10-minute exposure for each group of dosed corneas, opacity measurements and sodium fluorescein permeability were determined.
Observation period (in vivo):
Not applicable
Duration of post- treatment incubation (in vitro):
See Details on study design
Number of animals or in vitro replicates:
Not applicable
Details on study design:
The eyes were examined prior to use on the day of dosing. Any eye with a cornea exhibiting evidence of vascularization, pigmentation, opacity or scratches was discarded.
Corneas from eyes that were free of defects were dissected from the surrounding tissues. A 2-3 mm rim of sclera was left attached to each cornea. The corneas were then placed in a container of fresh HBSS.
The dissected corneas were mounted in specially designed holders that were separated into anterior and posterior chambers and filled separately. Each cornea was mounted allowing the epithelium of the cornea to project into the anterior chamber. The posterior chamber was filled with MEM solution ensuring contact with the endothelium. The anterior chamber was filled with MEM solution, ensuring contact with the epithelium. Each cornea was visually inspected again to ensure there were no defects.
The entire holder was incubated at 32ºC (± 1º) and allowed to equilibrate for at least one hour but not longer than two hours.
A pre-exposure determination of opacity was made for each cornea by measuring each against the blank supplied with the opacitometer. Any cornea with a value greater than 7 units was discarded.
Following the pretest observations, the MEM solution was removed from the anterior chamber. A volume of 0.75 ml of ethanol, MEM or test article was applied to the epithelium of each of the three positive controls, three negative controls or three test article-treated corneas in a manner, which ensured the entire cornea was covered. The closed-chamber method of dose administration was used.
All holders and corneas were placed in a horizontal position (anterior side up) in the 32ºC (± 1º) incubator. After 10 (± 1) minutes, the test article, ethanol or MEM solution was removed from the epithelium of the cornea and anterior chamber of the holder by washing with MEM solution containing phenol red. A final rinse was made with MEM without phenol red. The anterior and posterior chambers of the holders were refilled with fresh MEM solution. Opacity measurements were made following the 10-minute exposure and MEM solution refill.
All corneas were incubated at 32ºC (± 1º) for an additional two hours at which time the MEM solution in the anterior and posterior chambers was removed and the holders refilled with fresh MEM solution. A measurement of opacity was taken with each treated cornea compared to the blank supplied with the
OP-KIT. This reading was used in the final IVIS calculations.
Immediately following the two-hour opacity measurement, the MEM solution was removed from the anterior chamber and replaced with 1.0 ml of 0.4% sodium fluorescein solution in Dulbecco's Phosphate Buffered Saline (PBS). Each holder was returned to the 32ºC (±1º) incubator in a horizontal position (anterior side up) ensuring contact of the fluorescein with the cornea.
After 90 (± 5) minutes, the fluid from the posterior chamber was removed and the amount of dye, which passed through the cornea (permeability), was measured as the optical density at 490 nm by a spectrophotometer. A 1:1000 dilution of the fluorescein was prepared and measured in the spectrophotometer as a measure of consistency.
Data analysis
Individual corrected opacity scores were calculated by subtracting the pretest score from the ten-minute and two-hour scores. Corrected mean opacity scores were calculated by averaging the individual two-hour corrected opacity scores for a given dose group and subtracting the mean opacity score for the negative control group. A corrected mean opacity score was not calculated for the negative control, rather only the mean of the individual two-hour corrected opacity scores were calculated (with no subtraction of mean opacity score for negative control.)
Individual corrected optical densities were calculated by subtracting the mean optical density for the negative control group from the individual optical density values. Individual corrected optical densities were not calculated for the negative control group. Corrected mean optical densities were calculated by averaging the individual corrected optical density values for a given dose group. A corrected mean optical density was not calculated for the negative control, rather only the mean of the individual optical densities was calculated.
The In Vitro Irritancy Score (IVIS) for the test article and Vehicle control was calculated by adding the corrected mean opacity score to fifteen times the corrected mean optical density, as shown by the equation below. The calculation to obtain an IVIS for the positive control was performed in the same manner as the test article.
In Vitro Irritancy Score (IVIS) = Corrected Mean Opacity Score + (15 x Corrected Mean Optical Density Score)
The calculation to obtain an IVIS for the negative control was performed by adding the mean opacity score to fifteen times the mean optical density, as shown by the equation below.
In Vitro Irritancy Score (IVIS) = Mean Opacity Score + (15 x Mean Optical Density Score)

Based on the IVIS score, the test article was classified according to the prediction model described in DB-ALM Protocol No. 1271, a modification of the prediction model suggested by Gautheron, et al. (1994). Results from test situations should be compared to known materials tested under similar conditions. This classification system is the most consistent with recent regulatory reviews of the assay performance.
IVIS CLASSIFICATION
0 to 3 Non-Irritant
3.1 to 25 Mild Eye Irritant
25.1 to 55 Moderate Eye Irritant
55.1 and above Severe/Corrosive Eye Irritant
OECD Guideline #437 defines a substance that produces an IVIS of > 55 as Category 1, a substance that causes “Serious eye damage.”
IVIS UN GHS2
≤ 3 No Category
>3 to ≤55 No prediction can be made
>55 Category 1
The assay was accepted because the positive control had an IVIS that fell between two standard deviations of the historical mean.
Irritation parameter:
in vitro irritation score
Run / experiment:
Mean value for 3 experiments
Value:
74.83
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Mean of 3 experiments
Value:
61
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Based on an In Vitro Irritation Score of greater than 55, and as defined in OECD Guideline 437, the test article is in UN GHS Category 1. According to EURL ECVAM DB-ALM Protocol No. 127, Catalyst 1786B, is considered to be a severe/corrosive eye irritant.
Based on this result, also propan-1-ol,2-amino-2-methyl-, 4-methylbenzenesulphonate is considered severe/corrosive eye irritant.
Executive summary:

Based on results of OECD 437 study (Bovine Corneal Opacity and Permeability) the test item is considered to be a severe/corrosive eye irritant. Based on this result, also propan-1-ol,2-amino-2-methyl-, 4-methylbenzenesulphonate is considered severe/corrosive eye irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Additional information

Based on results of OECD 437 study (Bovine Corneal Opacity and Permeability)study, Catalyst 1786B is

considered to be a severe/corrosive eye irritant.

Based on this result, also propan-1-ol,2-amino-2-methyl-, 4-methylbenzenesulphonate is considered

severe/corrosive eye irritant.
.

Justification for classification or non-classification